# projects

application_id: 10881465
project_number: 1S10GM154287-01
project_title: Electrophoresis Imaging System
administering_ic: NIGMS
award_notice_date: 2024-06-26
opportunity_number: PAR-23-138
application_type: 1
activity_code: S10
ic: GM
serial_number: 154287
program_official: BECKETT, DOROTHY
project_start_date: 2024-07-01
project_end_date: 2025-06-30
study_section: Special Emphasis Panel[ZRG1 CDB-L (30)]
contact_pi_person_id: 10305487
contact_pi: BANGA, SIMRAN
other_pis: Not Applicable
congressional_district: 02
department: BIOLOGY
primary_duns: 077876258
primary_uei: U5GMACGETKJ1
duns_number: 077876258
uei: U5GMACGETKJ1
fips: US
organization_id: 9186501
organization_name: WESTERN KENTUCKY UNIVERSITY
organization_city: BOWLING GREEN
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 421011001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project SummaryThe objective of this RLI-S10 proposal is to acquire an electrophoresis imaging system to enhance research andteaching capabilities at the Western Kentucky University (WKU). An imaging system is a basic requirement inthe field of biological sciences which is commonly used for visualization documentation and analysis of gelelectrophoresis and western blotting techniques used for DNA and protein detections. In the Department ofBiology at WKU several investigators work on research projects that routinely need this instrument.Additionally several molecular biology and biochemistry laboratory courses use gel imaging systemthroughout the semester for experimental analysis. These research and teaching laboratories provide hands-onlearning opportunities which can substantially enhance research quality and learning experience of a largenumber of undergraduate students.The users on this application are actively engaged in research funded by internal and external funding agenciesand have expertise with research capabilities to engage students in a wide variety of biomedical research usingdifferent model systems and experimental analyses. The users seek funds through this proposal to replace their18-year-old imager Fluorchem HD2 which has limited imaging capabilities and is becoming increasinglydifficult to operate as it only runs on computers with Windows 7 that are becoming more and more scarce andare not updatable. Moreover the manufacturer is no longer supporting this gel imager thus making it difficultto change different parts of the old imager. The lack of a modern high-resolution functional imaging systemeffects the quality of data and reliability of analyses in education and research. The acquisition of a newChemDoc MP imaging system from Bio-Rad with up-to-date digital imaging capability will equip researcherseducators and students at WKU the ability to obtain higher resolution images of DNA and protein gels withgreater depth and accuracy.This imaging system will be housed in the Biotechnology Center at WKU and will be available as a sharedresource that will provide several learning and training opportunities for the student community across differentdepartments and majors at our primarily undergraduate institute. It will enable the diverse undergraduatepopulation to use basic laboratory equipment and gain skills in producing high quality research data. Theequipment will fulfill the imaging needs for four different research laboratories and five different teachinglaboratories wherein undergraduate students will gain valuable firsthand learning experience through the useof the instrument at our institute.

project_terms:
18 year old;Biochemistry;Biological Models;Biological Sciences;Biology;Biomedical Research;Biotechnology;Communities;Computers;DNA;Data;Documentation;Education;Educational process of instructing;Electrophoresis;Equipment;Functional Imaging;Funding;Funding Agency;Gel;Image;Kentucky;Laboratory Research;Learning;Manufacturer;Modernization;Molecular Biology;Population;Proteins;Research;Research Personnel;Research Project Grants;Resolution;Resource Sharing;Running;Students;Systems Analysis;Techniques;Universities;Visualization;Western Blotting;Work;digital imaging;experience;experimental analysis;gel electrophoresis;hands-on learning;high resolution imaging;imager;imaging capabilities;imaging system;instrument;laboratory curriculum;laboratory equipment;skills;student participation;teaching laboratory;training opportunity;undergraduate student

public_health_relevance:
Project NarrativeThis grant will fund the purchase of a ChemiDoc MP Imaging System an essential equipment routinely usedfor imaging and quantifying nucleic acids and proteins in gels and western blots which is necessary tocomplete various funded studies and fulfill degree requirements for biology majors. The requested instrumentwill fulfill the imaging needs of four research laboratories engaged in a wide area of research ranging frommicrobiology cell proliferation and tumor metastasis. Furthermore this imager will support learningobjectives of five different biology courses and enrich the educational experience of undergraduate studentsfrom multiple departments with different majors.


application_id: 10881027
project_number: 1R01HL163589-01A1
project_title: Targeting Endothelial Cell Mineralocorticoid Receptor Against Aortic Aneurysm in Females
administering_ic: NHLBI
award_notice_date: 2024-03-08
opportunity_number: PA-20-185
application_type: 1
activity_code: R01
ic: HL
serial_number: 163589
suffix: A1
program_official: STABLEY, JOHN N
project_start_date: 2024-06-01
project_end_date: 2028-05-31
study_section: Atherosclerosis and Vascular Inflammation Study Section[AVI]
contact_pi_person_id: 8664760
contact_pi: GUO, ZHENHENG
other_pis: GONG, MING C
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
Project SummaryAbdominal aortic aneurysm (AAA) is a severe vascular disease affecting millions of Americans with highmorality. Currently no medication has been approved to treat this devastating disease. Women are less andlater to develop AAA than men. Nevertheless AAA in women is more aggressive. It grows faster. It is morelikely to rupture at smaller diameters resulting in higher mortality with worse morbidity after surgical repair.Smoking promotes AAA in both men and women but women who smoke are at higher risk for AAA than men.Estrogen (E2) has long been believed to protect premenopausal women from AAA. However its effect on AAAin animal models and human clinical trials is controversial. Several AAA animal models have been developedand have contributed to our current understating of AAA. However one of the common limitations of theseanimal models is to use young animals to study AAA which occurs mainly in older people. To fill this significantgap we developed a relatively new AAA mouse model that requires using older male mice activation ofmineralocorticoid receptor (MR) by aldosterone (Aldo) and high salt intake to induce AAA. Surprisingly wefound that Aldo and salt (Aldo-salt) only induced AAA in male mice but not in female mice unless female micewere subjected to ovariectomy (Ovx) or nicotine. Mechanistically MR was upregulated by Aldo-salt with Ovx ornicotine in endothelial cells (EC) in the aorta with accumulation in the nucleus indicating E2 may protectfemale mice from AAA via suppressing MR expression and/or nuclear translocation in EC in the aorta.Interestingly Per2 a core circadian gene interacts with ER and MR and is required for E2 to suppress MRexpression. Moreover genetic deletion of MR in EC but not smooth muscle cell and myeloid cells inhibitedAldo-salt-induced AAA concordant with a reduction in ICAM1 upregulation in EC and neutrophil (N)infiltration in the aorta. Based on the literature and robust evidence from our preliminary data we hypothesizethat E2 inhibits Aldo-salt-induced MR protein upregulation and nuclear translocation via ER/Per2/MRinteraction in EC in the aorta thus protecting female mice from ICAM1 upregulation N infiltration and aorticaneurysm. Aim 1 is to define the mechanism by which E2 protects Aldo-salt-induced aortic aneurysm byinhibiting MR protein upregulation and nuclear translocation via ER in EC in the aorta in female mice with Ovxand nicotine; Aim 2 is to determine whether targeting the Per2/MR/ICAM1/N signaling can protect femalemice with Ovx or nicotine from Aldo-salt-induced aortic aneurysm. To achieve these goals 12-week-old or 12-month-old C57BL/6 iECERKO Per2KO iECPer2KO iECMRKO and WT control female mice will besubjected to Ovx or nicotine and then treated with E2/progesterone (P4)/dihydrotestosterone (DHT)/ICAM1/Ly6G antibody (Ab). The effect of hormone therapy genetic deletion and Ab blocking on aging/Aldo-salt-induced AAA will be determined. The proposed studies will shed new mechanistic insight into the pathologiesof AAA in women and provide preclinical evidence to help identify new therapeutic targets against AAA.

project_terms:
Abdominal Aortic Aneurysm;Accounting;Affect;Aging;Aldosterone;American;Aneurysm;Animal Model;Animals;Antibodies;Aorta;Aortic Aneurysm;Atherosclerosis;Blocking Antibodies;Cell Nucleus;Cessation of life;Clinical Trials;Data;Diameter;Disease;Endothelial Cells;Estrogens;Exhibits;Female;Genes;Genetic;Goals;Hormone replacement therapy;Human;Hypertension;ICAM1 gene;Infiltration;Intercellular adhesion molecule 1;Literature;Mineralocorticoid Receptor;Modeling;Molecular;Morality;Morbidity - disease rate;Mus;Myeloid Cells;Neutrophil Infiltration;Nicotine;Nuclear Translocation;Older Population;Operative Surgical Procedures;Ovariectomy;Pathology;Pharmaceutical Preparations;Postmenopause;Premenopause;Progesterone;Research;Risk Factors;Role;Rupture;Scheme;Signal Transduction;Smoke;Smoking;Sodium Chloride;Stanolone;Testing;Therapeutic;United States;Up-Regulation;Vascular Diseases;Woman;circadian;eplerenone;high risk;hormone therapy;insight;juvenile animal;male;men;mortality;mouse model;neutrophil;new therapeutic target;novel therapeutics;old mice;pre-clinical;receptor;receptor expression;repaired;salt intake;sex;sexual dimorphism

public_health_relevance:
Project NarrativeAbdominal aortic aneurysm (AAA) is a severe vascular disease affecting millions of Americans. Womendevelop AAA less and later than men but AAA in women is more aggressive with more rapid expansion ahigher tendency to rupture and higher mortality following rupture. This application aims to investigate themechanisms that underlie AAA in female mice and to identify new therapeutic targets to develop new drugs totreat AAA.


application_id: 10880732
project_number: 5P30AG072946-04
project_title: Core G: University of Kentucky Alzheimer's Disease Core Center
administering_ic: NIA
award_notice_date: 2024-06-21
opportunity_number: RFA-AG-21-019
application_type: 5
activity_code: P30
ic: AG
serial_number: 072946
project_start_date: 2021-08-01
project_end_date: 2026-06-30
study_section: ZAG1-ZIJ-G
subproject_number: 9600
contact_pi_person_id: 1870576
contact_pi: VAN ELDIK, LINDA J
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/Abstract: Research Education ComponentThe Research Education Component (REC) of the UK-ADRC offers a variety of research educational activitiesand comprehensive mentored research skills development programs that will enhance the development of thefuture workforce to meet the nations biomedical behavioral and clinical needs in Alzheimers disease andrelated dementias (ADRD) research. The REC will leverage resources within and outside the UK-ADRC tocreate an outstanding multidisciplinary and collaborative environment for training the next generation ofresearchers in scientific areas that parallel the theme of our ADRC (Transitions from Normal to Late-Life Multi-Etiology Dementias) and with an emphasis on increasing representation of researchers from diversebackgrounds. We will continue to build on a long history of collaborative and dedicated faculty a strongfoundation in multidisciplinary team science and an outstanding track record of success in mentoring andeducation of researchers across the training spectrum. We will also establish a new REC Scholar programaimed at junior investigators (Assistant Professors senior research associates or clinical fellows). Thisprogram will support junior investigators from diverse multidisciplinary fields to pursue mentored basictranslational or clinical research in ADRD and follow a customized training plan to help the scholars movetoward their career development goals. This training will be done in a supportive and collaborative academicenvironment with substantial training resources and an experienced and dedicated training faculty. Scholarswill have the opportunity to learn state-of-the-art research skills in disciplines that have been identified ascritically needed areas for the ADRC workforce of the future. Examples of training areas where the UK-ADRChas strong expertise include analysis of longitudinal clinical outcomes clinical trial design MRI imaging andnovel fluid biomarkers quantitative neuropathology and AD mimics data analysis/ study design in mixeddementias and health literacy and inequities. REC goals will involve interactions with all the UK-ADRC Coresand will be achieved through the following specific aims.Aim 1. Provide education programs and research skills development opportunities for investigators at UK.Aim 2. Identify select support and retain REC scholars from diverse backgrounds and disciplines to engagein ADRD research.Aim 3. Develop an individualized mentoring plan and educational program for each REC scholar to enableadvancement to independent research and funding in ADRD research.Aim 4. Evaluate progress of the REC scholars address barriers towards the goal of independence in ADRDresearch and refine delivery of the programs educational structure and processes.Following completion of the Program participants will have the knowledge expertise and confidence tosuccessfully pursue a long-term career in dementia research.

project_terms:
Acceleration;Achievement;Address;Advisory Committees;Alzheimer's Disease;Alzheimer's Disease Core Center;Alzheimer's disease related dementia;Area;Basic Science;Behavioral;Biological Markers;Clinical;Clinical Research;Clinical Trials Design;Communities;Competence;Data Analyses;Dedications;Dementia;Development;Discipline;Early Diagnosis;Education;Educational Activities;Environment;Etiology;Exposure to;Faculty;Foundations;Funding;Future;Goals;Image;Individual;Interdisciplinary Study;Kentucky;Knowledge;Leadership;Learning;Liquid substance;Magnetic Resonance Imaging;Mentors;Monitor;Outcome;Participant;Postdoctoral Fellow;Prevention Research;Process;Program Development;Recording of previous events;Research;Research Design;Research Personnel;Research Project Grants;Resources;Scholars Program;Science;Scientist;Standardization;Structure;System;Teacher Professional Development;Training;Training Programs;Translational Research;Universities;career;career development;collaborative environment;education planning;education research;experience;health inequalities;health literacy;high school;improved;innovation;instrument;investigator training;late life;longitudinal analysis;mixed dementia;multidisciplinary;neuropathology;next generation;novel;prevent;professor;programs;recruit;skill acquisition;skills;success;therapy development;training opportunity;treatment research;undergraduate student


application_id: 10880730
project_number: 5P30AG072946-04
project_title: Core E: University of Kentucky Alzheimer's Disease Core Center
administering_ic: NIA
award_notice_date: 2024-06-21
opportunity_number: RFA-AG-21-019
application_type: 5
activity_code: P30
ic: AG
serial_number: 072946
project_start_date: 2021-08-01
project_end_date: 2026-06-30
study_section: ZAG1-ZIJ-G
subproject_number: 9598
contact_pi_person_id: 9662252
contact_pi: SCHMITT, FREDERICK
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/Abstract: Outreach Recruitment and Engagement CoreThe Outreach Recruitment and Engagement (ORE) Core plays a central role in achieving UK-ADRC goals byfunctioning as a key link between the Center and the local and state communities. ORE Core programs andactivities have created and will maintain an educated local community eager to receive updated information onAD and to participate in our Centers research. Through ORE Core efforts the UK-ADRC will continue to workwith both the Commonwealth of Kentucky and UK partners in directing state and institutional responses tomeeting dementia health care needs and increasing health literacy in the elderly. ORE Core activities includerecruitment and retention of diverse participants into a longitudinal cohort with annual clinical examinations andbrain donation upon death. Other activities involve the development and testing of innovative outreach andengagement activities in the community to increase awareness of AD/ADRD plus the importance of researchand research participation. Over the past five years the ORE Core has taken the lead in developing innovativepartnerships and products to support research participation by African Americans the largest minority group inKentucky. We will continue to emphasize recruitment and retention of research participants at the earlieststages of the cognitive continuum (Cognitively Normal and MCI). These efforts involve engaging theseparticipants in the ADRC longitudinal cohort as well as activities to enhance agreement to brain donationwillingness to engage in affiliated clinical studies and therapeutic trials and donation of antemortembiospecimens. In the next cycle we will maintain and further build on these efforts and partnerships throughthe following specific aims:Aim 1. Recruit and retain participants into our longitudinal cohort affiliated research and NIA initiativesfocusing on improving recruitment and retention of African Americans and other URGs.Aim 2. Increase community awareness of AD and ADRD through the promotion of health literacy that furtherenhances recruitment and retention of minority participants in research.Aim 3. Evaluate the effectiveness of our activities with both qualitative and quantitative metrics.Aim 4. Support the UK-ADRC Cores to maximize national and international collaborations.The ORE Core plays a critical role in the UK-ADRC and works closely with the other Cores to supportrecruitment and retention activities for research protocols clinical trials and national initiatives; increasecommunity awareness of AD and maintain a strong presence in the African-American community; and supportoutreach initiatives for the lay community in collaboration with key partners. These functions are vital to the UK-ADRC mission to catalyze outstanding and innovative research outreach education and clinical programs.

project_terms:
Address;African American;African American population;Aging;Agreement;Alzheimer's Disease;Alzheimer's Disease Core Center;Alzheimer's disease related dementia;American;Autopsy;Awareness;Biological Markers;Brain;Brothers;Caring;Catchment Area;Censuses;Cessation of life;Church;Clinic;Clinical;Clinical Research;Clinical Trials;Cognitive;Collaborations;Communities;Consent;Data;Databases;Dementia;Development;Disease;Education;Elderly;Elements;Enrollment;Etiology;Event;Extramural Activities;Faith-based organization;Fostering;Foundations;Genetic;Goals;Grant;Health Promotion;Healthcare;Institution;International;Kentucky;Lead;Link;Longitudinal cohort;Measures;Minority;Minority Groups;Mission;Neck;Outcome;Participant;Pathology;Play;Protocols documentation;Reporting;Research;Research Activity;Research Support;Resources;Risk;Risk Assessment;Role;System;Testing;Therapeutic Trials;Time;Underrepresented Populations;Universities;Update;Work;checkup examination;clinical examination;cohort;community engagement;dementia risk;demographics;disparity reduction;effectiveness evaluation;efficacy evaluation;ethnic minority population;ethnoracial;health disparity;health literacy;improved;innovation;late life;meetings;mixed dementia;neuropathology;outreach;outreach program;participant retention;patient engagement;programs;racial minority population;recruit;research study;response;success;volunteer;willingness


application_id: 10880729
project_number: 5P30AG072946-04
project_title: Core D: University of Kentucky Alzheimer's Disease Core Center
administering_ic: NIA
award_notice_date: 2024-06-21
opportunity_number: RFA-AG-21-019
application_type: 5
activity_code: P30
ic: AG
serial_number: 072946
project_start_date: 2021-08-01
project_end_date: 2026-06-30
study_section: ZAG1-ZIJ-G
subproject_number: 9597
contact_pi_person_id: 1911366
contact_pi: NELSON, PETER T.
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/Abstract: Neuropathology CoreThe overall objective of the Neuropathology Core of the UK-ADRC is to support research on normal brainaging presymptomatic AD MCI early and late AD mixed dementia syndromes and other dementingdisorders. Autopsies will be performed by our Rapid Autopsy Team on longitudinally followed subjects from ourClinical Core. We will perform short post-mortem interval autopsies and we will maintain a high autopsy rate.This Core is optimally tailored to help address important research questions. The Core will provide brain tissueCSF and other biospecimens for investigators at UK other ADRCs and outside investigators. The Core willalso provide consensus conference determined diagnoses quantitation of neurofibrillary tangles neuriticplaques and diffuse plaques from 8 brain regions Ab quantitation Braak staging CERAD and NIA-ReaganInstitute staging on all autopsied cases along with evaluation of alpha-synuclein and TDP-43 proteinopathy.This brain bank has been operating continuously for over three decades with a strong track record so specialcare will be taken to ensure diagnostic excellence consistency and continuity. The Core will maintain a tissuebank of the above specimens and frozen serum plasma buffy coats and CSF from living patients. Specialemphasis will be placed on generating rigorous quantititative pathologic metrics from digital pathology andproviding investigators with specimens from cognitively intact control subjects with no Ab deposition andsparse tau pathology (successful cerebral aging) and many cases with mixed pathologies. Providing thesesamples will contribute to clinical-pathological correlation studies and cutting-edge research that includesponsored studies related to AD genomics oxidative stress hippocampal sclerosis/LATE dementia with Lewybodies Down syndrome and neuroinflammation. Frequent consensus conferences will be held with theClinical Biomarker and Data Management and Statistics Cores to help define clinical-pathological diagnoseson all autopsied subjects. The Neuropathology Core is strongly integrated with other Cores of the UK-ADRCand exploits unique opportunities to conduct clinical-pathological correlative studies on longitudinally followedsubjects. Through these methods we will better understand normal brain aging and the transition to multi-etiology dementia with the goal of contributing to therapeutic or preventive measures. The NeuropathologyCore complements the other Cores of the UK-ADRC to provide extremely essential diagnoses and tissuesamples that are required for many cutting-edge researchers at the University of Kentucky and elsewhere. Wewill build on our track record of excellence using innovative tools related to brain autopsies neuropathologicaldiagnoses tissue banking and clinical-pathological correlation. Our specific aims are:Aim 1: Provide state-of-the-art neuropathological and biospecimen repository servicesAim 2: Leverage neuropathology resources and expertise to contribute to research effortsAim 3: Integrate with other cores to contribute to administrative research and educational missions

project_terms:
Address;Aging;Alzheimer's Disease;Alzheimer's Disease Core Center;Area;Autopsy;Biological;Biological Markers;Biological Specimen Banks;Biometry;Brain;Brain Diseases;Brain imaging;Brain region;Caring;Catalogs;Cerebrospinal Fluid;Cerebrovascular Disorders;Cerebrum;Clinical;Clinical Trials;Cognitive;Collaborations;Consensus;Correlation Studies;Correlative Study;DNA;Data;Databases;Dementia;Dementia with Lewy Bodies;Deposition;Diagnosis;Diagnostic;Disease;Down's Syndrome;Education;Ensure;Etiology;Evaluation;Freezing;Frontotemporal Lobar Degenerations;Genetic;Genetic study;Genomics;Goals;Impaired cognition;Individual;Infrastructure;Investigation;Kentucky;Laboratory Research;Lesion;Memory;Methodology;Methods;Mission;Nerve Degeneration;Neurofibrillary Tangles;Oxidative Stress;Pathologic;Pathology;Patients;Plasma;Preventive measure;Process;Protocols documentation;Publishing;Research;Research Personnel;Research Support;Resources;Running;Sampling;Senile Plaques;Serum;Services;Specimen;Staging;Standardization;Syndrome;System;Tauopathies;Therapeutic;Thinness;Tissue Banks;Tissue Sample;Tissues;Universities;Work;age related;age related neurodegeneration;aging brain;alpha synuclein;blood product;brain tissue;cerebrovascular pathology;clinical center;cohort;data management;demented;digital;digital pathology;experience;genome wide association study;hippocampal sclerosis;innovation;late life;limbic-predominant age-related TDP-43 encephalopathy;meetings;mixed dementia;neuroinflammation;neuropathology;novel;pre-clinical;protein TDP-43;religious order study;statistics;symposium;synucleinopathy;tau Proteins;tool


application_id: 10880728
project_number: 5P30AG072946-04
project_title: Core C: University of Kentucky Alzheimer's Disease Core Center
administering_ic: NIA
award_notice_date: 2024-06-21
opportunity_number: RFA-AG-21-019
application_type: 5
activity_code: P30
ic: AG
serial_number: 072946
project_start_date: 2021-08-01
project_end_date: 2026-06-30
study_section: ZAG1-ZIJ-G
subproject_number: 9596
contact_pi_person_id: 12098486
contact_pi: ABNER, ERIN
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/Abstract: Data Management and Statistics CoreThe Data Management and Statistics (DMS) Core can be conceptualized as the lynchpin for integration of theADRC Cores and is vital to the success of the UK-ADRC. Its critical roles include managing a large centralizeddatabase consulting with ADRC-affiliated researchers and working to develop and apply innovative statisticalmethodology for data analysis. Data management efforts focus on collecting storing and sharing high qualitydata using a web-based platform. This focus begins with the leadership and vision and attention to detailprovided by the DMS Core. This core has an enviable track record of timely and accurate reporting of a highvolume of data to NACC. Further weekly Core meetings are popular with UK-ADRC investigators who find thatthe expert advice provided by our seasoned investigators improves their success in pilot studies grantapplications and publications. The Core also participates as a full partner to the research mission of the UK-ADRC emphasizing transitions in late life from normal to multiple etiology dementia. A key element of thisCore is the well-established track record of developing novel methodology to analyze data collected at the UK-ADRC and from other cohorts with a focus on elderly subjects transitions to MCI and eventually dementia. TheCore also provides training for students enrolled in the graduate programs in Gerontology Public HealthEpidemiology and Biostatistics Psychology and Statistics. It is committed to developing younger faculty tobecome productive ADRC investigators. In keeping with the mission of the UK-ADRC faculty in this Core alsocontribute to the dementia research community at large through service on external advisory committeesstudy sections manuscript reviews and data safety monitoring boards. The DMS Core will continue thesecritical responsibilities through the following specific aims.Aim 1: Maintain and expand an integrated data warehouse and suite of web-based data collection applicationsand reporting platforms for ADRC Cores and projects.Aim 2: Provide expertise on experimental design and statistical analysis.Aim 3: Support the clinical biomarker neuropathological educational and outreach missions of the ADRC.Aim 4: Contribute to the activities of the dementia community at large through service and research.

project_terms:
Advisory Committees;Aging;Alzheimer's Disease;Alzheimer's Disease Core Center;Applications Grants;Attention;Bioinformatics;Biological Markers;Biometry;COVID-19 pandemic;Clinical;Clinical Data;Clinical Trials;Clinical Trials Data Monitoring Committees;Cognitive;Collaborations;Communities;Data;Data Analyses;Data Collection;Dementia;Development;Education;Education and Outreach;Elderly;Elements;Enrollment;Environment;Epidemiology;Etiology;Evaluation;Event;Experimental Designs;Extramural Activities;Faculty;Funding;Generations;Genetic;Gerontology;Information Systems;Interruption;Kentucky;Leadership;Life;Literature;Manuscripts;Methodology;Mission;Neuroepidemiology;Observational Study;Online Systems;Participant;Pathology;Pilot Projects;Procedures;Productivity;Psychology;Public Health;Publications;Reporting;Research;Research Design;Research Methodology;Research Personnel;Resources;Risk Factors;Role;Sampling;Seasons;Services;Statistical Data Interpretation;Study Section;System;Tablets;Time;Training;Universities;Vision;central database;cohort;dashboard;data dictionary;data integration;data management;data warehouse;direct application;doctoral student;education research;electronic data capture system;improved;innovation;interest;late life;meetings;member;mixed dementia;neuropathology;novel;outreach;programs;recruit;statistics;student training;success;user-friendly;web app;web platform;web site


application_id: 10880725
project_number: 5P30AG072946-04
project_title: University of Kentucky Alzheimer's Disease Research Center
administering_ic: NIA
award_notice_date: 2024-06-21
opportunity_number: RFA-AG-21-019
application_type: 5
activity_code: P30
ic: AG
serial_number: 072946
program_official: ELLIOTT, CERISE
project_start_date: 2021-08-01
project_end_date: 2026-06-30
study_section: ZAG1-ZIJ-G(M1)
contact_pi_person_id: 1870576
contact_pi: VAN ELDIK, LINDA J
other_pis: Not Applicable
congressional_district: 06
department: NEUROSCIENCES
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/Abstract: OverallThe University of Kentucky Alzheimers Disease Research Center (UK-ADRC) is an experienced andcollaborative center that has facilitated pioneering research in AD and related dementias (ADRD) since itsinception in 1985. Our principal mission is to serve as the focal point for all AD-related activities at UK and thisregion of the United States by providing an environment and core resources that catalyze innovative researchoutreach education and clinical programs. Our signature resources include: 1) a cognitively normal group of~500 subjects followed longitudinally together with ~300 additional subjects who transitioned to MCI ordementia and all committed to brain autopsy upon death; 2) a strong autopsy program with clinical-neuropathological correlations and short postmortem interval research material; 3) a maturing programstudying the early preclinical biological emergence of mixed pathologies and how they contribute to late lifedementia states with an increasing focus on antemortem biomarker collection; 4) an integrated centralizeddatabase and innovative biostatistical expertise to characterize clinical and biological transitions; 5) asuccessful and close partnership with the African-American community and increased participation ofunderrepresented individuals in our longitudinal cohort and ADRC-affiliated research studies and clinical trials;and 6) a rich interdisciplinary training environment that provides multi-faceted educational opportunities forresearchers healthcare providers and our community partners. The overarching theme of the UK-ADRC is:Transitions from Normal to Late-Life Multi-Etiology Dementia. Our well-characterized longitudinal cohortand historically strong neuropathology program focused on normal aging preclinical disease states and earlycognitive transitions have been central to our success in defining early pathogenic mechanisms underlying thetransitions from normal cognitive aging to impairment. In addition these efforts have been a driving force in ourrecognition of the heterogeneity and multiple pathologies that characterize late-life dementia. The UK-ADRCwill continue to leverage our strengths to enhance our impact and Centerness by our focus on thisoverarching theme and the pursuit of four overall specific aims.Aim 1. Facilitate and enhance basic translational and clinical research in AD and related dementias.Aim 2. Provide the necessary resources and interactive environment to support and create new opportunitiesfor innovative research.Aim 3. Maintain and grow educational opportunities and community partnerships to promote awarenessincrease participation in research and provide an innovative and interdisciplinary training environment.Aim 4. Contribute to the national efforts and collaborative activities with other centers programs and groups toadvance AD/ADRD research education and care.

project_terms:
Address;African American;Aging;Alzheimer's Disease;Area;Autopsy;Awareness;Basic Science;Biological;Biological Markers;Biometry;Brain;Caring;Cessation of life;Clinical;Clinical Research;Clinical Trials;Cognitive;Cognitive aging;Collaborations;Collection;Communities;Community Health Education;Community Outreach;Dedications;Dementia;Development;Disease;Early identification;Education;Elderly;Ensure;Environment;Etiology;Family;Goals;Health Personnel;Heterogeneity;Impaired cognition;Impairment;Individual;Infrastructure;Institution;Kentucky;Knowledge;Longitudinal cohort;Mission;Neurodegenerative Disorders;Outcome;Pathogenicity;Pathology;Recommendation;Research;Research Personnel;Research Project Grants;Resources;Risk;Scholars Program;Training;Translating;Translational Research;United States;United States National Institutes of Health;Universities;aging brain;beneficiary;central database;clinical practice;cohort;collaborative environment;community partners;community partnership;comorbidity;data management;driving force;education research;experience;innovation;late life;neuropathology;next generation;normal aging;novel therapeutics;outreach;pre-clinical;programs;recruit;research study;statistics;success;volunteer

public_health_relevance:
NARRATIVE: OVERALLThe University of Kentucky Alzheimers Disease Research Center (UK-ADRC) facilitates and supportsbasic/translational and clinical research efforts to identify the early manifestations of disease and thepathogenic mechanisms underlying the transitions from normal aging to the development of cognitiveimpairment with a special focus on mixed pathology and co-morbidities that influence risk and outcomes inlate-life multi-etiology dementia. We are also dedicated to training the next generation of researchers and togrowing our educational programs and community partnerships to promote awareness of AD and relateddisorders and the importance of research and research participation.


application_id: 10880305
project_number: 5U19FD007082-05
project_title: Kentucky DPH Environmental Micro and Chemistry Food Surveillance and Protection.
administering_ic: FDA
award_notice_date: 2024-07-02
opportunity_number: PAR-20-105
application_type: 5
activity_code: U19
ic: FD
serial_number: 007082
program_official: LI, MEI-YING
project_start_date: 2020-09-01
project_end_date: 2025-06-30
study_section: ZFD1-ORA-K(01)1
contact_pi_person_id: 16381471
contact_pi: JOHNSON, BETH D
other_pis: Not Applicable
congressional_district: 01
department: Unavailable
primary_duns: 927049767
primary_uei: LECJQDCLHVE5
duns_number: 927049767
uei: LECJQDCLHVE5
fips: US
organization_id: 4242701
organization_name: KY ST CABINET/HEALTH/FAMILY SERVICES
organization_city: FRANKFORT
organization_state: KY
organization_type: Other Domestic Non-Profits
organization_zip: 406012321
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary: PAR-20-15 5/26/20The main objective of the Division of Laboratory Services (DLS) at the Kentucky Department forPublic Health is to maintain ISO/IEC 17025: 2017 accreditation (achieved in November 2018for food chemistry and microbiology testing) and enhance testing capabilities by expanding the scopeof current accreditation by officially adding WGS analyses for food microbiology. ISO/IEC 17025accreditation is one of the most important standards for testing laboratories and attests to thecompetency and technical capability of a laboratory to perform specific tasks. The results generatedare defensible to a recognized standard. In addition accreditation supports the traceability of technicalresults generated by a laboratory. In the event of a large-scale terrorist activity or other large-scaleevents affecting foods or food products States and Federal authorities can use laboratory test resultsfrom accredited laboratories to respond rapidly with streamlined analytical review and enforceregulatory compliance to protect the safety of the nation's food supply. DLS is the primary servicinglaboratory for conducting microbiological and chemical food analyses on behalf of the KY Statemanufactured food regulatory program (MFRPS) in the Department for Public Health / Food SafetyBranch which has a current food safety inspection contract with FDA and is enrolled in the MFRPS.DLS has a quality management system that is in compliance with the managerial and technicalrequirements of the ISO/IEC 17025:2017 standard. DLS is a Food Emergency Response Network(FERN) Laboratory and participates in Food proficiency testing and will continue to submit laboratoryresults through what will become the ORAPP as requested. The Division of Laboratory Servicessgoal is to enhance laboratory activities by bringing in new testing capabilities such as Cyclosporadetection for food micro and toxic metals by food chemistry.Funding of this proposal will assist the KY State MFRPS in achieving conformance with Standard 10Laboratory Support of the MFRPS and will contribute to production of accurate and reliable testdata a quicker acceptance of analytical results by FDA and other regulatory agencies forenforcement actions surveillance purposes and response to foodborne outbreaks. In addition DLSwill continue to participate in GenomeTrackr activities and PTs as well as develop partnerships withother agencies such as the KY Department of Agriculture and the USDA for sample acquisition andtesting.

public_health_relevance:
BETH JOHNSON4/2/20Kentucky DPH Environmental Micro and Chemistry Food Surveillance and ProtectionProject Narrative: PAR -20-15 3/25/20This funding is critical in order to provide support for the Food Safety Branch/KY State MFRPS andthe conformance of Standard 10. This proposal will allow DLS to increase and enhance the analyticalcapacity and testing diversity in both environmental microbiology and chemistry that can be providedto the Commonwealth of KY as we are the only Public Health Laboratory in the State of Kentucky.


application_id: 10878416
project_number: 1R01CA282254-01A1
project_title: Integrative Targeted Therapy for Melanoma
administering_ic: NCI
award_notice_date: 2024-03-22
opportunity_number: PA-20-185
application_type: 1
activity_code: R01
ic: CA
serial_number: 282254
suffix: A1
program_official: ZAMISCH, MONICA
project_start_date: 2024-04-01
project_end_date: 2029-03-31
study_section: Therapeutic Immune Regulation Study Section[TIR]
contact_pi_person_id: 7598539
contact_pi: YANG, JIN-MING
other_pis: SONG, JIANXUN JIM
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
PROJECT SUMMARY/ABSTRACTDespite breaking advances in melanoma treatment such as adoptive cell transfer and immune checkpointblockade the clinical outcomes remain unsatisfactory due to various factors that limit the efficacy of thetherapies. To meet these challenges in immunotherapy for solid tumors this project aims to defineeukaryotic elongation factor-2 kinase (eEF-2K) as a novel and effective immune-modulatory target that canbe exploited to significantly improve effectiveness of the current cancer immunotherapy. eEF-2K belongs tothe family of atypical -kinases and is an evolutionarily conserved regulator of protein synthesis a molecularprocess that affects energy metabolism. This kinase phosphorylates eEF-2 a 100-kDa protein thatpromotes ribosomal translocation from the A to P-site the reaction that induces movement of mRNA alongthe ribosome during translation. Phosphorylated eEF2 is unable to catalyze ribosomal translocation therebyinhibiting peptide elongation. Our preliminary studies strongly suggest that eEF-2K is an as-yet-unappreciated but critical regulator of antitumor immunity and that integrative targeting of this kinase maybeneficially maximize the potency of immunotherapeutic intervention against melanoma one of the mostaggressive and fatal neoplasms responsible for over 80% of skin cancer-related deaths. Building on ourpreliminary observations that eEF-2K is not only highly expressed in melanoma cells and patient specimensand contributes to poor therapeutic outcomes but is also abundantly expressed in immune cells such as Tcells and regulates their functional activity we propose to test the central hypothesis that eEF-2K modulatesantitumor immunity via its regulatory roles in both tumor cells and tumor-reactive immune cells andintegrative targeting of eEF-2K could be exploited as an innovative therapeutic strategy for treatment ofmelanoma. Through comprehensive cellular molecular and pre-clinical studies this multiple PIs project willpursue the following highly related and interactive aims: (1) Determine the role and in-depth mechanism ofeEF-2K in immune evasion; (2) Define the role of eEF-2K as a regulator of tumor-reactive immune cells; (3)Evaluate the antitumor efficacy of the eEF-2K-based and integrative targeted therapy. We have establishedthe humanized mouse (NOD-scid IL2Rgnull) melanoma models as well as murine syngeneic melanomasystems for this research and are well poised to accomplish the above objectives. This research isinnovative and significant because successful completion of this project would not only reveal eEF-2K as anovel and effective immuno-modulatory target for overcoming tumor immune-resistance as well asregulating immune cell functions but also provide new therapeutic opportunities to substantially improveimmunotherapy for advanced treatment-refractory melanoma through the eEF-2K-based integrative-targeted approach.

project_terms:
Adoptive Cell Transfers;Affect;B-Lymphocytes;BRAF gene;Ca(2+)-Calmodulin Dependent Protein Kinase;Cancer Biology;Cell Line;Cell Physiology;Cells;Cessation of life;Clinical;Clinical Research;Cytotoxic T-Lymphocytes;Data;Development;Effectiveness;Elements;Energy Metabolism;Enzymes;Eragrostis;Family;Goals;Human;Immune;Immune Evasion;Immunology;Immunotherapeutic agent;Immunotherapy;In Vitro;Intervention;Knockout Mice;Macrophage;Major Histocompatibility Complex;Malignant Neoplasms;Melanoma;Melanoma Cell;Melanoma patient;Messenger RNA;Modeling;Molecular;Movement;Mus;Mutation;Neoplasms;Organoids;Outcome;Patients;Peptides;Pharmacology;Phosphorylation;Phosphotransferases;Process;Productivity;Protein Biosynthesis;Proteins;Reaction;Refractory;Regulatory T-Lymphocyte;Research;Resistance;Ribosomes;Role;Safety;Site;Skin Cancer;Solid Neoplasm;Specimen;T-Lymphocyte;Testing;Therapeutic;Therapeutic Studies;Translations;Treatment Efficacy;Tumor Antigens;Tumor Cell Line;Tumor Immunity;Tumor-infiltrating immune cells;Woman;calmodulin-dependent protein kinase III;cancer immunotherapy;conditional knockout;cytotoxic CD8 T cells;design;experimental study;humanized mouse;immune checkpoint blockade;immune function;immune resistance;immunoregulation;improved;innovation;insight;men;mutant;neoplastic cell;novel;novel therapeutics;preclinical study;response;systems research;targeted treatment;therapeutic target;therapeutically effective;therapy outcome;treatment response;treatment strategy;tumor;tumor-immune system interactions

public_health_relevance:
Project NarrativeMelanoma one of the most aggressive and fatal neoplasms is the 5th most frequent cancer in men and7th most frequent cancer in women and is responsible for over 80% of the skin cancer-related deaths.By investigating the role and mechanism of elongation factor-2 kinase (eEF-2K) as a novelimmunomodulatory target and by assessing the antitumor efficacy of the eEF-2K-based integrativetargeted therapy we wish to provide innovative and effective immunotherapeutic strategies for patientswith immune poor-responsive melanoma.


application_id: 10878278
project_number: 1R21NS137256-01
project_title: Combinatorial approach to restore breathing after spinal cord injury
administering_ic: NINDS
award_notice_date: 2024-03-19
opportunity_number: PA-21-219
application_type: 1
activity_code: R21
ic: NS
serial_number: 137256
program_official: BAMBRICK, LINDA LOUISE
project_start_date: 2024-03-19
project_end_date: 2026-02-28
study_section: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]
contact_pi_person_id: 9380335
contact_pi: CHEN, MEIFAN
other_pis: ALILAIN, WARREN JOSEPH
congressional_district: 06
department: NEUROSCIENCES
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY / ABSTRACT More than half of human spinal cord injury (SCI) cases occur at the cervical level resulting in permanentrespiratory deficits for which there is no treatment. Injury-induced axon growth of spared respiratory pathways isa form of endogenous neural plasticity that can be harnessed to improve breathing. However experimentalstrategies to promote respiratory axon growth are lacking and the few existing approaches have translationallimitations. Without expanding the repertoire of molecular and/or cellular interventions to enhance axonalplasticity of the respiratory network following injury developing treatment to restore breathing will be unlikely.The objectives of this proposal are: first to determine if endogenous astrocytes can be reprogrammed toenhance structural plasticity of the respiratory system to improve breathing after SCI; and second based onevidence that coupling axon growth-promoting strategy with rehabilitative training can further augment functionalrecovery assess combinatorial effects of astrocyte reprogramming and respiratory training on recovery ofbreathing after SCI. The central hypothesis is that post-injury targeting of astrocytes combined with respiratorytraining will synergistically improve breathing after SCI. This hypothesis will be tested by pursuing two aims: 1)determine the effects of pre-injury astrocyte manipulation alone or in combination with respiratory training onstructural and functional plasticity of the respiratory system; and 2) assess post-injury and location-specificeffects of astrocyte manipulation alone or in combination with respiratory training on respiratory plasticity. Therationale for this proposal is that it will inform on the therapeutic potential of reprogramming endogenousastrocytes to promote axonal plasticity of the respiratory system which may be further harnessed byrehabilitative training to maximize recovery of breathing after SCI.

