# projects

application_id: 11196361
project_number: 1R16GM159605-01
administering_ic: NIGMS
award_notice_date: 2025-08-01
opportunity_number: PAR-24-145
application_type: 1
activity_code: R16
ic: GM
serial_number: 159605
program_official: FAUPEL-BADGER, JESSICA
project_start_date: 2025-08-01
project_end_date: 2029-07-31
study_section: Special Emphasis Panel[ZGM1 RCB-X (SF)]
contact_pi_person_id: 15077601
contact_pi: MARQUARDT, JOSEPH RONALD
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
budget_start_date: 2025-08-01
project_title:
Examination of Elm1 polarity and endocytosis for regulation of cellular morphogenesis in budding yeast

project_abstract:
Project Summary AbstractThe functionality of specific cells in multicellular organisms are linked to the specific morphologies that thosecells adopt. Extensive regulatory networks including polarization cytoskeletal dynamics exo- and endocyticmembrane trafficking and cell cycle control must be spatially and temporally controlled to ensure thatproliferation and cell division occur in a stereotypical fashion. Errors in properly establishing and maintainingcellular morphologies drive cellular pathologies including many cancers developmental disorders andneurodegenerative diseases such as Alzheimers. With so many different cellular processes being involved thecoordination between and among them has remained elusive and represents a fundamental question in cellularmorphogenesis control. Due to the simplicity of the model organism Saccharomyces cerevisiae the processesoutlined above have been extensively studied and are directly homologous to those in higher eukaryotes. Oneof the major regulations of cellular morphogenesis in budding yeast is the morphogenesis checkpoint composedof the sequential recruitment of the kinases Elm1 and Hsl1 and a methyltransferase Hsl7 that serves as a scaffoldat the bud neck (i.e. site of cell division) to sequester the mitotic CDK inhibitor Swe1 for proteosome-mediateddegradation. The degradation of Swe1 then allows cell cycle progression thereby linking the mitotic cycle withthe formation of a bud after genome duplication. Recent data that only active Elm1 can lead to the recruitmentof both Hsl1 and Hsl7 along with preliminary global phosphoproteomic and fluorescent microscopy data thatElm1 regulates polarity factors and endocytosis leads to the hypothesis that Elm1 can directly regulate Hsl7 (inaddition to Hsl1 as previously known) (Aim 1) and has expanded roles in synergy with the Cdc42 effector Ste20and the early endocytic protein Ede1 to control cellular morphogenesis (Aim 2). Both these potential regulatedeffectors of Elm1 are known to play roles in cell shape control and exhibited extensive differential phosphorylationwhen compared between wild-type cells and cells deleted for the ELM1 gene. The proposed study will employan integrative approach including gene editing live cell imaging and biochemistry to illustrate the regulatorycapacity of Elm1 on the hypothesized pathways. This study will impact the understanding of the complexitiesinvolved with cellular morphogenesis control and will fill a critical knowledge gap that can give insights importantto human health and development.

project_terms:
Address;Adopted;Alzheimer's Disease;Biochemistry;Biological;Biological Assay;Cell Culture Techniques;Cell Cycle;Cell Cycle Progression;Cell Cycle Regulation;Cell Physiology;Cell Shape;Cell division;Cells;Cellular Morphology;Complement;Complex;Coupled;Couples;Cytoskeleton;Data;Development;Electron Microscopy;Endocytosis;Eukaryota;Event;Exhibits;Experimental Models;Failure;Fluorescence;G2/M Transition;Gene Deletion;Genes;Genetic;Genome;Growth;Health;Human;In Vitro;Individual;Knowledge;Link;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Membrane;Methyltransferase;Microscopy;Mitosis;Mitotic;Modeling;Molecular;Morphogenesis;Morphology;Mothers;Mutagenesis;Neck;Neurodegenerative Disorders;Organism;Pathway interactions;Pattern;Phenocopy;Phenotype;Phosphorylation;Phosphorylation Site;Phosphotransferases;Play;Process;Proliferating;Proteins;Regulation;Regulation of Cell Shape;Reporting;Role;Saccharomyces cerevisiae;Saccharomycetales;Severities;Shapes;Site;Stable Isotope Labeling;Substrate Interaction;Time;Transferase;Ubiquitin;Yeast Model System;cell growth regulation;cell type;cellular pathology;daughter cell;developmental disease;experimental study;gene-editing approach;improved;inhibitor;insight;live cell imaging;microscopic imaging;model organism;multicatalytic endopeptidase complex;phosphoproteomics;polarized cell;recruit;scaffold;spatiotemporal;synergism;tool;trafficking