project_terms:
Acute;Adult;Anatomy;Animal Model;Applications Grants;Astrocytes;Axon;Breathing;Cell Nucleus;Cerebral cortex;Cervical;Cervical spinal cord injury;Ciliary Neurotrophic Factor;Corticospinal Tracts;Coupled;Coupling;Development;Forelimb;Frequencies;Glial Fibrillary Acidic Protein;Growth;Human;Hypoxia;Impairment;Individual;Injury;Intervention;Lateral;Leucine Zippers;Location;Maintenance;Measures;Mechanical Ventilators;Mediating;Modeling;Molecular;Motor;Mus;Neural Pathways;Neuronal Plasticity;Neurons;PF4 Gene;Pathway interactions;Phosphotransferases;Recovery;Recovery of Function;Rehabilitation therapy;Reporting;Respiratory System;Role;Serotonin;Shapes;Spinal Cord;Spinal Injections;Spinal cord injured survivor;Spinal cord injury;Synaptic plasticity;Tamoxifen;Testing;Therapeutic;Tidal Volume;Training;United States;Up-Regulation;axon growth;axonal sprouting;central nervous system injury;combinatorial;cytokine;functional plasticity;improved;in vivo;ischemic injury;motor recovery;nerve supply;neural network;normoxia;novel;overexpression;programs;regenerative;respiratory;restoration;synergism;translational approach;trend;ventilation

public_health_relevance:
Project NarrativePublic Relevance: Nearly 300000 individuals in the United States have a spinal cord injury and close to 60%are at the cervical level. As a result respiratory motor insufficiency is a major concern and necessitates theneed for a mechanical ventilator in order to breathe and survive. This grant application explores a novelcombinatorial approach to restore breathing by promoting axon growth of respiratory pathways and applyingrespiratory training.


application_id: 10877840
project_number: 5R01CA266579-03
project_title: Targeting Polo-Like Kinase 1 in Prostate Cancer to Enhance Therapeutic Efficacy
administering_ic: NCI
award_notice_date: 2024-06-07
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: CA
serial_number: 266579
program_official: XU, WANPING
project_start_date: 2022-07-01
project_end_date: 2027-06-30
study_section: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]
contact_pi_person_id: 10992448
contact_pi: LI, ZHIGUO
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Title: Targeting Polo-like kinase 1 in prostate cancer to enhance therapeutic efficacyAbstractProstate cancer (PCa) is the second most common cause of cancer death in men in the US. Over the pastseveral decades androgen deprivation therapy has been the primary therapeutic option for patients withadvanced PCa; however the majority of patients developed into a poor prognosis stage of castration-resistantprostate cancer (CRPC) which eventually led to mortality. And the current therapeutic agents for CRPCpatients only extend survival by around 2.5 - 5 months. Therefore novel and effective therapeutic strategies forCRPC patients are urgently needed. The long-term goals of this study are to identify druggable signalingpathways that offer more effective treatment options for patients with CRPC. The objective is to identify the roleof Plk1/p62/Nrf2 signaling pathway in CRPC and to exploit the potentially therapeutic strategies that could bebenefit the CRPC patients. The central hypothesis is that Nrf2 is activated by a noncanonical mechanisminvolving p62 phosphorylation by Plk1 in CRPC. Our hypothesis will be tested by pursuing Three Specific Aims:(1) to determine the novel role of Plk1 as regulator of cellular response to oxidative stress. (2) examine the roleof Plk1/p62/Nrf2 axis in tumor growth in mouse models. And (3) whether inhibition of Plk1/p62/Nrf2 signalingpathway enhance the efficacy of CRPC therapy. The expected results will reveal a novel molecular mechanismto show how Plk1 contributes to PCa progress and will open up new avenues for application of Plk1 inhibitorsas a therapeutic option. The team with expertise in Plk1 in mouse models Plk1 in cancer cell biology PCapathology GU oncology and biostatistics will be able to finish the proposed research in a timely manner.

project_terms:
Alleles;Androgens;Apoptosis;Autophagocytosis;Biometry;Breeding;Cancer Etiology;Cancer Patient;Cell Survival;Cells;Cellular biology;Cessation of life;Clinic;Clinical Research;Creativeness;Data;Disease;Enterobacteria phage P1 Cre recombinase;Fostering;Genetically Engineered Mouse;Goals;Health;Immune checkpoint inhibitor;Immunocompetent;Immunosuppression;Immunotherapy;Infiltration;Investigation;Lymphocyte;Malignant Neoplasms;Malignant neoplasm of prostate;Measurement;Mediating;Membrane;Mission;Molecular;Mus;Myelogenous;Myeloid Cells;Myeloid-derived suppressor cells;Oncology;Outcome;Oxidative Stress;PDL1 inhibitors;PDL1 pathway;PLK1 gene;Pathology;Patient-Focused Outcomes;Patients;Phosphorylation;Phosphotransferases;Play;Prognosis;Proliferating;Prostate Cancer therapy;Public Health;Reactive Oxygen Species;Refractory;Regulation;Research;Residual state;Role;Signal Pathway;Signal Transduction;Survival Rate;Testing;Therapeutic;Therapeutic Agents;Therapeutic Effect;Treatment Efficacy;Tumor Escape;Tumor Immunity;Tumor-infiltrating immune cells;Up-Regulation;Work;advanced prostate cancer;androgen deprivation therapy;androgen independent prostate cancer;anti-PD-L1 therapy;cancer cell;cell growth;comparative efficacy;design;effective therapy;immune cell infiltrate;improved;inhibitor;innovation;men;mortality;mouse model;neoplastic cell;novel;novel strategies;novel therapeutic intervention;nuclear factor-erythroid 2;pharmacologic;programmed cell death ligand 1;programs;promoter;prostate cancer cell;receptor;response;synergism;targeted treatment;therapeutically effective;tumor;tumor growth;tumor microenvironment;tumor xenograft;tumor-immune system interactions

public_health_relevance:
NarrativeThe proposed research is relevant to public health because it focuses on a novel therapeutic strategy forcastration-resistant prostate cancer. These studies will establish new avenues of investigation to developimproved therapeutics to treat this deadly disease and to greatly improve patient outcome. Thus theproposed research is relevant to NCI's mission of fostering creative discoveries and innovativeresearch strategies for protecting and improving health and reducing the burdens associated with cancer.


application_id: 10877329
project_number: 3R01AA029798-03S1
project_title: Phosphodiesterase 4 mediated pathogenic mechanisms in alcohol associated liver disease
administering_ic: NIAAA
award_notice_date: 2023-07-19
opportunity_number: PA-20-185
application_type: 3
activity_code: R01
ic: AA
serial_number: 029798
suffix: S1
program_official: RADAEVA, SVETLANA
project_start_date: 2021-09-22
project_end_date: 2026-06-30
study_section: Hepatobiliary Pathophysiology Study Section[HBPP]
contact_pi_person_id: 11058066
contact_pi: GOBEJISHVILI, LEILA
other_pis: Not Applicable
congressional_district: 03
department: PHYSIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
project_terms:
ADD-1 protein;Affect;Alcoholic Hepatitis;Alcoholic Liver Diseases;Alcohols;Animal Model;Apoptosis;Attenuated;Automobile Driving;CYP2E1 gene;Cell model;Cell physiology;Cessation of life;Complex;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Cytochrome P450;Data;Development;Disease;Enzymes;Ethanol;FDA approved;Fatty Acids;Fatty Liver;Genes;Goals;H19 gene;HIF1A gene;Heavy Drinking;Hepatic;Hepatocyte;Hydrolysis;Impairment;In Vitro;Inflammatory;Injury;Knockout Mice;Liver;Liver diseases;MAPK8 gene;Mediating;Metabolic;Mitogen-Activated Protein Kinases;PDE4B;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Phosphoric Monoester Hydrolases;Phosphorylation;Play;Population;Process;Regulation;Role;Second Messenger Systems;Signal Transduction;Specificity;Toxic effect;Transcriptional Regulation;United States;Untranslated RNA;Up-Regulation;Work;alcohol effect;cell injury;genetic manipulation;hypoxia inducible factor 1;in vitro Model;in vivo;inhibitor;lipid biosynthesis;lipid metabolism;liver injury;member;mortality;new therapeutic target;novel;oxidation;phosphatase-1 kinase;phosphodiesterase IV;phosphoric diester hydrolase;preclinical study;response;transcription factor


application_id: 10877234
project_number: 3R01AA028735-05S1
administering_ic: NIAAA
award_notice_date: 2023-07-27
opportunity_number: PA-17-297
application_type: 3
activity_code: R01
ic: AA
serial_number: 028735
suffix: S1
program_official: LIN, LI
project_start_date: 2021-11-01
project_end_date: 2025-06-30
study_section: Neurotoxicology and Alcohol Study Section[NAL]
contact_pi_person_id: 8774042
contact_pi: MESSAOUDI, ILHEM
other_pis: Not Applicable
congressional_district: 06
department: MICROBIOLOGY/IMMUN/VIROLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARYApproximately ~7% of alcohol-consuming individuals engage in chronic heavy drinking (CHD) which isassociated with increased susceptibility to infections as well as impaired wound healing and tissue repairresulting in poor post-operative outcomes. Evidence suggests that many of these defects are mediated byexcessive inflammatory responses originating from myeloid cells notably circulating monocytes and tissue-resident macrophages. These data were primarily generated from in vitro studies where monocytes from healthydonors or cell lines are treated high doses of ethanol. However the mechanisms underlying the effects of CHDcannot be fully understood by in vitro studies because immune cells carry out their functions in a multicellularenvironment in which alcohol has widespread effects. Due to a lack of studies utilizing reliable in vivo modelsour understanding of the mechanisms underlying aberrant inflammatory responses in the context of CHDremains incomplete. To address these knowledge gaps we propose to leverage a rhesus macaque model ofvoluntary ethanol self-administration that accurately mirrors human physiology and recapitulates complex humandrinking behavior. Using this model our lab has recently demonstrated that CHD results in transcriptional andepigenetic rewiring of circulating monocytes and splenic macrophages resulting in aberrant responses to LPSstimulation. However the functional implications of this reprogramming and the epigenetic mechanismscontrolling it remain unknown. Importantly because monocytes are short-lived circulating cells under constantrepopulation from the bone marrow these observations suggest perturbations of the hematopoietic niche.Preliminary single-cell analyses of hematopoietic progenitors point to a shift in differentiation potential towardsmore mature myeloid progenitors with alcohol. However a link between this observation in progenitor cells andtheir differentiated states in blood and tissue remains unclear. In this application we propose to test thehypothesis that chronic alcohol consumption reprograms the epigenetic landscape of monocyteprogenitors in the bone marrow giving rise to circulating monocytes poised towards a hyper-inflammatory response. We will first examine the impact of CHD on functional reprogramming of circulatingmonocytes implementing assays to test their ability to migrate phagocytose and generate proper metabolicresponses. We will next examine the effect of stimulation on the monocyte epigenetic landscape throughassessment of chromatin accessibility and abundance of specific histone modifications. Finally we will determinethe effect of CHD on the differentiation potential transcriptome activation and epigenetic rewiring of bonemarrow myeloid progenitors and integrate these data with those obtained from peripheral blood monocytes.Completion of this proposal will provide novel insight into the impact of CHD on myelopoiesis and mechanismsby which it compromised immunity and host defense as well as design interventions to mitigate these adverseevents and improve immunological outcomes.

project_terms:
ATAC-seq;Abstinence;Address;Adverse event;Alcohol consumption;Alcoholic Liver Diseases;Alcohols;Animals;Area;Bacterial Infections;Biological Assay;Biological Response Modifiers;Biology;Blood;Blood specimen;Bone Marrow;Cardiovascular Diseases;Categories;Cell Line;Cells;Chromatin;Chronic;Chronic Disease;Communicable Diseases;Complex;Data;Defect;Development;Dose;Environment;Epigenetic Process;Ethanol;Etiology;Event;Failure;Female;Gene Expression;Genetic Transcription;Goals;Health;Heavy Drinking;Hematopoietic;Hematopoietic stem cells;Heterogeneity;Homeostasis;Host Defense;Housing;Human;Immune;Immune Tolerance;Immunity;Immunocompetence;Immunologics;Immunology procedure;Impaired wound healing;In Vitro;Individual;Infection;Inflammation Mediators;Inflammatory;Inflammatory Response;Intercistronic Region;Intervention;Knowledge;Link;Macaca;Macaca mulatta;Macrophage;Mediating;Metabolic;Metabolism;Modeling;Myelogenous;Myeloid Cells;Myelopoiesis;Natural Immunity;Outcome;Patients;Peripheral;Peripheral Blood Mononuclear Cell;Phenotype;Physiology;Population;Postoperative Period;Predisposition;Promoter Regions;Reporting;Research;Respiratory Tract Infections;Risk;Sampling;Self Administration;Testing;Tissues;Virus Diseases;alcohol availability;alcohol effect;antimicrobial;cancer type;chronic alcohol ingestion;comparison control;cytokine;data integration;drinking behavior;epigenome;experimental study;fitness;histone modification;immune activation;improved;in vivo;in vivo Model;insight;male;migration;monocyte;next generation sequencing;nonhuman primate;novel;pathogen;peripheral blood;progenitor;programs;response;single cell analysis;single-cell RNA sequencing;stem cells;therapy design;tissue repair;transcriptome;transcriptomics;wound healing

public_health_relevance:
PROJECT NARRATIVE/RELEVANCEApproximately 7% of alcohol users engage in chronic heavy drinking (CHD) which is associated with increasedrisk of bacterial and viral infections as well as decreased tissue repair ability. These observations suggest afailure of innate immune cells to perform their functions. The proposed research aims to identify CHD-mediatedfunctional transcriptomic and epigenetic alterations in monocytes and their progenitors in the bone marrow withthe goal of better understanding the etiology of reduced immune fitness.


application_id: 10877190
project_number: 5R01AI167953-02
project_title: Invasion of the enteric nervous system by neurotropic Listeria monocytogenes
administering_ic: NIAID
award_notice_date: 2024-06-10
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: AI
serial_number: 167953
program_official: BAQAR, SHAHIDA
project_start_date: 2023-07-01
project_end_date: 2028-06-30
study_section: Bacterial Pathogenesis Study Section[BACP]
contact_pi_person_id: 2545336
contact_pi: D'ORAZIO, SARAH E. F.
other_pis: Not Applicable
congressional_district: 06
department: MICROBIOLOGY/IMMUN/VIROLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Listeria monocytogenes (Lm) are Gram-positive facultative intracellular bacteria that cause two types of braininfections in humans: diffuse (meningitis/meningoencephalitis) and focal brainstem (rhombencephalitis).Meningitis occurs in the setting of immune compromise likely due to the failure of the immune system to limitexponential growth of Lm in tissues such as spleen or liver. This leads to high titer bacteremia and either directinvasion of the blood-brain-barrier (BBB) or stealth transport of Lm associated with myeloid-derived cells thatcross the BBB. In contrast rhombencephalitis is an infection of a delayed nature that occurs in young otherwisehealthy immune competent people which suggests that the infection is dependent on bacterially encodedneurovirulence factors. The central hypothesis of this proposal is that the virulence factors which defineneurotropism during rhombencephalitis mediate critical early events in the intestines rather than in the brain.Support for this hypothesis comes from our preliminary data showing that when the neurotropic Lm are injectedintravenously (bypassing the gut phase of the infection) they do not disseminate to the brain. In addition othersshowed that rhombencephalitis isolates did not have an increased ability to survive and replicate in bovineorganotypic brain slices ex vivo relative to other Lm strains. Until recently rhombencephalitis could be studiedonly in cows or sheep due to the lack of a small animal model of Lm brainstem infections. However we recentlyshowed that some clinical isolates of Lm (UKVDL9 and SD4000) could preferentially colonize the brainstems ofmice late in the course of infection without reaching high titer in the blood. Both of the neurotropic strains wereported belong to lineage III the smallest and least characterized group of Lm isolates. The goal of this proposalis to define the factors that promote neurotropism by Lm UKVDL9 and SD4000 during the gut phase of listeriosis.We predict that neurotropic Lm could have an advantage in three different aspects of the intestinal infection;these form the three Specific Aims of the proposal. In Aim 1 we determine if the route used to cross the gutmucosa or inflammatory response induced promotes localization of neurotropic Lm strains in neural bundles inthe intestinal submucosa or within the vagal crypt endings surrounding lymphoid cryptopatches in the gut. InAim 2 we identify the novel Lm surface protein that mediates enhanced invasion of enteric glial cells the celltype that surrounds nerves in the gut. In Aim 3 we test the hypothesis that a truncated actA allele found inneurotropic Lm promotes an altered type of intracellular movement that allows the bacteria to migrate along theentire length of an axon all the way to the brainstem. This work will move the listeriosis field forward by providingthe first real insights into neurotropism during this life-threatening foodborne infection and could also lay thegroundwork for new areas of pathogenesis or microbiome-related research to understand how bacteria interactwith cells of the enteric nervous system.

project_terms:
Actins;Alleles;Animal Model;Area;Axon;Bacteremia;Bacteria;Bacterial Adhesins;Blood;Blood - brain barrier anatomy;Body System;Brain;Brain Stem;Bypass;Cattle;Cell Nucleus;Cells;Clinical;Coculture Techniques;Cranial Nerves;Data;Death Rate;Diffuse;Elderly;Endowment;Enteral;Enteric Nervous System;Event;Failure;Follow-Up Studies;Food Contamination;Goals;Growth;Gut Mucosa;Human;Immune;Immune system;Immunocompetent;In Vitro;Individual;Infection;Inflammatory;Inflammatory Response;Ingestion;Intestines;Intravenous;Invaded;Kinetics;Lamina Propria;Length;Life;Listeria;Listeria monocytogenes;Listeriosis;Liver;Lymphoid;Mediating;Membrane Proteins;Meningitis;Meningoencephalitis;Microscopic;Monitor;Motility;Movement;Mus;Mutagenesis;Myelogenous;Myenteric Plexus;Nature;Nerve;Nervous System;Neuroglia;Neurons;Neurotropism;Oral;Pathogenesis;Pattern;Persons;Phase;Process;Proline-Rich Domain;Proteins;Reporting;Research;Role;Route;Sheep;Slice;Speed;Spleen;Submucosa;Submucous Plexus;System;Tail;Testing;Time;Tissues;Vagus nerve structure;Variant;Virulence Factors;Work;blood-brain barrier crossing;cell type;enteric infection;foodborne;foodborne illness;foodborne infection;in vivo;insight;intestinal epithelium;live cell imaging;microbiome;microbiota;migration;mouse model;mutant;neonate;nerve supply;neural;neurotropic;neurovirulence;novel;pathogen;transmission process

public_health_relevance:
Ingestion of food contaminated by Listeria monocytogenes bacteria causes two different types of braininfection in humans. One type (meningitis) happens primarily in individuals with compromised immunesystems (for example neonates and the elderly); the other type (rhombencephalitis) occurs in otherwisehealthy people. The goal of this research is to identify the bacterial factors which allow Listeria to invadecranial nerves in the gut and spread directly to the brainstem resulting in rhombencephalitis.


application_id: 10876989
project_number: 5R01CA277946-02
project_title: Roles of mRNA Transfer in Cancer Cell-Platelet Communication
administering_ic: NCI
award_notice_date: 2024-06-27
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: CA
serial_number: 277946
program_official: WATSON, JOANNA M
project_start_date: 2023-07-01
project_end_date: 2028-06-30
study_section: Tumor Evolution, Heterogeneity and Metastasis Study Section[TEHM]
contact_pi_person_id: 10533977
contact_pi: XU, REN
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
The interaction between cancer cells and platelets plays important roles in regulating cancer cell function.Understanding how platelets communicate with cancer cells to modulate cancer cell colonization at distantorgans may identify novel strategies to halt cancer spreading. We recently showed that recruitment of platelet tocancer cells is essential for the colonization of circulating tumor cells (CTCs) at the secondary organs. Howeverthe molecular mechanism by which platelets modulate cancer cell function to promote cancer cell colonizationremains to be determined. By analyzing RNA-seq data from CTCs and primary tumors we found that platelet-specific mRNA was significantly enriched in CTCs. RNAscope and Translating Ribosome Affinity Purification(TRAP) analyses showed the delivery of platelet mRNA and translation of platelet-derived mRNA in cancer cells.In vivo functional screening identified multiple platelet-derived mRNAs contribute to colonization of breast cancercell at distant organs. These results reveal the new role of platelet mRNA in mediating intercellularcommunication and in promoting cancer cell spreading. The overall objective of this proposal is to define themolecular mechanism by which platelet mRNA is delivered into breast cancer cells and determine roles of plateletmRNA as the signaling molecular in promoting cancer cell colonization at distant organs. We showed that CD9expression in CTCs correlated with the accumulation of platelet-specific mRNA. Silencing CD9 in breast cancercells significantly reduced platelet mRNA transferring and colonization of cancer cells. Platelet factor 4 (PF4) isa small cytokine belonging to the CXC chemokine family that is highly expressed in platelets. We showed thatthe transfer of PF4 mRNA from platelets to breast cancer cells enhanced stemness and colonization of cancercells. Based on these results the central hypothesis of this proposal is that the CD9-dependent mRNA transfermediates the platelet-cancer cell communication and promotes cancer cell stemness. We propose the followingtwo aims to test this hypothesis and achieve our objective. Aim 1. Elucidate the mechanism by which plateletmRNA is transferred into cancer cells. Aim 2. Determine how the transfer of platelet PF4 mRNA in cancer cellspromotes cancer metastasis.

project_terms:
Affinity Chromatography;Binding Proteins;Biological Assay;Biology;Blood Platelets;Breast Cancer Cell;CXC Chemokines;CXCR4 Receptors;CXCR4 gene;Cancer Patient;Cell Communication;Cell Physiology;Cell fusion;Cells;Co-Immunoprecipitations;Communication;Complex;Cytokine Activation;Data;Distant;Family;Galectin 3;Genes;Genetic Engineering;Hematogenous;Incidence;Knockout Mice;Knowledge;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Membrane Fusion;Membrane Proteins;Messenger RNA;MicroRNAs;Microfluidic Microchips;Molecular;Neoplasm Circulating Cells;Neoplasm Metastasis;Organ;PF4 Gene;Pathway Analysis;Pathway interactions;Play;Population;Positioning Attribute;Primary Neoplasm;Proteins;Recurrence;Regulation;Research;Ribosomes;Role;Signal Transduction;Small RNA;Stromal Cell-Derived Factor 1;Testing;Tissues;Translating;Translations;breast cancer progression;cancer cell;cancer genetics;carcinogenesis;chemokine;confocal imaging;cytokine;extracellular vesicles;gain of function;genetic signature;human data;in vivo;inhibitor;insight;intercellular communication;loss of function;mRNA delivery;mouse model;multidisciplinary;neoplastic cell;novel;novel strategies;protein complex;recruit;screening;small molecule;stemness;therapeutic target;tissue culture;transcriptome sequencing;tumor progression

public_health_relevance:
Defining how mRNA transferring mediates the platelet-cancer cell interaction will fill a critical gap in ourknowledge about the intercellular communication during cancer progression. Elucidating the mechanism bywhich CD9 regulates platelet mRNA transferring will significantly expand our understanding about cell fusion inthe platelet-cancer cell interaction and help to identify a potential therapeutic target to suppress the platelet-induced cancer progression and metastasis. The study of platelet PF4 mRNA in regulating cancer cell stemnesswill reveal a chemokine regulation pathway and new roles of PF4 in cancer cell colonization.


application_id: 10876891
project_number: 5T32CA160003-12
project_title: Oncology Research Training for Surgeon-Scientists
project_terms: Oncology;Research Training;Scientist;Surgeon
administering_ic: NCI
award_notice_date: 2024-07-01
opportunity_number: PA-20-142
application_type: 5
activity_code: T32
ic: CA
serial_number: 160003
program_official: DAMICO, MARK W
project_start_date: 2011-07-01
project_end_date: 2028-06-30
study_section: Institutional Training and Education Study Section (F)[NCI-F]
contact_pi_person_id: 1901765
contact_pi: EVERS, BERNARD MARK
other_pis: HULL, PAMELA CARMEN;O'CONNOR, KATHLEEN L.
congressional_district: 06
department: SURGERY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
PROJECT SUMMARYThis application is a competitive renewal of Translational Oncology Research Training for Surgeon Scientistsa transformative training program at the University of Kentucky (UK) designed for qualified trainees in thesurgical disciplines and with an interest in oncology research. The program addresses critical nationaldeclines in the number of surgeon scientists engaged in cancer research through a two-year period ofintensive interdisciplinary mentored research training to prepare trainees to become independent scientistswho are well prepared to incorporate state-of-the-art techniques learned during their training period into asuccessful academic research career. Trainees (2 each year) typically enter the program followingcompletion of postgraduate year (PGY) 2 or 3 of their residency training or upon completion of the surgicalresidency and select either the basic science option (Track 1) or the healthcare delivery research option(Track 2). Opportunities in Track 1 span cell signaling tumor biology cancer progression and metastasis aswell as evolving areas such metabolomics oncogenomics and epigenetics. Track 2 a proposed new programcomponent provides training in cancer disparities implementation science and population-level enquiry. Inaddition to an intensive research experience trainees complete a Master of Science or PhD degree in clinicaland translational sciences and supplement their coursework with further development through a combinationof formal courses and professional skills development workshops and seminars in such areas as responsibleconduct of research reproducibility and manuscript and proposal development. Through regularly scheduledseminars and lectures available through the Markey Cancer Center their departments and prominent UKcenters including the Center for Clinical and Translational Science trainees engage in rich experiential anddidactic learning that prepares them as active contributors to the types of multidisciplinary teams that areessential for the optimal treatment of the complex cancer patient. The requirement to successfully completeeither a masters or PhD degree adds depth and breadth to this program of training broadening exposure toother UK scientists serving on thesis committees. The primary training faculty is composed of basic andpopulation scientists and clinician-scientists all of whom work collaboratively across disciplines; each primaryfaculty mentor is a recognized expert in his or her field and has a long record of research productivity in thetraining of young investigators. A pipeline mentor development mechanism allows us to develop promisingearly-career faculty members as mentors within our team-based mentoring approach. This program which iscommitted to fostering diversity in the community of surgeon scientists including women and those fromunderrepresented groups has been highly successful in achieving its goals to address alarming declines inthe number of active surgeon-scientists conducting oncology research. As a training faculty we arepassionate motivated and committed to the training of future academic surgeons.

public_health_relevance:
PROJECT NARRATIVEThe number of clinician scientists and in particular surgeon scientists is decreasing at an alarming rate; thisreduction negatively impacts the ability and rapidity to translate basic and clinical discoveries made in cancerresearch to the patient. Our training program representing a collaboration between the Markey Cancer Centerand the academic clinical departments (Departments of Surgery Pathology and Laboratory Medicine andOtolaryngology-Head & Neck Surgery and the Division of Gynecologic Oncology) at the University of Kentuckyis focused on the interdisciplinary training of future clinician scientists in the various surgical specialties anddisciplines. The overall objective of this program is to train clinician scientists in the skills and expertise in BasicScience (Track 1) and Healthcare Delivery Research (Track 2) to compete in the academic arena and to beactive participants in multidisciplinary cancer teams which are required for the care of the complex cancerpatient.


application_id: 10875606
project_number: 5R01DA055872-03
administering_ic: NIDA
award_notice_date: 2024-06-17
opportunity_number: PA-20-183
application_type: 5
activity_code: R01
ic: DA
serial_number: 055872
program_official: LEE-WINN, ANGELA EUNJI
project_start_date: 2022-08-15
project_end_date: 2027-06-30
study_section: Health Promotion in Communities Study Section[HPC]
contact_pi_person_id: 11085214
contact_pi: YOUNG, APRIL MARIE
other_pis: Not Applicable
congressional_district: 06
department: PUBLIC HEALTH & PREV MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PUBLIC HEALTH
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-07-01
project_title:
Kentucky Outreach Service Kiosk (KyOSK): Reducing HIV HCV and Overdose Risk in Rural Appalachia through Harm Reduction Kiosks

project_abstract:
AbstractThe proposed project will test an innovative approach to reducing harms related to the epidemics of injectiondrug use overdoses hepatitis C (HCV) and to imminent HIV outbreaks in rural Appalachian Kentucky whichhas long been an epicenter of these intertwined crises. Our research has shown that the region has high ratesof HCV overdose injection drug use condomless sex and dense risk networks that could kindle an HIVoutbreak. Following a 2014 HIV outbreak in neighboring Indiana and a national analysis of HIV/HCV outbreakvulnerability among people who inject drugs (PWID) revealing that 54 of Kentuckys 120 counties ranked in thetop 5% nationally Kentucky passed landmark legislation permitting counties to operate syringe serviceprograms (SSPs). Despite an arduous county-level approval process Kentucky has succeeded in opening 80SSPs more than any other U.S. state. Unfortunately this robust harm reduction infrastructure remains under-utilized in rural settings. Data from our research funded by NIDAs National Rural Opioid Initiative revealed thatnearly half of PWID had never used the existing staffed SSPs and over 24 months of follow-up SSP uptakeremained low and program drop-out was not uncommon. The most frequent reason cited for having neverused an SSP was fear of stigma. Evidence suggests that PWID in the region want a range of harm reductionservice models and among those who report stigma as a reason for not using the staffed SSPs the mostdesired model is a vending machine or kiosk. Harm reduction kiosks have been operating globally for morethan 30 years and research has demonstrated that they can expand syringe access. Yet very few kiosksoperate in the U.S. and none operate in rural areas where they might be especially beneficial. Researchsuggests that kiosks might be a cost-effective way to expand syringe access when coupled with staffed SSPsbut their implementation impact and cost-effectiveness have not been rigorously evaluated. In response wepropose a type 1 hybrid effectiveness trial to test the effectiveness implementation outcomes and costeffectiveness of a community-tailored harm reduction kiosk in reducing HIV hepatitis C and overdose riskbehavior in rural Appalachia. Our kiosk or KyOSK (KY Outreach Service Kiosk) will be supplied withinjection equipment naloxone fentanyl test strips hygiene kits condoms and other supplies as well as aninnovative call-back feature for facilitated referral to needed services by trained recovery coaches. The KyOSKwill be tailored to the local context through a community-engaged process and a Kiosk Design Team involvingpeople who use drugs and local and state leaders. Interest in reduction kiosks is soaring nationwide and theproposed project would provide critical and timely data to inform scale-up of this model especially in ruralareas of the country that have been severely impacted by substance use related harms.

project_terms:
Appalachian Region;COVID-19;Callback;Communities;Country;County;Coupled;Data;Disease Outbreaks;Dropout;Drug user;Effectiveness;Epidemic;Epidemiology;Equipment;Fright;Funding;HIV;HIV/HCV;Harm Reduction;Health;Hepatitis C;Hepatitis C Therapy;Hepatitis C Transmission;Home;Hour;Huntington Disease;Hybrids;Hygiene;Indiana;Infrastructure;Injecting drug user;Injections;Judgment;Kentucky;Laws;Letters;Medicaid;Methods;Modeling;Naloxone;Names;National Institute of Drug Abuse;Needle-Exchange Programs;Nevada;Newly Diagnosed;Opioid;Overdose;Persons;Pharmaceutical Preparations;Process;Puerto Rico;Qualitative Research;Quasi-experiment;Recording of previous events;Recovery;Reporting;Research;Research Infrastructure;Resources;Risk;Risk Reduction;Rural;Rural Appalachia;Science;Service delivery model;Services;Sorbus;Statutes and Laws;Surveys;Syringes;Testing;Time;Training;Transportation;Unsafe Sex;West Virginia;cohort;community academic partnership;community engagement process;condoms;cost effective;cost effectiveness;design;effectiveness study;effectiveness testing;effectiveness trial;experience;fentanyl test;flexibility;follow-up;implementation evaluation;implementation outcomes;improved;injection drug use;innovation;interest;lectures;outreach services;overdose death;overdose risk;overdose risk behaviors;programs;response;rural area;rural setting;scale up;social stigma;substance use;test strip;uptake

public_health_relevance:
NarrativeThe proposed study will test the effectiveness implementation outcomes and cost effectiveness of acommunity-tailored harm reduction kiosk in reducing HIV hepatitis C and overdose risk behavior in ruralAppalachia. The proposed project will take place in two counties in Appalachian Kentucky an epicenter for theintertwined national crises of injection drug use overdoses and hepatitis C.


application_id: 10875554
project_number: 5R01DK125801-05
administering_ic: NIDDK
award_notice_date: 2024-07-03
opportunity_number: PA-18-330
application_type: 5
activity_code: R01
ic: DK
serial_number: 125801
program_official: HALES, CRAIG MAURICE
project_start_date: 2020-07-15
project_end_date: 2026-06-30
study_section: Community-Level Health Promotion Study Section[CLHP]
contact_pi_person_id: 10552456
contact_pi: WILLIAMS, LOVORIA B
other_pis: Not Applicable
congressional_district: 06
department: OTHER HEALTH PROFESSIONS
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF NURSING
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-07-01
project_title:
Enhancing the Diabetes Prevention Program to promote weight loss among non-responders in a community based lifestyle intervention

project_abstract:
PROJECT SUMMARYObesity is the number one and most preventable Type 2 diabetes (T2D) risk factor yet despite a $20 billionannual expenditure on diet and weight loss efforts 87% of US adults are overweight or obese. Disparities alsopersist as Non-Hispanic Black adults have a higher obesity prevalence (46.8%) than non-Hispanic Whites(37.9%) and suffer higher rates of Type 2 diabetes (T2D). The Diabetes Prevention Program (DPP) lifestyleintervention (LI) demonstrated the clinical benefits of lifestyle intervention and garnered the Center for DiseaseControl (CDC) endorsement as the gold standard LI program for US adults. Reimbursable by the Center forMedicare and Medicaid Services (CMS) the DPP LI is currently disseminated nationally and the national DPP.While the DPP LI is effective critical populations dont achieve clinically significant weight loss in the currentgroup-based translation paradigm. This is particularly true for Black DPP participants who show the lowestadjusted percent weight loss across (3.2%) among all racial/ethnic groups. A lack of weight loss in the earlyweeks of intervention is a known predictor of post-treatment outcomes and continues to be a major barrier toweight loss for Black participants. Additional research on early intervention with a focus on populations thatexperience disparities is urgently needed as the new CMS payment structure (based on weight loss metrics)may further limit access to the DPP for Blacks. This project proposes a cluster randomized control trial with500 Black participants who are nested in 20 community sites primarily churches. Trained community healthworkers will deliver a group-based 6-month long DPP Group Lifestyle Balance (DPP-GLB) over 18 sessionsand nonresponders will be identified at four weeks. Nonresponders in the intervention group only will receiveweekly telephone support from the CHWs to provide individual-level enhanced treatment to help themovercome barriers to adherence to the program goals. These activities will meet the following Specific Aims: 1)To evaluate differences over time in the primary outcome of weight and secondary outcomes (i.e. physicalactivity level blood pressure and dietary behaviors) between nonresponders in the intervention groupcompared to nonresponders in the active control group. 2) To examine potential mediators (social supportself-efficacy motivation stress) and moderators (age sex socioeconomic status) of the relationship betweentreatment group and early weight loss response in the both nonresponders and responders.3) To evaluate thecost of the intervention arm by comparing the incremental cost and weight loss with the active control arm.Outcome measures include weight (primary); secondary outcomes include blood pressure physical activitydietary behaviors mediation and moderator effects and cost. If found to efficacious the enhanced strategiesfor nonresponders could be standardized as a supplement for use with the national DPP and may besupported by current DPP payers.

project_terms:
Adherence;Adopted;Adult;African American population;Aftercare;Age;Behavior;Black Populations;Black race;Blood Pressure;Body Weight decreased;Centers for Disease Control and Prevention (U.S.);Church;Clinical;Communities;Community Health Aides;Cost Analysis;Diet;Disparity;Disparity population;Early Intervention;Equilibrium;Ethnic Population;Expenditure;Future;Gender;Goals;Individual;Intervention;Intervention Studies;Life Style;Mediating;Mediation;Mediator;Mission;Modeling;Morbidity - disease rate;Motivation;National Institute of Diabetes and Digestive and Kidney Diseases;Non-Insulin-Dependent Diabetes Mellitus;Not Hispanic or Latino;Obesity;Outcome;Outcome Measure;Participant;Pattern;Persons;Phase;Physical activity;Population;Prevalence;Psychosocial Factor;Public Health;Randomized Controlled Trials;Research;Research Personnel;Risk Factors;Self Efficacy;Site;Social support;Socioeconomic Status;Standardization;Stress;Structure;Telephone;Time;Training;Translations;Treatment outcome;United States Centers for Medicare and Medicaid Services;Variant;Weight;Work;active control;active control group;arm;clinically significant;cost;cost effective;diabetes prevention program;dietary;experience;group intervention;human old age (65+);improved;incremental cost;intervention effect;intervention program;lifestyle intervention;male;meetings;mortality risk;overweight adults;payment;personalized medicine;personalized strategies;primary outcome;programs;racial population;response;secondary outcome;sex;sociodemographic variables;standard care;success;treatment arm;treatment group;weight loss intervention

public_health_relevance:
Project NarrativeThe proposed research is relevant to public health because African Americans/Blacks suffer with higherobesity rates and have more trouble losing weight loss than others. Trained Community Health Workers willdeliver the Diabetes Prevention Program (DPP); early during the program the researchers will identifyparticipants who are not losing weight and the Community Health Workers will offer these participants extrasupport to help them overcome weight loss barriers. If this extra support works the National DPP and otherscan adopt it to achieve better weight loss outcomes among DPP participants thereby having a significantpublic health impact.


application_id: 10875490
project_number: 5R00HG011657-04
project_title: Analysis of Somatic Mutations in Longitudinal Whole-genome Sequencing Data
administering_ic: NHGRI
award_notice_date: 2024-09-10
opportunity_number: PA-20-188
application_type: 5
activity_code: R00
ic: HG
serial_number: 011657
program_official: CHADWICK, LISA
project_start_date: 2023-07-01
project_end_date: 2027-01-31
study_section: NSS
contact_pi_person_id: 15791317
contact_pi: STEELY, CODY
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY While recent efforts have focused on better understanding the germline mutation rate of differenttypes of DNA variants the dynamics of somatic mutations in the human genome are poorly understood.Somatic mutations are a well-known cause of cancer and may play a causative role in other diseases andaging. Analyses of somatic mutations have generally been limited to single-cell or low-coverage studies.To accurately assess the rate of somatic mutations over time would require a longitudinal high coveragedataset. For ~450 individuals in the Utah CEPH (Centre d'Etude du Polymorphism Humain) pedigreesblood was drawn at two timepoints approximately 15 years apart. This proposal describes experiments todetermine the rate of somatic mutations throughout the human genome by utilizing high-coverage (720x)whole-genome sequencing data at both of these timepoints in a subset of CEPH individuals. The genomesincluded in this study will be used to determine the rate of somatic mutations and improve ourunderstanding of differences in this rate between individuals. Building on previous work performed at theUniversity of Utah we will determine the relationship between the germline and somatic mutation rate.Further using detailed phenotypic data collected for these individuals experiments will be performed todetermine how this rate is correlated with disease outcomes such as cancer and cardiovascular disease.From this work a series of filtering algorithms will be produced to allow for comprehensive analysis ofsomatic mutations occurring between two timepoints in the same individual. This dataset provides me witha unique opportunity to study somatic mutations over time using high-quality data.This proposal builds upon my experience in analyzing mobile element-mediated somatic mutationsin longitudinal whole-genome data of cancer patients and my recent work analyzing germline shorttandem repeat mutations in the CEPH pedigrees. The K99 portion of this project will focus on determiningthe rate of somatic mutations in longitudinal high-coverage whole-genome sequencing data while creatingfiltering algorithms to improve our detection capabilities. The additional training I will receive during thisperiod will lay the foundation of an independent research program that will determine the significance ofsomatic mutations in the human genome and how these relate to disease outcomes.

project_terms:
Age;Aging;Algorithmic Software;Algorithms;Blood;Body mass index;Cancer Etiology;Cancer Patient;Cardiovascular Diseases;Cells;Collection;Copy Number Polymorphism;DNA;DNA Repair;Data;Data Set;Detection;Disease;Disease Outcome;Elements;Event;Family;Foundations;Frequencies;Generations;Genetic Polymorphism;Genome;Germ Cells;Germ Lines;Germ-Line Mutation;Goals;Hematopoiesis;Human;Human Genome;Individual;Malignant Neoplasms;Measures;Mediating;Modeling;Mutation;Organoids;Phenotype;Play;Postdoctoral Fellow;Process;Research;Role;Sampling;Series;Short Tandem Repeat;Single Nucleotide Polymorphism;Somatic Mutation;Testing;Time;Tissues;Training;Universities;Utah;Variant;Work;career;career development;computational pipelines;design;experience;experimental study;genetic pedigree;genome sequencing;human tissue;improved;member;phenotypic data;programs;time use;variant detection;whole genome

public_health_relevance:
PROJECT NARRATIVEMuch remains unknown about the rate and dynamics of human somatic mutations which are knowndrivers of cancer and are hypothesized to play a role in aging. This proposal aims to determine the rateand significance of somatic mutations in the human genome and their relationship to disease outcomes.


application_id: 10874706
project_number: 5R01NS119337-05
project_title: Enhanced Mitochondrial Viability via Engineered Hyrdogels for Intrathecal Spinal Cord Delivery
administering_ic: NINDS
award_notice_date: 2024-07-25
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: NS
serial_number: 119337
program_official: BAMBRICK, LINDA LOUISE
project_start_date: 2020-09-30
project_end_date: 2026-06-30
study_section: Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section[BNVT]
contact_pi_person_id: 11775081
contact_pi: PATEL, SAMIRKUMAR
other_pis: Not Applicable
congressional_district: 06
department: PHYSIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/AbstractMitochondrial dysfunction is pivotal to the neuropathological sequelae following traumatic spinal cordinjury (SCI). During this initial time window there is a significant loss of mitochondria with aninflammatory/oxidative environment that perpetuates the pathophysiology. It is hypothesized that torescue the cellular damage occurring following SCI one must replace damaged mitochondria while alsochanging the damaging microenvironment. We have documented that maintaining endogenousmitochondrial bioenergetics with acetyl-l-carnitine (ALC) an alternative mitochondrial biofuel or reducingoxidative stress by replenishing endogenous antioxidant glutathione (GSH) with N-acetylcysteine amide(NACA) after SCI results in increased but limited long-term functional neuroprotection. We have alsoreported that acute mitochondrial transplantation (MitoTxp) using intraspinal injections of mitochondriaisolated from rat soleus muscle significantly preserved bioenergetic function 48hr post-SCI. Howeverthis was sporadically successful due to the challenges of both accumulating mitochondria at the site ofinjury and maintaining their viability prior to cellular uptake. In the current proposal we will develop athermo-gelling erodible hydrogel system for the localized delivery of viable mitochondria to test theneuroprotective efficacy of combined MitoTxp and pharmaceutical interventions (ALC and/or NACA) aftercontusion SCI. The use of an injectable hydrogel will permit the development of a local environment whichcan aide in maintaining mitochondrial health through optimization of the hydrogel niche. We will determine1) optimum constituents for isolated mitochondria to remain viable for extended periods in polymerichydrogels 2) whether exogenous mitochondria transplanted via less invasive intrathecal route equallypreserve integrity of bioenergetics compared to intraspinal route and 3) consequences of acute ordelayed MitoTxp in combination with ALC and/or NACA on bioenergetics oxidative stress and functionalneuroprotection after SCI.

project_terms:
Acute;Antioxidants;Biochemical;Bioenergetics;Cell Count;Cells;Confocal Microscopy;Cytosol;Development;Dose;Engineering;Environment;Fostering;Functional disorder;Gel;Glutathione;Health;Histologic;Homeostasis;Hyaluronic Acid;Hydrogels;Hypersensitivity;In Vitro;Inflammatory;Injectable;Injury;Intervention;Intrathecal Injections;Kinetics;Knowledge;Label;Levocarnitine Acetyl;Locomotion;Maintenance;Mechanics;Methylcellulose;Mitochondria;Molecular Chaperones;Muscle Mitochondria;N-Acetylcysteinamide;Organelles;Osmotic Pressure;Outcome Measure;Oxidative Stress;PC12 Cells;Pharmacologic Substance;Polymers;Production;Property;Proteins;Rattus;Recovery of Function;Reporting;Research;Route;Site;Soleus Muscle;Spinal Cord;Spinal Cord Contusions;Spinal Injections;Spinal cord injury;System;Testing;Therapeutic Intervention;Time;Tissues;Transplantation;cell injury;combinatorial;design;dosage;experimental study;extracellular;functional outcomes;improved;in vivo;in vivo evaluation;injured;innovation;insight;mitochondrial dysfunction;neuropathology;neuroprotection;novel;preservation;uptake

public_health_relevance:
NarrativeThe current proposal is an innovative research plan to determine for the first time whether administration ofantioxidant (NACA) or alternative biofuel (ALC) known to maintain mitochondrial bioenergetics and promotefunctional neuroprotection after contusion spinal cord injury (SCI) in combination with novel intrathecal injectionof isolated muscle mitochondria embedded in a thermo-gelling erodible hydrogel system to protect mitochondrialviability fosters greater neuroprotective efficacy. The use of an injectable hydrogel will permit the developmentof a local environment which can aide in maintaining mitochondrial health through optimization of the hydrogelniche. The knowledge gained from the proposed experiments will provide direct insight into the use of hydrogelsystems for organelle delivery in vivo and the potential of this novel combinatorial therapeutic intervention(s) tomaintain cellular bioenergetics while reducing oxidative stress following SCI to promote tissue sparing andfunctional recovery.


application_id: 10874607
project_number: 5KL2TR001996-08
project_title: Institutional Career Development Core
administering_ic: NCATS
award_notice_date: 2024-07-10
opportunity_number: PAR-18-940
application_type: 5
activity_code: KL2
ic: TR
serial_number: 001996
program_official: DOYLE, JAMIE MIHOKO
project_start_date: 2016-08-15
project_end_date: 2026-06-30
study_section: ZTR1-SRC(99)
contact_pi_person_id: 1901822
contact_pi: KELLY, THOMAS H.
other_pis: BUSH, MATTHEW LEE
congressional_district: 06
department: PSYCHOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY  KL2 INSTITUTIONAL CAREER DEVELOPMENT The University of Kentucky Center for Clinical and Translational Science (CCTS) proposes to sustain andenhance the current KL2 program currently in its ninth year of National Institutes of Health (NIH) support. Byproviding two to three years of release time (75% effort) and research funding support for mentored careerdevelopment the program is designed to accelerate the academic growth for the next generation of leaders inclinical and translational research (CTR). The program has four programmatic objectives: 1) to provide acurriculum that meets core training needs of CTR scholars 2) to support a mentored program of researchtraining that expedites development of research careers 3) to support personalized training programs thatexpedite CTR career development and 4) to provide continuous assessment and quality improvement of bothindividual scholar career development and overall KL2 program. The program has garnered strong institutionalsupport; across the nine years the initial two NIH-supported training slots have been expanded to seven slots(four NIH-supported three institutionally supported). The program supports career development of scholarswith research interests that cross the lifespan (prenatal through elderly) and the full spectrum of clinical andtranslational science including translational clinical community/policy studies and clinical and translationalresearch (CTR) methods/processes (e.g. biomedical informatics) focusing on a broad array of health topics.Scholars and mentors represent a wide range of disciplines and colleges including Medicine NursingDentistry Pharmacy Health Sciences Public Health Education Engineering and Arts and Sciences. Allprogram graduates (n=18) remain actively engaged in CTR have made important contributions to sciencethrough published research and have successfully competed for extramural funding with 14 as principalinvestigators. We are requesting renewed NIH support of four KL2 scholar training slots. The training of aminimum of three additional institutionally sponsored early-career scholars will continue to be fully integratedwith these NIH-supported scholars to sustain a cohort of at least seven scholars. The foundation of theproposed program will continue to be practical research experiences within multidisciplinary teams guided byexperienced mentors with a Faculty Oversight Committee monitoring the successful career development ofthese future CTR leaders. Educational technology promotes vigorous yet efficient competency trainingprograms. Further our enhanced team science training programs will focus specifically on developingleadership skills. Institutionally sponsored pipeline programs targeting undergraduates medical studentsresidents fellows and clinical instructors several focused on underrepresented minorities will support theavailability of a strong and diverse pool of candidates for the KL2 program. In sum the KL2 program isaccelerating the career development of future leaders of the biomedical research workforce who are wellprepared to address todays complex research challenges and spearhead future advances in human health.

project_terms:
Acceleration;Address;Arts;Biomedical Research;Clinical;Clinical Research;Clinical Sciences;Communities;Competence;Complex;Dentistry;Discipline;Discipline of Nursing;Education;Educational Curriculum;Educational Technology;Elderly;Engineering;Extramural Activities;Faculty;Foundations;Funding;Future;Growth;Health;Health Sciences;Human;Individual;Institution;Kentucky;Leadership;Medical Students;Medicine;Mentors;Monitor;Pharmacy facility;Policies;Principal Investigator;Process;Public Health;Publishing;Research;Research Methodology;Research Training;Science;Time;Training;Training Programs;Training Support;Translational Research;Underrepresented Minority;United States National Institutes of Health;Universities;biomedical informatics;career;career development;clinical center;cohort;college;design;experience;improved;instructor;interest;life span;multidisciplinary;next generation;prenatal;programs;research and development;skills;undergraduate student


application_id: 10874530
project_number: 5TL1TR001997-08
project_title: NRSA Training Core
administering_ic: NCATS
award_notice_date: 2024-06-17
opportunity_number: PAR-18-940
application_type: 5
activity_code: TL1
ic: TR
serial_number: 001997
program_official: DOYLE, JAMIE MIHOKO
project_start_date: 2016-08-15
project_end_date: 2026-06-30
study_section: ZTR1-SRC(99)
contact_pi_person_id: 7577019
contact_pi: STOOPS, WILLIAM WALTON
other_pis: WHITEHURST, LAUREN
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY  TL1 TRAINING PROGRAM The University of Kentucky (UK) Center for Clinical and Translational Science (CCTS) proposes to sustainand enhance the current pre-doctoral and post-doctoral TL1 program currently in its ninth year of NationalInstitutes of Health (NIH) support. By providing a multidisciplinary training program that integrates traineesacross diverse fields and offers rigorous and solid translational research education the TL1 program haseffectively prepared clinicians- and scientists-in-training for careers as leaders in clinical and translationalscience. The UK TL1 program features substantial collaborations across a robust cohort of productiveinvestigators a talented pool of qualified applicants solid infrastructure and strong institutional support. Theprogram takes advantage of the physical juxtaposition of UKs six health care colleges (Medicine NursingPharmacy Public Health Health Sciences Dentistry) and key disciplines on the main campus (e.g.Engineering Social Work Biology Psychology Education) to train scholars across wide-ranging fieldsnecessary for successful clinical and translational research (CTR). The program supports career developmentof scholars with research interests that cross the lifespan (prenatal through elderly) and the full spectrum ofclinical and translational science including translational clinical community/policy studies and CTRmethods/processes (e.g. biomedical informatics) focusing on a broad array of health topics. The TL1 traineesare making important contributions to science through published work and all of the program graduates areactively engaged in CTR. This program and other CCTS-sponsored efforts are engaging underserved studentsin projects focused on health disparities of Kentucky and the Central Appalachian area. We are requestingrenewed NIH support for eight TL1 scholars. The foundation of the proposed program will continue to bepractical research experiences within multidisciplinary teams guided by experienced mentors along witheducational and training offerings such as certificate Masters and PhD degrees to ensure successful careerdevelopment of these future CTR leaders. Scholar competency assessments based on the Clinical ResearchAppraisal Inventory serve to guide new program offerings with the theory that trainees who have highconfidence in their skills are more likely to pursue a career in CTR. UK CCTS-developed pipeline programstargeting professional and graduate students including new initiatives to support health equities researchersand trainees from under-represented groups will ensure the availability of a strong pool of candidates for theTL1 program. In sum the TL1 program is designed to accelerate career development of future leaders in thetranslational science workforce who will be prepared to address todays complex research challenges andspearhead advances in human health.Project Summary/Abstract

project_terms:
Acceleration;Address;Appalachian Region;Area;Biological Assay;Biology;Blood flow;Characteristics;Clinical;Clinical Research;Clinical Sciences;Clinical and Translational Science Awards;Collaborations;Communication;Communities;Competence;Complex;Data Science;Dentistry;Development;Discipline;Discipline of Nursing;Disparity;Doctor of Philosophy;Education;Educational Activities;Educational Status;Elderly;Engineering;Ensure;Equipment and supply inventories;Ethics;Feedback;Fellowship;Foundations;Funding;Future;Goals;Growth;HIV;Health;Health Sciences;Healthcare;Human;Incubators;Infrastructure;Institution;Interdisciplinary Study;Interview;Kentucky;Leadership;Learning;Legal patent;Macular degeneration;Medical;Medicine;Mentors;Methods;Minority Access;Mission;Monitor;National Research Service Awards;Pharmaceutical Preparations;Pharmacy facility;Policies;Population;Positioning Attribute;Postdoctoral Fellow;Preparation;Process;Productivity;Psychology;Public Health;Publications;Publishing;Qualifying;Rare Diseases;Research;Research Methodology;Research Personnel;Research Training;Residencies;Resources;Role;Scholars Program;Science;Scientist;Social Work;Solid;Students;TNFSF15 gene;Talents;Text;Time Management;Training;Training Programs;Training and Education;Translational Research;Underrepresented Populations;Underrepresented Students;United States National Institutes of Health;Universities;Work;biomedical informatics;career;career development;clinical center;clinical effect;cohort;college;design;doctoral student;education research;experience;graduate student;health disparity;health equity;improved;instructor;interest;investigator training;life span;multidisciplinary;patient oriented;pre-doctoral;prenatal;professional students;professor;programs;skills;summer research;theories;translational scientist;underserved students


application_id: 10874439
project_number: 5R01NS114404-05
project_title: BMAL1/ARNTL plays a critical non-circadian role in secondary tissue damage after contusive SCI
administering_ic: NINDS
award_notice_date: 2024-06-10
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: NS
serial_number: 114404
program_official: BAMBRICK, LINDA LOUISE
project_start_date: 2020-08-15
project_end_date: 2026-05-31
study_section: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]
contact_pi_person_id: 7612305
contact_pi: HETMAN, MICHAL
other_pis: SARASWAT, SUJATA OHRI
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Circadian rhythms regulate a wide spectrum of biological processes of critical importance for organismalhealth. Perturbations of those rhythms underlie many pathologies including systemic inflammation depressionand neurodegeneration. Mechanistically circadian rhythms are driven by intrinsic oscillatory changes in geneexpression that are orchestrated by several regulators of gene transcription and mRNA translation forming thecore oscillator circuitry. Those key regulators most importantly the non-redundant transcription/translationfactor BMAL1/ARNTL are active in most cells throughout the body and undergo circadian entrainment byexternal time cues such as light or feeding. At the organismal level the pro-rhythmic role of the oscillator iswidely recognized as a critical contributor to homeostasis. BMAL1 effects that are independent of the centralrhythm include anti-oxidant protection in the brain life span regulation contributions to atherosclerosis andendoplasmic reticulum (ER) stress-sensitization of cancer cells. Those or similar tissue-specific functions ofBMAL1 may affect the outcome after SCI. However clock function at the molecular level has never beeninvestigated in the context of SCI. Unexpectedly we found that: (i) moderate contusive thoracic SCIupregulates BMAL1 in penumbral oligodendrocytes (OLs) coinciding with induction of the ER stress response(ERSR)-activated pro-apoptotic transcription factor CHOP and ER stress-mediated apoptosis of OLs (ii) afterSCI Bmal1-/- mice show improved locomotor recovery and white matter sparing (WMS) as well as selectivedownregulation of Chop and its pro-apoptotic target gene death receptor 5 (Dr5) and reduced bloodextravasation and inflammation with extensive changes in microglia/macrophage (MM) and endothelial (EC)-specific gene expression. Also pharmacological enhancement of the negative feedback inhibition of BMAL1reduces ER stress toxicity in OPC cultures. These exciting findings suggest a novel role of BMAL1 in thepathogenesis of SCI which may include OL-cell autonomous regulation of CHOP-mediated OL apoptosisand/or EC/MM-cell autonomous modulation of post-SCI hemorrhage/vascular dysfunction/cytotoxic neuro-inflammation. Therefore we will test the hypothesis that BMAL1 regulates OL EC and/or MM gene expressionthat contributes to SCI-associated white matter loss and impaired locomotor recovery. To test this hypothesiswe will: (i) determine the cell autonomous roles of OL- MM- and EC-BMAL1 in SCI-associated white matterdamage and locomotor recovery (ii) identify mechanism(s) that underlie BMAL1-mediated enhancement ofSCI-driven white matter loss and (iii) evaluate mediators of the negative feedback inhibition of BMAL1 aspharmacological targets for interventions to reduce SCI-associated white matter loss and locomotorimpairment. We will use a moderate T9 SCI contusion model in wild type or cell type-selective Bmal1-/- miceand non-toxic CNS-permeable drugs targeting the feedback regulation of BMAL1. This research may uncovernovel previously unrecognized contributions of BMAL1 to `secondary tissue injury after SCI.

project_terms:
ARNTL gene;Acute;Affect;Agonist;Antioxidants;Apoptosis;Apoptotic;Arrhythmia;Atherosclerosis;Biological Process;Blood;Blood coagulation;Brain;Cardiovascular Diseases;Cell Count;Cell Proliferation;Cells;Cervical spinal cord injury;Cessation of life;Circadian Dysregulation;Circadian Rhythms;Clinical;Complex;Contusions;Cues;Down-Regulation;Drug Targeting;Endothelial Cells;Endothelium;Enhancers;Extravasation;Feedback;Functional disorder;Gene Expression;Genes;Genetic Transcription;Health;Hemoglobin;Hemorrhage;Homeostasis;Human;Impairment;Inflammation;Injury;Intervention;Intrinsic drive;Knock-out;Light;Locomotor Recovery;Macrophage;Malignant Neoplasms;Mediating;Mediator;Mental Depression;Metabolic syndrome;Microglia;Modeling;Molecular;Mus;Mutant Strains Mice;Natural Immunity;Nerve Degeneration;Oligodendroglia;Organ;Outcome;Pathogenesis;Pathology;Periodicity;Permeability;Phosphorylation;Play;Protein Kinase;Proteins;Proteolipids;Recovery;Recovery of Function;Regulation;Regulator Genes;Reporting;Repression;Research;RiboTag;Role;Secondary to;Signal Transduction;Spinal Cord;Spinal Cord Contusions;Spinal cord injury;TNFRSF10B gene;Technology;Testing;Thoracic spinal cord structure;Time;Tissues;Toxic effect;Transcription Repressor;Vascular Diseases;adaptive immunity;angiogenesis;biological adaptation to stress;cadherin 5;cancer cell;cell type;circadian;cytotoxic;effective therapy;endoplasmic reticulum stress;experimental study;feeding;gain of function;improved;improved outcome;inhibitor;insight;life span;loss of function;mRNA Translation;neuroinflammation;new therapeutic target;novel;pharmacologic;selective expression;systemic inflammatory response;tissue injury;transcription factor;transcription factor CHOP;transcriptome sequencing;translation factor;white matter;white matter damage

public_health_relevance:
Project narrativeCurrently there are no clinically effective treatments to improve outcome after traumatic spinal cord injury(SCI). This proposal will examine the role of novel candidate mediators of secondary tissue damage followingSCI. Hence new therapeutic targets may be identified to enhance functional recovery after SCI.


application_id: 10874266
project_number: 2R15GM132818-02
project_title: Characterization of SAM gene mutation impacts on cellular processes and genome instability
administering_ic: NIGMS
award_notice_date: 2024-04-11
opportunity_number: PAR-21-155
application_type: 2
activity_code: R15
ic: GM
serial_number: 132818
program_official: MACARTHUR, LINDA
project_start_date: 2020-03-01
project_end_date: 2027-04-30
study_section: Special Emphasis Panel[ZRG1 MGG-C (81)]
contact_pi_person_id: 11294477
contact_pi: STROME, ERIN D
other_pis: Not Applicable
congressional_district: 04
department: BIOLOGY
primary_duns: 072879760
primary_uei: LN53C9E23GH6
duns_number: 072879760
uei: LN53C9E23GH6
fips: US
organization_id: 656601
organization_name: NORTHERN KENTUCKY UNIVERSITY
organization_city: HIGHLAND HEIGHTS
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 410990001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
AbstractIn Saccharomyces cerevisiae Sam1 and its paralog Sam2 play roles in the methyl cycle catalyzing thebiosynthesis of AdoMet. Despite Sam1 and Sam2 having high levels of homology and findings that both proteinslocalize to the cytoplasm differences in abundance and regulation of expression speak to the differential functionand use of these proteins by the cell. In humans three genes MAT1A MAT2A and MAT2B encode subunitsof the homologous AdoMet synthetases. These genes and their product AdoMet have been implicated inmultiple cancer types but the mechanism of action is not well understood because both increases and decreasesin expression are associated with cancers. Our group has conducted studies of SAM gene dosage anddetermined the impacts of changes in AdoMet synthetase genes on genome stability. SAM1 and SAM2 clearlyoperate by two distinct mechanisms to impart different impacts on genome stability. This proposal contains thenext logical steps to improve our understanding of the SAM genes and impacts of changes to the methyl cycleon cellular processes including genome stability. Through the first iteration of this grant we have found that theincreased instability in sam2/sam2 cells is linked to increased dNTP levels and studies proposed here aimto define the mechanism of increased dNTPs and how they increase recombination and breakage/NDJ events.We also found that the increased stability in sam1/sam1 cells is not due to increased GSH or polyamines ordecreased ROS and therefore hypothesize stability may come from the increased AdoMet levels in methylationsor via suppressing more reactive methyl donors. We seek to define the protective effects of increased AdoMetas well as changes in the proteomes of our mutants due to changes in AdoMet-dependent methyltransferasefunction. We also propose studies to better understand the regulation and functionality of the Sam1 and Sam2proteins to provide context to the opposite effects observed due to loss of one or the other. Together thesestudies will aid our understanding of the differences in the roles of the unlinked SAM1 and SAM2 genes and howaltered expression of the homologous genes and/or changes in AdoMet levels might be implicated in diseasedevelopment and treatments. Finally these studies will train numerous undergraduate students in hypothesis-based research utilizing the genetically malleable yeast system ideal for teaching genetics and molecular biologyand focusing on their development as scientists and scientifically literate citizens. This proposal meets the statedobjectives of the R15 AREA program by involving undergraduate students in hypothesis driven research andstrengthening the research environment at NKU.

project_terms:
Alkylation;Anabolism;Binding;Biological Assay;Biomedical Research;Cell Physiology;Cells;Chromosomal Stability;Chromosome Mapping;Cytoplasm;D Cells;Data;Development;Disease;Educational process of instructing;Environment;Event;Excision;Folic Acid;Funding;Gene Conversion;Gene Deletion;Gene Dosage;Gene Mutation;Genes;Genetic;Genetic Recombination;Genome;Genome Stability;Genomic Instability;Goals;Grant;Homologous Gene;Human;Individual;Institution;Investigation;Kentucky;Ligase;Link;Malignant Neoplasms;Methylation;Methyltransferase;Micro Array Data;Modeling;Modernization;Molecular;Molecular Biology;Mutation;Nature;Nucleotides;Pathway interactions;Phenotype;Play;Point Mutation;Polyamines;Process;Production;Promoter Regions;Proteins;Proteome;Proteomics;Public Health;Regulation;Research;Ribonucleotide Reductase;Role;Saccharomyces cerevisiae;Scientist;System;Techniques;Testing;Training;Universities;Yeasts;cancer therapy;cancer type;defined contribution;differential expression;improved;insight;interest;methionine adenosyltransferase;methyl group;multidisciplinary;mutant;nucleotide metabolism;paralogous gene;programs;protective effect;scientific literacy;transcriptome sequencing;treatment planning;undergraduate student

public_health_relevance:
Project NarrativeThe objective of the proposed research is relevant to public health because S-adenosylmethionine (AdoMet)synthetase genes and AdoMet have been implicated in multiple cancer types but the mechanism of action isnot well understood because both increases and decreases in expression are associated with cancers. Ourgroup has conducted studies on the AdoMet synthetase genes SAM1 and SAM2 in S. cerevisiae anddetermined the opposite nature of impacts of deletion of these paralogous genes on genome stability and othercellular pathways. In addition to advancing the field towards a more complete mechanistic understanding ofregulation of AdoMet and a detailed characterization of the impacts of mutations; including effects on the methylcycle and the individual steps in genome stability changes this multi-disciplinary project meets the statedobjectives of the AREA program by offering undergraduate students hands-on training in classical genetics andmodern molecular techniques and strengthens the research environment at Northern Kentucky University.


application_id: 10874071
project_number: 1R15MH134003-01A1
administering_ic: NIMH
award_notice_date: 2024-05-28
opportunity_number: PAR-21-154
application_type: 1
activity_code: R15
ic: MH
serial_number: 134003
suffix: A1
program_official: TALKOVSKY, ALEXANDER MAXWELL
project_start_date: 2024-06-01
project_end_date: 2027-05-31
study_section: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]
contact_pi_person_id: 12482819
contact_pi: MEKAWI, YARA
other_pis: Not Applicable
congressional_district: 03
department: PSYCHOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_title:
Effects of Psychosocial Stress on Threat-Related Attention: Testing a Brief Mindfulness Intervention

project_abstract:
Modified Project Summary/Abstract Section: Chronic psychosocial stress is a public health problem and known predictor of severe mental health symptoms. While there is a strong link between chronic psychosocial stress and adverse mental health little is known about the transdiagnostic mechanisms that explain how persistent psychosocial stress exposure can lead to psychological symptoms and what interventions may target these mechanisms among Black Americans in particular. Our scientific premise is that chronic psychosocial stress can lead to disproportionately allocating ones attention to threatening stimuli (i.e. threat-related attention) a known predictor of stress-related symptoms and that this threat-related attentional tendency can be modified by a brief mindfulness intervention. We also posit that identity-based factors are key individual differences that can shape the degree to which psychosocial stress influences attentional processes and the degree to which a mindfulness intervention mitigates threat-related attention. We will recruit 200 Black adults from the community who have experienced chronic psychosocial stress to complete a lab study to target three specific aims which are to: 1) Use eye-tracking methods to examine if chronic psychosocial stress (vs. non-psychosocial stress) leads to a greater threat-related attention 2) Test if a brief mindfulness meditation (vs. neutral audio) reduces threat-related attention and 3) Investigate if individual factors influence a) the effect of the psychosocial stress manipulation on attentional processes and b) the efficacy of the mindfulness manipulation on threat-related attention. In addition this project has a strong undergraduate training component designed to stimulate undergraduate students interest in research and provide both hands-on experiences and comprehensive mentorship needed for a successful research career. Overall this project fills gaps in the literature by investigating how chronic psychosocial stress exposure affects threat-related attentional processes whether such processes can be changed via a mindfulness intervention and for whom such an intervention is most efficacious. We do so using a novel manipulation of chronic psychosocial stress identification of an objective psychological mechanism reliable and precise assessment of attentional processes using eye-tracking methods and experimental manipulation of mindfulness thus addressing current limitations in this research area. Findings from this project will advance research on understanding and overcoming the psychological consequences of chronic psychosocial stress exposure. Developing nuanced understandings of how psychosocial stress affects mental health and how it can be treated are vital steps in eliminating adverse mental health outcomes.

project_terms:
Address;Adult;Affect;African American student;Anxiety;Area;Arousal;Attention;Biological;Black American;Black Populations;Black race;Communities;Data;Data Reporting;Development;Diagnostic;Diagnostic Factor;Disadvantaged;Emotions;Esthesia;Etiology;Experimental Designs;Exposure to;Fostering;Individual;Individual Differences;Interruption;Intervention;Link;Literature;Maintenance;Mental Depression;Mental Health;Mentorship;Methods;Modeling;Outcome;Pathological anxiety;Pathway interactions;Patient Self-Report;Population;Process;Psychopathology;Public Health;Race;Research;Risk;Sampling;Shapes;Stimulus;Stress;Structure;Symptoms;System;Testing;Thinking;Training;Treatment Effectiveness;Work;anxious;attentional bias;biological adaptation to stress;career;culturally appropriate intervention;design;experience;health disparity;innovation;interest;marginalized community;mindfulness;mindfulness intervention;mindfulness meditation;novel;personalized medicine;post-traumatic stress;psychologic;psychological symptom;racial difference;racial identity;racial population;racism;recruit;response;undergraduate student;underserved community;visual tracking

public_health_relevance:
Modified Public Health Relevance Section: Black Americans experience significant mental health consequences due to chronic psychosocial stress exposure; yet little is known about the psychological mechanisms through which psychosocial stress leads to negative outcomes and whether such mechanisms can be altered using brief mindfulness interventions. To address this we aim to investigate (a) if threat-related attention  a novel understudied transdiagnostic factor that reflects when ones attention is disproportionately allocated to threatening stimuli  is such a mechanism in the stress-mental health link (b) if a brief mindfulness intervention can reduce threat-related attention and (c) if social group salience a key individual difference factor exacerbates psychosocial stresss effects and amplifies the benefits of a mindfulness intervention. To carry out this project rigorous experimental designs and innovative eye-tracking methods in a Black community sample will be used and findings from this project can inform the development of etiological and treatment models for this population.


application_id: 10873591
project_number: 2P20GM103436-24
project_title: Alteration and Renovation
administering_ic: NIGMS
award_notice_date: 2024-04-29
opportunity_number: PAR-23-100
application_type: 2
activity_code: P20
ic: GM
serial_number: 103436
project_start_date: 2001-09-30
project_end_date: 2029-04-30
study_section: Special Emphasis Panel[ZGM1 RCB-9 (IN)]
subproject_number: 9168
contact_pi_person_id: 10465930
contact_pi: ASHLEY, NOAH TODD
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/Abstract:Western Kentucky University (WKU) is a regional comprehensive institution located insouthcentral Kentucky that is a member of the Kentucky INBRE program. Since the inception ofWKU in joining KY INBRE in 2002 a number of faculty members have been successful inreceiving funding from NIH and in training undergraduate students to perform biomedicalresearch. The objective of the Alteration and Renovation project outlined herein is to enhanceand maintain the research capacity of WKU to enable high-quality research in the fields ofmicrobiology genetics physiology and neurobiology. More specifically this proposal requeststo replace and upgrade essential "workhorse" research equipment (an autoclave cage/bottlewasher) located on the third floor of the Engineering and Biological Sciences (EBS) building thatare in disrepair and obsolete (spare parts are no longer made to service these units). The oldautoclave and cage/bottle washer are located in the WKU Biotechnology Center (2172 sq. ft)and the WKU Vivarium (1726 sq. ft) respectively on the third floor of EBS. The currentautoclave in the WKU Biotechnology Center is currently nonfunctional which has createdunnecessary delays and barriers to conducting research. The current cage/bottle washer is stilloperational but will likely fail in the next several years. These needed upgrades will directlyaffect one WKU faculty member with a current NIH R15 grant who relies heavily upon a workingcage/bottle washer to maintain a mouse colony five other WKU faculty members that arecurrently or previously funded by KY INBRE and/or NIH and 20-25 undergraduate students thatwork with these faculty members to carry out biomedically relevant research. In addition theOgden College of Science and Engineering at WKU is currently developing a new Neurosciencemajor that will attract new students interested in biomedical research. In developing thecurriculum for this new major there is a need for potentially new faculty hires in the fields ofBehavioral Neuroscience and Systems Neuroscience. If these new hires plan to utilize rodentmodels then it is necessary that a fully functioning cage/bottle washer be available for use.These needed upgrades to basic (yet essential) research equipment will enable current andfuture faculty staff and students to continue to carry out high-quality biological research withequipment that is reliable and working properly.

project_terms:
Affect;Animal Experimentation;Animals;Award;Behavioral;Biological Sciences;Biology;Biomedical Research;Biotechnology;Direct Costs;Educational Curriculum;Engineering;Equipment;Expenditure;Faculty;Floor;Funding;Future;Future Teacher;Genetic;Grant;Institution;Kentucky;Microbiology;Molecular Biology;Mus;Neurobiology;Neurosciences;Physiology;Request for Proposals;Research;Research Personnel;Rodent Model;Science;Services;Students;System;Training;United States National Institutes of Health;Universities;Work;biological research;college;cost;faculty support;interest;member;programs;recruit;square foot;undergraduate student


application_id: 10873590
project_number: 2P20GM103436-24
project_title: Data Science Core
administering_ic: NIGMS
award_notice_date: 2024-04-29
opportunity_number: PAR-23-100
application_type: 2
activity_code: P20
ic: GM
serial_number: 103436
project_start_date: 2001-09-30
project_end_date: 2029-04-30
study_section: Special Emphasis Panel[ZGM1 RCB-9 (IN)]
subproject_number: 9167
contact_pi_person_id: 7948398
contact_pi: ROUCHKA, ERIC C
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Data Science Core Summary The Data Science Core for Biomedical Research (DSC) based at the University of Louisville HealthScience Campus and the University of Kentucky consists of several components designed to strengthen theresearch capacity of researchers and build upon data science training for faculty staff and students at primaryundergraduate institutions (PUIs) within the larger KY INBRE network. Components of the DSC include theBioinformatics Training and Education Center (BTEC) Genomics Training and Education Center (GTEC) ImageTraining and Education Center (ITEC) and the Predictive Analytics and Data Science (PADS) Hub that worktogether with the University of Louisville Bioinformatics Core (BC) and Sequencing Technology Center (STC).In order to fulfill the mission of the DSC within the KY INBRE network seven specific aims have been establishedthat will (1) support the generation and analysis of genomic datasets from Illumina Pacific Biosciences andOxford Nanopore sequencing technologies; (2) provide hands-on training in imaging genomics andbioinformatic technologies; (3) provide expertise on experimental design and usage of appropriate statisticalmethodologies; (4) aid in the integration of publicly available data from resources such as dbGAP GTExGenome Data Commons The Cancer Genome Atlas and ENCODE; (5) provide workshops for undergraduatesgraduates staff and faculty; (6) support data science initiatives at PUIs; and (7) provide PUI access to scientificcores in IDeA states across the southeast region.

project_terms:
Address;Applications Grants;Area;Artificial Intelligence;Bioinformatics;Biological Sciences;Biomedical Research;Centers of Research Excellence;Cloud Computing;Computer software;Core Facility;Data Commons;Data Science;Data Science Core;Data Scientist;Development;Educational workshop;Equipment;Experimental Designs;Faculty;Funding;Funding Mechanisms;Generations;Genome;Genomics;Genotype-Tissue Expression Project;Health Sciences;Hybrids;Image;Image Analysis;Institution;Kentucky;Machine Learning;Manuscripts;Methodology;Mission;Participant;Postdoctoral Fellow;Predictive Analytics;Preparation;Research;Research Personnel;Research Support;Research Training;Resources;Sampling;Schedule;Students;System;Teacher Professional Development;Technology;The Cancer Genome Atlas;Training;Training and Education;Universities;Work;biomedical data science;data resource;database of Genotypes and Phenotypes;design;genomic data;graduate student;insight;interest;nanopore;novel sequencing technology;sequencing platform;single cell sequencing;sound;summer research;symposium;undergraduate student;voucher


application_id: 10873589
project_number: 2P20GM103436-24
project_title: Developmental Research Project Program (DRPP)
administering_ic: NIGMS
award_notice_date: 2024-04-29
opportunity_number: PAR-23-100
application_type: 2
activity_code: P20
ic: GM
serial_number: 103436
project_start_date: 2001-09-30
project_end_date: 2029-04-30
study_section: Special Emphasis Panel[ZGM1 RCB-9 (IN)]
subproject_number: 9166
contact_pi_person_id: 9258139
contact_pi: MATTINGLY, BRUCE A
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Developmental Research Project Program SummaryThe overarching goals of the Developmental Research Project Program (DRPP) are: 1) to continue to increasebiomedical research capacity in Kentucky by assisting faculty at the primarily undergraduate institutions (PUIs)become competitive for independent NIH research funding and 2) to provide the highest quality research trainingto undergraduate students. To achieve these goals the DRPP provides training mentoring and researchfunding to PUI investigators to be successful in competing for new and competing renewal NIH R15 and/or R16awards. These two award mechanisms serve our dual purposes of supporting high quality faculty research whileproviding outstanding hands-on research experiences for undergraduate students. Modeled after NIH R15/R16application guidelines and review procedures the DRPP supports and manages two research fundingmechanisms (Pilot Project (PP) and Research Projects (RP)) from solicitation of proposals through scientificreview and approval. The DRPP also provides grant writing workshops one-on-one mentoring site-visits andother consulting services. While primarily aimed at early stage investigators the PP and RP grant mechanismsprovides support to productive investigators at all stages of career development. Complemented by otherresearch support and training programs provided by the Administrative and Data Science Cores the DRPP aimsto build a sustainable statewide biomedical research network.

project_terms:
Applications Grants;Award;Biomedical Research;Career Mobility;Core Facility;Data;Data Science;Data Science Core;Development;Discipline;Educational workshop;Eligibility Determination;Faculty;Funding;Funding Mechanisms;Goals;Grant;Guidelines;Infrastructure;Institution;K-Series Research Career Programs;Kentucky;Mentors;Modeling;Pilot Projects;Preparation;Procedures;Process;Productivity;Program Research Project Grants;Research;Research Personnel;Research Project Grants;Research Support;Research Training;Services;Site Visit;Students;Training;Training Programs;Underrepresented Populations;United States National Institutes of Health;Universities;Work;Workforce Development;Writing;career;career development;college;experience;faculty research;hands on research;programs;research and development;research faculty;success;training opportunity;undergraduate research experience;undergraduate student


application_id: 10873588
project_number: 2P20GM103436-24
project_title: Administrative Core
administering_ic: NIGMS
award_notice_date: 2024-04-29
opportunity_number: PAR-23-100
application_type: 2
activity_code: P20
ic: GM
serial_number: 103436
project_start_date: 2001-09-30
project_end_date: 2029-04-30
study_section: Special Emphasis Panel[ZGM1 RCB-9 (IN)]
subproject_number: 9165
contact_pi_person_id: 1871981
contact_pi: BICKFORD, MARTHA E
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Administrative Core Summary The Administrative Core will provide leadership and direction to enable the KY INBRE network to growin a purposeful and managed way. The Administrative Core will provide oversight of the DevelopmentalResearch Project Program and Data Science Core and coordinate the activities of the governance committeesand overall network. In addition to this global management of the network the specific duties of theAdministrative Core will include management of programs to engage students in research recruit faculty withbiomedical research experience provide promising early career scientists with mentored research experiencesdevelop curricula that includes research and provide infrastructure support to the network. Specific duties ofthe Administrative Core also include management of the budget development of predictive financial plans andtracking and reporting outcomes. In the next funding cycle the Administrative Core will work with the other KYINBRE components to continue to build research capacity and develop a strong biomedical research workforcein KY. We propose to accomplish these goals via the following specific aims: (1) provide research experiencesfor students; (2) promote curriculum development in KY institutions; (3) recruit faculty with biomedical researchtraining and mentor early career scientists; (4) provide sound management of KY INBRE funds and ensurefinancial support of PUIs; and (5) evaluate the KY INBRE program and report outcomes.

project_terms:
Advisory Committees;Applications Grants;Biomedical Research;Budgets;Collaborations;Data Science Core;Development;Education;Educational Curriculum;Educational workshop;Ensure;Faculty;Faculty Recruitment;Financial Support;Funding;Geographic Distribution;Goals;Home;Infrastructure;Institution;Joints;Kentucky;Laboratory Research;Leadership;Manuscripts;Mentors;Outcome;Peer Review;Peer Review Grants;Population;Postdoctoral Fellow;Program Research Project Grants;Publications;Reporting;Research;Research Infrastructure;Research Personnel;Research Support;Research Training;Resource Sharing;Science;Scientist;Students;Teacher Professional Development;Training;Universities;Work;career;career development;curriculum development;equipment acquisition;experience;high school;meetings;programs;recruit;research faculty;sound;student participation;symposium;undergraduate student


application_id: 10873587
project_number: 2P20GM103436-24
project_title: IDeA Networks of Biomedical Research Excellence in Kentucky
administering_ic: NIGMS
award_notice_date: 2024-04-29
opportunity_number: PAR-23-100
application_type: 2
activity_code: P20
ic: GM
serial_number: 103436
program_official: ZHOU, YANG
project_start_date: 2001-09-30
project_end_date: 2029-04-30
study_section: Special Emphasis Panel[ZGM1 RCB-9 (IN)]
contact_pi_person_id: 1871981
contact_pi: BICKFORD, MARTHA E
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
KY INBRE Overall Summary The Kentucky Institutional Development Award (IDeA) Network of Biomedical Research Excellence (KYINBRE) is a collaborative network of educational institutions working to build capacity for health-related andbiomedical research in the Commonwealth of Kentucky. The KY INBRE network is currently composed of 25institutions that are geographically distributed across the state of Kentucky. The partner institutions include 2research intensive universities and 7 primarily undergraduate institutions (PUIs). Another 16 PUIs participate inKY INBRE activities. The KY INBRE program is managed by 4 interactive components. The Administrative Coreoversees student research faculty recruitment curriculum development the budget and financial plan as wellas internal evaluation and reporting. The governance committees provide oversight evaluation and guidance toensure adherence of the KY INBRE to its mission in building research capacity across the state. TheDevelopmental Research Project Program provides research funding mentoring oversight and training toenable KY INBRE faculty to successfully compete for independent NIH funding. The Data Science Core provideseducation training and equipment access to assist investigators and trainees collect efficiently analyze andshare research data. In the next funding cycle these 4 components will work together to continue to buildbiomedical research capacity strengthen research culture develop faculty research careers and providestudents with research opportunities to help develop a strong biomedical research workforce in Kentucky. Wepropose to accomplish these goals with the following overall specific aims: 1) provide engaging researchexperiences to recruit KY undergraduate students into biomedical science majors/careers; 2) promote researchinfrastructure and curriculum development in KY institutions; 3) develop research skills of faculty and trainees tobuild research capabilities in KY; and 4) recruit faculty with biomedical research training and provide mentoredcareer development to build research capacity in KY institutions.

project_terms:
Adherence;Award;Biomedical Research;Budgets;Core Facility;Data;Data Analyses;Data Science;Data Science Core;Development;Diagnosis;Education;Ensure;Equipment;Evaluation;Faculty;Faculty Recruitment;Funding;Geography;Goals;Growth;Health;Healthcare;Institution;Kentucky;Laboratory Research;Mentors;Mission;Oranges;Privatization;Program Research Project Grants;Recruitment Activity;Reporting;Research;Research Infrastructure;Research Personnel;Research Training;Science;Students;Technology;Training;Training and Education;United States National Institutes of Health;Universities;Work;career;career development;college;course development;curriculum development;data sharing;experience;faculty research;human disease;improved;infrastructure development;member;programs;recruit;skills;undergraduate research;undergraduate student

public_health_relevance:
Project NarrativeThe goals of the KY INBRE are to build capacity for biomedical research and provide training todevelop the research and healthcare workforce in the Commonwealth of Kentucky. These goalswill lead to the improved diagnosis and treatment of human diseases.