public_health_relevance:
Project NarrativeRegulation of cell shape is critical for the normal development of organisms however the complexities ofmulticellular organisms have made understanding the mechanisms of cellular morphogenesis difficult. Using anintegrative approach of gene editing live-cell imaging and biochemistry in the budding yeast model system thisstudy aims to improve our understanding of these mechanisms. With errors in cell shape linked to developmentaldisorders and cancers insights of this study are relevant to human health.


application_id: 11196269
project_number: 1S15OD039777-01
project_title: Modernization of the Clinical and Translational Research Vivarium Environmental Monitoring System
administering_ic: OD
award_notice_date: 2025-08-04
opportunity_number: PAR-24-259
application_type: 1
activity_code: S15
ic: OD
serial_number: 039777
program_official: SPECTOR, JEFFREY O
project_start_date: 2025-08-15
project_end_date: 2026-08-14
study_section: Special Emphasis Panel[ZRG1 KUDS-S (90)]
contact_pi_person_id: 8666997
contact_pi: SHERWOOD, LESLIE C.
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:
PROJECT SUMMARY/ABSTRACTThe University of Louisville (UofL) is an Institution of Emerging Excellence (IEE) and one of 23states designated by the National Institutes of Health (NIH) as an Institutional DevelopmentAward (IDeA) state serving the research needs of medically underserved communities. As partof the IDeA state program UofL is the recipient of four NIH funded Centers of BiomedicalResearch Excellence (COBRE) projects to target local and regional health crises in Kentuckyand Appalachia. These include centers in 1) Center for Cardiometabolic Science 2)Microbiomics and Inflammation 3) Hepatobiology and Toxicology and 4) Cancer Immunologyand Immunotherapy. UofL is requesting $345933 for an Avidity Watchdog EX EnvironmentalMonitoring and Light Control System for the Clinical and Translational Research Buildingvivarium (CTRV). The CTRV houses animals for 3 of the 4 UofL COBRE projects including thestates only Germ-Free/Gnotobiotic Mouse Facility the universitys rodent imaging core andanimals utilized by 64 investigators in 16 departments. The CTR vivarium is the largestvivarium on campus with capacity of >12000 mouse cages. The new environmental monitoringsystem will allow for enhanced monitoring of the vivarium utilized for a diverse range of researchsubjects and species including mice rats hamsters and zebrafish. The innovation of the AvidityEnvironmental Monitoring and Light Control System will allow real-time monitoring and will issueremote alarms for all vivarium housing rooms to several veterinary and facility staff allowing fortimely management environmental problems which will advance operations minimize researchdisruption and strengthen the integrity of the research by reducing variables. The currentSiemens monitoring system is unreliable and has the limitation of only notifying one criticalalarm at a time. In addition the Avidity system can be connected to the Avidity automatedwatering system and detect leaks to the cage rack level with remote alarms to alert veterinaryand facility staff of leaks in the watering system preventing adverse flooding of animal cages.Our current system (Siemens) cannot detect water leaks and to our knowledge the Aviditysystem is the only system capable of doing so. We installed the Avidity environmentalmonitoring system (including Avidity autowatering) in our newest vivarium and our long-termobjective is to install this monitoring system and Avidity autowatering in all our vivaria (includingCTRV) in the future to assure enhanced animal welfare and reduce environmental variability ofresearch data. A broad diverse range of investigators and their research efforts in bothbiomedical and basic sciences will benefit from this equipment in this shared-use facility.