application_id: 10873348
project_number: 5R01DK126777-04
project_title: ABIN1 dysfunction in Lupus Nephritis
administering_ic: NIDDK
award_notice_date: 2024-06-26
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: DK
serial_number: 126777
program_official: CHAN, KEVIN E
project_start_date: 2021-09-01
project_end_date: 2026-06-30
study_section: Pathobiology of Kidney Disease Study Section[PBKD]
contact_pi_person_id: 8638278
contact_pi: POWELL, DAVID W.
other_pis: CASTER, DAWN
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project SummaryLupus nephritis (LN) is a common and severe complication of systemic lupus erythematosus (SLE) andcurrent therapies are toxic and frequently ineffective. LN is more prevalent and more likely to cause kidneyfailure in African American patients [1-3]. SLE has strong genetic components but the relationship ofgenetic susceptibility to prognosis in African Americans is poorly understood. Previous studies showedvariants of TNIP1 are associated with SLE and LN susceptibility [4-7]. We reported a strong association forthe TNIP1 rs4958881 polymorphism with LN in African American patients from a large-scale SLEgenotyping study [8]. Our preliminary data show an association of the rs4958881 variants with severity andprogression of LN in African Americans. TNIP1 encodes the protein ABIN1 that functions as a physiologicalinhibitor of NF-B a prominent immune regulator [9 10]. We reported previously that loss of the molecularfunction of ABIN1 in mice results in SLE-like autoimmunity and glomerulonephritis [8 11 12].While there is evidence that ABIN1 regulation of NF-B plays a role in autoimmunity and development ofLN a number of critical gaps in knowledge remain. First what molecular mechanisms mediate ABIN1-dependent enhanced risk of LN and are they specific for different immune cell types? Second does alteredABIN1 function induced by TNIP1 polymorphisms play a role in the racial disparity of LN? Third do TNIP1polymorphisms have different pathologic molecular and cellular effects in African Americans comparedwith White Americans?Three Specific Aims are proposed to address these significant questions. Aim 1: Compare the Associationof theTNIP1 variant rs4958881 on LN in White and African Americans. Aim 2: Determine the effects of theTNIP1 variant rs4958881 on monocyte neutrophils and B cell activity in patients with LN. Aim 3. Determinethe mechanisms by which loss of ABIN1 molecular function alters monocyte neutrophil and B cell functionusing ABIN1 transgenic mice. The animal experiments will be interpreted in conjunction with similarexperiments in Aim 2 using the same cells isolated from blood of LN patients with the TNIP1 rs4958881 riskvariant.This is a Multi-PI proposal with a Cell and Molecular Biologist/Biochemist (Dr. David W. Powell) and aClinical Nephrologist/Scientist (Dr. Dawn J. Caster). These investigators have published many of thereports pertaining to TINIP1/ABIN1 function in LN via genetic and animal studies and are now poised withrecent preliminary findings to evaluate causative roles for a TNIP1 polymorphism in severity andprogression and specific cellular and molecular events in human LN. The translational and population-targeted nature of these studies will provide impactful insights that will lead to precision diagnostics andtherapeutics for high-risk African American LN patients.

project_terms:
Address;African American;African American population;Alleles;Animal Experiments;Animals;Autoimmunity;B-Lymphocytes;Binding Proteins;Biological Response Modifiers;Blood;Bone Marrow;CXCL10 gene;CXCR3 gene;Cell Maturation;Cell Physiology;Cell Separation;Cells;Clinical;Complication;Data;Development;Diffuse;Disease;Disease Outcome;Event;Functional disorder;Genes;Genetic;Genetic Polymorphism;Genetic Predisposition to Disease;Genotype;Glomerulonephritis;Human;Immune;Immune Complex Glomerulonephritis;Inflammation Mediators;Inflammatory;Interleukin-6;Investigation;Kidney;Kidney Failure;Knowledge;Lupus Nephritis;Mature T-Lymphocyte;Mediating;Molecular;Mus;Mutation;Nature;Nuclear;Outcome;Pathologic;Patients;Peripheral;Physiological;Polyubiquitin;Precision therapeutics;Predisposition;Production;Prognosis;Proteins;Proteinuria;Publishing;Race;Regulation;Reporting;Research Personnel;Risk;Role;Sampling;Scientist;Serum;Severities;Severity of illness;Systemic Lupus Erythematosus;T-Lymphocyte;TNF gene;Target Populations;Transcriptional Regulation;Transgenic Mice;Transgenic Organisms;Transplantation;Validation;Variant;Wild Type Mouse;anti-dsDNA antibodies;caucasian American;cell type;chemokine;cohort;cytokine;diagnostic biomarker;disorder risk;experimental study;genetic variant;high risk;inhibitor;insight;monocyte;neutrophil;novel diagnostics;personalized diagnostics;podocyte;protein function;racial disparity;risk variant;therapeutic target

public_health_relevance:
Project NarrativeThis study will determine the cellular and molecular mechanisms by which genetic variants for theABIN1 gene TNIP1 regulates monocyte neutrophil and B cell activity in lupus nephritis. Successfulcompletion of this study will define novel and precision diagnostics and targets for the treatment ofhigh-risk African American systemic lupus erythematosus patients with lupus nephritis.


application_id: 10872259
project_number: 5R37CA234002-05
project_title: Targeting 6-Phosphofructo-2-Kinase to increase efficacy of CDK4/6 Inhibitors
administering_ic: NCI
award_notice_date: 2024-06-26
opportunity_number: PA-19-056
application_type: 5
activity_code: R37
ic: CA
serial_number: 234002
program_official: FORRY, SUZANNE L
project_start_date: 2020-07-09
project_end_date: 2025-06-30
study_section: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]
contact_pi_person_id: 8320211
contact_pi: IMBERT-FERNANDEZ, YOANNIS
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
We have recently discovered a novel oncogenic mechanism whereby cyclin D1 bypasses CDK4/6 inhibitionresulting in the stimulation of 6-phosphofructo-2-kinase (PFKFB3) and glucose metabolism. The objective of thisproposal is to characterize the role of PFKFB3 in mediating adaptation or resistance to CDK4/6 inhibition and todefine new approaches to increase the efficacy of CDK4/6 inhibitors in order to enable durable responses instage IV HR+ breast cancer patients. Deregulation of the estrogen receptor (ER)-cyclin D1-CDK4/6 pathway isa hallmark of ER+ breast cancer that has prompted the development of CDK4/6 inhibitors. Althoughadministration of CDK4/6 inhibitors to patients with ER+ advanced breast cancers have resulted in animprovement in progression free survival almost all patients invariable develop resistance and relapse over time.Activation of glucose metabolism upon CDK4/6 inhibition is becoming increasingly evident. A key stimulator ofglycolysis is the PFKFB3 enzyme which synthesizes fructose 26-bisphosphate (F26BP) a potent allostericactivator of the rate-limiting 6-phosphofructo-1-kinase (PFK1). F26BP controls flux throughout the entireglycolytic pathway and as a result is required for the proliferation of cancer cells. In preliminary studies weprovide evidence that PFKFB3 expression and activity is increased in response to CDK4 inhibition in ER+ breastcancer cells and breast cancer patient tumors. Notably we show that a PFKFB3 inhibitor PFK-158 increasesthe anti-tumor activity of anti-CDK4 targeted therapy in vitro and in vivo. We postulate that PFKFB3 is anessential regulatory effector of the cyclin D1-CDK4/6 axis that serves to attenuate CDK4/6 inhibition effects bystimulating glucose metabolism. Furthermore we hypothesize that genetic or pharmacological inhibition ofPFKFB3 will increase the efficacy of CDK4/6 inhibitors by disabling the ability of the cell to sustain sufficientglucose metabolism necessary for survival and growth. Aim 1 will determine the mechanism by which CDK4/6inhibition induces PFKFB3 expression. Aim 2 will determine the effects of combined CDK4/6 and PFKFB3inhibition on glucose metabolism cell cycle growth and survival in vitro. Aim 3 will examine the metabolic andgrowth effects of pharmacological CDK4/6 and PFKFB3 inhibition as monotherapies and in combination inmouse models of breast cancer in vivo. We anticipate that our studies will support the clinical testing of PFKFB3inhibitors in combination with CDK4/6 inhibitors to increase the survival of advanced ER+ breast cancer patients.

project_terms:
6-Phosphofructo-2-kinase;6-Phosphofructokinase;Attenuated;Automobile Driving;Binding;Biological Availability;Breast Adenocarcinoma;Breast Cancer Cell;Breast Cancer Model;Breast Cancer Patient;Breast Cancer cell line;Bypass;CDK4 gene;Cell Cycle;Cell Cycle Progression;Cells;Clinical;Clinical Trials;Cyclin D1;Cyclins;Development;Disabling;ERBB2 gene;Enzymes;Estradiol;Estrogen Receptors;Estrogen receptor positive;FDA approved;Fructose;Genetic;Genetic Transcription;Glucose;Glycolysis;Glycolysis Induction;Growth;In Vitro;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Metabolic;Metastatic breast cancer;Oncogenic;Oral;Pathway interactions;Patients;Phase;Phase I/II Trial;Phosphorylation;Progression-Free Survivals;Proliferating;Relapse;Resistance;Resistance development;Retinoblastoma Protein;Role;Testing;Time;advanced breast cancer;base;blood glucose regulation;cancer cell;combinatorial;cyclin D3;cyclin-dependent kinase 6;design;early phase clinical trial;efficacious treatment;glucose metabolism;hormone receptor-positive;hormone therapy;improved;in vivo;inhibitor;mouse model;novel;novel strategies;overexpression;pharmacologic;prevent;rational design;research clinical testing;response;targeted treatment;therapy resistant;treatment response;tumor

public_health_relevance:
While clinical responses to CDK4/6 inhibition have been remarkable metastatic breast cancer remainsincurable. The proposed studies will provide the mechanistic base for the combined targeting of PFKFB3 and CDK4/6. The results should facilitate the rational design of combinatorial phase I/II trials of PFKFB3 inhibitors with CDK4/6 agents for the treatment of stage IV ER+ breast adenocarcinoma patients.


application_id: 10867508
project_number: 5R01NR019456-05
administering_ic: NINR
award_notice_date: 2024-06-26
opportunity_number: RFA-NR-20-001
application_type: 5
activity_code: R01
ic: NR
serial_number: 019456
program_official: AKUBU-ODERO, MAUREEN KALAMBU
project_start_date: 2020-09-07
project_end_date: 2026-02-28
study_section: ZNR1-REV-W(23)
contact_pi_person_id: 9701191
contact_pi: MUDD, GIA
other_pis: Not Applicable
congressional_district: 06
department: OTHER HEALTH PROFESSIONS
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF NURSING
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-07-01
project_title:
Heart of the Family: A Cardiovascular Disease and Type 2 Diabetes Risk Reduction Intervention in High-Risk Rural Families

project_abstract:
ABSTRACTRural populations in the U.S. have disproportionately higher prevalence of cardiovascular disease (CVD) andtype 2 diabetes (T2D) compared to urban populations. Many rural communities also have greater risk factorburden than urban communities including unhealthier diet higher rates of physical inactivity obesity andsmoking and higher prevalence of hypertension hypercholesterolemia and hyperglycemia. Compoundingthese are poor socioeconomic conditions and limited health resources. Hispanic residents of rural communitiesmay experience worse CVD and T2D disease and risk burden than non-Hispanic residents due to higher ratesof poverty lower educational attainment and greater barriers accessing resources. U.S. Hispanics haveamong the highest rates of T2D of any racial or ethnic group. Culturally responsive lifestyle modificationinterventions are needed to reduce T2D and CVD risk in rural Hispanic and non-Hispanic populations.Modification strategies commonly target individuals and while these may result in behavior change immediatepost-intervention sustained engagement in healthy behaviors is seldom achieved. Family engagement inlifestyle interventions may support sustained engagement in healthy behaviors especially in rural and Hispanicpopulations that often have greater reliance on family members for social support. We will conduct arandomized controlled trial to compare the effects of a dyadic intervention Heart of the Family to an activecontrol intervention. We will compare 3-month (short-term) and 12-month (long-term) impact of the Heart of theFamily intervention on biological and behavioral T2D and CVD risk factors and evaluate whether ethnicitymoderates intervention effects. We will also examine how each active intervention dyad membersengagement in healthy lifestyle behaviors and level of support for their partners engagement in healthylifestyle behaviors affects their own and their partners outcomes. A family focused intervention may bettersupport long-term engagement in healthy lifestyle behaviors to reduce T2D and CVD risk among at-risk ruralHispanics and non-Hispanics. Further this community-based intervention has significant potential for broadimplementation to successfully address T2D and CVD health disparities across U.S. Hispanic communities.

project_terms:
Address;Adult;Affect;Age;Behavior;Behavioral;Biological;Blood Pressure;Body mass index;Cardiovascular Diseases;Cause of Death;Collaborations;Communities;Controlled Study;Data;Death Rate;Diabetes Mellitus;Disease;Disparity;Economic Conditions;Education;Ethnic Origin;Ethnic Population;Face;Family;Family member;Feedback;Geography;Glycosylated hemoglobin A;Health;Health Resources;Health behavior;Heart;Heart Diseases;High Prevalence;Hispanic;Hispanic Populations;Hyperglycemia;Hypertension;Individual;Intervention;Kentucky;Life Style Modification;Lipids;Mediating;Modeling;Modification;Non-Insulin-Dependent Diabetes Mellitus;Not Hispanic or Latino;Nutritional;Obesity;Outcome;Participant;Pattern;Physical activity;Population;Poverty;Prediabetes syndrome;Prevalence;Public Health;Randomized;Randomized Controlled Trials;Research;Research Design;Resources;Risk;Risk Factors;Risk Management;Risk Reduction;Rural;Rural Community;Rural Population;Self Care;Social support;Testing;Tobacco use;Unhealthy Diet;Urban Community;Urban Population;Weight maintenance regimen;active control;behavior change;behavioral outcome;burden of illness;cardiovascular disorder risk;community based participatory research;community intervention;community partners;comorbidity;comparison control;comparison intervention;culturally appropriate intervention;diabetes risk;efficacy testing;ethnic disparity;experience;family support;good diet;group intervention;health disparity;health inequalities;healthy lifestyle;high risk;hispanic community;hypercholesterolemia;improved;indexing;intervention effect;lifestyle intervention;lifetime risk;member;physical inactivity;poor health outcome;post intervention;racial disparity;racial population;rural Hispanic;rural dwellers;rural families;rural residence;smoking prevalence;social;socioeconomics

public_health_relevance:
NARRATIVERural populations in the U.S. are disproportionately burdened by cardiovascular disease and type 2 diabetes.Lifestyle modification interventions are needed that support long-term engagement in risk-reducing healthbehaviors. Our proposal will study the effects of a family focused lifestyle intervention that is culturally tailoredfor use with rural Hispanic and non-Hispanic adults and will have significant potential for broad disseminationto reduce T2D and CVD health disparities in rural U.S. communities.


application_id: 10867345
project_number: 5R01HG011598-04
project_title: Utility of Genomic Sequencing in Community Care Contexts
administering_ic: NHGRI
award_notice_date: 2024-07-05
opportunity_number: PAR-20-254
application_type: 5
activity_code: R01
ic: HG
serial_number: 011598
program_official: STERLING, RENE
project_start_date: 2021-09-22
project_end_date: 2025-12-31
study_section: Special Emphasis Panel[ZRG1-SEIR-S(80)S]
contact_pi_person_id: 10692185
contact_pi: BROTHERS, KYLE BERTRAM
other_pis: COOPER, GREGORY MICHAEL
congressional_district: 03
department: PEDIATRICS
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACTEfforts to translate genomic sequencing technologies into clinical care have faced ongoing challenges definingand measuring utility. Evaluation of utility (and disutility) is particularly difficult in the context of efforts totranslate genomic sequencing technologies like exome sequencing (ES) and genome sequencing (GS) to thediagnosis of children with undiagnosed genetic conditions since these conditions are rarely responsive topharmacological interventions and parents often express a wide variety of reasons for wanting a genomicdiagnosis for their child. We hypothesize that previous efforts to identify the effects (positive negative andneutral) of ES and GS have missed important dimensions of utility that fall in the middle ground betweenconventional notions of clinical and personal utility. Most of the care and services that improve functioning andquality of life for children with complex genetic conditions occur outside doctors offices: physical therapy;occupational therapy; speech-language pathology; behavioral intervention and other mental healthcare; andspecial education services. However it is unknown whether receiving a genomic diagnosis currently providesutility or disutility in these community contexts and what evidence might be needed to increase utility andminimize disutility. This project will address this gap through a rigorous study of potential and actual effects thatchildren with undiagnosed genetic conditions might experience in community settings as a result of receiving agenomic diagnosis. The overall aim of this study is to identify (1) community-based utilities currently beingrealized following genomic diagnosis (2) perspectives of community-based professionals regarding thepotential utility of such diagnoses and (3) sources of information (including medical professionals parentsupport groups and social media) that might support utility for rare genetic conditions.

project_terms:
Address;Area;Behavior;Behavior Therapy;Caregivers;Caring;Child;Child Care;Childhood;Clinical;Communities;Community Healthcare;Community of Practice;Complex;Diagnosis;Dimensions;Disease;Evaluation;Face;Family;Focus Groups;Future;Genetic;Genetic Diseases;Genomics;Health;Health Personnel;Healthcare;Impairment;Intervention;Interview;Language;Measures;Medical;Mental Health;Mental Health Services;Musculoskeletal;National Human Genome Research Institute;Occupational Therapist;Occupational Therapy;Operative Surgical Procedures;Parents;Pathologist;Physical therapy;Professional Practice;Qualifying;Quality of life;Research;Resources;Rural Population;Schools;Sensory;Services;Shapes;Site;Source;Special Education;Speech;Speech Therapy;Speech-Language Pathology;Structure;Support Groups;Technology;Testing;Therapeutic;Translating;Underserved Population;United States Preventative Services Task Force;base;clinical application;clinical care;clinical diagnostics;clinical research site;cohort;community based service;community setting;exome sequencing;experience;falls;family support;functional improvement;genetic testing;genome sequencing;pharmacologic;physical therapist;policy implication;social implication;social media;structural determinants;teacher;translational potential

public_health_relevance:
PROJECT NARRATIVEFamilies with children who have identified deficits in speech and/or sensory or musculoskeletal impairmentswithout a known cause may be referred for genetic testing to find out whether there is a genetic cause.However there is little research into how parents and caregivers use this diagnosis to inform decisions abouttherapeutic services access to school services or how a genomic diagnosis informs the practice of thecommunity professionals who provide these services. This project will examine how a genomic diagnosisshapes the care that children receive from community professionals including physical and occupationaltherapists speech-language pathologists special education teachers behavior analysts and mental healthproviders.


application_id: 10866982
project_number: 1R21CA284179-01A1
project_title: Statistical Methods for Identification and Evaluation of Predictive Biomarkers in Cancer
administering_ic: NCI
award_notice_date: 2024-07-04
opportunity_number: RFA-CA-23-014
application_type: 1
activity_code: R21
ic: CA
serial_number: 284179
suffix: A1
program_official: GUAN, PING
project_start_date: 2024-07-04
project_end_date: 2026-06-30
study_section: Special Emphasis Panel[ZCA1 TCRB-5 (J1)]
contact_pi_person_id: 10443718
contact_pi: CHEN, LI
other_pis: WANG, CHI
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
Project Summary Relapsed/refractory cancer is a principal cause of cancer-related death. Targeted therapies whichrepresent a new generation of cancer therapies have advanced the treatment for relapsed/refractory patients.However treatment effects are still heterogeneous. Only a fraction of patients who are treated with these newtherapies experience clinically beneficial outcomes. Therefore it is critical to identify new predictive biomarkersthat can further stratify patient into subgroups that are most likely to yield a favorable or unfavorable treatmenteffect. Analysis of non-randomized phase II clinical trial data to identify predictive biomarkers is particularlyimportant because such information is crucial to guide efficient subsequent randomized phase II or enrichedphase III trials and improve the success rate of clinical drug development. In non-randomized phase II trialsprogression-free survival (PFS) has been increasingly considered as an important clinical endpoint. As thesetrials do not have an independent control arm the PFS on the most recent prior treatment on which the patienthad experienced progression has been suggested to serve as the patient-specific control. The ratio of pairedPFSs on the new versus prior treatments is used to evaluate treatment efficacy. The PFS ratio has become animportant endpoint in the era of precision oncology. However using paired PFS data to identify and evaluatepredictive biomarkers from non-randomized phase II trials has been hampered due to major challenges instatistical methods. First the identification of predictive biomarkers is typically achieved by testing theinteraction effects in multivariable models which usually requires large sample sizes. As phase II trials usuallyhave small sample sizes detecting interaction effects is challenging. Second it is challenging to deal with high-dimensional candidate biomarkers. Third the PFS ratio endpoint is dependently censored which creates achallenge for accurate statistical inference because traditional methods for censored data require independentcensoring assumption. Fourth there is a lack of clinically meaningful statistical measures to evaluate andcompare the accuracy of predictive biomarkers. To address these challenges we propose to a) develop novelsemiparametric statistical models to identify and combine predictive biomarkers; and b) develop new clinicallymeaningful statistical measures to evaluate and compare the accuracy of predictive biomarkers based onpaired PFS data from non-randomized phase II trials. We will implement the statistical methods into an Rpackage as well as a web-based application. We will also apply these new methods to three precisionmedicine clinical cohorts. Our new methods will establish a systematic and effective framework to advance thepredictive biomarker analysis based on paired PFS data from non-randomized phase II trials which will havedirect impact on drug development by facilitating more informed design for further validation in randomizedtrials.

project_terms:
Acceleration;Accounting;Address;Area Under Curve;Biological Markers;Cancer Etiology;Cancer Patient;Case Study;Cessation of life;Characteristics;Clinical;Clinical Drug Development;Clinical Trials;Data;Death Rate;Evaluation;FDA approved;Failure;Gene Expression;Generations;Goals;Immune checkpoint inhibitor;Joints;Letters;Malignant Neoplasms;Measures;Methods;Modeling;Natural History;Non-Small-Cell Lung Carcinoma;Outcome;Pathologic;Patients;Phase;Phase II Clinical Trials;Prediction of Response to Therapy;Progression-Free Survivals;Randomized;Refractory;Relapse;Reporting;Research Personnel;Sample Size;Standardization;Statistical Methods;Statistical Models;Subgroup;Suggestion;Testing;Therapy trial;Time;Treatment Efficacy;Validation;absorption;arm;biomarker evaluation;biomarker validation;cancer clinical trial;cancer therapy;candidate marker;checkpoint therapy;clinical effect;clinical practice;cohort;design;drug development;experience;high dimensionality;improved;interest;novel;novel therapeutics;patient stratification;phase II trial;phase III trial;precision medicine;precision oncology;predictive marker;predictive signature;randomized trial;randomized clinical trials;refractory cancer;relapse patients;semiparametric;skills;standardize measure;success;targeted treatment;treatment effect;tumor;user friendly software;user-friendly;web app

public_health_relevance:
Project NarrativeThis project aims to develop new statistical methods for identification and evaluation of biomarkers that canpredict treatment effect for cancer patients. The success of this project will enable predictive biomarkeranalysis from non-randomized clinical trial data and thus will have a direct impact on drug development andclinical practice.


application_id: 10866645
project_number: 1R03DE033707-01
project_title: Cobalamin in Porphyromonas gingivalis Pathogenicity
administering_ic: NIDCR
award_notice_date: 2024-04-05
opportunity_number: PAR-21-084
application_type: 1
activity_code: R03
ic: DE
serial_number: 033707
program_official: MCNEALY, TAMARA L
project_start_date: 2024-04-06
project_end_date: 2026-03-31
study_section: Special Emphasis Panel[ZDE1 YM (09)]
contact_pi_person_id: 79184346
contact_pi: GHODS, SHIRIN
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project SummaryPeriodontitis is a polymicrobial-driven and prevalent inflammatory disease of the tissues supporting the teethin adults with adverse effects on overall human health. Studies have revealed that cobalamin (vitamin B12)transporters are highly active in the periodontal microbiome associated with the periodontal pockets ofindividuals with periodontitis. Yet the functional correlation between cobalamin utilization and the pathogenicpotential of periodontal pathogens remains largely unknown. Our studies have elucidated an interconnectionbetween cobalamin utilization stress responses and the virulence potential of Porphyromonas gingivalis(Pg) a key periodontal pathogen in periodontitis disease. As a potent redox sensor cobalamin promotes cellularhomeostasis under redox-changing stresses caused by nutritional limitation and reactive oxygen species (ROS).These stressors represent intrinsic attributes of the inflammatory mechanisms to eliminate infections. Based onour findings and that cobalamin plays a significant role in maintaining cellular homeostasis under redox-changing stresses we hypothesize that cobalamin acts as a key redox-active mediator orchestratinggenomic and metabolic adaptations thereby enabling the pathogen to overcome diverse stressesand foster pathogenicity. To investigate this hypothesis we propose two specific aims. Specific Aim 1. Theimpact of cobalamin on the genomic-metabolic adaptations in Pg strain 381 under stress conditions. This aimwill investigate; i) the impact of cobalamin on the gene expression profile of Pg under two separate biologicallyrelevant stresses including iron limitation and ROS availability. To this end we will perform RNA sequencingfollowed by RT-qPCR-based validation; and ii) the impact of cobalamin on the metabolic profile of Pg cellsgrown under the stress conditions by performing untargeted and targeted metabolomic analyses. Overall thisaim will greatly inform about the intricate connections between cobalamin utilization and the genomic-metabolicadaptations in Pg under biologically relevant stress conditions. Specific Aim 2. To understand cobalamin-regulated virulence potential and survival of Pg strain 381 in the presence of host defense mechanisms. We willdetermine: i) the effect of cobalamin on the virulence potential of Pg cells mediated by proteases known asgingipains; and ii) the impact of cobalamin on the survival of Pg and its immunostimulatory potential usingwhole blood killing and neutrophil assays. This aim will enable us to determine the impact of cobalamin on Pg'sability to survive within the host and modulate its pathogenic potential. Upon completion of the proposedstudies for the first time we will uncover the biological significance of cobalamin utilization in Pg's survivaland pathogenesis during infection. Understanding the role of cobalamin in the pathogenesis of periodontalpathogens has the potential to open new avenues for therapeutic interventions in periodontal disease.

project_terms:
Adult;Adverse effects;Anaerobic Bacteria;Applications Grants;Bacteria;Biological;Biological Assay;Cells;Cobalamin;Cobalt;Data;Disease;Disease Progression;Ensure;Etiology;Exhibits;Fostering;Foundations;Gene Expression Profile;Gene Expression Regulation;Genes;Genomics;Growth;Health;Homeostasis;Host Defense Mechanism;Human;Immune response;Individual;Infection;Inflammatory;Iron;Laboratories;Mediating;Mediator;Metabolic;Modification;Molecular;Mouth Diseases;Nutritional;Outcome Study;Oxidation-Reduction;Pathogenesis;Pathogenicity;Pathway interactions;Peptide Hydrolases;Periodontal Diseases;Periodontal Pocket;Periodontitis;Play;Porphyromonas gingivalis;Proliferating;Reactive Oxygen Species;Research;Role;Stress;Therapeutic Intervention;Time;Tissues;Tooth structure;Up-Regulation;Validation;Virulence;Virulence Factors;Vitamin B 12;Whole Blood;biological adaptation to stress;differential expression;environmental stressor;gingipain;insight;metabolic profile;metabolomics;microbial;microbiome;neutrophil;oxidation;pathogen;periodontopathogen;sensor;stressor;transcriptome sequencing;virulence gene

public_health_relevance:
PROJECT NARRATIVEPeriodontitis is a prevalent oral disease in adults. This study seeks to elucidate the biological significance ofcobalamin (Vitamin B12) utilization in the survival and pathogenesis of Porphyromonas gingivalis amajor contributing pathogen to periodontitis.


application_id: 10866546
project_number: 5R01EY034092-02
project_title: Cortical basis of binocular depth perception
administering_ic: NEI
award_notice_date: 2024-07-01
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: EY
serial_number: 034092
program_official: CLAYTON, EDWIN C
project_start_date: 2023-07-01
project_end_date: 2024-07-22
study_section: Special Emphasis Panel[ZRG1-ICN-U(02)M]
contact_pi_person_id: 10356866
contact_pi: MCGEE, AARON W
other_pis: SAMONDS, JASON M
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
AbstractThe functional properties of the visual system are most sensitive to disruptions of normal vision duringdevelopmental critical periods. Interestingly the critical periods for several functional properties such as oculardominance and acuity overlap during development. Abnormal vision during these overlapping critical periodsbecause of cataracts or misalignment of the two eyes for example is the cause of amblyopia. Amblyopia is aprevalent visual disorder in children and can present with any of several visual problems including lower visualacuity and impaired depth perception. Yet how depth perception is affected by abnormal vision has remainedelusive. In the proposed research we investigate the circuit basis for the development and plasticity of depthperception in the mouse. The development of stereoscopic vision is much slower than other characteristics ofvision and relies on complex properties of binocular disparity. Disparity between the eyes is what produces theperception of depth. We will characterize multiple dimensions of its development and plasticity by takingadvantage of a natural depth discrimination task that depends on binocular vision. Over this same period wewill measure with two-photon microscopy how complex disparity properties are refined in the visual cortex andarea LM (a secondary binocular visual area) as well as how and when they are sensitive to abnormal vision.Understanding the properties of binocular depth perception and the development of those properties will providea foundation for developing therapeutic approaches to treat developmental visual disorders such as amblyopiathat cause stereovision deficits.

project_terms:
Adult;Affect;Age;Amblyopia;Attenuated;Behavioral;Binocular Vision;Biological Assay;Blindness;Calcium;Cataract;Characteristics;Child;Childhood;Complex;Data;Depth Perception;Development;Dimensions;Discrimination;Disease;Disparity;Eye;Felis catus;Foundations;Genetic;Image;Impairment;Knowledge;Lazy Eyes;Measures;Mission;Monocular Vision;Mus;Neurons;Ocular Dominance;Perception;Performance;Population;Primates;Property;Psychometrics;Public Health;Rattus;Refractive Errors;Research;Rodent;Role;Surgical sutures;Symptoms;Systems Development;Task Performances;Testing;Therapeutic;Therapeutic Intervention;United States National Institutes of Health;Vision;Vision Disorders;Vision Disparity;Visual;Visual Acuity;Visual Cortex;Visual System;Visual impairment;area striata;critical developmental period;critical period;deprivation;designer receptors exclusively activated by designer drugs;discrimination task;excitatory neuron;experience;experimental study;extrastriate visual cortex;improved;in vivo calcium imaging;monocular deprivation;mouse model;neural circuit;postnatal;response;spatial vision;stereoscopic;targeted treatment;timeline;tool;two photon microscopy;vision development

public_health_relevance:
Project NarrativeAbnormal vision during a childhood critical period can cause amblyopia also known as lazy eye a disordercomprising several deficits in spatial vision including impaired binocular depth perception. The proposedresearch is relevant to public health because knowledge of the neuronal basis and developmental timeline ofbinocular depth perception will improve our understanding of targets for therapeutic intervention. The proposedresearch is relevant to the mission of the NEI/NIH to increase understanding of how the development of thevisual system and visual experience results in binocular depth perception.


application_id: 10865838
project_number: 1K99ES036286-01
project_title: Unraveling the molecular link between heavy metal exposure and triple negative breast cancer
administering_ic: NIEHS
award_notice_date: 2024-08-16
opportunity_number: PA-20-188
application_type: 1
activity_code: K99
ic: ES
serial_number: 036286
program_official: HUMBLE, MICHAEL C
project_start_date: 2024-08-16
project_end_date: 2026-07-31
study_section: Special Emphasis Panel[ZES1 LWJ-W (K9)]
contact_pi_person_id: 78018391
contact_pi: NAIL, ALEXANDRA NICHOLE
other_pis: Not Applicable
congressional_district: 03
department: PHARMACOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that lacks targeted therapies.Individuals with Breast Cancer 1 (BRCA1) gene mutations have a significantly higher risk of developing TNBCin their lifetimes compared to the rest of the population. TNBC disproportionately affects young Black womenand the mortality rate from TNBC is significantly higher among Black women. Although TNBC incidence ishigher in Black women compared to other groups the incidence of germline BRCA1 mutations is significantlylower in Black women highlighting the need to pinpoint additional factors responsible for TNBC disparities.Residential segregation created and perpetuated by discriminatory housing practices has led to predominantlyBlack communities being located in close proximity to industrial sites including Superfund sites that arecommonly contaminated with heavy metals including cadmium (Cd). Cd is a heavy metal group 1 carcinogenthat has a long biological half-life in the human body. Epidemiological studies demonstrate that Cd exposureincreases breast cancer risk and in vitro studies determined that Cd exposure promotes TNBC initiation innormal human breast cells. Cd is known to displace zinc (Zn) from Zn coordinating proteins and several Zncoordinating proteins are important for DNA double-strand break (DSB) repair including RAD50 and BRCA1.Cd promotes higher levels of DSBs and sister chromatid exchanges indicative of DSB repair pathwayinhibition. Whether Cd promotes TNBC initiation and progression by disruption of DSB signaling and repairincluding direct inhibition of RAD50 or BRCA1 remains to be established. I hypothesize that Cd exposurepromotes TNBC initiation and progression by disruption of multilateral DSB signaling and repair. Theexperiments proposed to test this hypothesis will be conducted in two phases. During the mentored K99phase mass spectrometry single-molecule imaging using isolated recombinant proteins and DNA curtainassays and CRISPR-based editing will be employed to determine how Cd directly targets DSB repair proteinsto disrupt DSB Repair pathway choice. While in the mentored phase the candidate will take advantage ofcareer development resources made available by the University of Louisville Center for IntegrativeEnvironmental Health Sciences and will apply research and career development skills to didactic lecturingmentoring writing and presentation opportunities. In the non-mentored R00 phase of the project technicalskills gained from the K99 phase will be used for mechanistic studies to interrogate the role of Cd-inducedfusion genes in TNBC development (Aim 2). These experiments will provide data needed for initialindependent publications and preliminary data for R-series grants and will establish an independent directionfor the candidate from her mentor.

project_terms:
Affect;Anchorage-Independent Growth;Area;BRCA mutations;BRCA1 gene;Binding;Biological;Biological Assay;Biophysics;Black race;Breast;Breast Cancer Risk Factor;Breast Cancer gene;Breast Epithelial Cells;Cadmium;Carcinogens;Cell Separation;Cells;Chronic;Clonal Expansion;Clustered Regularly Interspaced Short Palindromic Repeats;Communities;Complex;Cysteine;DNA;DNA Adducts;DNA Double Strand Break;DNA Repair;Data;Death Rate;Development;Double Strand Break Repair;Environmental Exposure;Environmental Health;Exposure to;Gene Deletion;Gene Fusion;Gene Mutation;Genetic;Germ Lines;Germ-Line Mutation;Goals;Grant;Half-Life;Heavy Metals;Hispanic Women;Housing;Human;Human body;Immunocompromised Host;In Vitro;Incidence;Individual;Industrialization;Lateral;Link;Malignant - descriptor;Malignant Breast Neoplasm;Mass Spectrum Analysis;Measures;Mediating;Mentors;Metal exposure;Methods;Mind;Modeling;Molecular;Mus;Mutation;Nonhomologous DNA End Joining;Not Hispanic or Latino;Nuclear;Pathway interactions;Peptides;Phase;Phosphotransferases;Population;Prevalence;Proteins;Publications;Recombinant DNA;Recombinant Proteins;Research;Resource Development;Rest;Role;Series;Signal Transduction;Sister Chromatid Exchange;Site;Technical Expertise;Testing;Tissues;Training;United States National Institutes of Health;Universities;White Women;Writing;Zinc;Zinc Fingers;aggressive breast cancer;ataxia telangiectasia mutated protein;base editing;black women;brca gene;breast cancer survival;cancer health disparity;cancer initiation;carcinogenesis;career development;epidemiology study;experimental study;fusion gene;high risk;homologous recombination;innovation;lectures;mammary;meter;molecular imaging;mutation carrier;next generation sequencing;overexpression;programs;protein function;recombinational repair;repaired;research and development;residential segregation;single molecule;skill acquisition;superfund site;targeted treatment;triple-negative invasive breast carcinoma;tumor;tumor progression;tumorigenic

public_health_relevance:
Disruption of DNA double-strand break (DSB) repair promotes triple negative breast cancer (TNBC). Theoverarching goal of this study is to determine the molecular mechanisms responsible for disruption of DSBrepair elicited by cadmium (Cd) exposure to promote TNBC. These studies will elucidate a fundamentalmechanism not currently recognized that can explain TNBC disparities.


application_id: 10865580
project_number: 1K99DA060267-01
administering_ic: NIDA
award_notice_date: 2024-03-27
opportunity_number: PA-20-187
application_type: 1
activity_code: K99
ic: DA
serial_number: 060267
program_official: LAO, GUIFANG
project_start_date: 2024-07-01
project_end_date: 2026-06-30
study_section: Special Emphasis Panel[ZDA1 MXS-T (J1)]
contact_pi_person_id: 78355881
contact_pi: REGNIER, SEAN
other_pis: Not Applicable
congressional_district: 06
department: PSYCHIATRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-07-01
project_title:
Adapting and Testing a Smoking Cessation Intervention in Adults with Intellectual and Developmental Disabilities

project_abstract:
ABSTRACTCigarette smoking is the leading cause of preventable death in the United States. Despite a substantial decreasein cigarette smoking over the past decade cigarette smoking accounts for nearly half a million deaths nationallymore than alcohol and illicit drug use combined. People living with intellectual and developmental disabilities(IDDs) are exceptionally vulnerable to dangers posed by cigarette smoking because it may worsen healthconditions common among people with IDDs including diabetes and asthma. People living with IDDs are at anincreased risk of developing a tobacco use disorder (TUD) have a lower likelihood of entering treatment andhave a higher probability of dropping out of treatment. These issues highlight serious health equity concerns forpeople with IDDs including stigma exclusion underrepresentation and lack of access to high quality care andmay contribute to both the onset of cigarette smoking and serve as barriers to tobacco treatment enrollmentthus making people with IDDs vulnerable to persistent TUD and tobacco-related disease. The goal of thisK99/R00 Pathway to Independence Award is to use a community engaged approach to elucidate treatmentdifficulties in IDD populations and use the information gained from the community to adapt and test an evidence-based smoking cessation intervention. Achieving this goal is a crucial step in a larger process of establishing anessential line of research treating TUDs with people with IDDs. Through this K99 we aim to complete 40 semi-structed interviews with staff and patients actively engaged and not engaged in tobacco treatment to 1) identifybarriers that contribute to low TUD treatment enrollment and high drop-out rates for people with IDDs and 2)select and adapt an existing intervention for use with those with IDDs. Through the R00 we will utilize the resultsof our K99 to evaluate the feasibility acceptability and initial efficacy of a tailored behavioral smoking cessationintervention in this population. The modified intervention based on findings from the K99 will be implementedin a feasibility trial in people with IDDs. Outcomes will include intervention feasibility and acceptability (primaryoutcome) self-reported cigarette smoking (secondary outcome) and cigarette smoking measured by expiredbreath carbon monoxide (secondary outcome). The results of this project will inform the development andimplementation of a larger randomized controlled trial to be conducted as part of a future R01 grant. This projectwill fill a profound research gap by understanding significant smoking treatment barriers and developing andpiloting a tailored smoking cessation intervention for people with IDDs. This award will include substantial trainingand mentorship from a diverse group of K99 mentors who will supplement Dr. Regniers experience in theapplication of evidence-based treatments to IDD populations and provide him with skills in implementationscience clinical trial research community engagement and professional development that will help him obtainhis goal of becoming a leader in addiction research in people with IDDs.

project_terms:
Address;Adult;Alcohols;Asthma;Award;Behavior Therapy;Behavioral;Carbon Monoxide;Cessation of life;Clinical;Clinical Trials;Collaborations;Communities;Consult;Data;Development;Developmental Disabilities;Diabetes Mellitus;Disadvantaged;Disease;Dropout;Drops;Enrollment;Evidence based intervention;Evidence based practice;Evidence based treatment;Exclusion;Feedback;Foundations;Future;General Population;Goals;Grant;Health;Healthcare;Human Development;Impairment;Incentives;Intellectual functioning disability;Intervention;Interview;Lived experience;Maps;Measures;Mentors;Mentorship;Modeling;Modernization;Modification;Outcome;Participant;Pathway interactions;Patient Self-Report;Patients;Persons;Pilot Projects;Population;Positioning Attribute;Poverty;Preparation;Probability;Process;Provider;Publishing;Quality of Care;Randomized Controlled Trials;Research;Research Training;Review Literature;Risk;Smoke;Smoking;Smoking Cessation Intervention;Smoking treatment;Suggestion;Testing;Time;Tobacco;Tobacco Use Disorder;Tobacco use;Token Economy;Training;United States;Vocabulary;Vulnerable Populations;Work;acceptability and feasibility;addiction;career development;cigarette smoking;community engaged approach;community engagement;contingency management;design;evidence base;experience;feasibility trial;health equity;illicit drug use;implementation science;improved;individualized medicine;preventable death;primary outcome;secondary outcome;skills;smoking cessation;smoking prevalence;social health determinants;social stigma;substance use;systematic review;treatment research

public_health_relevance:
PROJECT NARRATIVEThis project will increase our understanding of critical cigarette smoking treatment barriers for people living withintellectual and developmental disabilities. This project will also bridge a significant treatment-focused researchgap between people with intellectual disabilities and the general population. The studies proposed in thisK99/R00 will identify and adapt a tailored evidence-based smoking cessation treatment for people withintellectual and developmental disabilities (IDDs) utilizing stakeholder feedback and perspectives.


application_id: 10864812
project_number: 5R01DE030100-04
administering_ic: NIDCR
award_notice_date: 2024-07-02
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: DE
serial_number: 030100
program_official: SAIFUDEEN, ZUBAIDA
project_start_date: 2021-07-01
project_end_date: 2026-06-30
study_section: Clinical Data Management and Analysis Study Section[CDMA]
contact_pi_person_id: 10376668
contact_pi: CLARKSON, MELISSA
other_pis: Not Applicable
congressional_district: 06
department: RADIATION-DIAGNOSTIC/ONCOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-07-01
project_title:
Developing standardized graphic libraries for anatomy: A focus on human craniofacial anatomy and phenotypes

project_abstract:
Project summaryCommunicating about anatomical concepts and patient-specific anatomy is fundamental to medicine.Anatomy of the head and face (craniofacial anatomy) is complex and facial morphology varies withinand among populations. Orofacial cleftswhich are among the most common congenital anomaliesdisplay a range of severities and may be preset at more than one site. There is a need to communicate rapidly and accurately about craniofacial anatomy in clinicalpractice medical education and when using clinical data in research. To address this challenge wepropose to create simple standardized graphics of craniofacial anatomy and phenotypes. Our collectionsof graphics or graphic libraries will serve as complements to textual representations and will bedesigned for use within clinical research and educational software applications. Our approach todesigning the graphics is based on four requirements: that the graphics be composable extensibleidentifiable and created using scalable vector graphics (SVGs). We will first develop graphics for adult and developmental anatomy then for phenotype variationsand malformations. We will also develop prototypes for two web-based toolsone that incorporatesgraphics into the Human Phenotype Ontology and the other for documenting craniofacial phenotypesand malformations in clinical settings. By offering a new paradigm for communicating about anatomy ourgraphic libraries will become crucial components of the next generation of software applications forclinical practice research and education.

project_terms:
Address;Adult;Anatomic Models;Anatomy;Clinical;Clinical Data;Clinical Medicine;Collection;Communication;Complex;Computer software;Computers;Correlation Studies;Data Set;Developmental Anatomy;Documentation;Education;Environment;Evaluation;Face;Future;Genotype;Head;Human;Informatics;Libraries;Maps;Measurement;Medical Education;Medical Illustration;Medical Research;Medicine;Methods;Morphology;Nature;Ontology;Patient Care;Patients;Persons;Phenotype;Physical Anthropology;Play;Population;Positioning Attribute;Production;Research;Role;Severities;Site;Standardization;Terminology;Text;Time;Variant;Visual;Work;clinical application;clinical practice;congenital anomaly;craniofacial;design;malformation;model organism;multidisciplinary;next generation;orofacial cleft;preservation;prototype;real world application;skills;tool;tool development;vector;web app;web-based tool

public_health_relevance:
Project narrativeThis project will produce a large library of graphics depicting craniofacial anatomy. These graphics will bedesigned for use in software applications for clinical practice research and education and will help tofacilitate rapid and accurate communication.


application_id: 10863907
project_number: 5R41AG082600-02
project_title: Noninvasive sleep enhancement and behavior monitoring technologies for Alzheimer's model mice
administering_ic: NIA
award_notice_date: 2024-08-08
opportunity_number: PAS-19-317
application_type: 5
activity_code: R41
ic: AG
serial_number: 082600
program_official: SARE, RACHEL
project_start_date: 2023-07-01
project_end_date: 2026-06-30
study_section: Special Emphasis Panel[ZRG1-NV-G(13)B]
contact_pi_person_id: 1883852
contact_pi: O'HARA, BRUCE FREDERICK
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 964938455
primary_uei: D9DRUX8SM4V9
duns_number: 964938455
uei: D9DRUX8SM4V9
fips: US
organization_id: 10032136
organization_name: SIGNAL SOLUTIONS, LLC
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 405060001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
The aims of this project are to develop new technologies to identify and track sleep and wakeabnormalities present in mouse models of Alzheimers disease (AD) as well as to test a sleep enhancementtechnology for applications in AD animal research. Signal Solutions LLC has previously developed andcommercialized a piezoelectric based system for noninvasive high-throughput sleep and wake monitoring ofrodents. Automated scoring of sleep and wake allows for simultaneous recordings of many animals over longerperiods with little burden on the researcher rivalling EEG/EMG methods that are more complicated andexpensive to perform. Behavioral changes in sleep and wake can precede memory loss in the progression of Alzheimersdisease (AD). Clinical studies suggest sleep disturbances are exhibited in a high percentage of AD patients.Animal models of AD also display sleep disturbances and some models show changes in wake behaviorsbefore the molecular hallmarks and memory problems appear as clearly occurs in human AD. In the treatmentof AD a potential therapeutic target is preventing the aggregation of pathogenic forms of amyloid-beta (A-beta)and tau. Waste clearance in the brain has been shown to be increased with increased sleep includingclearance of A-beta. Recently non-pharmacological approaches using mechanical devices for rocking haveshown promise for sleep enhancement which could be applied to AD research. The specific aims of this project are to 1) Develop advanced sleep/wake tracking technology: Add anew multipoint touch sensor to our current piezoelectric technology that together will identify specific behaviorsassociated with AD progression tested with AD mouse model 3xTg. 2) Develop Sleep EnhancementTechnology: Modify our current MouseQwake sleep-disruption system for mechanical sleep-enhancementwith companion sleep and wake tracking capabilities.Anticipated Outcomes: The envisioned product is a home cage sensor and software that will allowresearchers to accurately measure changes in sleep and wake during long-term AD disease progression aswell as track subtle changes in behavior in AD model mice. This system will minimize the amount of work timetesting behaviors and time for analyzing the videos or electrophysiology that is currently a major bottleneck.An expanded MouseQwake system will provide a tool for sleep manipulation of both sleep enhancement anddisruption as well as simultaneous sleep/wake and behavioral recording. If successful a Phase II investigationwill involve large scale studies of multiple AD rodent models and continue iterative improvements to bothhardware and software developed in phase I.

project_terms:
3xTg-AD mouse;Abeta clearance;Acceleration;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid beta-Protein;Animal Disease Models;Animal Experimentation;Animal Model;Animals;Behavior;Behavior monitoring;Behavioral;Brain;Classification;Clinical Research;Collaborations;Communities;Companions;Computer software;Consumption;Detection;Development;Devices;Discrimination;Disease;Disease Progression;Early Intervention;Early identification;Electroencephalography;Electrophysiology (science);Enhancement Technology;Exhibits;Floor;Funding;Future;Goals;Home;Human;Industrialization;Intervention;Investigation;Letters;Longitudinal Studies;Measures;Mechanical Stimulation;Mechanics;Memory;Memory Loss;Methods;Modeling;Modification;Molecular;Monitor;Mus;Neurodegenerative Disorders;Nonpharmacologic Therapy;Operative Surgical Procedures;Outcome;Pathogenicity;Pathology;Phase;Physiology;Pre-Clinical Model;Rattus;Recording of previous events;Research;Research Personnel;Resources;Rodent;Rodent Model;Running;Signal Transduction;Sleep;Sleep Disorders;Sleep disturbances;Small Business Innovation Research Grant;Small Business Technology Transfer Research;Symptoms;System;Technology;Testing;Time;Touch sensation;Wakefulness;Work;Workload;behavior test;commercialization;comorbidity;disease model;feasibility testing;glymphatic flow;improved;improvement on sleep;mechanical device;mouse model;new technology;non rapid eye movement;non-invasive system;pharmacologic;preclinical study;pressure;prevent;prototype;sensor;sensor technology;side effect;sleep quality;software development;tau Proteins;therapeutic target;tool;wasting

public_health_relevance:
Sleep disruption is now recognized not only as an early symptom of Alzheimers Disease (AD)but also a contributor to its ongoing development and thus sleep enhancement is a promisingapproach to slow the disease. This proposal intends to provide new technology to facilitatepreclinical studies in AD model mice including long term monitoring of behaviors associatedwith disease progression and a new method to manipulate and enhance sleep in mice toassess effects on disease and interventions.


application_id: 10863848
project_number: 5R01MD016236-04
project_title: Researching Equitable Sleep Time (REST) in Appalachia
administering_ic: NIMHD
award_notice_date: 2024-07-05
opportunity_number: PAR-20-164
application_type: 5
activity_code: R01
ic: MD
serial_number: 016236
program_official: GILLMAN, ARIELLE SAMANTHA
project_start_date: 2021-09-26
project_end_date: 2026-06-30
study_section: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]
contact_pi_person_id: 14786675
contact_pi: MOLONEY, MAIREAD
other_pis: MOGA, DANIELA CLAUDIA
congressional_district: 06
department: SOCIAL SCIENCES
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Insufficient sleep (habitual sleep duration of 6 hours) is a costly prevalent public health problem associatedwith numerous negative health outcomes. Prior research suggests that insufficient sleep is more prevalentamong health disparity populations (e.g. racial minorities adults of low socioeconomic status) but ourunderstanding of the mechanisms and consequences of sleep disparities in rural populations is limited. Thepresent study Researching Equitable Sleep Time in Kentucky Communities (REST-KY) focuses onAppalachian adults an NIH-designated health disparity population whose serious health inequities includemultiple health morbidities and premature mortality. Six of the counties with the highest concentration ofinsufficient sleep in the nation are in Central Appalachian Kentucky (KY) where 25-58% of adults reportinsufficient sleep 15+ nights/month. These counties are severely economically distressed yet nearby countieswith comparable economic distress rurality and demographic homogeneity are not hotspots of insufficientsleep. Use of a mixed methods longitudinal design will allow us to evaluate mechanisms contributing to bothsleep deficiencies and health in this rural community. Knowledge gaps include 1) Sparse insights into specificindividual- social- and societal-level factors contributing to sleep deficiencies in Appalachian adults.; 2) It is notknown if regional sleep and health disparities share the same underlying mechanisms; and 3) Critical points ofvariance between hotspot and non-hotspot counties have not been examined. We will recruit a cohort of 400adults from 6 insufficient sleep hotspot counties (n=200) in Appalachian KY and 6 similarly rural andeconomically distressed non-hotspot counties. Recruitment will be stratified across hotspot and non-hotspotcounties by key demographic factors linked to sleep deficiencies (e.g. age sex race/ethnicity) to promote countycluster-level comparisons. Specific Aims. 1. Use mixed methods to compare how individual social and societalfactors linked to sleep deficiencies differ between insufficient sleep hotspot and non-hotspot counties. 2.Evaluate mechanisms driving sleep deficiencies and health outcomes over time. Bi-directional models of sleepand health outcomes will be examined. 3. Quantify day-to-day sleep reactivity (i.e. the degree to which daytimedistress impacts sleep) and test if individual differences in sleep reactivity predict worsened health outcomesover time. Differences by sex and county cluster (hotspot vs. non-hotspot) will also be examined in Aims 2-3.Our multiple sophisticated objective and subjective data collection methods made possible by ourinterdisciplinary teams varied expertise will advance scientific knowledge about biological behavioralemotional and social contributions to sleep health. This holistic approach explicitly acknowledges theinseparable overlap between health function and sleep. Our findings will offer unprecedented insight into the bi-directional relationships between sleep and health in an understudied rural health disparity population. Resultswill inform strategies to reduce sleep disparities thus having strong potential for public health impact.

project_terms:
Address;Adult;Age;Alcohols;Anxiety;Appalachian Region;Attitude;Automobile Driving;Behavioral;Belief;Biological;Birds;C-reactive protein;Cardiovascular Diseases;Cardiovascular system;Caring;Child Sexual Abuse;Cirrhosis;Cognitive;Communities;County;Data Collection;Demographic Factors;Diabetes Mellitus;Diet;Disease;Disparity;Distress;Economics;Emotional;Equity;Ethnic Origin;Exercise;Eye;Face;Family;Financial Hardship;Glycosylated Hemoglobin;Glycosylated hemoglobin A;Health;Health Disparities Research;Health Status Indicators;Health behavior;Heart Diseases;Heart Rate;Hour;Immunologics;Individual;Individual Differences;Interview;Kentucky;Knowledge;Lead;Link;Malignant Neoplasms;Measurement;Measures;Mediating;Memory;Mental Depression;Mental disorders;Metabolic;Methods;Modeling;Morbidity - disease rate;Neurocognitive Deficit;Obesity;Outcome;Overdose;Participant;Perception;Physical activity;Predictive Factor;Premature Mortality;Process;Productivity;Public Health;Race;Recording of previous events;Reporting;Research;Risk;Rural;Rural Appalachia;Rural Community;Rural Population;Scientific Advances and Accomplishments;Series;Sex Differences;Sleep;Sleep Deprivation;Smoking;Social support;Societal Factors;Southeastern United States;Stress;Substance Use Disorder;Substance abuse problem;Suicide;Surveys;System;Task Performances;Testing;Time;Trauma;United States;United States National Institutes of Health;Violence;Well in self;Work;cognitive task;cohort;cost;demographics;design;economic impact;ethnic minority;health determinants;health disparity;health disparity populations;health inequalities;holistic approach;innovation;insight;interest;longitudinal design;low socioeconomic status;mortality;protective factors;racial minority;recruit;rural dwellers;rural health disparities;rurality;self reliance;sex;sleep health;social;social determinants;social factors;substance use

public_health_relevance:
PROJECT NARRATIVEWe know that rural residents in the Appalachian region of the Southeastern United States have the nationshighest rates of insufficient sleep (habitual sleep duration 6 hours) but the reasons for this are unclear. Thisissue is particularly concerning as these same rural residents also face substantially higher than average ratesof negative health outcomes including heart disease cancer diabetes obesity depression and substance usedisorders. We will follow a group of Appalachian adults over the course of two years to track their sleepphysical and mental well-being and health behavior (e.g. substance use smoking diet exercise) in order tobetter understand the culturally relevant factors that predict difficulties with both sleep and health in this uniqueand underserved rural population.


application_id: 10862622
project_number: 5R21ES035322-02
administering_ic: NIEHS
award_notice_date: 2025-05-28
opportunity_number: RFA-ES-19-011
application_type: 5
activity_code: R21
ic: ES
serial_number: 035322
program_official: TROTTIER, BRITTANY
project_start_date: 2023-06-08
project_end_date: 2026-05-31
study_section: ZES1-LWJ-W(R2)1
contact_pi_person_id: 7102409
contact_pi: HAYNES, ERIN N
other_pis: Not Applicable
congressional_district: 06
department: PUBLIC HEALTH & PREV MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PUBLIC HEALTH
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2025-06-01
project_title:
Extent of PFAS Contamination Resulting from a Fire at a Hazardous Waste Incinerator in East Liverpool Ohio

project_abstract:
On June 27 2022 a hazardous waste incinerator in East Liverpool Ohio a rural low-income community caught fire. The incinerator is one of only eight receiving per- and polyfluoroalkyl substances (PFAS) for incineration and received the most shipments in the past year. PFAS referred to as forever chemicals represent a large group of synthetic chemicals including PFOA PFOS GenX and encompass approximately 5000 different compounds. PFAS exposure has been linked with toxic health effects and the consequences of PFAS incineration including the potential of incomplete combustion are currently unknown. Due to a longstanding over 10-year community-academic partnership with the community our team had recently characterized PFAS in soil surrounding the incinerator thereby providing our team with a unique opportunity to determine the impact of the fire on PFAS contamination and the extent of this contamination throughout the community. Through our ongoing research partnerships we have immediate access to recruiting families in the community to participate in successfully accomplish the following time-sensitive specific aims: Aim 1: Characterize post-fire PFAS soil concentrations at the same locations as previously collected and identify geospatial patterns in concentrations to discern differences pre- and post-fire. Aim 2: Determine the extent of PFAS exposure in the community by measuring PFAS in residential soil drinking water household dust and blood samples from individuals who live in close proximity to the incinerator to begin to identify the route of exposure to PFAS exposure in the community. Aim 3: Engage the community throughout the process. We will work through our existing partnerships to inform residents of the study host community meetings and provide report-back materials to both community and individuals. We will also develop a website to keep the community informed about the process. This study will provide key information for community members regulators and scientists about community PFAS exposure following a fire disaster at a hazardous waste incinerator.

project_terms:
Animals;Area;Back;Biological;Birth Weight;Blood;Blood specimen;Chemicals;Cholesterol;Coal;Collection;Communities;Disasters;Dust;Engineering;Environmental Health;Environmental Impact;Epidemiology;Exposure to;Family;Fertility;Film;Fire - disasters;Focus Groups;Hazardous Waste;Health;House Dust;Household;Human;Immune response;Impairment;Incineration;Individual;Link;Location;Low income;Malignant Neoplasms;Measurable;Measures;Medicine;Metadata;Methods;Ohio;Participant;Pattern;Plasma;Poly-fluoroalkyl substances;Process;Public Health;Publishing;Recommendation;Reporting;Research;Rural;Scientist;Serum;Smoke;Soil;Source;Testing;Time;United States National Academy of Sciences;Work;aqueous;clinical care;cohort;community academic partnership;community engaged research;community engagement;community partners;drinking water;epidemiology study;exposed human population;exposure route;innovation;meetings;member;recruit;research clinical testing;research study;soil sampling;web site

public_health_relevance:
Project NarrativeThis study explores community exposure to per- and polyfluoroalkyl substances (PFAS) following a fire at anearby hazardous waste incinerator. Community exposure will be determined by analyses of pre- and post-firesoil sampling and engagement of residents in a study to determine their household exposure. This study willprovide valuable information for community members decision-makers and scientists about community PFASexposure from incinerators particularly following a fire disaster.


application_id: 10861863
project_number: 5R01NR020478-03
administering_ic: NINR
award_notice_date: 2024-06-18
opportunity_number: PA-20-183
application_type: 5
activity_code: R01
ic: NR
serial_number: 020478
program_official: HUSS, KAREN
project_start_date: 2022-08-31
project_end_date: 2024-09-30
study_section: Clinical Management in General Care Settings Study Section[CMGC]
contact_pi_person_id: 11595895
contact_pi: WU, JIA-RONG
other_pis: Not Applicable
congressional_district: 06
department: OTHER HEALTH PROFESSIONS
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF NURSING
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-07-01
project_title:
Improving medication adherence using family-focused and literacy-sensitive strategies in patients with heart failure

project_abstract:
Project SummaryMedication adherence is thought by many providers and researchers to be the most important self-carebehavior yet it is also the most problematic. Poor medication adherence can cause poor quality of life (QoL)hospitalization and death. In the United States approximately 125000 deaths per year are due to poormedication adherence and up to 50% of heart failure (HF) patients are re-hospitalized within 6 months of aprevious HF exacerbation and one of the most common causes is poor medication adherence. Lifelong andusually complex medication regimens are needed for patients with HF yet 40-60% of HF patients havesuboptimal medication adherence. Health literacy plays a significant role in suboptimal medication adherence.Support by a care partner (CP; usually a family member) can improve adherence and reduce hospitalizations.Although some interventions have improved HF patients adherence improvements were small and effectswere not sustained. To enhance and sustain intervention effects we will use an approach that is literacy-sensitive and incorporates social support. Using easy-to-understand language for patients and CPs we willtest an interactive behavioral family-focused and literacy-sensitive (FamLit) intervention delivered by nursesincorporating evidence-based multi-components (e.g. teach-back coaching role-playing goal setting) toengage both patients and CPs in improving and sustaining medication adherence and health outcomes. Wewill conduct a randomized controlled trial to evaluate the efficacy of FamLit intervention on medicationadherence hospitalization death and QoL. We will randomly assign 164 dyads of patients and their primaryCPs (patients-CPs) to either the FamLit intervention or an attention-control group. Both groups will have an in-person session (delivered on the day of a clinic appointment for regular follow-up) one month after baselineand phone boosters every other week for up to 3 months. FamLit group sessions will focus on improvingmedication adherence and control group sessions will focus on general health issues. Our aims are to: 1) testthe efficacy of the FamLit intervention compared to an attention control group on outcomes (i.e. primary:medication adherence and secondary: a) HF hospitalization or all-cause death b) QoL c) social support andd) communication) over 12 months; 2) determine if TPB-related intermediate outcomes (attitudes subjectivenorms perceived behavioral control) mediate the effects of the intervention on medication adherence; 3)examine whether each dyad members a) health literacy b) social support and c) communication moderatethe effect of the FamLit intervention on medication adherence; and 4) determine how each dyad membersattitudes subjective norms perceived behavioral control social support and communication affect their ownand their partners QoL over 12 months using the innovative Actor-Partner Interdependence Model. TheFamLit intervention if efficacious holds potential to improve/sustain medication adherence and reducehospitalizations and death. We will follow up with an effectiveness-implementation hybrid trial as our next step.

project_terms:
Address;Adherence;Adverse effects;Affect;Agreement;Appointment;Attitude;Back;Behavior;Behavior Control;Behavioral;Caring;Cause of Death;Cessation of life;Chronic;Clinic;Communication;Complex;Control Groups;Educational Materials;Educational process of instructing;Event;Family;Family member;Friends;Goals;Health;Health Promotion;Heart failure;Hospitalization;Individual;Instruction;Intervention;Language;Learning;Link;Mediating;Medical;Modeling;Morbidity - disease rate;Motivation;Nurses;Outcome;Partner Communications;Patient Care;Patient Compliance;Patients;Persons;Pharmaceutical Preparations;Planning Theory;Play;Prevention;Primary Care;Printing;Provider;Quality of life;Randomized;Randomized Controlled Trials;Reading;Regimen;Research;Research Personnel;Role;Role playing therapy;Self Care;Social support;Spouses;Symptoms;Telephone;Testing;Time;Treatment Efficacy;United States;Work;Writing;attentional control;comparison control;comparison intervention;effectiveness/implementation trial;efficacy evaluation;efficacy testing;empowerment;evidence base;family support;follow-up;fourth grade;group intervention;health literacy;high risk;hospital readmission;improved;innovation;interest;intervention effect;literacy;low health literacy;medication compliance;member;mortality;multi-component intervention;older patient;optimism;pilot test;post intervention;primary outcome;secondary outcome;skills

public_health_relevance:
Project NarrativePeople with heart failure who do not take their medications as prescribed are at high risk of complicationsleading to hospitalization death and poor quality of life. In the proposed intervention nurses will use easy-to-understand language to coach patients and their care partners to help them work together and build skills toovercome their individual barriers to adherence in order to improve and sustain patient medication adherence.If effective this intervention will support long-term medication adherence thus reducing hospitalizations anddeaths related to heart failure.


application_id: 10861711
project_number: 5U60OH008483-19
project_title: Kentucky Occupational Safety and Health Surveillance Program
administering_ic: NIOSH
award_notice_date: 2024-05-24
opportunity_number: PAR-20-312
application_type: 5
activity_code: U60
ic: OH
serial_number: 008483
program_official: O'NEILL, EDUARDO
project_start_date: 2021-07-01
project_end_date: 2025-06-30
study_section: ZOH1-EHG(03)
contact_pi_person_id: 12619306
contact_pi: NORTHCUTT, CAITLIN A
other_pis: Not Applicable
congressional_district: 06
department: PUBLIC HEALTH & PREV MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PUBLIC HEALTH
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Kentucky (Ky) ranks as the 12th worst state for nonfatal occupational injury rates and the 20th worst for fataloccupational injuries/illnesses. The Ky Occupational Safety and Health Surveillance (KOSHS) expandedprogram (KOSHS fundamental program and Fatality Assessment Control and Evaluation [FACE]Occupational Motor Vehicle Injury Surveillance [OMVIS] and Drug-Associated Work-Related Injury Surveil-lance [DAWRIS] expanded projects) focuses on population-based and case-based surveillance of work-relatedinjuries/illnesses in Ky a southeastern HHS Region 4 state. Specific aims are to: 1) identify and access multi-source KOSHS fundamental program and FACE OMVIS and DAWRIS expanded project surveillance dataand evaluate new surveillance data sources for occupational health indicators (OHI); 2) manage and performquality control and surveillance quality improvement on surveillance data; 3) calculate 20 CSTE/ NIOSH OHIs13 Ky-specific OHIs and Ky employment profile; FACE OMVIS and DAWRIS surveillance data; incidenceand prevalence rates; and trends; 4) perform case-based surveillance through FACE onsite investigations andhigh adult blood lead level follow-up investigations; 5) conduct epidemiological analyses of KOSHS fundamen-tal FACE OMVIS and DAWRIS surveillance and investigation data; 6) disseminate public health recommen-dations for workplace interventions and policies using trainings reports hazard alerts publications etc.;application of communication technologies such as websites social media presentations toolkits tradejournals and the NIOSH OH clearinghouse; and new and existing partnerships and collaborations with tradeassociations state agencies organizations and NIOSH etc. that integrate KOSHS results with partnersintervention and outreach activities. KOSHS will participate in grantee meetings and conference calls; and 7)perform a process impact and outcome evaluation of the KOSHS fundamental program and FACE OMVISand DAWRIS expanded projects. Ad hoc KOSHS fundamental program advisory work groups will be estab-lished by priority focus area. Novel KOSHS areas targeted for surveillance and research include worker deathsby suicides; OHIs on work-related injuries using EMS and syndromic surveillance data; drug overdose deathsby industry; light medium and heavy vehicle crash OHIs; a recovery-friendly workplace toolkit; dump trucksemi-truck pedestrian worker and construction worker fatalities; high commercial vehicle crash locationsrates ratios and savings; work-related older driver injuries; OHIs on drug-involved occupational injuries andfatalities after a work-related injury; estimates of drug overdose rates and times based on injury disability andloss of work; effect of occupational injuries on subsequent fatal overdose or fatal drug-related work injury andrisk profiles; and assessment of drug-involved worker injury risk. Advanced statistical methodologies such asmachine learning and probabilistic data linkage will be used. Integration of the KOSHS team with NIOSH andNIOSH-funded programs Safe Communities CDC-funded programs and National Safety Council is planned.

public_health_relevance:
The proposed Kentucky Occupational Safety and Health Surveillance (KOSHS) program will 1) identifyindustries occupations and worker populations at high risk for work-related injuries and illnesses; 2) identifyrisk factors trends and emerging issues; 3) identify gaps in and improve occupational injury and illnesssurveillance systems; and 4) develop interventions for the prevention of occupational injuries. When injuryprevention knowledge is attained by the worker injuries on the job and the economic costs of injuries willdecrease because there will be fewer workers compensation claims. Fewer occupational fatalities will occurand the severity of occupational injuries will be reduced.


application_id: 10861046
project_number: 5R01DC021325-02
project_title: ACTIVITY-DRIVEN PLASTICITY OF THE HAIR CELL CYTOSKELETON
administering_ic: NIDCD
award_notice_date: 2024-05-15
opportunity_number: RFA-DC-23-001
application_type: 5
activity_code: R01
ic: DC
serial_number: 021325
program_official: FREEMAN, NANCY
project_start_date: 2023-06-07
project_end_date: 2025-05-31
study_section: ZDC1-SRB-Z(41)
contact_pi_person_id: 12084410
contact_pi: VELEZ ORTEGA, ALEJANDRA CATALINA
other_pis: Not Applicable
congressional_district: 06
department: PHYSIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT The mechanosensitivity of the inner ear hair cells depends on cellular projections known asstereocilia organized in rows of increasing height with mechano-electrical transduction (MET) channelslocated at the tips of shorter row stereocilia. The core of stereocilia consists of a highly crosslinkedparacrystalline array of actin filaments. While crosslinker proteins are constantly renewed the renewal ofactin is limited to the stereocilia tips. We previously reported that the stereocilia actin core exhibits activity-dependent plasticity (Velez-Ortega et al. eLife 2017). We showed that the blockage of MET channelsor the breakage of the tip links that gate these channels lead to the selective shortening of transducingstereocilia (i.e. the stereocilia that harbor MET channels) while the non-transducing tallest row stereociliaremain unaffected. Once the MET blockage is removed or the tip links regenerate the stereocilia regrow.Our preliminary data also show that this MET-dependent stereocilia remodeling can affect the restingtension within the MET machinery in seconds. Thus this process may dynamically regulate the sensitivityof hair cells to sound-induced vibrations and hence the sensitivity of our hearing. Yet the exactmechanisms of MET-dependent stereocilia remodeling are still obscure. It is unknown even whether theactivity-dependent plasticity of the stereocilia cytoskeleton is limited to the regions of active actin renewalor can expand beyond this region into the stable part of the stereocilia shaft. Here we hypothesize thatthe MET activity regulates the extent of the stereocilia cytoskeleton undergoing active actin remodeling.To test this Aim 1 will evaluate MET-dependent changes in actin dynamics within the stereocilia and thecuticular plate an actin-rich structure supporting the stereocilia bundle. Aim 2 will evaluate MET-drivenchanges in the ultrastructural organization of stereocilia actin with transmission electron microscopytomography. Since the MET-dependent stereocilia remodeling was studied so far only in young postnatalhair cells Aim 3 will assess whether this phenomenon is present also in the mature adult auditory haircells. In Aim 4 we begin to explore the molecular players involved in the MET-driven stereociliaremodeling by evaluating the expression of so-called stereocilia row identity proteins in a mutant mousemodel that exhibits MET-dependent actin remodeling not only in transducing stereocilia but alsounexpectedly in non-transducing stereocilia. The study is significant because it may clarify how exactlya hair cell performs fine adjustments of the architecture of the stereocilia bundle thereby maintaining thesensitivity of our hearing throughout a lifetime. In addition stereocilia shorteningand perhaps theireventual disappearancecould occur after noise exposure (when the MET current is reduced due to tiplink breakage) or in certain cases of congenital deafness (due to impaired MET current). Therefore thisstudy will expand our knowledge of the molecular mechanisms of various types of hearing loss.

project_terms:
Actins;Adult;Affect;Architecture;Auditory;Cells;Cochlea;Crosslinker;Cytoskeleton;Data;Development;Exhibits;F-Actin;Filament;Fluorescence Recovery After Photobleaching;Freeze Substitution;Freezing;Hair;Hair Cells;Hearing;Height;Impairment;In Situ;Inner Hair Cells;Ions;Knowledge;Label;Labyrinth;Lead;Length;Link;Maintenance;Measures;Mediating;Microfilaments;Molecular;Morphology;Mus;Myosin ATPase;Natural regeneration;Noise-Induced Hearing Loss;Organelles;Organism;Pattern;Physiological;Polymers;Process;Protein Isoforms;Proteins;Rattus;Reporting;Rest;Sampling;Scanning Electron Microscopy;Sensory;Shapes;Stereocilium;Structure;Supporting Cell;Testing;Transmission Electron Microscopy;beta Actin;cellular microvillus;congenital deafness;crosslink;depolymerization;experimental study;gamma Actin;hearing impairment;mutant mouse model;new therapeutic target;noise exposure;polymerization;postnatal;sound;tomography;vibration

public_health_relevance:
PROJECT NARRATIVE Our sense of hearing relies on the survival of a limited number of inner ear sensory cells throughoutour entire lifetime. This project will provide clues about the molecular machinery regulating the stabilityand shape of the inner ear sensory organelles known as stereocilia. The identification of these molecularplayers might uncover novel therapeutic targets to maintain the integrity of stereocilia in some types ofcongenital or noise-induced hearing loss.


application_id: 10858550
project_number: 3K12DA035150-12S1
project_title: Kentucky BIRCWH Program: Training the Next Generation of Women's Health Scholars
administering_ic: NIDA
award_notice_date: 2023-08-03
opportunity_number: PA-20-272
application_type: 3
activity_code: K12
ic: DA
serial_number: 035150
suffix: S1
program_official: BABECKI, BETH
project_start_date: 2022-08-01
project_end_date: 2027-07-31
study_section: Special Emphasis Panel[ZRG1(50)]
contact_pi_person_id: 1896366
contact_pi: CURRY, THOMAS E
other_pis: Not Applicable
congressional_district: 06
department: OBSTETRICS & GYNECOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
ABSTRACTOver the past 20 years the BIRCWH Program at the University of Kentucky (UK) has been extremelysuccessful in creating a research environment to prepare early career scientists to develop the necessary skillsto become independent NIH-supported researchers dedicated to improving womens health. Thisadministrative supplement will add a 5th BIRCWH scholar. Dr. JungHee Kang is currently a Post DoctoralScholar at UK in our College of Nursing and mentored by Dr. Debra Moser. Under the direction of Dr. MoserDr. Kang focuses her research on reducing cardiovascular disease (CVD) risk among women caregivers.Relative to men women are disproportionately represented in informal caregiver roles and handle the mostchallenging and stressful caregiving tasks. A focus on the health of caregivers is strategically important for boththe patient and caregivers physical and mental health. Women caregivers are at increased risk for developingcardiovascular disease (CVD) due to the stress of caring for their loved ones or friends and limited time fortheir own self-care such as eating a healthy diet getting exercise and stress management. Depression is amajor risk factor for CVD; because caregiver responsibilities can increase stress the risk of depression andanxiety is high in caregivers. Caregivers have substantially higher risk of developing depression than non-caregivers. Here we hypothesize that persistent psychological stress in caregivers can result in a monotonousdiet decreased diet quality and depression thereby increasing CVD risk or progression. To date there hasbeen no investigation of the mediating role of diet quality and depressive symptoms between caregiver stressand CVD risk in female or male caregivers. Data from a completed 12-month prospective randomizedcontrolled trial of female and male caregivers (n=311) will be used to test the following aims during theBIRCWH Post-Doctoral training. The purpose of the completed trial was to test an intervention (RuralIntervention for Caregivers Heart Health [RICHH]) designed to improve self-care of CVD risk factors amongcaregivers and decrease CVD risk. For this BIRCWH Post Doctoral Scholar 2 specific aims are posed. Dr.Kangs research has direct relevance for NIDA UK BIRCWHs funder and her research addresses both sexdifferences and womens health. Aim 1. Determine whether diet quality (including substance use) anddepressive symptoms mediate the association between caregiver stress and CVD risk factors among female andmale informal caregivers. Aim 2. Evaluate the longitudinal effect of RICHH on caregiver stress diet qualityalcohol consumption depressive symptoms and CVD risk by sex among informal caregivers. Expected Impact:This mediational research will inform future development of dietary interventions to reduce CVD risk and toimprove quality of life in caregivers by identifying the mechanisms of actions needed for effective interventiondevelopment. Training: his Administrative Supplement will provide training for Dr. Kang through theexisting UK BIRCWH career development and mentorship program.

project_terms:
Address;Administrative Supplement;Alcohol consumption;Anxiety;Cardiac health;Cardiovascular Diseases;Caregivers;Caring;Data;Dedications;Development;Diet;Dietary Intervention;Discipline of Nursing;Disease Progression;Eating;Environment;Exercise;Female;Friends;Future;Healthcare;Intervention;Investigation;Kentucky;Mediating;Mental Depression;Mental Health;Mentors;Mentorship;National Institute of Drug Abuse;Patients;Postdoctoral Fellow;Psychological Stress;Quality of life;Randomized Controlled Trials;Research;Research Personnel;Risk;Risk Factors;Role;Rural;Scientist;Self Care;Sex Differences;Stress;Testing;Time;Training;United States National Institutes of Health;Universities;Woman;Women's Health;cardiovascular disorder risk;cardiovascular risk factor;career;career development;caregiver interventions;caregiver stress;caregiving;college;depressive symptoms;design;effective intervention;good diet;high risk;improved;informal caregiver;loved ones;male;men;next generation;physical conditioning;post-doctoral training;programs;prospective;sex;skills;stress management;substance use;therapy development

public_health_relevance:
NARRATIVERelative to men women are disproportionately represented in informal caregiver roles and handle the mostchallenging and stressful patient caregiving tasks. Increased stress among caregivers can increase CVD risk yetthe longitudinal pathways explaining CVD development including the effect of caregiver stress diet qualityalcohol or substance use and depressive symptoms have not been investigated by sex. By using existing datafrom the Rural Intervention for Caregivers Heart Health the proposed research can be completed in 1 year andwill inform future development of sex-specific interventions to reduce CVD risk for caregivers.


application_id: 10857224
project_number: 5R01DC018273-05
project_title: Neural mechanisms underlying integration of taste and smell
administering_ic: NIDCD
award_notice_date: 2024-05-31
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: DC
serial_number: 018273
program_official: SABRI, MERAV
project_start_date: 2020-07-02
project_end_date: 2027-06-30
study_section: Chemosensory Systems Study Section[CSS]
contact_pi_person_id: 8305266
contact_pi: SAMUELSEN, CHAD L
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY ABSTRACT Although interactions between the senses of smell and taste are a key factor for guiding food choices theneural mechanisms underlying the multisensory integration of odors and tastes remain largely unknown. A morethorough understanding of these neurobiological processes will provide better insight into diseases characterizedby unhealthy food choices such as obesity or diabetes. Eating food simultaneously activates the olfactory andgustatory systems to generate enduring odor-taste associations. The primary cortical area for taste gustatorycortex (GC) is a principal site of convergent gustatory and olfactory information. Recent work from our labdetermined that functionally distinct populations of neurons in GC represent different properties of individualunpaired odors or tastes. However how neurons in GC represent odor-taste mixtures as well as the neuralmechanisms that underlie integration and processing of smell and taste remain unclear. Recent behavioral andphysiological studies show that cortico-cortical interactions between sensory cortices are fundamental tomultisensory integration suggesting that projections from the functionally distinct anterior (aPC) and posterior(pPC) regions of piriform cortex (i.e. olfactory cortex) modulate multimodal chemosensory processing in GC.Using rats as a model system this proposal will combine behaving electrophysiology and optogenetic techniquesto investigate how the circuit between neurons in GC and the functionally distinct regions of piriform cortexmediates multisensory integration of odors and tastes. The Specific Aims will test the following hypotheses: Aim1: Different populations of neurons in GC encode the chemical identity and hedonic value of odor-taste mixtures.Aim 2: Neurons in GC that respond to both odors and tastes receive aPC input representing the chemical identityof odor-taste mixtures. Aim 3: Neurons in GC that respond to both odors and tastes receive pPC inputrepresenting the hedonic value of odors and odor-taste mixtures. The results of each Specific Aim will contributefundamental knowledge about the cortico-cortical circuitry underlying the integration of smell and taste andprovide a necessary prelude for investigating the role that these cortico-cortical circuits play in guiding foodchoices.

project_terms:
Anterior;Area;Association Learning;Behavior;Behavioral;Biological Models;Categories;Chemicals;Data;Diabetes Mellitus;Disease;Eating;Electrophysiology (science);Fiber;Food;Goals;Health;Individual;Knowledge;Mediating;Neurobiology;Neurons;Obesity;Odors;Olfactory Cortex;Olfactory Pathways;Outcome;Perception;Physiological;Play;Population;Process;Property;Publishing;Rattus;Resolution;Role;Sampling;Sensory;Sensory Process;Signal Transduction;Site;Smell Perception;Stimulus;Taste Perception;Techniques;Testing;Work;experience;hedonic;insight;multimodality;multisensory;neuromechanism;nutrition;optogenetics;piriform cortex;preference;response;sensory cortex;sensory integration;taste system

public_health_relevance:
PROJECT NARRATIVE Associations between the senses of smell and taste (i.e. flavors) are an essential factor in determining whichfoods we choose to eat; however the neural mechanisms underlying the multisensory integration of odors andtastes remain unclear. We use a combination of behaving electrophysiology and optogenetics to investigate howinteractions between the olfactory and gustatory cortices contribute to multisensory integration of smell and taste.These results will provide new insight into the circuit mechanisms underlying the perception of flavor.


application_id: 10855896
project_number: 1R01NS136272-01
administering_ic: NINDS
award_notice_date: 2024-03-20
opportunity_number: PA-20-185
application_type: 1
activity_code: R01
ic: NS
serial_number: 136272
program_official: BAMBRICK, LINDA LOUISE
project_start_date: 2024-03-20
project_end_date: 2029-02-28
study_section: Biomaterials and Biointerfaces Study Section[BMBI]
contact_pi_person_id: 14321924
contact_pi: PARK, JONGHYUCK
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-03-20
project_title:
Harnessing engineered drug-free polymeric nanoformulations to reprogram innate immune cells for spinal trauma

project_abstract:
Project Summary/AbstractThe endogenous tissue regeneration after traumatic spinal cord injury (SCI) is limited due to an inhibitoryenvironment by secondary biological events including inflammatory responses. These events result in neural celldeath and demyelination leading to various inflammation-mediated disorders. The long-term goal of this study isto develop effective acute intervention strategies that limit secondary injuries thereby creating a permissiveenvironment that supports regeneration. To achieve this goal polymer based-nanoparticle (NP) formulations willbe employed to reprogram the circulating innate cells in the blood after trauma. The scientific premise of theproposed research is based on preliminary data demonstrating that intravenously administered NPs target thepro-inflammatory sub-set of immune cells prior to extravasation to the injury and reprogram their traffickingpatterns and phenotypes that limit inflammation and additional tissue damage thereby inducing enhancedregeneration. Particularly the immunomodulation is mediated by the physicochemical properties of NPsindicating that NPs functions can be engineered differently to influence immune trafficking and phenotypes. Theproposed engineered-NP formulations differentially reprogram innate cells specifically immunomodulatoryeffects of NPs are sex-dependent and importantly these effects are solely mediated by distinctivephysicochemical properties of NPs without the active biologics that can cause unfavorable off-target effects. Inthis proposal key physicochemical parameters of NP formulations will be identified for effectiveimmunomodulation in males and females respectively since the differences in physiological factors betweensexes play a critical role in inflammation after spinal trauma. Aim 1 will focus on interactions between differentNP formulations and innate cells in circulation to identify more effective NP design factors that limit inflammationin both sexes. Distinct physicochemical properties of NPs will differently affect innate cells trafficking andphenotype which will be sex-dependent and subsequently reprogram an inhibitory environment. NP-induceddifferential cellular internalization phenotype activation pharmacokinetic profiles as well as biodistribution ofNPs will be investigated. Aim 2 will investigate the long-term impacts of NPs on anatomical and functionalregeneration after SCI with a more focused set of NP formulations based on Aim 1. Initially NP-associatedimmune cells will be investigated then the extent of axonal regrowth and remyelination synaptogenesis andfunctional recovery in the chronic phase of SCI will be assessed. Collectively the proposed studies will have thepotential to be a transformational therapy by identifying the relationship between physicochemical parametersand immune modulation for effective NP formulations to support regeneration. Notably NPs are made of FDAapprovedpolymeric biomaterial enabling them to be readily stored for immediate administration non-invasivelyas a means to modulate the innate immune system for functional enhancement.