project_terms:
Alcoholism;Animal Experimentation;Animal Experiments;Animal Housing;Animal Welfare;Animals;Appalachian Region;Area;Avidity;Award;Basic Science;Centers of Research Excellence;Clinical Research;Communicable Diseases;Data;Development;Diagnostic radiologic examination;Embryology;Environmental Monitoring;Equipment;Floods;Funding;Future;Gastroenterology;Germ-Free;Gnotobiotic;Hamsters;Health;Health Sciences;Hepatology;Housing;Human;Immunology;Inflammation;Institution;Kentucky;Light;Lighting;Modernization;Monitor;Mus;Neurology;Notification;Oncology;Pharmacology;Rattus;Research;Research Personnel;Research Subjects;Research Support;Rodent;Science;System;Temperature;Time;Time Management;Toxicology;Translational Research;United States National Institutes of Health;Universities;Water;Zebrafish;animal facility;cancer immunotherapy;cardiometabolism;clinical translation;innovation;medically underserved;microbiome research;operation;prevent;programs;real time monitoring;rodent imaging;square foot;tumor immunology;underserved community

public_health_relevance:
NarrativeThe University of Louisville (UofL) an Institution of Emerging Excellence (IEE) located in anInstitutional Development Award (IDeA) program state requests funds ($345933.00) tomodernize our 35373 net sq. ft. shared-use Clinical Translational Research Building (CTR)Animal Facility which provides animal housing and research support space for rodent andaquatic animal species utilized to advance human health by NIH-funded investigators from 16departments on the Health Sciences Campus. This modernization includes installation of anAvidity Watchdog EX Environmental and Lighting Monitoring system which will monitor andcontrol temperature and lighting variables which are critical to control in animal experiments foranimal welfare and valid robust research data. The human health research areas studied withanimals housed in the CTR include hepatology immunology oncology alcoholism embryologyneurology infectious diseases pharmacology diagnostic radiology gastroenterology andothers.


application_id: 11195163
project_number: 5R03DA061626-02
administering_ic: NIDA
award_notice_date: 2025-08-14
opportunity_number: PAS-21-270
application_type: 5
activity_code: R03
ic: DA
serial_number: 061626
program_official: BORGMANN, KATHLEEN RUTH
project_start_date: 2024-09-30
project_end_date: 2026-08-31
study_section: HIV Comorbidities and Clinical Studies Study Section[HCCS]
contact_pi_person_id: 9706320
contact_pi: GIPSON-REICHARDT, CASSANDRA D
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
budget_start_date: 2025-09-01
project_title:
Neuroimmune and Cognitive Consequences of Nicotine Use in a Rodent Model of HIV: Implications for Anti-Retroviral Therapies

project_abstract:
PROJECT SUMMARY/ABSTRACTThis A-START R03 will examine the role of volitional nicotine use in exacerbating neuroimmune consequencesof HIV using a rat model in support of a larger R01. Clinically persons living with HIV (PLWH) are 2-3 times morelikely than the average population to use nicotine-containing products and are less likely to quit. Furthercombined anti-retroviral therapy (cART) does not reverse neurocognitive impairments induced by HIV infectionand PLWH often present with comorbid anxiety and depression which smoking is used as a coping strategy.Despite these clinical associations the mechanisms underlying these relationships have not been thoroughlyexamined using preclinical models which can provide sensitive assessments of these relationships. We havefound that chronic nicotine self-administration (SA) is associated with neurobiological adaptations within theneuroimmune system of the nucleus accumbens core (NAcore) region of the addiction/reward pathway. Theprefrontal cortex (PFC) and amygdala additional regions within the reward pathway play a role in preclinicalmodels of drug use cognition and anxiety and thus may critically contribute to nicotine/HIV interactions. Ourpreliminary data show that NAcore cytokine profiles are suppressed by nicotine SA and microglia are sex-specifically impacted by nicotine use whereby females show heightened vulnerability. Conversely we show thatblood serum pro-inflammatory cytokines are increased following nicotine SA in females. We further show thatnicotine seeking is critically regulated by NAcore microglia indicating that these neuroimmune cells may haveoutsized control over nicotine-motivated behavior. Together these immune consequences of nicotine use mayhave implications for PWH because HIV is characterized by profound inflammation. We hypothesize thatchronic volitional nicotine SA improves HIV-associated neurocognitive disorders (HAND) and anxiety butexacerbates HIV-induced neuroimmune signaling leading to greater use motivation. Here we will utilize theEcoHIV viral construct during nicotine SA to recapitulate microglial infection as well as neurocognitiveimpairments and anxiety-like behavior seen in the clinical condition. We will evaluate if chronic nicotine SAenhances cognitive functioning as measured via delayed matching to sample (DMTS) a memory task andanxiety-like behaviors in open field testing (Aim 1) and if this is associated with enhanced NAcore PFC andamygdala microglial reactivity both in EcoHIV-infected and non-infected microglia (Aim 2). We will further test ifnicotine and EcoHIV interact to further dysregulate NAcore PFC amygdala and blood serum cytokine profiles(Aim 2). Importantly we will test the ability of cART treatment to impact these neurobehavioral endpoints. Thesestudies will define how nicotine-induced changes in neuroimmune signaling are impacted by EcoHIV infectiona better understanding of how nicotines volitional exposure may influence cognitive performance and anxiety-like behavior and how ART may impact these effects which will lead to a larger R01 to fully examine sex-specificnovel neurobiological mechanisms of immune system dyshomeostasis after EcoHIV infection and nicotine use.