project_terms:
Acids;Acute;Affect;Anatomy;Anti-Inflammatory Agents;Artificial nanoparticles;Axon;Biocompatible Materials;Biodistribution;Biological;Biological Process;Biological Products;Blood;Cell Death;Cells;Cessation of life;Chronic Phase;Circulation;Data;Demyelinations;Development;Diagnosis;Disease;Drug Kinetics;Engineering;Environment;Event;Extravasation;FDA approved;Female;Formulation;Functional Regeneration;Functional disorder;Gene Expression;Genes;Glucocorticoids;Goals;Growth;Immune;Immune response;Immunotherapeutic agent;Individual;Infiltration;Inflammation;Inflammatory;Inflammatory Response;Injury;Innate Immune System;Intervention;Macrophage;Mediating;Methylprednisolone;Natural regeneration;Neurons;Organ;Outcome;Patients;Pattern;Pharmaceutical Preparations;Pharmacologic Substance;Phenotype;Physiological;Play;Polymers;Population;Property;Recovery of Function;Research;Role;Secondary to;Sex Differences;Site;Spinal Cord;Spinal cord injury;Spleen;Testing;Therapeutic;Tissues;Trauma;Triage;axon regeneration;clinical application;design;immune cell infiltrate;immunoregulation;intravenous administration;male;minimally invasive;monocyte;nanoformulation;nanoparticle;nanopolymer;nanotherapeutic;neural;neutrophil;novel strategies;novel therapeutics;peripheral blood;permissiveness;programs;remyelination;response;risk/benefit ratio;sex;synaptogenesis;therapeutic effectiveness;tissue injury;tissue regeneration;tool;trafficking

public_health_relevance:
Project NarrativeTissue regeneration after spinal cord trauma is limited by additional biological events including inflammationwhich induce an inhibitory local microenvironment leading to cellular death and functional deficits.lmmunotherapeutic nanoparticles with different physicochemical factors without using active pharmaceuticalingredients interact with circulating immune cells and reprogram their function to mitigate inflammation andmodify the microenvironment in favor of regeneration. The proposed studies will identify crucial parameters ofnanoparticles for the development of effective nanotherapeutics which will contribute to the development ofpotentially effective practical therapy for spinal cord trauma.


application_id: 10854926
project_number: 5K23DA054309-02
administering_ic: NIDA
award_notice_date: 2024-05-02
opportunity_number: PA-20-206
application_type: 5
activity_code: K23
ic: DA
serial_number: 054309
program_official: LAO, GUIFANG
project_start_date: 2023-06-15
project_end_date: 2028-05-31
study_section: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]
contact_pi_person_id: 15234572
contact_pi: MEADOWS, AMY LYNN
other_pis: Not Applicable
congressional_district: 06
department: PSYCHIATRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-06-01
project_title:
Improving Opioid Use Disorder Treatment Retention Outcomes Using Mindfulness in Childhood Trauma Survivors

project_abstract:
ABSTRACTThis Mentored Patient-Oriented Research Career Development Award (K23) application seeks support forresearch training to augment the candidates knowledge and skills in co-occurring childhood trauma and opioiduse disorder (OUD) in order to support her progress to become an independent investigator. During the awardthe candidate will develop and implement a research program related to technology-based mindfulnessinterventions and use of biomarkers to improve engagement in medication treatment for opioid-use disorder(MOUD) in those who have experienced childhood trauma. The central hypothesis is that changes in autonomicfunction and inflammation mediate the relationship between childhood trauma and poor treatment retention inMOUD and that mobile mindfulness training (mMT) is feasible in this population with potential benefits toemotional inflammatory and autonomic function. This proposal includes training activities to ensure Dr.Meadows achieves the following career goals: 1) Training in the discovery interpretation and assessment ofpotential biomarkers to assess the link between childhood trauma and outcomes 2) Advanced training in thedesign and implementation of clinical interventions and 3) Training in the analysis and interpretation of data.The mentorship team includes experts in the following areas of research: substance use disorders (Drs. Rushand Martin) intervention development (Dr. Rush) and advisors with expertise in the use of mobile mindfulnesstraining for substance use disorder (Dr. Reynolds) inflammatory biomarker evaluation (Dr. Moylan) heart ratevariability (Dr. Minassian) trauma treatment (Dr. Sprang) and advanced statistical modeling (Dr. McLouth). Dr.Meadows will apply the skills from the training to test the three specific aims: 1) Demonstrate baseline differencesin autonomic function inflammation and treatment engagement between those with a history of childhoodtrauma and those without childhood trauma or post-traumatic stress disorder enrolled in MOU 2) Implement andevaluate mMT in childhood trauma-exposed individuals enrolled in MOUD in order to a) demonstrate feasibilityand acceptability and b) estimate effect sizes for improvements in emotional health autonomic function andinflammation and 3) Assess whether mMT improves treatment engagement and retention in MOUD. Theproposed research is innovative because it will provide insight into the relationship between potential biomarkersand treatment engagement in MOUD. It is also highly significant because it focuses on a mobile intervention thatcan be readily adapted as an adjunct to existing treatment programs to improve outcomes. The research trainingplan mentorship and institutional support will facilitate Dr. Meadowss transition to becoming an independentphysician-scientist to better serve the needs of individuals with co-occurring childhood trauma exposure andsubstance use who are at the highest risk of treatment dropout and poor outcomes.

project_terms:
Adherence;Age;Applied Skills;Area;Autonomic nervous system;Award;Biological;Biological Markers;Buprenorphine;C-reactive protein;Chronic;Clinic;Clinical;Cues;Data;Data Analyses;Dropout;Early treatment;Educational Intervention;Effectiveness;Emotional;Enrollment;Ensure;Exposure to;Goals;Health;Individual;Inflammation;Inflammatory;Informal Social Control;Institution;Interleukin-6;Intervention;K-Series Research Career Programs;Kentucky;Knowledge;Left;Link;Mediating;Mediator;Mentored Patient-Oriented Research Career Development Award;Mentorship;Mindfulness Training;National Institute of Drug Abuse;Nervous System Physiology;Opioid;Outcome;Pain;Parasympathetic Nervous System;Participant;Patient Self-Report;Patients;Pharmaceutical Preparations;Physicians;Physiological;Population;Post-Traumatic Stress Disorders;Recording of previous events;Recovery;Recurrence;Reporting;Research;Research Personnel;Research Support;Research Training;Risk;Risk Factors;Science;Scientist;Self-control as a personality trait;Serum;Signal Transduction;Statistical Models;Stress;Substance Use Disorder;Survivors;Sympathetic Nervous System;Technology;Testing;Training;Training Activity;Trauma;Treatment Factor;Treatment outcome;Universities;Work;acceptability and feasibility;addiction;adverse childhood events;biological systems;biomarker evaluation;biomarker identification;career;career development;clinical development;clinical implementation;comorbidity;craving;depressive symptoms;design;early childhood;experience;heart rate variability;high risk;improved;improved outcome;inflammatory marker;innovation;insight;methadone treatment;mindfulness;mindfulness intervention;novel;online delivery;opioid use;opioid use disorder;pediatric trauma;perceived stress;potential biomarker;predicting response;premature;programs;protective factors;psychologic;reduced substance use;relapse risk;return to use;skills;skills training;substance use;therapy development;trauma exposure;treatment adherence;treatment program;treatment response;treatment risk

public_health_relevance:
PROJECT NARRATIVEChildhood trauma survivors have higher rates of treatment dropout during medication treatment for opioid usedisorder (MOUD) with those who leave treatment early being at extremely high risk for recurrence of opioid usedisorder (OUD). Autonomic nervous system dysregulation and inflammation may mediate risk for dropout and/orreturn to use during MOUD in childhood trauma survivors but mindfulness interventions may normalizepsychological and physiological changes attributable to early childhood stress. The proposed project willimplement a research program to elucidate the interplay of biological and psychological risk and protectivefactors associated with treatment retention in individuals in MOUD to guide the development of clinicalinterventions improve treatment adherence and reduce the risks of OUD.


application_id: 10854827
project_number: 5R00AA029467-04
administering_ic: NIAAA
award_notice_date: 2024-07-12
opportunity_number: PAR-19-343
application_type: 5
activity_code: R00
ic: AA
serial_number: 029467
program_official: CUI, CHANGHAI
project_start_date: 2021-08-06
project_end_date: 2026-05-31
study_section: NSS
contact_pi_person_id: 11656822
contact_pi: JARAMILLO, ANEL ARIANA
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-06-01
project_title:
Neuropeptide-dependent parabrachial control of the BNST during alcohol abstinence-induced negative affect

project_abstract:
PROJECT SUMMARY/ABSTRACT Abstinence from alcohol use induces a negative affective state that can lead to maladaptive responsesto stress and relapse. Preclinical studies have begun to identify neurocircuits and peptide targets that regulatenegative affect during abstinence. As the field has begun to develop a deeper understanding of the circuitriesparticipating in addiction and negative affect the next step is to understand how communication within thesecircuits is modulated particularly at the neuropeptide and microcircuit level. The bed nucleus of the striaterminalis (BNST) is a fundamental component of abstinence-relevant neurocircuitry as it modulates stress andalcohol-related behavior in a neuropeptide-dependent manner. To investigate peptide-specific BNST circuitrymodulating negative-affect during abstinence we will focus on afferents from the parabrachial nucleus (PBN)a brainstem region that functions as a danger signal. PBN projections to the BNST release calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating polypeptide (PACAP) peptides thatmodulate pain and fear circuits respectively. Our studies implicate heterogenous and sexually dimorphiccontrol within the PBNBNST circuit as PBN projections induce heterogeneous ex vivo activity in BNST cellsand female-specific anxiety-like behavior with BNSTPBN activation. Furthermore our preliminary studiessuggest a role for the PBN in alcohol-withdrawal as inactivation is anxiolytic following alcohol exposure. Thisproposal will significantly build on this foundational evidence by investigating how CGRP and PACAPcontribute to PBNBNST circuit induced abstinence-induced behavior in vivo and ex vivo activity.Accordingly the mentored K99 phase will build on my in vivo fiber photometry recordings and provide trainingin ex vivo recordings to determine the role of CGRP on BNSTPBN activity abstinence-induced behavior(AIM1) and the contribution of PACAP on the CGRP-neuromodulation (AIM2). The independent R00 phasewill investigate the role of PACAP on BNSTPBN at the microcircuit level and alcohol-related states with thegoal to further delineate the intricacies of peptide crosstalk (AIM3). The proposed studies and related careerdevelopment training plan in this MOSAIC Pathway to Independence Award collectively provide the idealmechanism to transition the applicant to a career as an independent addiction neuroscientist. The results willsignificantly advance our understanding of neurocircuit mechanisms at the peptide and microcircuit level inprotracted abstinence while informing the use of peptidergic pharmacotherapies in alcohol use disorders.

project_terms:
Abstinence;Affect;Alcohol consumption;Alcohol withdrawal syndrome;Alcohols;Animal Model;Anti-Anxiety Agents;Anxiety;Award;Behavior;Behavioral;Biological Availability;Brain Stem;Calcitonin Gene-Related Peptide;Cell Nucleus;Cells;Chronic;Clinical Trials;Communication;Complex;Corticotropin-Releasing Hormone;Data;Development;Electrophysiology (science);Ethanol;Female;Fiber;Fright;Goals;Individual;Learning;Maintenance;Measures;Mental Depression;Mentors;Mus;Neural Pathways;Neurons;Neuropeptides;Pain;Pathway interactions;Peptides;Peripheral Nervous System;Pharmacological Treatment;Pharmacology;Pharmacotherapy;Phase;Photometry;Population;Pre-Clinical Model;Regulation;Relapse;Reporter;Research;Resolution;Role;Sex Differences;Signal Transduction;Site;Specificity;Stress;Structure of terminal stria nuclei of preoptic region;Synapses;System;Testing;Training;Transgenic Animals;Transgenic Organisms;addiction;affective disturbance;alcohol abstinence;alcohol behavior;alcohol exposure;alcohol use disorder;anxiety-like behavior;career;career development;cell type;chronic alcohol ingestion;comorbidity;diagnostic tool;experience;hypothalamic-pituitary-adrenal axis;in vivo;insight;interest;negative affect;neural circuit;neurophysiology;neuroregulation;novel;parabrachial nucleus;peptide hormone;pituitary adenylate cyclase activating polypeptide;polypeptide;preclinical study;response;sex;sexual dimorphism;skills;sobriety;therapeutic target;vapor

public_health_relevance:
PROJECT NARRATIVEAlcohol use disorder is often comorbid with anxiety depression and stress thereby making it harder tomaintain sobriety. To alleviate negative affective disturbances in abstinence this project will provide insight onnovel peptide targets within neural pathways that will lead to better diagnostic tools and treatment options.


application_id: 10854771
project_number: 5P30ES026529-07
project_title: Center for Appalachian Research in Environmental Sciences-Pilot Project Program (PPP)
administering_ic: NIEHS
award_notice_date: 2024-05-13
opportunity_number: RFA-ES-20-006
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
project_start_date: 2017-05-01
project_end_date: 2028-04-30
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 8173
contact_pi_person_id: 1896366
contact_pi: CURRY, THOMAS E
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY  Pilot Project ProgramThe University of Kentucky Center for Appalachian Research and Environmental Science (UK-CARES) PilotProject Program (PPP) aims to support highly innovative and collaborative research studies that will enhancethe ability to identify and capitalize on the Centers science themes and build community-academicpartnerships across the translational spectrum. This goal will be accomplished by providing pilot funds alongwith guidance and support for innovative time-sensitive preliminary studies and community projects thatimprove our understanding of environmental exposures human biology and disease. Specifically the aims ofthe PPP are to 1) support new opportunities for innovative collaborative environmental health research; 2)enhance interactions and expand the critical mass of investigators with expertise and experience in multi-disciplinary translational environmental health research at UK and in Appalachian communities; 3) provideguidance and support to ensure the success of UK-CARES Pilot Projects; and 4) evaluate utilizationefficiency quality and impact of the PPP. Strong institutional support of the PPP from UK is a hallmark of ourproposal. In fact UK entities will provide matching funds representing 37% of the total funds allocated for pilotprojects. The PPP will provide three general categories of pilot research funding opportunities consistent withthe science themes and strategic vision of UK-CARES. First Pilot grants will generate new preliminary dataand support (a) established Center members to catalyze new research opportunities consistent with Centerscience themes; (b) non-member scientists to expand collaborations and bring new dimensions to the Center;and (c) creative early-stage investigators to establish competitive research programs. Second Communitygrants will provide direct support to community organizations with a UK faculty collaborator to address a priorityscience theme. Third Mini grants will foster rapid time-sensitive development of or access to new and noveltechnologies as well as community-engaged research. The PPP will communicate collaborate coordinateand create synergy across Center cores and programs to ensure that pilot-funded investigators receive theassistance they need to develop and carry out their pilot projects. The PPP will engage investigators andcommunity stakeholders both within UK-CARES and outside the Center as reviewers and grantees toaddress questions related to environmental pathways (e.g. water air) to exposures human biology and newcontaminants and emerging threats. The overall progress of the PPP and how effectively it has promotedenvironmental health research will be monitored through the existing tracking and evaluation component ofUKs Center for Clinical and Translational Science in coordination with the Administrative Core. Incorporatingpilot-funded faculty into the Center will have a major impact on expanding the ability of our Center to examineimportant questions related to emerging environmental health issues and novel technologies and to bolster thedevelopment of the next generation of environmental health scientists.

project_terms:
Address;Air;Appalachian Region;Award;Categories;Clinical;Clinical Sciences;Collaborations;Communication;Communities;Core Facility;Creativeness;Data;Development;Dimensions;Discipline;Disease;Emerging Technologies;Ensure;Environmental Exposure;Environmental Health;Environmental Science;Evaluation;Exposure to;Faculty;Fostering;Funding;Funding Opportunities;Goals;Grant;Health Sciences;Human Biology;IACUC;Institution;Institutional Review Boards;Investigation;Kentucky;Lead;Leadership;Legal patent;Manuscripts;Monitor;Pathway interactions;Pilot Projects;Publishing;Research;Research Personnel;Resources;Rural Appalachia;Science;Scientist;Strategic vision;Time;Translational Research;United States National Institutes of Health;Universities;Water;Work;clinical center;community academic partnership;community building;community engaged research;community organizations;design;electronic data;experience;high risk;improved;innovation;meetings;member;multidisciplinary;new technology;next generation;novel;population based;pre-clinical;programs;research study;success;synergism;translational pipeline


application_id: 10854765
project_number: 5P30ES026529-07
project_title: Center for Appalachian Research in Environmental Sciences-Community Engagement Core (CEC)
administering_ic: NIEHS
award_notice_date: 2024-05-13
opportunity_number: RFA-ES-20-006
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
project_start_date: 2017-05-01
project_end_date: 2028-04-30
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 8172
contact_pi_person_id: 1871398
contact_pi: DIGNAN, MARK B
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY- Community Engagement Core (CEC)The University of Kentucky Center for Appalachian Research in Environmental Sciences (UK-CARES)Community Engagement Core (CEC) will grow maintain and enhance strong sustained multidirectionalcommunity-academic partnerships that 1) support meaningful community engagement; 2) build environmentalhealth literacy; 3) reduce environmental health risks; and 4) decrease health disparities in rural Appalachia.Decades of legacy mining and fracking operations as well as an aging water infrastructure have resulted inexposure to water and air contaminants which have led to community concerns about water and air quality aswell as emerging environmental health threats. The CEC will build on a strong foundation of successfulcommunity engagement and support environmental health science (EHS) by connecting investigators withcommunity partners to promote projects consistent with the three science themes of the Center(a) HealthImpacts of Waterborne Contaminants; (b) Health Impacts of Indoor & Outdoor Airborne Contaminants; and (c)Emerging Environmental Health Threats. The CEC will use an iterative multidirectional process that bringslocal knowledge into the Center leverages UK-CARES investigator strengths and institutional support reportsback research findings with at-risk communities and encourages solution-focused communication amongcommunity and organizational stakeholders. Specifically the aims of the CEC are to: 1) foster and cultivatemultidirectional community-academic partnerships engaged in UK-CARES research that is responsive toregional environmental health issues needs and concerns; 2) translate and disseminate EHS findings throughscience communication and advocacy training to foster clinical decision making and policy formation; and 3)strengthen partnerships with community and healthcare stakeholders in UK-CARES environmental healthresearch across the translational spectrum. First we will engage our Stakeholder Advisory Board members tooffer culturally appropriate insight that will inform and assist Center investigators in their research. The CECwill use formal (e.g. focus groups) and informal (e.g. listening sessions) means to engage in multi-directionaldialogue with community stakeholders to assess environmental health concerns. In turn the CEC will serve asa bridge to and from the community to facilitate community engagement in EHS that leverages the strengths ofUK-CARES and is responsive to community concerns. Second will provide training in effective sciencecommunication and advocacy with healthcare providers faculty and community stakeholders. We will build onour impactful science communication training curriculum to prepare scientists for effective multi-modaldissemination of findings including use of evidence-based advocacy skills with policymakers. Lastly we willcollaborate with the Integrated Health Sciences Facility Core to create tailored multi-modal report backapproaches to reach healthcare providers to promote clinical decision making related to how the environmentaffects health in the region and policymakers to promote policy formation that fosters environmental justice.

project_terms:
Address;Advocacy;Affect;Aging;Air;Analytical Chemistry;Appalachian Region;Attention;Back;Bacteria;Catchment Area;Chemicals;Chronic Disease;Chronic Obstructive Pulmonary Disease;Chronically Ill;Coal;Collaborations;Colorectal Cancer;Communication;Communication Programs;Communities;Community Healthcare;Core Facility;County;Diabetes Mellitus;Disease;Disinfection;Educational Curriculum;Ensure;Environment;Environmental Exposure;Environmental Health;Environmental Risk Factor;Environmental Science;Exposure to;Faculty;Floods;Focus Groups;Fostering;Foundations;Funding;Grant;Health;Health Personnel;Health Sciences;Healthcare;Infrastructure;Institution;Kentucky;Knowledge;Link;Malignant Breast Neoplasm;Malignant Neoplasms;Malignant neoplasm of lung;Metabolic Diseases;Mining;Names;Natural Disasters;Obesity;Particulate Matter;Pilot Projects;Policies;Policy Maker;Process;Public Health;Reduce health disparities;Reporting;Research;Research Methodology;Research Personnel;Resources;Risk;Rural Appalachia;Science;Scientist;System;Training;Translating;Trust;Universities;Water;Water Pollutants;Work;air contaminant;citizen science;clinical decision-making;community academic partnership;community engaged research;community engagement;community organizations;community partners;environmental justice;evidence base;health assessment;health communication;health literacy;health science research;hydraulic fracturing;insight;investigator training;member;multimodality;novel;operation;people of color;programs;skills;socioeconomic disadvantage;toxicant;translational pipeline;waterborne


application_id: 10854755
project_number: 5P30ES026529-07
administering_ic: NIEHS
award_notice_date: 2024-05-13
opportunity_number: RFA-ES-20-006
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
project_start_date: 2017-05-01
project_end_date: 2028-04-30
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 8171
contact_pi_person_id: 14229942
contact_pi: UNRINE, JASON
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-05-01
project_title:
Center for Appalachian Research in Environmental Sciences - Analytical Chemistry Core for Environmental Sciences (ACCESS)

project_abstract:
PROJECT SUMMARY- Analytical Chemistry Core for Environmental Sciences (ACCESS)The University of Kentucky Center for Appalachian Research in Environmental Sciences (UK-CARES)ACCESS will provide Center investigators with priority access to biological and environmental sample analysisusing state-of-the-science technologies services and instrumentation for studies related to the UK-CARESthree science themes: Health Impacts of Waterborne Contaminants (WATER); Health Impacts of Indoor andOutdoor Airborne Contaminants (AIR); and Emerging Environmental Health Threats (EMERGING THREATS).To optimize efficiency ACCESS uses the following two existing laboratory facilities to leverage resourcesavailable to these facilities and extend the capabilities ACCESS: the Environmental Chemistry and ToxicologyLaboratory (College of Agriculture Food and Environment) and the Small Molecule Mass Spectrometry Facility(College of Medicine) to measure organic chemical environmental pollutants trace-elements theirmetabolites and related molecules of interest to UK-CARES investigators. Effective use of these facilities byUK-CARES investigators will require both routine analysis and new method development and validation.Specifically Aim 1 of ACCESS is to provide measurements of panels of environmental chemicals. We willprovide technically robust methods for detection and quantification of a range of halogenated organics:polychlorinated biphenyls dioxins trihalomethanes and haloacetonitriles per- and poly- fluorinated alkylsubstances non-halogenated organics including flame-retardants environmental phenols and trace-elementsto support EHS research across the translational spectrum. Aim 2 is to develop or adapt novel methods tosupport ongoing needs of UK-CARES investigators. Methods will be developed de novo or adapted from theliterature. We will use our Thermo TSQ Altis Plus triple stage quadrupole mass spectrometer to develop andvalidate survey methods that can profile environmental chemicals in multiple classes using a single analyticalworkflow and use high-resolution MS methods employing our Thermo Exploris 240 orbitrap mass spectrometerfor untargeted profiling of environmental chemicals in relevant matrices. Techniques for spatial analysismicroanalysis and speciation analysis of trace-elements are refined for environmental health studies using ourAgilent 7900 ICP-MS and associated peripherals. Aim 3 is to work with administrative and data managementfunctions of the Center to enable robust fiscal oversight project management sample tracking and datareporting. We will work in tandem with the Integrated Health Sciences Facility Core and the AdministrativeCore to ensure that Center members receive priority access that the activities of ACCESS are aligned with theUK-CARES strategic vision of the three science themes and that services and outcomes are tracked throughthe online IHSFC Research Support Portal. ACCESS will provide reliable technically robust methods andservices while pursuing opportunities for innovation. Services provided by the core will support UK-CARESmembers efforts to make innovative contributions to environmental health science.

project_terms:
Address;Agriculture;Analytical Chemistry;Appalachian Region;Biological;Biological Monitoring;Chemicals;Clinical;Coal;Communities;Core Facility;County;Coupled;Data;Data Reporting;Dioxins;Disease;Disinfection;Ensure;Environment;Environmental Health;Environmental Pollutants;Environmental Science;Exposure to;Flame Retardants;Food;Funding;Gas Chromatography;Grant;Health;Health Sciences;High Pressure Liquid Chromatography;Individual;Inductively Coupled Plasma Mass Spectrometry;Industrialization;Infrastructure;Institution;Kentucky;Laboratories;Liquid Chromatography;Literature;Mass Spectrum Analysis;Measurement;Measures;Medicine;Methods;Monitor;Office of Administrative Management;Organic Chemicals;Outcome;Particulate Matter;Peripheral;Phenols;Poly-fluoroalkyl substances;Polychlorinated Biphenyls;Process;Recovery;Research;Research Personnel;Research Project Grants;Research Support;Resolution;Resources;Rural Appalachia;Sampling;Science;Services;Strategic vision;Superfund;Survey Methodology;Technical Expertise;Techniques;Technology;Trace Elements;Translational Research;Trihalomethanes;Universities;Validation;Water Pollutants;Work;air contaminant;analytical method;base;college;community engaged research;community engagement;cost;cost effective;data management;detection method;drinking;environmental chemical;environmental chemistry;environmental toxicology;faculty support;halogenation;health science research;innovation;instrument;instrumentation;interest;laboratory facility;mass spectrometer;member;method development;novel;operation;small molecule;toxicant;translational pipeline;waterborne


application_id: 10854749
project_number: 5P30ES026529-07
administering_ic: NIEHS
award_notice_date: 2024-05-13
opportunity_number: RFA-ES-20-006
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
project_start_date: 2017-05-01
project_end_date: 2028-04-30
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 8170
contact_pi_person_id: 6457660
contact_pi: BAUER, JOHN ANTHONY
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-05-01
project_title:
Center for Appalachian Research in Environmental Sciences-Integrated Health Sciences Facility Core (IHSFC)

project_abstract:
PROJECT SUMMARY  Integrative Health Sciences Facility CoreThe University of Kentucky Center for Appalachian Research in Environmental Sciences (UK-CARES)Integrated Health Sciences Facility Core (IHSFC) will facilitate translational research in environmental healthscience (EHS) ranging from basic clinical exposure assessment and communication research to supportand sustain collaborative multidisciplinary connections and academic-community partnerships. A key elementof the IHSFC is the formation of four EHS translational research hubs: 1-Molecular Toxicology; 2-ClinicalResearch and Data Sciences; 3-Community Exposure Assessment; and 4-Environmental HealthCommunication. Each hub will provide content expertise support and access to EHS methodologies andservices and facilitate project development across the translational research spectrum. The hub structure willenhance disciplinary diversity within the IHSFC and support campus-wide integration and cross-Centercommunication. The IHSFC will build on our record of early success refining our operational model andtargeting new partnerships among Center members while providing expert consultation translational researchsupport and team building strategies across the Centers re-aligned science themes: (a) Health Impacts ofWaterborne Contaminants (WATER); (b) Health Impacts of Indoor and Outdoor Airborne Contaminants (AIR);and (c) Emerging Environmental Health Threats (EMERGING THREATS). Specifically the IHSFC aims to 1)provide access to EHS research services 2) deliver EHS project support and 3) enhance translationalresearch partnerships. First the IHSFC Research Support Portal will direct the flow of investigator requests toIHSFC staff and relevant hub leaders who will link Center members to the appropriate cores (e.g. AnalyticalChemistry Core for Environmental Sciences and Community Engagement Core) and resources (e.g. datamanagement and statistical analysis) for project facilitation. The Portal will facilitate coordination prioritizationtracking and use of facility core services Center-wide. Second IHSFC hub leaders will provide EHS bestpractices workshops and training sessions in collaboration with the Career Development Program. Third wewill establish Rapid Response Teams comprised of the hub leaders and other Center members to promoteresearch translation and partnerships enabling prompt responses to community identified EHS threats andnew exposures. The IHSFC will fulfill the need for a centralized and accessible core that supportsmultidirectional EHS research activities within the Center across UK campus with community investigatorsand with other EHS Core Centers providing timely consultation and support for an impactful portfolio of EHSresearch projects while fostering a highly collaborative institutional EHS culture. The IHSFC will expandexpertise and services enhancing the cores central role in daily UK-CARES operations and provide theinfrastructure to facilitate the progression and expansion of EHS from fundamental questions into testingclinical practice and public health impact to improve public health and clinical practice in environmental health.

project_terms:
Address;Analytical Chemistry;Appalachian Region;Area;Back;Categories;Clinical;Clinical Data;Clinical Research;Clinical Sciences;Collaborations;Communication;Communication Research;Communities;Consultations;Core Facility;Data;Data Analyses;Data Science;Development;Dimensions;Disasters;Educational workshop;Elements;Environmental Exposure;Environmental Health;Environmental Science;Evaluation;Fostering;Funding;Goals;Growth;Health;Health Sciences;Human;Infrastructure;Institution;Institutional Review Boards;Integrative Medicine;Kentucky;Laboratories;Leadership;Link;Methodology;Methods;Modeling;Molecular Toxicology;National Institute of Environmental Health Sciences;Output;Patients;Peer Review;Pilot Projects;Policy Maker;Process;Program Development;Public Health;Public Health Practice;Publishing;Reporting;Research;Research Activity;Research Methodology;Research Personnel;Research Project Grants;Research Support;Resources;Review Literature;Role;Sampling;Science;Scientist;Services;Statistical Data Interpretation;Strategic Planning;Structure;Testing;Toxicology;Training;Translational Research;Universities;Water;Work;biobank;career development;clinical practice;cohort;community academic partnership;community building;community collaboration;community engagement;community partners;data management;health assessment;health communication;health science research;health training;high risk;improved;innovation;meetings;member;multidisciplinary;novel;novel strategies;operation;prevent;repository;response;service coordination;success;translational health science;translational impact;translational pipeline;waterborne


application_id: 10854745
project_number: 5P30ES026529-07
project_title: Center for Appalachian Research in Environmental Sciences-Administrative Core
administering_ic: NIEHS
award_notice_date: 2024-05-13
opportunity_number: RFA-ES-20-006
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
project_start_date: 2017-05-01
project_end_date: 2028-04-30
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 8169
contact_pi_person_id: 1906116
contact_pi: HAHN, ELLEN J
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY  Administrative CoreThe University of Kentucky Center for Appalachian Research in Environmental Sciences (UK-CARES)Administrative Core will coordinate oversee and evaluate all programmatic and scientific activities and leadcross-disciplinary career development initiatives while providing and receiving support from the IntegratedHealth Sciences Facility Core the Analytical Chemistry Core for Environmental Sciences the CommunityEngagement Core the Pilot Project Program and our community partners. The Administrative Core leadershipis comprised of highly regarded senior scientists and research mentors who are well qualified to operate anEnvironmental Health Sciences Core Center (EHS CC) that is responsive to the concerns of people in ruralAppalachia and to advance EHS across the translational spectrum. The Administrative Core will activelycollaborate with all Center members community and academic promoting their research and involving them inCenter decision-making and strategic programmatic activities as well as engaging with other UK Centers andEHS CCs. The organizational structure of UK-CARES will allow for optimal multidirectional Center-Community-University communications and institutional support. Three Advisory Boards will inform our research provideadvice and support help us form and maintain robust community-academic partnerships and evaluateprogram progress: 1) a 12-member Stakeholder Advisory Board representing higher education environmentaljustice groups healthcare and public health in rural Appalachia; 2) an Internal Advisory Board comprised of 10high-level campus and community decision makers; and 3) a 4-member External Advisory Board of prominentnational leaders in EHS. The Administrative Core has four Aims to: 1) coordinate monitor and evaluate theCenters scientific and programmatic activities; financial oversight and regulatory compliance; productivity; andeffectiveness as intellectual needs change; 2) facilitate internal multidirectional communication and responsibleconduct of research; 3) facilitate external multidirectional communication; and 4) cultivate careers in EHS witha focus on underrepresented minority faculty. The Core will ensure effective internal and externalcommunications by directing monthly Executive Committee meetings; coordinating an Annual ScientificRetreat monthly scientific work groups with Center members and a seminar series; and partnering with keycommunity and state partners via social media our website and other scientific and professional venues. TheCores Career Development Program will recruit and support early-stage investigators (ESIs) to becomeindependent EHS researchers and facilitate established investigators to transition to an EHS research focusthrough maximizing the use of Center services cross-disciplinary activities and mentorship. CareerDevelopment Program funding will support independent investigators newly recruited to UK from outside UK-CARES or Center member ESIs with partial salary support. In the first cycle the Administrative Core hasgrown the Center as a recognizable entity in EHS and public health in rural Appalachia.

project_terms:
Administrator;Affect;Analytical Chemistry;Appalachian Region;Chronically Ill;Clinical;Collaborations;Communication;Communities;Community Outreach;Core Facility;Decision Making;Dedications;Discipline;Discipline of Nursing;Disparity;Educational workshop;Effectiveness;Ensure;Environment;Environmental Exposure;Environmental Health;Environmental Science;Evaluation;Event;Faculty;Funding;Goals;Grant;Health;Health Sciences;Healthcare;Institution;Kentucky;Lead;Leadership;Learning;Letters;Manuscripts;Mentors;Mentorship;Mission;Monitor;National Institute of Environmental Health Sciences;Outcome;Persons;Pilot Projects;Population;Procedures;Process;Productivity;Professional Organizations;Program Development;Public Health;Public Relations;Publishing;Qualifying;Reporting;Research;Research Personnel;Resource Sharing;Risk;Rural Appalachia;Science;Scientist;Senior Scientist;Series;Services;Strategic Planning;Superfund;Trace Elements;Training;Translating;Translational Research;Underrepresented Minority;Universities;Wages;career;career development;college;community academic partnership;community center;community engagement;community partners;design;effectiveness evaluation;environmental justice;health science research;higher education;improved;meetings;member;operation;organic contaminant;organizational structure;programs;recruit;responsible research conduct;social media;socioeconomic disadvantage;success;translational pipeline;waterborne;web site;working group


application_id: 10854744
project_number: 5P30ES026529-07
project_title: Center for Appalachian Research in Environmental Sciences
administering_ic: NIEHS
award_notice_date: 2024-05-13
opportunity_number: RFA-ES-20-006
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
program_official: THOMPSON, CLAUDIA L
project_start_date: 2017-05-01
project_end_date: 2028-04-30
study_section: Environmental Health Sciences Review Committee[EHS(P)]
contact_pi_person_id: 7102409
contact_pi: HAYNES, ERIN N
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY  OverallThe University of Kentucky Center for Appalachian Research in Environmental Sciences (UK-CARES) willbuild on our early successes capitalize on lessons learned and enhance our mission through a dual focus onbetter understanding exposure pathways and emerging environmental health threats and optimizing researchtranslation. Our Mission is to focus on exposure pathways to better match with community concerns and toemphasize research translation. Our Values reflect strong multidirectional community-academic partnershipswith a renewed commitment to meaningful processes procedures and policies that respect and promotediversity equity and inclusivity. Responsible conduct of research is at the foundation of our Centerappreciating the essential value of rigorous and reproducible multidisciplinary team science. Our goals are to(a) advance multidisciplinary environmental health science (EHS); (b) analyze organic contaminants and trace-elements; (c) cultivate early-stage stage and established investigators; (d) learn with and from the communityhelping to inform and translate our research; and (e) build science communication skills with investigators andcommunity partners to boost research translation. We will advance EHS across the translational spectrumaround three highly integrated science themes informed by residents of rural Appalachia: 1) Health Impacts ofWaterborne Contaminants (WATER); 2) Health Impacts of Indoor and Outdoor Airborne Contaminants (AIR);and 3) Emerging Environmental Health Threats (EMERGING THREATS). The central hypothesis is thatexposure to established contaminants via environmental exposure pathways (e.g. water air) and emergingenvironmental health threats combined with lifestyle and societal risk factors contributes to thedisproportionately high incidence of chronic diseases and health disparities in rural Appalachia. UK-CARESdraws on a strong and diverse base of EHS and community-engaged research to meet the needs ofcommunities in rural Appalachia. We will support and mentor investigators so they can reach the translationalmilestones in research: (1) asking fundamental questions; (2) applying and synthesizing; (3) implementing andadjusting; (4) moving ideas to practice; and (5) creating impact. In short UK-CARES will leverage its resourcesto enhance EHS at UK while also reducing health risks and disparities in rural Appalachia. An IntegratedHealth Sciences Facility Core Analytical Chemistry Core for Environmental Sciences and CommunityEngagement Core are integral to this effort as these cores will provide dedicated support in analyticalchemistry trace-elements analysis biospecimen management and bioinformatics and bridge Center andcommunity priorities. The Pilot Project Program supports developing research and new scientific directionsadvancing the careers of scientists interested in tackling challenging environmental health questions. UK-CARES will positively impact rural Appalachia through collaborative EHS designed to generate anddisseminate new knowledge and translate research to inform clinical decision making and policy development.

project_terms:
Acceleration;Address;Affect;Air;Air Pollution;Analytical Chemistry;Appalachian Region;Arsenic;Asthma;Bioinformatics;Career Mobility;Chemicals;Chromium;Chronic Disease;Chronic Obstructive Pulmonary Disease;Clinical Data;Clinical Research;Coal Mining;Colorectal Cancer;Communication;Communities;Community Outreach;Complex;Core Facility;Data Science;Dedications;Diabetes Mellitus;Discipline;Disparity;Dissemination and Implementation;Environmental Exposure;Environmental Health;Environmental Impact;Environmental Pollutants;Environmental Science;Exposure to;Faculty;Fostering;Foundations;Funding;Geology;Goals;Grant;Health;Health Promotion;Health Sciences;Heart;Heart Diseases;Incidence;Infrastructure;Joints;Kentucky;Knowledge;Lead;Learning;Life Style;Malignant Neoplasms;Malignant neoplasm of lung;Measures;Medically Underserved Area;Mentors;Mentorship;Mission;Molecular Toxicology;Natural Gas;Nickel;Obesity;Oils;Particulate;Pilot Projects;Policies;Policy Developments;Population;Procedures;Process;Public Health;Radon;Reproducibility;Research;Research Personnel;Research Project Grants;Resources;Risk;Risk Factors;Rural Appalachia;Science;Scientist;Services;Severe Acute Respiratory Syndrome;Superfund;Trace Elements;Training;Translating;Translational Research;Universities;Water;Water Pollutants;air contaminant;base;career;career development;citizen science;clinical decision-making;community academic partnership;community engaged research;community engagement;community partners;design;disease disparity;environmental justice;equity diversity and inclusion;experience;exposure pathway;health assessment;health communication;health disparity;health equity;health science research;improved;innovation;interest;member;multidisciplinary;novel;organic contaminant;outreach;population health;programs;research facility;research study;responsible research conduct;rural dwellers;skills;socioeconomic disadvantage;success;synergism;tobacco smoke exposure;translational pipeline;wastewater surveillance;water quality;waterborne

public_health_relevance:
PROJECT NARRATIVE  OverallThe University of Kentucky Center for Appalachian Research in Environmental Sciences (UK-CARES) willenhance programmatic and scientific capacity to facilitate innovative discovery and new understandings ofenvironmental exposure pathways of concern to our community (e.g. water air emerging threats). Furtherthe Center will foster career development of environmental health scientists interested in tackling challengingenvironmental health questions facing rural Appalachia. UK-CARES will achieve these goals by providingadvanced infrastructure and expertise cross-disciplinary training and mentorship and multidirectionalcommunity-academic partnerships to reduce health risks and health disparities in rural Appalachia.


application_id: 10852188
project_number: 3P20GM125504-06S2
project_title: Functional Microbiomics Inflammation and Pathogenicity
administering_ic: NIGMS
award_notice_date: 2023-08-07
opportunity_number: PA-20-272
application_type: 3
activity_code: P20
ic: GM
serial_number: 125504
suffix: S2
program_official: CUPIT, PAULINE
project_start_date: 2018-03-01
project_end_date: 2028-02-29
contact_pi_person_id: 7355414
contact_pi: LAMONT, RICHARD J
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
ABSTRACT Inflammation is essential to protect us against infection. To contain the infection leukocytes must rapidly sensepathogens and recruit additional immune cells to infected tissues. However once the infection is containedinflammation must also be quickly resolved to avoid collateral tissue damage caused by activated immune cells.Therefore initiation and resolution of inflammation are tightly regulated processes. Lipid mediators ofinflammation are essential for both the initiation and resolution of inflammation. Leukotriene B4 (LTB4) is a pro-inflammatory lipid rapidly produced in response to infection. LTB4 binding to the BLT1 receptor recruits andactivates resident and circulating leukocytes to sites of infection and LTB4/BLT1 signaling is required toeffectively control infections. However persistent LTB4 synthesis can also lead to chronic inflammation andtissue damage associated with inflammatory diseases such as gout asthma and silicosis. Becausedysregulation of LTB4 impacts both acute and chronic inflammation defining the specific contribution of thispotent chemoattractant to the regulation of inflammation is essential to understanding the molecular mechanismsof inflammatory initiation and resolution. We have demonstrated that dysregulation of LTB4-mediatedinflammation occurs during both silica-induced sterile inflammation (i.e. persistent LTB4 production) and Yersiniapestis infection (i.e. inhibited LTB4 production). While we have established a role for this signaling pathway inboth diseases the precise nature of this dysregulation and its impact on inflammatory cell programming remainsa critical gap in our knowledge pertaining to LTB4 regulation of inflammatory responses. Therefore the goal ofthis project is to use the Core Resource Centers at the University of Louisville's COBREs and the KentuckyINBRE to define the temporal and spatial regulation of inflammation during LTB4 dysregulation induced by silicainhalation or Y. pestis infection. We will achieve this through the application of cutting-edge technologiesincluding single cell RNA sequencing and imaging mass cytometry. Defining these mechanisms of regulation iskey to understanding how inflammation is properly controlled and can reveal potential therapeutic interventionsto better treat infection and diseases resulting from chronic inflammation.

project_terms:
Acute;Affinity;Asthma;Bacterial Infections;Binding;Biology;Cells;Cementation;Centers of Research Excellence;Cessation of life;Chemotactic Factors;Chemotaxis;Chronic;Collaborations;Core Facility;Cytometry;Data;Development;Disease;Environment;Exposure to;Fibrosis;Flow Cytometry;Funding;Future;Generations;Goals;Gout;Grant;Image;Immune;Immune Evasion;Immune response;Immunologist;Infection;Infection Control;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;Inhalation;Kentucky;Knowledge;LTB4R gene;Laboratories;Leukocytes;Leukotriene B4;Lipids;Location;Lung;Mediating;Molecular;Mycoses;National Institute of General Medical Sciences;Nature;Parasitic infection;Pathogenesis;Pathogenicity;Pathway interactions;Plague;Pneumonic Plague;Population;Process;Production;Pulmonary Inflammation;Regulation;Resolution;Resources;Role;Sentinel;Signal Pathway;Signal Transduction;Silicon Dioxide;Silicosis;Site;Spatial Distribution;Sterility;Technology;Therapeutic Intervention;Time;Tissues;Universities;Yersinia pestis;cancer immunotherapy;chronic inflammatory disease;defined contribution;immune modulating agents;improved;inflammatory milieu;innovative technologies;interest;lipid mediator;microbiome research;mouse model;multiplexed imaging;pathogen;programs;receptor;recruit;response;single-cell RNA sequencing;tool;transcriptome sequencing;transcriptomics;tumor immunology

public_health_relevance:
NARRATIVEInflammation is required to control infection but chronic inflammation can also have deleterious effects ontissues. Therefore defining the mechanisms involved in the regulation of inflammation will significantly improveour current understanding of both acute immune responses to infection and chronic inflammatory diseases.Moreover these mechanisms can be targeted for improved immunomodulatory therapeutics.


application_id: 10851206
project_number: 3R01HL163977-02S1
project_title: Carol Act Supplement to Data-driven optimization of therapy for heart failure
administering_ic: NHLBI
award_notice_date: 2023-08-25
opportunity_number: PA-20-272
application_type: 3
activity_code: R01
ic: HL
serial_number: 163977
suffix: S1
program_official: SHANBHAG, SUJATA MADHUKAR
project_start_date: 2022-05-01
project_end_date: 2026-04-30
contact_pi_person_id: 8356696
contact_pi: CAMPBELL, KENNETH S
other_pis: LEE, LIK CHUAN ;WENK, JONATHAN F
congressional_district: 06
department: PHYSIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
ABSTRACTThis proposal is submitted in response to NOT-HL-23-078 Administrative supplements to encourage researchin valvular heart disease and seeks 12 months of additional support for HL163977 Data-driven optimization oftherapy for heart failure. The parent R01 is active until 2026.The overarching goal of HL163977 is to develop a computer model of the heart that can be used to testtherapeutic strategies and optimize treatments for patients who have heart failure. Aim 1 develops a systemcalled MyoVent as a test-bed for implementing baroreflex control and myocardial growth. Aims 2 and 3 use thetechniques developed with MyoVent and deploy them in a more sophisticated 3D framework called MyoFE tocreate patient-specific personalized models.The team has made rapid progress and Aim 1 is now mostly complete. The breakthrough was accomplished bydeveloping algorithms that modulate concentric (wall thickening / thinning) and eccentric (chamber dilation /constriction) growth in response to physiologic signals. Specifically the model assumes that hearts growconcentrically to stabilize the intracellular ATP concentration while eccentric growth is sensitive to the passiveintracellular stress sensed by titin filaments. These growth laws reproduce the patterns of cardiac growthobserved in clinically-relevant conditions including hypertension exercise and destabilization of the myosinsuper-relaxed state.This supplement will extend the simulations to valvular heart disease. The objective is focused. The team willtest whether the growth laws predict the patterns of eccentric and concentric growth observed clinically in patientswith mitral valve insufficiency (including mitral valve prolapse) and stenosis and aortic valve insufficiency andstenosis. This will be accomplished in a single year by a highly-qualified and experienced post-doc who will workunder the supervision of the contact PI.

project_terms:
3-Dimensional;Administrative Supplement;Algorithms;Aortic Valve Insufficiency;Baroreflex;Beds;Blood;Cardiac;Circulation;Clinical;Computer Models;Computer software;Data;Dilated Cardiomyopathy;Disease;Exercise;Filament;Goals;Growth;Heart;Heart Diseases;Heart Valve Diseases;Heart failure;Hypertension;Hypertrophic Cardiomyopathy;Laws;Left ventricular structure;Mitral Valve;Mitral Valve Insufficiency;Mitral Valve Prolapse;Mitral Valve Stenosis;Modeling;Mutation;Myocardial;Myosin ATPase;Parents;Patients;Pattern;Physiological;Postdoctoral Fellow;Pregnancy;Proteins;Qualifying;Relaxation;Research;Signal Transduction;Stenosis;Stress;Supervision;System;Techniques;Testing;Therapeutic;Therapeutic Intervention;Thinness;Time;Work;aortic valve;blood pump;clinical phenotype;clinically relevant;computer program;connectin;constriction;experience;parent grant;response;simulation;therapeutic evaluation;treatment optimization

public_health_relevance:
NARRATIVEThis project develops computer programs that can predict how a patient's heart will grow and adapt whenvalves become diseased and either restrict flow or allow blood to leak backwards. The long-term goal is tocreate software that cardiologists can use to optimize therapies for patients who have valvular heart failure.


application_id: 10850912
project_number: 5R16GM149498-02
project_title: Brain Development after Early-Life Antipsychotic Treatment
administering_ic: NIGMS
award_notice_date: 2024-03-22
opportunity_number: PAR-21-169
application_type: 5
activity_code: R16
ic: GM
serial_number: 149498
program_official: BASKIR, RUBIN SAM
project_start_date: 2023-06-01
project_end_date: 2027-04-30
study_section: ZGM1-RCB-A(SU)
contact_pi_person_id: 1893500
contact_pi: BARDGETT, MARK EDWARD
other_pis: Not Applicable
congressional_district: 04
department: PSYCHOLOGY
primary_duns: 072879760
primary_uei: LN53C9E23GH6
duns_number: 072879760
uei: LN53C9E23GH6
fips: US
organization_id: 656601
organization_name: NORTHERN KENTUCKY UNIVERSITY
organization_city: HIGHLAND HEIGHTS
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 410990001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
7. Project Summary/Abstract This is an application for a Support of Research Enhancement (SuRE) R16 award. These grants areintended to support small scale research projects at institutions like Northern Kentucky University that do notreceive substantial NIH funding with an additional emphasis on providing biomedical research experiences tostudents from groups traditionally underrepresented in biomedical and health science and enhancing theresearch environment at the university. Antipsychotic drugs (APDs) are widely used in children mainly as off-label treatments for a multitude ofpediatric psychiatric disorders despite the lack of basic research documenting their effects on later brain andbehavioral function. One concern is that APD exposure during early brain development alters later sensitivity todrugs of abuse. Our previous NIH-funded research showed that adult rats administered the APD risperidoneearly in life are hyperactive exhibit enhanced locomotor and rewarding responses to the psychostimulant D-amphetamine and display alterations in forebrain dopamine transporters and receptors. These data weregenerated by undergraduate students at NKU many of whom served as first- or co- authors on publishedpapers and some of whom went on to pursue graduate study in psychology. Having ascertained that early-life risperidone modifies responses to psychostimulant drugs that directlytarget dopamine synapses we now seek to determine if behavioral and neural sensitivity to other classes ofdrugs such as opioids that indirectly work though dopamine pathways is enhanced by early-life risperidone.The proposed work will ascertain whether behavioral neural and genetic responses to the opioid drugoxycodone are altered in adult rats administered risperidone early in life (daily injections from postnatal day14-42). This issue is especially germane to NKU students since our geographic area is marked by relativelyhigh rates of opioid use and overdose. Overall the proposed research will address the following questions: 1)Does early-life APD administration enhance the rewarding effects of oxycodone during adulthood? 2)Does early-life APD administration increase neural sensitivity to oxycodone in the forebrain duringadulthood? and 3) Does early-life APD administration modify patterns of forebrain gene transcriptioninduced by oxycodone during adulthood? The last aim will be achieved by collaborating with the nearbyUniversity of Louisville to quantify mRNA expression in tissue samples using next-generation RNA-Seqtechnology. A concomitant goal of this work will be to continue engaging NKU undergraduate students in theexecution analysis and reporting of research. The proposed work will take advantage of training andpedagogical resources offered by NKU and the KY-INBRE program to enhance these experiences and in turncontribute to the overall research environment at NKU.

project_terms:
Adult;Affect;Amphetamines;Antipsychotic Agents;Attention deficit hyperactivity disorder;Award;Basic Science;Behavioral;Bioinformatics;Biomedical Research;Brain;Brain region;Child;Childhood;Collaborations;Control Groups;Core Facility;Data;Development;Dextroamphetamine;Disease;Disruptive Behavior Disorder;Dopamine;Dopamine Agonists;Dopamine Receptor;Dose;Drug Exposure;Environment;Exhibits;Extinction;FOS gene;Funding;Genetic;Genetic Transcription;Geographic Locations;Goals;Grant;Health Sciences;Hyperactivity;Immediate-Early Genes;Injections;Institution;Kentucky;Label;Laboratory Rat;Life;Long-Term Effects;Mental disorders;Mentors;Messenger RNA;Metabolic;Modification;Neurons;Neurosciences;Neurotransmitter Receptor;Nucleus Accumbens;Opioid;Outcome;Oxycodone;Paper;Pathway interactions;Pattern;Pharmaceutical Preparations;Pharmacotherapy;Policy Maker;Population;Prosencephalon;Psychology;Publishing;Rattus;Reporting;Research;Research Project Grants;Research Support;Resources;Rewards;Risk;Risperidone;Science;Scientist;Series;Short-Term Memory;Students;Substance abuse problem;Synapses;Techniques;Technology;Time;Tissue Sample;Training;Transcript;Underrepresented Populations;United States;United States National Institutes of Health;Universities;Work;age related;boys;college;conditioned place preference;conditioning;dopamine transporter;drug of abuse;experience;girls;high risk;late life;mRNA Expression;member;model organism;neural;next generation;opioid overdose;opioid use;postnatal;programs;psychostimulant;response;transcriptome sequencing;undergraduate student

public_health_relevance:
8. Project NarrativeThe use of antipsychotic drugs in pediatric populations has increased dramatically over the past 30 yearsdespite a lack of basic research documenting the effects of these drugs on brain and behavioral development.This research will use laboratory rats to ascertain whether early-life antipsychotic drug administration leads togreater behavioral and neural sensitivity to opioid drugs in adulthood. This research will provide scientistspolicy-makers and practitioners with critical information regarding the impact of prolonged antipsychotic drugtreatment during development on the risk of substance abuse in later life as well as offer transformativeresearch experiences in neuroscience to college undergraduates in Kentucky hailing from groupsunderrepresented in biomedical science.


application_id: 10850701
project_number: 5R01AG068331-05
administering_ic: NIA
award_notice_date: 2024-05-21
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: AG
serial_number: 068331
program_official: YAO, ALISON Q
project_start_date: 2020-09-15
project_end_date: 2026-05-31
study_section: Molecular Neurogenetics Study Section[MNG]
contact_pi_person_id: 9202423
contact_pi: EBBERT, MARK T W
other_pis: Not Applicable
congressional_district: 06
department: OTHER HEALTH PROFESSIONS
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-06-01
project_title:
Using long-range technologies as a multi-omic approach to understand Alzheimers disease in brain tissue

project_abstract:
PROJECT SUMMARY/ABSTRACTOur long-term goal is to help develop a meaningful therapeutic and pre-symptomatic diagnosticfor Alzheimers disease because while a disease-altering therapeutic is essential it will not besufficient without a diagnostic that identifies disease before symptoms onset. We seek tocontribute to these long-term goals by helping identify specific molecular modifications andtherefore specific mechanisms driving disease using long-range optical DNA mapping andsequencing technologies. Unfortunately most Alzheimers disease genes are only implicatedthrough common non-functional variants and it is still unclear how most Alzheimers diseasegenes are involved in disease. Likewise individual RNA isoforms in diseased brains for topAlzheimers disease genes and their involvement in disease are poorly understood. Functionalvariants and RNA sequencing at the isoform level in diseased brain tissue will provide specificmechanisms to target for therapeutics and diagnostics. Large short-read sequencing efforts arealready ongoing to identify small functional variants involved in Alzheimers disease but structuralDNA variantsmany of which directly affect downstream RNA and proteinsalso causeneurodegenerative diseases. We hypothesize that undiscovered SVs and aberrant RNA isoformsplay a direct role in Alzheimers disease. A thorough study in diseased brain using long-rangeDNA and RNA technologies will complement current short-read efforts providing importantdisease insights.

project_terms:
Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease diagnostic;Alzheimer's disease risk;Automobile Driving;Biology;Brain;Brain Diseases;Clinic;Complement;Complex;DNA;DNA mapping;DNA sequencing;Data;Data Set;Detection;Development;Diagnostic;Disease;Genes;Goals;Grant;Individual;Intervention;Maps;Methods;Modification;Molecular;Mutation;Neurodegenerative Disorders;Nucleotides;Optics;Phenotype;Play;Prognosis;Protein Isoforms;Proteins;RNA;RNA Splicing;Research Personnel;Role;Sampling;Symptoms;Technology;Therapeutic;Validation;Variant;Work;advanced disease;brain control;brain health;brain tissue;cohort;design;differential expression;disease diagnosis;disease diagnostic;frontal lobe;gain of function;genome-wide;genome-wide analysis;insight;multiple omics;programs;risk variant;targeted treatment;transcriptome sequencing

public_health_relevance:
PROJECT NARRATIVEOur overarching scientific premise is that Alzheimers disease interventions and pre-symptomatic disease diagnostics remain elusive in part because we still do not understandexactly how top genes are driving disease. Our group seeks to help develop a pre-symptomaticdisease diagnostic and a meaningful therapy by identifying specific molecular modifications andtherefore specific mechanisms driving disease using long-range optical DNA mapping andsequencing technologies.


application_id: 10850016
project_number: 3R01DA057605-01S2
project_title: Administrative Supplement - Rapid Actionable Data for Opioid Response in Kentucky (RADOR-KY)
administering_ic: NIDA
award_notice_date: 2023-08-21
opportunity_number: PA-20-272
application_type: 3
activity_code: R01
ic: DA
serial_number: 057605
suffix: S2
program_official: KURAMOTO-CRAWFORD, SATOKO JANET
project_start_date: 2022-09-29
project_end_date: 2025-09-29
contact_pi_person_id: 12111311
contact_pi: SLAVOVA, SVETLA STEFANOVA
other_pis: TALBERT, JEFFERY C
congressional_district: 06
department: BIOSTATISTICS & OTHER MATH SCI
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PUBLIC HEALTH
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
AbstractSystematic and algorithmic biases in machine learning (ML) modeling and underlying definitionsfor capturing opioid overdose may result in inaccuracies in burden measures for disparate groupspotentially leading to an ineffective and unequal distribution of harm reduction and preventionresources. Identifying and evaluating data and model biases and health disparities is critical toeffective public health practice and research. This project is a supplement to RADOR-KY (RapidActionable Data for Opioid Response in Kentucky; 1-R01 DA057605-01). The RADOR-KY projectwill build a robust state-wide surveillance system for opioid use disorder (OUD) including opioidoverdose integrating multiple data sources to monitor and predict drug overdose mortality andmorbidity. The system will be used by stakeholders to inform data-driven action supporting thecoordination and targeting of prevention and treatment efforts. As proposed in the parent grantfor this supplement the RADOR-KY system will integrate several data sources includingEmergency Medical Services (EMS) data to develop machine learning predictive models andforecasting for opioid overdoses to inform public health and public safety agencies actions andplanning. The proposed administrative supplement of RADR-KY will improve our understandingof the ethical aspects of these machine learning/artificial intelligence methods. EMS run data foropioid overdose surveillance is a promising new system that overcomes limitations of traditionaldata sources such as prolonged delays and omission of non-clinical overdose events. Whilerecent national standards have improved the structural components of EMS encounter data thequality and completeness of such data still necessitate reliance on patient care narratives for caseassertion. There have been a host of opioid overdose definitions proposed typically focused onkeyword matches or other rule-based criteria with little emphasis on definition validationcomparative evaluations or demographic parity. Critically no previous models whether machinelearning or rule-based have considered demographic fairness in their approaches. Leveragingour access to over 3.5 million EMS detailed encounter records access under RADOR-KYs datause agreement along with expert-labeled and extracted data we aim to assess these proposedmodels against our own machine learning natural language processing classifier particularlyconsidering disparate populations. The specific aims are to 1) Evaluate potential bias in the opioidoverdose data and definitions and identify suitable definitions for each specific sub-population;and 2) Identify address and generate bias-aware ML-ready datasets.

project_terms:
Address;Administrative Supplement;Affect;Agreement;Algorithms;Area;Artificial Intelligence;Awareness;Caring;Clinical;Communities;County;Data;Data Linkages;Data Set;Data Sources;Development;Disparate;Disparity population;Emergency medical service;Ethics;Evaluation;Event;Funding;Goals;Harm Reduction;Human;Informatics;Intervention;Kentucky;Label;Link;Location;Machine Learning;Measurement;Measures;Mission;Modeling;Monitor;Morbidity - disease rate;Natural Language Processing;Opioid;Outcome;Overdose;Parents;Patient Care;Patients;Performance;Pharmaceutical Preparations;Play;Population;Predictive Analytics;Prevention;Process;Public Health;Public Health Practice;Records;Reporting;Research;Resources;Risk;Role;Running;Safety;Statistical Models;System;Systematic Bias;Time;Transportation;United States National Institutes of Health;Validation;Visual;Visualization;Visualization software;Work;algorithmic bias;artificial intelligence method;comparative;computerized data processing;data ingestion;design;health disparity;improved;inequitable distribution;knowledge base;machine learning algorithm;machine learning model;machine learning prediction;model development;mortality;multiple data sources;novel;opioid overdose;opioid use disorder;overdose prevention;parent grant;parent project;parity;population based;predictive modeling;residence;response;social health determinants;tool;web app

public_health_relevance:
Project NarrativeEmergency Medical Services (EMS) run data for opioid overdose surveillance is a promising new systemthat overcomes limitaons of tradional data sources such as prolonged delays and omission of non-clinical overdose events. There have been a host of proposed opioid overdose machine learning or rule-based EMS denions and models but none of them have considered demographic fairness in theirapproaches. Leveraging our access to over 3.5 million EMS detailed encounter records access underRADOR-KYs data use agreement along with expert-labeled and extracted data we aim to assess theseproposed models against our own machine learning natural language processing classier parcularlyconsidering performance and fairness for disparate populaons.


application_id: 10849965
project_number: 3R03DE031854-02S1
project_title: The Control of LPS Heterogeneity and Virulence by C-di-AMP Signaling in P. gingivalis
administering_ic: NIDCR
award_notice_date: 2023-05-26
opportunity_number: PAR-21-084
application_type: 3
activity_code: R03
ic: DE
serial_number: 031854
suffix: S1
program_official: MCNEALY, TAMARA L
project_start_date: 2022-04-01
project_end_date: 2025-03-31
study_section: National Institute of Dental and Craniofacial Research Special Grants Review Committee[DSR]
contact_pi_person_id: 14927473
contact_pi: MORADALI, FATA
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
project_abstract:
Project SummaryPeriodontitis is a highly prevalent infectious inflammatory disease of the tissues supporting the teeth that canlead to tissue destruction alveolar bone resorption formation of the deep periodontal pocket and tooth loss.Etiological models suggest that periodontitis is driven by a synergistic community of virulent bacteria that triggerhost inflammatory responses below the gum line resulting in disease progression. Among recognized pathogensthe Gram-negative highly proteolytic anaerobe Porphyromonas gingivalis (Pg) has been stronglyimplicated in periodontitis. Pg strains produce lipopolysaccharide (LPS) macromolecules as the maincomponents of the outermost layer of the cells that have been repeatedly shown to stimulate innate immuneresponses. Intriguingly Pg strains can diversify the structure of LPSs in response to biologically relevant stimulito temporarily disguise themselves evade the immune system protect from stresses and promote survival.Accordingly at least four LPS variants have been identified in Pg strains that may act as agonists or antagoniststo activate innate immune responses. A specific form of LPSs called A-LPS serves to anchor a series ofdestructive proteolytic enzymes known as gingipains on the cell surface. These virulence factors collectively playprominent roles in the pathological outcome of infection by being involved in various activities including tissuedestruction host-defense perturbation immune system evasion and bone resorption. However we do not yetknow the mechanisms of the regulation of LPS heterogeneity and its biological importance during pathogenesis.We discovered that Pg strains have evolved with c-di-AMP signaling pathway in which the c-di-AMP synthasePGN_0523 (dacpg) and the c-di-AMP phosphodiesterase PGN_0521 (pdepg) control the essential turnover of c-di-AMP and in turn cell viability within biofilms LPS heterogeneity the diffusion of gingipains into thesurrounding milieu and virulence potential. We will investigate how c-di-AMP turnover regulates theheterogeneity and immunostimulatory properties of LPSs and affects gingipain-associated virulence potential.To this end two specific aims are proposed and each aim includes a set of separate experiments and assays:Specific Aim 1: To understand c-di-AMP-controlled heterogeneity of LPSs in Pg. Specific Aim 2: Tounderstand the impact of c-di-AMP-dependent variation of LPS on the innate immune response and gingipains-associated virulence. Upon completion of the proposed studies we will learn how c-di-AMP signalingcontrols LPS heterogeneity impacts immunostimulatory responses and the virulence potential of Pg. Since c-di-AMP signaling does not exist in mammals our findings will inform about a novel druggable target.

project_terms:
Adenosine;Adenosine Monophosphate;Adult;Affect;Agonist;Anaerobic Bacteria;Anti-Inflammatory Agents;Applications Grants;Bacteria;Biological;Biological Assay;Bone Resorption;Cell Survival;Cell Wall;Cell membrane;Cell physiology;Cell surface;Cells;Chemical Structure;Communities;Cytoprotection;Data;Detection;Development;Diffusion;Disease;Disease Progression;Equilibrium;Etiology;Genes;Heterogeneity;Host Defense;Immune Evasion;Immune system;Infection;Inflammatory;Inflammatory Response;Innate Immune Response;Learning;Link;Lipopolysaccharides;Mammals;Membrane;Microbial Biofilms;Modeling;Modification;Molecular;Outcome;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Peptide Hydrolases;Periodicity;Periodontal Pocket;Periodontitis;Physiology;Play;Population;Porphyromonas gingivalis;Post-Translational Protein Processing;Production;Property;Regulation;Role;Series;Signal Pathway;Signal Transduction;Stimulus;Stress;Structure;System;Systemic disease;TLR4 gene;Therapeutic;Tissues;Tooth Loss;Tooth structure;United States;Variant;Virulence;Virulence Factors;Virulent;alveolar bone;antagonist;cytokine;economic impact;experimental study;extracellular;gingipain;macromolecule;mutant;neutrophil;new therapeutic target;novel;pathogen;pathogenic bacteria;phosphoric diester hydrolase;receptor;response;socioeconomics

public_health_relevance:
PROJECT NARRATIVEPeriodontitis afflicts ~ 50% of the adult population in the United States with substantial socio-economic impacts. Porphyromonas gingivalis has been strongly implicated in periodontitis. Theproposed studies will decipher the regulatory role of a novel signaling pathway that controls cellwall components virulence and fundamental aspects of P. gingivalis physiology andpathogenesis.


application_id: 10848778
project_number: 3P40OD019794-10S1
project_title: Ambystoma Genetic Stock Center - Revision to Include Curation and Informatics Component
administering_ic: OD
award_notice_date: 2024-05-03
opportunity_number: RFA-OD-23-001
application_type: 3
activity_code: P40
ic: OD
serial_number: 019794
suffix: S1
program_official: CONTRERAS, MIGUEL A
project_start_date: 2015-03-01
project_end_date: 2025-02-28
study_section: Special Emphasis Panel[ZRG1 BTC-J (55)]
contact_pi_person_id: 7876973
contact_pi: VOSS, STEPHEN RANDAL
other_pis: Not Applicable
congressional_district: 06
department: SOCIAL SCIENCES
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
The Ambystoma Genetic Stock Center (AGSC) at the University of Kentucky (UK) is the only federally fundedresource center that distributes laboratory axolotls (Ambystoma mexicanum) a salamander that provides livingmaterials in support of biomedical research nationally and internationally. Most notably axolotls are uniqueamong vertebrates in being able to regenerate numerous tissues and body parts. These include the spinalcord limbs jaw retina brain heart and tail all of which can be regenerated at any point during embryoniclarval and adult life. Also axolotls are used by researchers that work in additional areas includingneurobiology ecotoxicology development physiology cell biology genetics genomics and evolution. This isan exciting time for the axolotl community as its incredibly large genome (32 Gb) was recently sequenced andassembled. New and assessable resources are allowing cutting edge technologies like gene-editing and singlecell RNA sequencing to be performed for the first time approaches that are rapidly accelerating discoveriesusing axolotl models. Since 2020 31 different axolotl-associated projects have been awarded by NIH withsupport coming from multiple institutes (NICHD NHLBI NIDDK NIGMS NINDS OD NEI and NCI). NIHsupport is catalyzing advances in biomedical research through its support of the axolotl and the AGSCincreasing the likelihood that investigators will use axolotl models in the future.During the current funding period the AGSC is maintaining and generating high quality axolotl stocks that areneeded by a growing number of NIH-funded investigators. Husbandry and management practices have beenmodified to increase availability of post-embryonic stocks. Also new transgenic and knock-out stocks havebeen imported into the AGSC and cryopreservation methods are under development to preserve and moreefficiently manage stocks. The proposed Curation and Informatics Component in this revision application willincrease data management efficiencies. Specifically multiple types of data including animal andenvironmental data will be managed within a software package that enables mobile data entry and retrieval. Asecond objective of the Curation and Informatics Component is to better serve and interface with AGSCstakeholders. A research software designer will be recruited to manage the AGSC website and overall datamanagement plan and a curator / outreach coordinator will be recruited to develop new website content and tointerface with axolotl stakeholders. Overall the project will increase the AGSCs impact in biomedical researchand education ensuring the distribution and long-term sustainability of axolotl resources to NIH-fundedinvestigators.

project_terms:
Acceleration;Address;Adolescent;Adopted;Adult;Ambystoma;Ambystoma mexicanum;Animals;Area;Award;Biological;Biomedical Research;Body part;Brain;Breeding;Cellular biology;Collaborations;Collection;Communities;Complement;Computer software;Cryopreservation;Custom;Data;Data Reporting;Databases;Development;Disease;Education;Embryo;Embryonic Development;Ensure;Equipment and supply inventories;Evolution;Funding;Future;Genes;Genetic;Genome;Genomics;Germ;Health;Heart;Human;Informatics;Infrastructure;International;Jaw;Kentucky;Knock-out;Laboratories;Life;Limb structure;Louisiana;Metadata;Methods;Modeling;National Heart Lung and Blood Institute;National Institute of Child Health and Human Development;National Institute of Diabetes and Digestive and Kidney Diseases;National Institute of General Medical Sciences;National Institute of Neurological Disorders and Stroke;Natural regeneration;Neurobiology;Organ Model;Physiology;Population;Positioning Attribute;Postembryonic;Practice Management;Process;Protocols documentation;Reproducibility;Research;Research Personnel;Research Support;Resources;Retina;Retrieval;Salamander;Shipping;Spinal Cord;System;Tail;Technology;Time;Tissues;Transgenic Organisms;Translating;United States National Institutes of Health;Universities;Vertebrates;Work;Writing;cost;data management;design;electronic data;genetic resource;handheld equipment;health record;improved;multiple data types;operation;organ regeneration;outreach;preservation;recruit;single-cell RNA sequencing;sperm cell;sperm cryopreservation;timeline;tissue repair;user friendly software;water quality;web site;wireless

public_health_relevance:
Living stock resources are needed for the Mexican axolotl so that investigators can developresearch models and translate biological information that is relevant to human health anddisease. The Mexican axolotl is a primary vertebrate model for organ regeneration tissuerepair and post-embryonic development.


application_id: 10848459
project_number: 5R01NS079507-10
administering_ic: NINDS
award_notice_date: 2024-03-27
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: NS
serial_number: 079507
program_official: LEENDERS, MIRIAM
project_start_date: 2012-09-30
project_end_date: 2026-03-31
study_section: Special Emphasis Panel[ZRG1-MDCN-M(91)S]
contact_pi_person_id: 9358186
contact_pi: BAUER, BJOERN
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-04-01
project_title:
Novel Therapeutic Strategies to Resolve Neurovascular Inflammation and Repair Blood-Brain Barrier Dysfunction in Epilepsy

project_abstract:
Blood-brain barrier dysfunction is recognized as both a cause and consequence of seizures in epilepsy. Two keycharacteristics of barrier dysfunction in epilepsy include 1) neurovascular inflammation and 2) barrier leakageboth of which have been linked to seizures. In spite of increasing evidence supporting that glutamate causesblood-brain barrier dysfunction knowledge of the associated underlying mechanisms remain to be fully defined.Moreover therapeutic options for restoring barrier function are currently not available. Thus there is an unmetcritical need to determine how glutamate promotes blood-brain barrier inflammation and leakage and to developtargeted strategies to restore barrier function. The consequence of this unmet need is that development of noveltreatments to improve seizure control in epilepsy will likely remain a clinical challenge. The long-term goal of theinvestigator is to contribute toward the development of mechanism-based strategies to repair blood-brain barrierdysfunction in brain diseases. The overall objective in this application is to establish the efficacy of a mechanism-based intervention to treat blood-brain barrier dysfunction in epilepsy thereby vertically extending what has beenlearned under current funding. Based on preliminary data the central hypothesis of this project is that glutamatesignaling mediates blood-brain barrier dysfunction and that therapeutic intervention targeting this mechanismwill resolve seizure-induced neurovascular inflammation repair barrier leakage and reduce seizure burden. Therationale for the proposed research is that its successful completion will provide a robust framework for thecontinued development and clinical translation of a novel evidence-based therapeutic intervention to help treatseizures in patients with epilepsy. The hypothesis will be tested by pursuing three specific aims: 1) Identifysignaling steps responsible for seizure-induced inflammation of the blood-brain barrier. 2) Determine themechanism responsible for capillary leakage at the human blood-brain barrier and 3) Develop a therapeuticintervention to reduce seizure burden in a chronic epilepsy model. Under Aim 1 signaling steps that lead toseizure-mediated neuroinflammation will be determined in capillaries isolated from knockout mouse models andverified in vivo. Under Aim 2 key signaling steps that trigger barrier leakage will be determined in human braincapillaries from seizure-free control individuals and from patients with epilepsy. Under Aim 3 an interventiontherapy designed to repair barrier dysfunction will be developed and the therapeutic benefit of this strategy onreducing seizure burden will be evaluated in a rat chronic epilepsy model. The proposed research is innovativebecause it represents a substantive departure from the status quo by shifting the focus to molecular targets atthe blood-brain barrier to resolve neurovascular inflammation restore barrier function and improve epilepsysymptoms. The proposed research is significant because it holds the promise of a novel therapeutic approachto repair barrier dysfunction that has translational potential for clinical use to advance treatment of patients withepilepsy and other seizure disorders with underlying barrier dysfunction.

project_terms:
Agonist;Arachidonate 5-Lipoxygenase;Attenuated;Automobile Driving;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood capillaries;Brain Diseases;Cell Adhesion Molecules;Characteristics;Chronic;Clinical;Combined Modality Therapy;Data;Data Reporting;Development;Disease;Endothelium;Epilepsy;Extracellular Matrix Proteins;Extravasation;FPR2 gene;Feedback;Functional disorder;Funding;Glutamates;Goals;Human;Individual;Inflammation;Intervention;Knockout Mice;Knowledge;LOX gene;Lead;Learning;Leukocytes;Leukotrienes;Link;Lipoxygenase;Matrix Metalloproteinases;Mediating;Mission;Modeling;Molecular Target;Mus;National Institute of Neurological Disorders and Stroke;Nervous System Disorder;Neurons;PTGS2 gene;Pathway interactions;Patients;Prostaglandins;Proteins;Public Health;Publishing;Rattus;Research;Research Personnel;Seizures;Signal Transduction;Symptoms;Testing;Therapeutic;Therapeutic Intervention;Tight Junctions;United States National Institutes of Health;cerebral capillary;clinical translation;cyclooxygenase 2;evidence base;expectation;glutamatergic signaling;improved;in vivo;innovation;mouse model;neuroinflammation;neurotransmitter release;neurovascular;new therapeutic target;novel;novel therapeutic intervention;repaired;therapy design;translational potential;vascular inflammation

public_health_relevance:
The proposed research is relevant to public health because it is expected to identify molecular targets that can be exploited to repair the blood-brain barrier after seizure-induced neuroinflammation and dysfunction. Thistherapeutic strategy is expected to improve seizure control in patients with epilepsy. Thus the proposed research is relevant to the part of the NIH/NINDS mission that pertains to developing fundamental knowledge that will help reduce the burden of neurological disease.


application_id: 10846793
project_number: 5R01DC019054-05
project_title: GIPC3 multifunctional myosin adaptor in mammalian auditory hair cells
administering_ic: NIDCD
award_notice_date: 2024-05-08
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: DC
serial_number: 019054
program_official: FREEMAN, NANCY
project_start_date: 2020-06-10
project_end_date: 2026-05-31
study_section: Special Emphasis Panel[ZRG1-IFCN-E(02)M]
contact_pi_person_id: 8360158
contact_pi: FROLENKOV, GREGORY I
other_pis: VANDER KOOI, CRAIG
congressional_district: 06
department: PHYSIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
GIPC3 a member of G-Interacting Protein C-terminus (GIPC) family is known to be essential forhearing. Eleven mutations in GIPC3 spread throughout its three structural domains cause inheritedautosomal recessive hearing loss. However the molecular basis for GIPC3 function in the auditorysystem and the mechanisms by which these human mutations result in hearing loss are unknown. Wehave recently determined the structure of GIPC3 bound to a prototypical receptor and determined themolecular mechanism of GIPC3 activation and its subsequent binding to MYO6 the unconventionalmyosin that is expressed in the auditory hair cells and is essential for hearing. These biochemical andstructural studies allowed us to predict the effects of known deafness-related mutations in GIPC3 on itsactivation and MYO6 binding. We have generated two new mouse models one that is lacking functionalGIPC3 and another one with a W301X point mutation in Gipc3 that corresponds to a mutation with themost severe auditory phenotype in humans. This study will explore the central hypothesis that GIPC3 hasa dual role in the auditory hair cells. We hypothesize that in stereocilia GIPC3 is involved in shapingmechanotransduction and hair bundle structure through its interactions with CDH23/myosin-VIIa andmyosin-XVa respectively. In the cell body GIPC3 is essential for apical endocytosis at the pericuticularneckless region due to its interaction with myosin-VI. All these functions are crucial for normal hearing.However the exact molecular mechanisms that determine the resting tension in the mechanotransduc-tion machinery as well as gradation of stereocilia heights and diameters in the auditory hair cell bundlesare still enigmatic. Likewise very little is known about molecular mechanisms and even the role ofpericuticular neckless endocytosis in the hair cell function. The expected outcomes of this study are touncover (a) the precise mechanism of deafness associated with GIPC3 deficiency and (b) thephysiological role of GIPC3 in hair cell functions especially in mechanotransduction formation of the hairbundle architecture and endocytosis at the pericuticular neckless. Deciphering the function of GIPC3protein and its known mutations is a critical step towards the development of therapies for the treatmentand/or prevention of GIPC3-dependent deafness and hearing loss.

project_terms:
Actins;Adopted;Affect;Age;Age Months;Ankle;Apical;Architecture;Auditory;Auditory system;Belief;Binding;Biochemical;Biochemistry;C-terminal;CDH23 gene;Cadherin Domain;Cell Physiology;Cells;Cellular Structures;Complex;Consensus;Coupling;Custom;DLG4 gene;Data;Development;Diameter;Dimerization;Endocytosis;Epidermal Growth Factor Receptor Pathway Substrate 8;Family;Family member;Hair;Hair Cells;Hearing;Height;Human;Inherited;Inner Hair Cells;Knowledge;Label;Labyrinth;Link;MYO7A gene;Mechanics;Mediating;Molecular;Motor;Mouse Strains;Mus;Mutation;Myosin ATPase;N-terminal;Outcome Study;Patients;Phenotype;Physiological;Point Mutation;Positioning Attribute;Prevention;Protein Family;Proteins;Receptor Activation;Reporting;Rest;Role;Shapes;Site;Structure;Surface;Synaptic Transmission;Therapeutic;Time;Ubiquitin;Vesicle;WHRN gene;autosome;cell type;deaf;deafness;dimer;hearing impairment;in vivo;insight;live cell imaging;mechanotransduction;member;mouse model;mutant;myosin VI;myosin XVA;nanobodies;normal hearing;novel;prevent;receptor;receptor binding;response;structural biology;therapy development;trafficking;two-photon;uptake

public_health_relevance:
Advancement in our understanding of molecular mechanisms of key molecules in the inner ear isa prerequisite to developing therapeutic strategies for hearing loss. The studies outlined in thisproposal explore structural and functional effects of all eleven reported patient mutations in GIPC3protein that have been identified to date as a cause of non-syndromic autosomal recessive deafnessDFNB72. In addition since GIPC3 is a previously unexplored molecular partner of other deafnessproteins our study will provide fundamental knowledge into the pathophysiological mechanisms of otherforms of deafness that will help to reduce the burden of human hearing loss.


application_id: 10846726
project_number: 5R21ES035320-02
project_title: Impact of Landfill Mitigation Efforts to Reduce Air Toxics in Bristol Tennessee and Virginia
administering_ic: NIEHS
award_notice_date: 2024-04-02
opportunity_number: RFA-ES-19-011
application_type: 5
activity_code: R21
ic: ES
serial_number: 035320
program_official: O'FALLON, LIAM
project_start_date: 2023-05-23
project_end_date: 2025-08-31
study_section: ZES1-LWJ-W(R2)1
contact_pi_person_id: 7102409
contact_pi: HAYNES, ERIN N
other_pis: Not Applicable
congressional_district: 06
department: PUBLIC HEALTH & PREV MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PUBLIC HEALTH
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
AbstractFor over a year residents of Bristol Tennessee (TN) and Virginia (VA) have experienced significant exposureto landfill emissions including volatile organic compounds (VOCs) such as benzene toluene and hydrogensulfide. Ambient levels of these air toxics have been measured by the EPA and the Virginia Department ofEnvironmental Quality. Based on the concentrations found during these sampling events a Plan of Action wasreleased on July 6 2022 to begin incremental steps towards mitigating the air toxics emanating from thelandfill. This Plan of Action presents a critical opportunity to measure the impact of this environmental policy toimprove air quality and reduce odors. Since October 2021 Haynes (PI) has been developing a community-academic research partnership with Bristol residents to identify research strategies to identify their indoor andoutdoor exposures and potential health impacts. The residents have reported their experiences as an endlessnightmare with non-stop odor that stays in the house and its hard to breathe. Given our partnership withthe City Manager and community residents we are poised to evaluate the impacts of an environmentalpolicy to reduce air toxics and odors and evaluate the potential long-term health consequences related to theseexposures. We propose these highly time-sensitive specific aims: Aim 1: Characterize indoor and outdoorconcentrations of VOCs including benzene and hydrogen sulfide in and around homes of Bristol VA/TNresidents prior to the implementation of the mitigation action plan. Aim 2: Characterize indoor and outdoorconcentrations of VOCs and hydrogen sulfide in and around homes of Bristol VA/TN residents after eachstage of the mitigation action plan in order to determine the impact of the various strategies to mitigateexposures. Aim 3: Evaluate the impact of the landfill and the mitigation plan on odor detection quality of lifeand stress of residents. This time-sensitive research is critical to inform future landfill mitigation efforts asnumerous communities across the country face challenges associated with municipal solid waste facilities.

project_terms:
Acrolein;Affect;Air;Air Pollutants;Benzene;Breathing;Censuses;Chemicals;Cities;Collaborations;Collection;Communities;Country;Detection;Development;Ecological momentary assessment;Effectiveness;Engineering;Ensure;Environmental Health;Environmental Impact;Environmental Policy;Event;Exposure to;Face;Faculty;Future;Health;Health Hazards;High temperature of physical object;Home;Hour;Household;Hydrogen Sulfide;Industry;Investigation;Liquid substance;Location;Low Income Population;Measurement;Measures;Municipalities;Neighborhoods;Nightmare;Odors;Personal Communication;Pharyngeal structure;Poverty;Quality of life;Recommendation;Reporting;Research;Sampling;Solid;Stress;Symptoms;Tennessee;Time;Toluene;Toxicology;United States;Universities;Virginia;air monitoring;air sampling;community academic partnership;community partners;experience;falls;follow-up;improved;landfill;meetings;operation;pollutant;recruit;response;sample collection;sensor;student training;toxicant;volatile organic compound;wasting

public_health_relevance:
Project NarrativeA community-academic team will quantify the impact of a mitigation action plan to reduce air toxics and odorsat a landfill in Bristol Virginia.


application_id: 10846684
project_number: 5K01ES033289-03
project_title: Evaluating mechanisms of sex differences in environmentally-induced metabolic diseases
administering_ic: NIEHS
award_notice_date: 2024-06-04
opportunity_number: PAR-21-172
application_type: 5
activity_code: K01
ic: ES
serial_number: 033289
program_official: SCHUG, THADDEUS
project_start_date: 2022-06-03
project_end_date: 2025-05-31
study_section: ZES1-LWJ-S(K1)
contact_pi_person_id: 14294360
contact_pi: WAHLANG, BANRIDA
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Mechanistic studies pertaining to sex-based differences in metabolic syndrome (MetS) are currently insufficientto explain and prevent the higher prevalence of certain MetS symptoms in women versus men andhigher prevalence of other symptoms such as hyperlipidemia in men versus women. MetS describes aconstellation of risk factors such as abdominal adiposity hypertension glucose intolerance/hyperglycemiaand dyslipidemia leading to diabetes and cardiovascular morbidity. High-caloric intake and sedentary lifestylehabits are among key players shown to induce symptoms of MetS. However exposures to environmentalchemicals such as persistent organic pollutants (POPs) often dictated by socio-economic status andeducation levels have been increasingly identified as additional key players leading to MetS consequences.Previous studies showed that exposures to POPs such as organochlorine pesticides (OCPs) andpolychlorinated biphenyls (PCBs) in in-vivo models and human studies were associated with diabetes obesityand non-alcoholic fatty liver disease which are hallmarks for MetS development. Furthermore using in-vitro models and diet-induced obesity mouse models we had previously demonstrated that the liver wasthe predominant target organ of toxicity to POPs including PCBs and mechanism(s) of toxicity wereprimarily through activation of hepatic receptors leading to metabolic disruption. The liver has long beenestablished as a sexually dimorphic organ and it is therefore important to address POPs toxicity in term ofbiological differences or sex. Additionally POPs such as OCPs are endocrine disrupting chemicals having theability to interact with androgen or estrogen receptors and potentially promoting variable effects in men andwomen. However most epidemiologic studies demonstrating associations between POPs exposure with livertoxicity/metabolic diseases including diabetes either focused on agricultural workers who were mostly men oradjusted for sex; but POPs exposures occur in both men and women and thus their health risks may vary.POPs exposures today is primarily through ingestion of contaminated food and water and serum levels canvary depending on sex and gender. Hence it is relevant to examine exposures to POPs such as OCPs basedon environment-sex-gene interactions to better address such discrepancies.

project_terms:
Address;Affect;Agricultural Workers;Androgen Receptor;Automobile Driving;Award;Binding;Biological;Biological Markers;Body Composition;Cardiovascular system;Chemicals;Chlordan;Development;Diabetes Mellitus;Disease;Dose;Dyslipidemias;Educational Status;Endocrine;Endocrine Disruptors;Endocrine disruption;Energy Intake;Environment;Environmental Epidemiology;Environmental Exposure;Environmental Health;Estrogen Receptors;Ethnic Origin;Exhibits;Exposure to;Female;Food Contamination;Future;Gender;Glucose Intolerance;Goals;Gonadal Steroid Hormones;Grant;Habits;Health;Health Care Costs;Hepatic;Hepatotoxicity;High Fat Diet;High Prevalence;Home;Human;Hyperglycemia;Hyperlipidemia;Hypertension;Incidence;Ingestion;Injury;Investigation;Isoptera;Knowledge;Lipids;Liver;Measures;Metabolic;Metabolic Diseases;Metabolic syndrome;Metabolism;Molecular;Morbidity - disease rate;Mus;Obesity;Organ;Outcome;Pathology;Policy Maker;Polychlorinated Biphenyls;Population;Postmenopause;Predisposition;Prevalence;Process;Proteome;Proteomics;Public Health;Race;Receptor Activation;Receptor Signaling;Reporting;Research;Resistance;Risk;Risk Factors;Serum;Sex Differences;Signal Pathway;Socioeconomic Status;Symptoms;Techniques;Testing;Therapeutic;Toxic effect;Training;Vulnerable Populations;Water;Woman;Work;Xenobiotics;abdominal fat;arm;authority;bioaccumulation;design;diet-induced obesity;effective intervention;environmental chemical;epidemiology study;gene interaction;glucose tolerance;in vitro Model;in vivo Model;male;men;mouse model;non-alcoholic fatty liver disease;nutrition;organochlorine pesticide;organochlorine pesticide exposure;persistent organic pollutants;prevent;receptor;sedentary lifestyle;sex;sex disparity;sexual dimorphism;toxicant;women versus men

public_health_relevance:
Project NarrativeMechanistic studies pertaining to sex-based differences in the metabolic syndrome are currently insufficient toexplain and prevent the higher prevalence of certain metabolic conditions in women versus men and higherprevalence of other symptoms such as hyperlipidemia in men versus women. In addition epidemiologic studieshave reported that exposure to environmental chemicals such as persistent organic pollutants includingorganochlorine pesticides yield different health outcomes in men and women and therefore the current projectaims to evaluate the underlying cellular mechanisms impacted by sexual dimorphism that potentially drive suchdifferences. The concepts and information that will be gained from this grant will better address sex disparitiesin environmental health as well as provide health authorities with further knowledge to identify metabolicsyndrome-related factors in susceptible populations and design sex-specific therapeutic strategies to bettercontrol future health care costs.


application_id: 10846676
project_number: 5R01CA243529-05
administering_ic: NCI
award_notice_date: 2024-05-01
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: CA
serial_number: 243529
program_official: CHEN, WEIWEI
project_start_date: 2020-06-01
project_end_date: 2026-05-31
study_section: Drug Discovery and Molecular Pharmacology Study Section[DMP]
contact_pi_person_id: 9351620
contact_pi: TSODIKOV, OLEG V
other_pis: LEGGAS, MARKOS ;ROHR, JURGEN T
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-06-01
project_title:
Mechanistic and pharmacologic studies of selective mithramycin analogues targeting EWS-FLI1 in Ewing sarcoma

project_abstract:
Ewing sarcoma family of tumors (ESFT) is a family of resilient devastating cancers of bone and soft tissueaffecting primarily children and young adults. Current highly cytotoxic combination therapy of five drugs providesonly 30% overall survival. The aberrant transcription factor EWS-FLI1 present only in tumor cells is the oncogenicdriver of EWS. However transcription factors were believed to be undruggable until a recent NCI screeningfound mithramycin (MTM) to act as a potent EWS-FLI1 antagonist. MTM has proven to be too toxic with a narrowtherapeutic window and poor pharmacokinetic (PK) properties. Here we propose mechanistic and pharmacologystudies of novel MTM analogues (MTM-SA) with significantly reduced toxicity increased target specificity andgreatly improved PK properties. In contrast to other analogues reported elsewhere which still suffer from poorPK properties the MTM-SA analogs display superior kinetics and reduced toxicity. The goal of this project is togain molecular insights into the mode of action of MTM via structural biochemical and pharmacological studiesto generate a highly efficacious and selective anti-ESFT treatment. To aid synthetic efforts in Aim1 and identifyanalogues with clinical potential we will perform molecular structure-function level studies in Aim 2 to determinehow transcription factor EWS-FLI1 interacts with DNA microsatellite repeats and transcription factor Runx2 (eacha necessary interaction for oncogenesis) and how these oncogenic functions are disrupted by MTM-SA. In Aim3 will assess the in vitro cytotoxicity and target selectivity to identify analogues that will be evaluated inpharmacologic studies that will assess toxicity in humanized liver mice PK and metabolism as well as efficacyin xenograft and PDx models of Ewing Sarcoma. The project will be carried out by a team with an establishedcollaboration who have extensive experience in fragment-based drug design and semi-synthetic routes of naturalproducts X-ray crystallographic biophysical and molecular biology studies and pharmacological evaluations.We expect that these structure-function studies will identify a lead-candidate that could enter a clinical trial forthe treatment of ESFT.

project_terms:
Affect;Animal Model;Anti-tumor Natural Products;Antineoplastic Agents;Binding;Biochemical;Biological;Biological Assay;Biophysics;Bone Tissue;Cell model;Cells;Child;Childhood;Clinical;Clinical Treatment;Clinical Trials;Collaborations;Combined Modality Therapy;Complex;Crystallography;DNA;DNA Binding;DNA Binding Domain;DNA Sequence;Data;Derivation procedure;Development;Drug Design;Drug Kinetics;EWS-FLI1 fusion protein;Elements;Enhancers;Evaluation;Ewings sarcoma;FLI1 gene;Family;Foundations;Genetic Transcription;Goals;Higher Order Chromatin Structure;Human;In Vitro;Investigational Therapies;Kinetics;Liver;Malignant Bone Neoplasm;Metabolism;Microsatellite Repeats;Modeling;Molecular;Molecular Biology;Molecular Structure;Mus;Natural Products;Oncogenic;Patients;Pharmaceutical Preparations;Pharmacology;Pharmacology Study;Phase I/II Clinical Trial;Plasma;Plicamycin;Preclinical Testing;Property;Proteins;Public Health;Reporter;Reporting;Route;Satellite DNA;Shunt Device;Side;Site;Specificity;Structure;Testing;Therapeutic;Toxic effect;Translating;Tube;X-Ray Crystallography;Xenograft Model;analog;antagonist;cancer cell;cancer diagnosis;cytotoxic;cytotoxicity;design;drug candidate;drug clearance;effective therapy;experience;improved;inhibitor;insight;lead candidate;mouse model;neoplastic cell;novel;patient derived xenograft model;pharmacologic;programs;resilience;screening;soft tissue;transcription factor;transcriptional reprogramming;tumor;tumorigenesis;young adult

public_health_relevance:
Ewing sarcoma and other Ewing family tumors are poorly treatable bone and soft tissue cancers diagnosedpredominantly in children and young adults. This project is relevant to public health because it aims to developselective chemotherapeutics to treat Ewing sarcoma through investigating oncogenic mechanisms of thecausative agent of Ewing sarcoma transcription factor EWS-FLI1. This mechanistic inquiry will becomplemented by pharmacological studies and aid the development of selective anti-Ewing sarcomatherapeutics.


application_id: 10845083
project_number: 3P01AG078116-02S1
project_title: Strategies for targeting astrocyte reactivity in Alzheimer's disease and related dementias.
administering_ic: NIA
award_notice_date: 2023-08-16
opportunity_number: PA-20-272
application_type: 3
activity_code: P01
ic: AG
serial_number: 078116
suffix: S1
program_official: OPANASHUK, LISA A
project_start_date: 2022-09-01
project_end_date: 2027-06-30
study_section: ZAG1(M4)
contact_pi_person_id: 1880587
contact_pi: NORRIS, CHRISTOPHER MARK
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
CORE A Supplement: Abstract-SummaryThis supplement will operate under the umbrella of Core A of the parent P01 to support the generation of newtransgenic mouse lines in which genes-of-interest can either be expressed or knocked down (using doxycyclineinducible system) selectively in brain astrocytes. Two lines will be created for each research project (an Astro-on and an Astro-off line) to target signaling constituents relevant to the reactive astrocyte phenotype and linkedto Alzheimers disease (AD) or AD-related dementias (ADRDs): MMP9 (Project 1) IR (Project 2) SLC1A2(Project 3) and SUR2B (Project 4). New mouse models will significantly provide greater consistency interms of (1) the uniformity of astrocytes targeted and (2) the extent of overexpression/knock-down. This advanceis expected to reduce mouse-to-mouse variability and increase statistical power. New transgenic models willalso streamline study design by eliminating the need for injecting multiple AAV reagents (e.g. one AAV forastrocyte targeting another AAV for measuring Ca2+) in a single mouse at different time points. This advancewill greatly simplify data interpretation while simultaneously reducing the number of invasive procedures permouse. Finally new transgenic models will be readily available to the scientific community to verify ourfindings or generate new avenues of research which will promote experimental rigor and further delineate therole of reactive astrocytes in ADRDs.

project_terms:
Aging;Agreement;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid;Animals;Area;Astrocytes;Behavioral;Brain;Cells;Cerebrovascular Disorders;Communities;Critiques;Data Analyses;Dementia;Dependovirus;Disease model;Doxycycline;Electrophysiology (science);Experimental Designs;Functional disorder;Funding;Gel;Generations;Genes;Glutamates;Goals;Human Resources;Impairment;Individual;Insulin Receptor;Label;Letters;Link;MMP9 gene;Maintenance;Measures;Medicine;Microelectrodes;Modeling;Molecular;Mus;Neurons;Operative Surgical Procedures;Parents;Pathology;Phenotype;Phosphorylation;Pilot Projects;Positioning Attribute;Postdoctoral Fellow;Procedures;Proto-Oncogene Proteins c-akt;Published Comment;Quality Control;Reagent;Receptor Signaling;Research;Research Design;Research Project Grants;Role;Signal Pathway;Signal Transduction;Specificity;System;Techniques;Testing;Tetracyclines;Time;Training;Transgenic Mice;Transgenic Model;United States National Institutes of Health;Validation;Western Blotting;biomarker validation;brain tissue;catalyst;college;design;experimental study;human subject;in vivo;interest;knock-down;mouse model;overexpression;pre-clinical;programs;promoter;skills;uptake;voltage clamp


application_id: 10844668
project_number: 4R33DC019602-03
project_title: Hearing Healthcare Assessment in Rural Communities (HHARC)
administering_ic: NIDCD
award_notice_date: 2023-08-10
opportunity_number: RFA-DC-19-001
application_type: 4
activity_code: R33
ic: DC
serial_number: 019602
program_official: KING, KELLY ANNE
project_start_date: 2021-08-04
project_end_date: 2026-07-31
study_section: ZDC1-SRB-R(39)
contact_pi_person_id: 11512687
contact_pi: BUSH, MATTHEW LEE
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARYHearing loss in adults is the third most common chronic health condition in the United States with a prevalenceof over 20% in younger adults and over 40% in older adults. Untreated hearing loss causes a measurable impacton health and social occupational and emotional well-being of adults. Only 26% of adults have had a diagnostichearing test within the past 5 years and delayed hearing loss diagnosis and treatment may lead to communicationimpairment with profound effects on education employment and overall health. The prevalence of hearing lossis higher among adults living in rural communities compared with those in urban settings; furthermore ruraladults with hearing loss may never receive treatment or may be delayed in diagnosis and/or treatment comparedwith urban adults. Rural health clinics (RHCs) represent a federally designated health system care that providesprimary care within rural underserved communities; however hearing healthcare services have not been asignificant component of RHC care delivery. RHCs are ideally positioned to partner with rural communities todevelop an intervention that can help rural adults navigate different aspects of hearing healthcare such aseducation prevention screening diagnosis and treatment. The goal of this study is to assess the utilization ofhearing healthcare among rural adults through RHCs with the R21 phase of the program and then develop aculturally responsive RHC patient navigation program (PNP) to promote utilization of hearing healthcare. Toconduct this study we will partner with 10 high-need under-resourced RHCs within rural Appalachian countiesin Kentucky and utilize the PRECEDE-PROCEED model (PPM) to systematically assess the rural adult hearinghealth and healthcare priorities needs and resources to inform intervention development. During the R21 phasewe will 1) conduct a social and epidemiological assessment of rural adult hearing healthcare and 2) assess theorganizational and environmental factors influencing hearing healthcare utilization in RHCs. The milestones ofthe R21 include the determination of the prevalence of hearing loss and hearing healthcare utilization in ruraladults establishment of rural adult hearing healthcare priorities and development of a community advisory boardand a rural provider taskforce. During the R33 phase we will 1) develop of a community-based hearing healthcarepatient navigation program for RHCs and 2) pilot test the rural hearing healthcare navigation program. Themilestones of the R33 phase include the development of a PNP protocol assessment of the impact of thenavigator on rural adults obtaining diagnostic audiogram and evaluation of the PNP feasibility acceptability andappropriateness. This study is significant because it aims to reduce access to care barriers to timely diagnostichearing testing for rural adults to prevent negative consequences. This research is innovative in developmentand pilot testing of a novel intervention not previously assessed in adult hearing healthcare within an RHC setting.Our results will impact the field by partnering with communities to inform the development and delivery ofinnovative patient supportive interventions to improve rural hearing healthcare access.

project_terms:
Address;Administrator;Adult;Advisory Committees;Affect;Appalachian Region;Area;Certification;Chronic;Communication impairment;Communities;Country;County;Depressed mood;Development;Diagnosis;Diagnostic;Disease;Education;Elderly;Employment;Enabling Factors;Enrollment;Environmental Risk Factor;Epidemiology;Evaluation;Face;Geographic state;Goals;Health;Health Personnel;Health Services Accessibility;Healthcare;Healthcare Systems;Hearing;Hearing Tests;Intervention;Kentucky;Life;Measurable;Medical;Medical Economics;Methods;Morbidity - disease rate;Occupational;Outcome;Patients;Phase;Population;Positioning Attribute;Precede-Proceed Model;Predisposing Factor;Prevalence;Prevention;Primary Care;Protocols documentation;Provider;Public Health;Reinforcing Factor;Research;Resources;Rural;Rural Appalachia;Rural Community;United States;Vulnerable Populations;Well in self;barrier to care;care delivery;experience;health care availability;health care delivery;health care service;health care service utilization;hearing impairment;hearing loss treatment;improved;innovation;medical specialties;medically underserved;mortality;novel;patient navigation;pilot test;practice-based research network;preference;prevent;primary care practice;primary care services;programs;rural area;rural health clinic;rural patients;rural underserved;screening;social;therapy development;treatment comparison;underserved community;urban setting;virtual;young adult

public_health_relevance:
PROJECT NARRATIVEHearing loss affects over 40 million adults in the United States and can negatively impact many areas of life foradults. The lack of access to diagnostic hearing tests prevents timely diagnosis and treatment of hearing lossespecially among adults who live in rural areas. This study will (1) evaluate the experiences and challenges inobtaining hearing tests among adults who live in rural areas and are patients at rural health clinics and (2)develop a program in partnership with rural patients and medical providers which can help rural adults geteasier access to hearing tests.


application_id: 10844647
project_number: 5R01DK133184-03
project_title: The Role of DENND5B in Dietary Lipid Absorption
administering_ic: NIDDK
award_notice_date: 2024-05-20
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: DK
serial_number: 133184
program_official: SENGER, STEFANIA
project_start_date: 2022-07-15
project_end_date: 2027-05-31
study_section: Nutrition and Metabolism in Health and Disease Study Section[NMHD]
contact_pi_person_id: 14386534
contact_pi: GORDON, SCOTT M
other_pis: Not Applicable
congressional_district: 06
department: PHYSIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project SummaryPostprandial plasma triacylglyceride levels are independently associated with risk of cardiovasculardisease. The intestine plays a key role in the regulation of dietary triacylglyceride absorption bypackaging and secreting lipids in chylomicron particles. The intracellular steps of chylomicronbiogenesis and transport have been fairly well described however there is a significant gap in ourunderstanding of the mechanism for the final steps of chylomicron secretion by enterocytes specificallypost-Golgi transport and secretion. We recently identified a protein that plays a critical role in thispathway DENND5B. Our newly generated Dennd5b-/- mouse demonstrates an essential role for thisgene in Golgi to plasma membrane transport of chylomicron secretory vesicles. Dennd5b-deficient miceare resistant to diet-induced: obesity changes in plasma lipids and atherosclerosis. In humans exomesequencing studies reveal that a common DENND5B variant is correlated with body mass index. Thesestudies establish an important role for DENND5B in post-Golgi chylomicron secretion and a subsequentinfluence on body composition and peripheral lipoprotein metabolism. The overall objective of thisproposal is to gain fundamental knowledge about the process of dietary lipid absorption by the intestineand to examine the impact of this process on systemic metabolic health. This objective aligns well withthe NIH mission to seek fundamental knowledge about living systems and to apply this knowledge toenhance health. The Specific Aims of this proposal use our novel mouse model and in vitroexperiments to examine the mechanistic role of DENND5B in the intestine and its systemic metaboliceffects. Aim 1 will quantify the impact of Dennd5b on dietary lipid absorption and generate acomprehensive spatial single-cell RNAsequencing data set for examination of gene networks thatparticipate in regulation of dietary lipid absorption. Aim 2 will examine the mechanism underlyingDennd5b action in CM transport. Furthermore this aim will use mass spectrometry and interactomicsanalysis to expand our understanding of this process by identifying other interacting proteins which mayform a complex to facilitate chylomicron secretion by the intestine. Aim 3 will determine the impact ofDennd5b on enterocyte metabolic function and peripheral lipid metabolism. Successful completion ofthis proposal will fill a significant knowledge gap in the process of dietary lipid absorption. This work willadvance the field by providing mechanistic details for a key step in chylomicron secretion that can affectsystemic lipid homeostasis and metabolic health.

project_terms:
AGFG1 gene;Acute;Address;Affect;Apolipoproteins B;Atherosclerosis;Autophagocytosis;Biogenesis;Bioinformatics;Body Composition;Body mass index;Cardiometabolic Disease;Cardiovascular Diseases;Cell membrane;Cells;Chylomicrons;Circulation;Co-Immunoprecipitations;Complex;Conscious;Data;Data Set;Diet;Dietary Fats;Dyslipidemias;Enterocytes;Equilibrium;Esterification;Exhibits;Fasting;Fat-Soluble Vitamin;Fatty acid glycerol esters;Fistula;Foundations;Genes;Golgi Apparatus;Guanine Nucleotide Exchange Factors;Health;High Fat Diet;Homeostasis;Human;In Vitro;Ingestion;Insulin Resistance;Intestinal Absorption;Intestinal Secretions;Intestines;Knowledge;Link;Lipids;Lipolysis;Lipoproteins;Literature;Lymph;Maintenance;Mass Spectrum Analysis;Measurement;Measures;Membrane Fusion;Metabolic;Metabolism;Methods;Mission;Mitochondria;Modeling;Mucous Membrane;Mus;Non-Insulin-Dependent Diabetes Mellitus;Nonesterified Fatty Acids;Obesity;Organism;Particle Size;Pathway interactions;Peripheral;Plasma;Play;Process;Proteins;Publishing;Regulation;Resistance;Risk Factors;Role;Secretory Vesicles;Sucrose;Tissues;Tracer;Transmembrane Transport;Triglycerides;United States National Institutes of Health;Variant;Very low density lipoprotein;Wild Type Mouse;Work;absorption;cardiometabolism;cardiovascular disorder risk;cardiovascular risk factor;cell type;crosslink;dietary;exome sequencing;experimental study;gene network;gene regulatory network;improved;insight;intestinal epithelium;lipid metabolism;mouse model;novel;particle;response;single-cell RNA sequencing;trafficking;transcriptome;uptake

public_health_relevance:
Project NarrativeThe absorption of dietary lipids and their transport to the circulation is essential for the maintenance ofwhole-body lipid metabolism and energy homeostasis; however elevated postprandial plasma lipidspecifically triacylglyceride (TAG) is a significant independent risk factor for cardiovascular disease.This project will provide mechanistic insight into a newly discovered role for the protein DENND5B inthe absorption of dietary TAG and its impact on cardiometabolic health. The overall objective of thisproposal is to gain fundamental knowledge about the process of dietary lipid absorption by the intestineand its impact on metabolic health.


application_id: 10844641
project_number: 5R21AI178652-02
administering_ic: NIAID
award_notice_date: 2024-04-16
opportunity_number: PA-20-195
application_type: 5
activity_code: R21
ic: AI
serial_number: 178652
program_official: UPADHYAY, MEENU MISHRA
project_start_date: 2023-05-19
project_end_date: 2026-04-30
study_section: Prokaryotic Cell and Molecular Biology Study Section[PCMB]
contact_pi_person_id: 8869391
contact_pi: KOROTKOVA, NATALIA
other_pis: Not Applicable
congressional_district: 06
department: MICROBIOLOGY/IMMUN/VIROLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-05-01
project_title:
Genetic screen to define the regulation of beta-hemolysin toxin expression in Streptococcus agalactiae

project_abstract:
Group B Streptococcus (GBS) is a normal constituent of the intestinal and vaginal florain 1530% of healthy adults. The bacterium can however cause infections in elderly andimmunocompromised patients and pregnant women and is the main cause of fatal invasivedisease in newborns. GBS translocation through epithelial endothelial and placental barriers isfacilitated by a pore-forming toxin -hemolysin also known as the -hemolytic pigmented lipidor granadaene. To identify factors involved in the regulation of -hemolysin expression wedeveloped new peptide-free culture media for screening of a transposon mutant library of GBSCJB111. The pilot screens identified nine novel genetic loci associated with positive andnegative modulation of -hemolysin expression. Based on preliminary findings we hypothesizethat GBS possesses a regulatory mechanism that tailors -hemolysin expression to theenvironment. To unravel the mechanism we will employ transposon mutant library screeningRNA-seq and metabolomics analyses isolation and de novo sequence determination ofsecreted peptide-based repressors. The results of this exploratory work have the potential tolead to the development of a novel inhibitor of the invasion state of GBS.

project_terms:
Abbreviations;Adult;Agar;Antibiotic Prophylaxis;Antibiotic Resistance;Bacteria;Binding;Blood;Blood - brain barrier anatomy;Blood Circulation;Cell Separation;Central Nervous System;Chemicals;Colon;Culture Media;Cytolysins;Detection;Development;Disease;Endothelium;Environment;Epithelium;Family;Folic Acid;Gene Expression;Genes;Genetic Screening;Genetic Transcription;Goals;Gram-Positive Bacteria;Group B Streptococcus colonization;Hemolysin;Human;Immune;Immune Evasion;Immunocompromised Host;Induction of Apoptosis;Infection;Invaded;Libraries;Lipids;Meningitis;Mothers;Neonatal meningitis;Newborn Infant;Niacinamide;Nutrient;Oligopeptides;Pathway interactions;Peptide Sequence Determination;Peptides;Phagocytes;Phagocytosis Induction;Pigments;Placenta;Pregnant Women;Preventive measure;Production;Proteins;Regulation;Repression;Research;Sepsis;Sequence Determination;Serum;Signal Transduction;Small Intestines;Starch;Streptococcal Infections;Streptococcus Group B;System;Testing;Therapeutic;Toxin;Vaccines;Virulence;Virulence Factors;Water;Work;blood-brain barrier disruption;clinically relevant;gastrointestinal;genomic locus;gut microbiota;in vivo;inhibitor;inorganic phosphate;intestinal epithelium;metabolomics;microbiome;microbiota;microorganism;mutant;neonatal sepsis;novel;novel therapeutics;older patient;pathogen;placental membrane;prevent;quorum sensing;screening;small molecule;transcriptome sequencing;transmission process;treatment group;vaginal microbiota;women patients

public_health_relevance:
Streptococcus agalactiae is the leading cause of neonatal sepsis and meningitis and animportant pathogen in pregnant women and elderly patients. The proposed research has apotential to lead to the development of a novel drug selectively repressing the invasion state ofStreptococcus agalactiae.


application_id: 10844417
project_number: 5P20GM113226-09
project_title: Project 4 - Smita Ghare PhD
administering_ic: NIGMS
award_notice_date: 2024-03-20
opportunity_number: PAR-19-312
application_type: 5
activity_code: P20
ic: GM
serial_number: 113226
project_start_date: 2016-06-10
project_end_date: 2026-03-31
study_section: ZGM1-RCB-3
subproject_number: 6814
contact_pi_person_id: 11468892
contact_pi: GHARE, SMITA S
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Alcoholic liver disease (ALD) carries a high morbidity and mortality and has no FDA approved therapy.Sustained hepatic inflammation is an important factor in progression of alcoholic liver disease and elevatedhepatic and circulating levels of CCL2 and CXCL2 chemokines are seen in both early and later stages of liverdisease. However the molecular mechanisms involved in alcohol-induced upregulation of these chemokinesare not completely elucidated. Emerging evidence indicates that alcohol affects epigenetic regulatorymechanisms and thus significantly contributes to the development of hepatic pathology. Post-translationalmodifications (PTMs) specifically acetylation is important for gene transcription and is maintained by Histonedeacetylases (HDACs) and histone acetyltransferases (HATs). In this regard we have shown that bingealcohol exposure alters expression of hepatic HDAC and also affect global hepatic histone H3 acetylation. Therole of Class I HDACs has been also described in inflammation with a particular pro-inflammatory role forHDAC3. In the context of chemokine expression our preliminary data examining the effects of chronic ethanolon CCL2 upregulation showed that in correlation with increased promoter histone acetylation there was anincrease in the binding of critical transcription factor NFB-p65 to the CCL2 promoter. Further the data showthat a dietary HDAC inhibitor (tributyrin - prodrug of butyrate) attenuates alcohol-induced CCL2 and CXCL2expression neutrophil infiltration and prevents hepatic inflammation and injury. Based on these findings wehypothesize that chronic alcohol-induced alterations in hepatic HDACs drive pathogenicposttranslational modifications of histones and non-histone proteins specifically transcription factorNFB upregulating CCL2 and CXCL2 chemokines expression contributing to liver inflammation andinjury. The major goal of this proposal is to conduct studies that determine the molecular mechanismsunderlying chronic alcohol-induced chemokine upregulation and the development of ALD. Moreover theproposal examines the potential of nutrition-based interventions targeted at HDAC inhibition in mitigatingalcohol-induced chemokine expression and liver inflammation/injury. The specific aims of the proposal are: 1)Examine the role of alcohol-induced promoter histone modifications in regulating pro-inflammatoryCCL2 and CXCL2 chemokine expression in ALD; 2) Determine the role of HDAC mediated regulation ofNFB transactivation function and chemokine expression in ALD; and 3) Evaluate the therapeuticpotential of tributyrin in attenuating CCL2 and CXCL2 chemokine expression and development of ALD.We expect that the results of our study will provide critical molecular insights and facilitate the development oftherapeutic interventions for ALD.

project_terms:
Acetylation;Affect;Alcoholic Hepatitis;Alcoholic Liver Diseases;Alcohols;Attenuated;Binding;Biological Models;Biopsy;Butyrates;CXC Chemokines;CXCL2 gene;Centers of Research Excellence;Chronic;Clinical;Cytokine Activation;DNA Binding;Data;Deacetylation;Development;Doctor of Philosophy;Epigenetic Process;Ethanol;FDA approved;Fatty acid glycerol esters;Genes;Genetic Transcription;Goals;HDAC3 gene;Hepatic;Hepatocyte;Histone Acetylation;Histone Deacetylase;Histone Deacetylase Inhibitor;Histone H3;Histones;IL8 gene;Inflammation;Inflammatory;Injury;Intervention;Knockout Mice;Ligands;Liver diseases;Macrophage Activation;Mediating;Modification;Molecular;Morbidity - disease rate;Mus;Myeloid Cells;Neutrophil Infiltration;Organ;Oxidative Stress;Pathogenicity;Pathology;Patients;Plasma;Play;Post-Translational Protein Processing;Preventive;Prodrugs;Regulation;Role;Serum;Severity of illness;Stimulus;Testing;Therapeutic;Therapeutic Intervention;Toxicology;Transactivation;Transcriptional Activation;Up-Regulation;Work;alcohol effect;alcohol exposure;beta-Chemokines;chemokine;chromatin remodeling;cohort;cytokine;dietary;histone acetyltransferase;histone modification;in vitro Model;in vivo;insight;liver inflammation;liver injury;mortality;non-histone protein;nucleocytoplasmic transport;nutrition;p65;prevent;promoter;recruit;response;therapeutic development;transcription factor;translational study;tributyrin


application_id: 10844410
project_number: 5P20GM113226-09
project_title: Biorepository and Animal Core
administering_ic: NIGMS
award_notice_date: 2024-03-20
opportunity_number: PAR-19-312
application_type: 5
activity_code: P20
ic: GM
serial_number: 113226
project_start_date: 2016-06-10
project_end_date: 2026-03-31
study_section: ZGM1-RCB-3
subproject_number: 6810
contact_pi_person_id: 9367804
contact_pi: CAVE, MATTHEW C
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary Abstract  Animal Model and Biorepository Core (Core D)The Animal Model and Biorepository Core (Core D) of the Hepatobiology and Toxicology Center provides theessential expertise facilities resources and standardized services required for impactful liver research. TheCore focuses on the needs of the COBREs junior investigators but it also serves other Center members andliver investigators. The Core enhances infrastructure as well as the technical and academic capabilities of theCenter and the Institution as a whole. Core Ds primary functions are to provide COBRE members with accessto: (i) animal models of liver disease (including the characterization of these models); (ii) primary liver cells; and(iii) previously collected de-identified biological specimens from human subjects with liver disease.The Cores experimental model services include: animal exposure; husbandry; necropsy with tissue collectionprocessing and biorepository storage; phenotyping and liver histology; as well as the isolation of primary hepaticcells for ex vivo and in vitro studies. The Core will assist COBRE members in developing new experimentalanimal models and in vitro systems to study liver disease. The Core will serve as a liaison to non-duplicativeanimal research resources at UofLs two other COBRE Centers to maximize overall impact. Core personnel willensure uniformity of husbandry as well as sample collection processing and evaluation so that the same set ofcharacteristics is measured in each model. This uniformity ensures that the data generated within the COBREare consistent and that results of one experiment will be directly comparable with the results of another. TheCores human biorepository enables access to a unique inventory of previously collected de-identified biologicalsamples from subjects with liver diseases (e.g. alcoholic liver disease occupational/environmental liverdiseases liver cancer etc.) in order to promote translational research. Core D will assist COBRE members withthe necessary regulatory approvals for their research. In addition to its function as a service core Core D willpromote the education and training of the COBRE junior investigators and members.To function as a vital integrative component of the COBRE providing services not only for its members but alsofor the Institution as a whole Core D has the following Specific Aims: 1) To foster the development and successof current and future COBRE projects. 2) To educate and train investigators. 3) To develop new protocols andtechniques. 4) To become an integral and self-sustaining component of the COBRE.

project_terms:
Address;Alcoholic Liver Diseases;Animal Experimentation;Animal Model;Animals;Autopsy;Biological;Biology;Centers of Research Excellence;Characteristics;Data;Development;Ensure;Equipment and supply inventories;Evaluation;Experimental Animal Model;Experimental Models;Fees;Fostering;Future;Germ-Free;Gnotobiotic;Goals;Hepatocyte;Histology;Human;Human Resources;IACUC;In Vitro;Individual;Infrastructure;Institution;Institutional Review Boards;Liver;Liver diseases;Maintenance;Malignant neoplasm of liver;Measures;Mission;Modeling;Mus;Occupational;Operative Surgical Procedures;Phenotype;Procedures;Protocols documentation;Research;Research Personnel;Resources;Sampling;Service delivery model;Services;Specimen;Standardization;Structure;System;Techniques;Tissue Banks;Toxicology;Training;Training and Education;Translational Research;biobank;biological specimen archives;career development;design;experimental study;flexibility;gut microbiome;human subject;interest;investigator training;meetings;member;metabolic phenotype;sample collection;success


application_id: 10844407
project_number: 5P20GM113226-09
project_title: Omics Core
administering_ic: NIGMS
award_notice_date: 2024-03-20
opportunity_number: PAR-19-312
application_type: 5
activity_code: P20
ic: GM
serial_number: 113226
project_start_date: 2016-06-10
project_end_date: 2026-03-31
study_section: ZGM1-RCB-3
subproject_number: 6808
contact_pi_person_id: 8487327
contact_pi: ZHANG, XIANG
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Abstract: The primary function of OMICS Core (Core B) is to provide members of the University of LouisvilleHepatobiology and Toxicology COBRE with the expertise resources and facilities needed for metabolomicproteomic and bioinformatic analyses of biological samples collected to study liver injury nutrition gut:liverinteractions and liver:environment/toxicant/drug interactions. Core B personnel will assist with the design ofsample collection protocols will drive the development and the execution of novel and robust chromatographicmethods for sample separation and mass spectrometric methods for the analysis of proteins peptides andmetabolites with a goal of providing a greater understanding of the evolution of molecular mechanisms thatcorrelate with or participate in liver dysfunction. Core B will ensure uniformity and standardization in samplepreparation method development instrument performance data collection data reporting and data sharing.Core B endeavors to contribute to the overall success and utility of the COBRE and to enhance the infrastructureand the technical and academic capabilities of the institution as a whole. In addition to its function as a servicecore Core B will also promote the education and training of the COBRE members and other biomedicalinvestigators with regards to the state-of-the-art omics technologies; with particular attention to the COBRE juniorinvestigators. Furthermore Core B will become an independent and self-supporting entity using a setcomprehensive approaches that have been already implemented and demonstrated their success in our PhaseI COBRE.During the Hepatobiology and Toxicology COBRE Phase II period the goals of Core B will be addressed by thefollowing Specific Aims:1) To support current COBRE and UofL Health Science Center (HSC) projects.2) To educate and train mentees and other investigators.3) To develop new protocols and techniques.4) To become self-sustaining feature of the COBRE and UofL HSC.

project_terms:
Address;Applications Grants;Attention;Award;Bioinformatics;Biological;Biological Assay;Centers of Research Excellence;Chemicals;Chromatography;Clinical Research;Communities;Complex Mixtures;Continuing Education;Data;Data Analyses;Data Collection;Data Reporting;Derivation procedure;Development;Dimensions;Disease;Drug Interactions;Education;Ensure;Environment;Equipment;Fee-for-Service Plans;Funding;Future;Goals;Health Sciences;Hepatology;Human Resources;Individual;Infrastructure;Institution;Intervention Studies;Leadership;Liver;Liver Dysfunction;Liver diseases;Malignant neoplasm of liver;Mass Spectrum Analysis;Methods;Modality;Modeling;Modification;Molecular Evolution;Peptides;Performance;Phase;Preparation;Privatization;Procedures;Protein Analysis;Protein Fragment;Proteins;Proteomics;Protocols documentation;RNA;Reagent;Research;Research Activity;Research Personnel;Research Support;Resources;S10 grant;Sampling;Science;Services;Standardization;Statistical Data Interpretation;Techniques;Technology;Toxicology;Training;Training and Education;Translational Research;United States National Institutes of Health;Universities;career;career development;clinical infrastructure;data sharing;design;epitranscriptomics;experimental study;fatty liver disease;innovation;instrument;liver development;liver injury;meetings;member;metabolomics;method development;molecular marker;non-alcoholic;novel;nutrition;operation;problem drinker;programs;sample collection;small molecule;success;theories;tool;toxicant


application_id: 10844402
project_number: 5P20GM113226-09
project_title: Administrative Core
administering_ic: NIGMS
award_notice_date: 2024-03-20
opportunity_number: PAR-19-312
application_type: 5
activity_code: P20
ic: GM
serial_number: 113226
project_start_date: 2016-06-10
project_end_date: 2026-03-31
study_section: ZGM1-RCB-3
subproject_number: 6807
contact_pi_person_id: 1902075
contact_pi: MCCLAIN, CRAIG J.
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
The University of Louisville Hepatobiology and Toxicology COBRE is a multidisciplinary group of investigators focusing on the liver and liver injury gut:liver interactions and liver:environment/toxicant/drug interactions alcoholic and non-alcoholic liver injury infectious liver diseases liver cancer and new liver therapies. The purpose of the administrative core is to provide administrative fiscal and scientific oversight for this Phase II COBRE. This includes the overall career development and research goals of the Phase II COBRE (including formative and summative evaluation and specific milestones); the career development plans for junior faculty (including plans for transitioning to independence); plans for replacing key personnel (e.g. Project PIs Core leaders overall PI pilot project PIs); oversight of the pilot projects; oversight of the biostatistical support services; and disseminating information to the lay and scientific communities.  Liver diseases are some of the most common rapidly increasing and poorly recognized health problems afflicting Americans. For example Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis is the most common cause of abnormal liver enzymes in the US affecting about 25% of adults and about 10% of children. Alcoholic Liver Disease is an increasing problem among those who drink. Importantly there is no FDA-approved therapy for either NASH or ALD. Toxicant-Induced Liver Injury is an increasingly recognized industrial/environmental problem. Viral Liver Diseases (Hepatitis A B and C) remain major health problems related to drug abuse and homelessness. Hepatocellular carcinoma and Hepatitis C are major causes for liver related morbidity and liver transplantation in the US. Drug-Induced Liver Injury is the major reason new drugs do not come to market and the major cause of fulminant liver failure in the US. Personalized Medicine is increasingly recognized as an important aspect of drug therapy; and most drugs are metabolized in the liver.  Building on the success of the Phase I COBRE Administrative Core the specific aims of this Phase II COBRE Administrative Core are:  1. continue to provide overall administrative fiscal and scientific oversight  2. enhance and grow the career development enterprise for project PIs  3. enhance and grow the career development/mentor development enterprise for the mentors  4. enhance and grow the research goals of the COBRE  5. continue to provide a process for replacing key personnel  6. continue to provide and enhance a summative and formative evaluation process for the COBRE  including specific milestones  7. continue to provide a robust pilot project program to grow the overall research goals of the COBRE  8. disseminate pertinent information to the scientific and lay community

project_terms:
Acute Liver Failure;Adult;Affect;Alcoholic Liver Diseases;Alcohols;American;Area;Bioinformatics;Biometry;Budgets;Center Core Grants;Centers of Research Excellence;Child;Clinical Trials;Communities;Community Outreach;Country;Development;Development Plans;Diabetes Mellitus;Drug Interactions;Drug abuse;Ensure;Environment;Environmental Health;Enzymes;Evaluation;FDA approved;Faculty;Funding;Goals;Grant;Health;Hepatitis A;Hepatitis C;Homelessness;Human Resources;Individual;Industrialization;Kentucky;Letters;Liver;Liver diseases;Malignant neoplasm of liver;Marketing;Mentors;Morbidity - disease rate;National Institute of Environmental Health Sciences;National Institute on Alcohol Abuse and Alcoholism;Obesity;Overweight;Pharmaceutical Preparations;Pharmacology and Toxicology;Pharmacotherapy;Phase;Physicians;Pilot Projects;Population;Primary carcinoma of the liver cells;Process;Public Health;Qualifying;Research;Research Infrastructure;Research Personnel;Rural;Scientist;Services;Structure;Superfund;Teacher Professional Development;Text;Toxicology;United States National Institutes of Health;Universities;Viral hepatitis;career development;drug induced liver injury;faculty mentor;formative assessment;improved;liver injury;liver metabolism;liver transplantation;microbiome;microbiome research;multidisciplinary;non-alcoholic;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel therapeutics;opioid abuse;personalized medicine;problem drinker;programs;recruit;research and development;senior faculty;success;toxicant;tumor immunology;viral liver disease