project_terms:
Adherence;Age;Amygdaloid structure;Animals;Anxiety;Brain;Cells;Chronic;Clinical;Cognition;Cognitive;Consequences of HIV;Coping Skills;Cytokine Suppression;Data;Drug usage;Female;Genes;Goals;HIV;HIV Infections;HIV-associated neurocognitive disorder;Immune;Immune system;Impaired cognition;Impairment;Infection;Inflammation;Inflammatory;Intake;Macrophage;Measures;Memory;Mental Depression;Microglia;Modeling;Motivation;Neurobiology;Neurocognition;Neurocognitive;Neurocognitive Deficit;Neuroimmune;Neuroimmune system;Nicotine;Nicotine Dependence;Nucleus Accumbens;Outcome;Pathway interactions;Performance;Peripheral;Persons;Pharmacotherapy;Population;Pre-Clinical Model;Prefrontal Cortex;Rattus;Reporting;Research;Rewards;Rodent;Rodent Model;Role;Saline;Sampling;Self Administration;Serum;Shapes;Signal Transduction;Smoking;Testing;Ventral Striatum;Viral;Viral reservoir;Virus;Withdrawal;Woman;Work;addiction;antiretroviral therapy;anxiety-like behavior;cognitive change;cognitive enhancement;cognitive function;cognitive performance;cognitive task;comorbidity;coping;cytokine;experience;field study;improved;motivated behavior;neurobehavioral;neurobiological mechanism;neuroinflammation;nicotine exposure;nicotine seeking behavior;nicotine self-administration;nicotine use;novel;preclinical evaluation;sex;smoking cessation;smoking initiation;years of life lost

public_health_relevance:
PROJECT NARRATIVE Persons living with HIV (PLWH) are 2-3 times more likely than the average population to use nicotine-containing products and although nicotine use may improve HIV-associated neurocognitive disorders (HAND)it may also exacerbate neurobiological sequelae induced by HIV infection such as neuroinflammation despiteuse of anti-retroviral therapies (ART). The proposed research has the potential to uncover novel neurobiologicalmechanisms by which nicotine use alleviates some of the cognitive dysfunction associated with HIV infection butexacerbates neuroimmune dysregulations utilizing the EcoHIV virus in a rat model of nicotine use.


application_id: 11194418
project_number: 5U01AA026980-07
project_title: Integrated therapies for alcohol use and ALD (ITAALD) Network -UofL Clinical Center
administering_ic: NIAAA
award_notice_date: 2025-09-05
opportunity_number: RFA-AA-24-004
application_type: 5
activity_code: U01
ic: AA
serial_number: 026980
program_official: GAO, PETER
project_start_date: 2018-08-01
project_end_date: 2029-06-30
study_section: ZAA1-DD(05)C
contact_pi_person_id: 1902075
contact_pi: MCCLAIN, CRAIG J.
other_pis: SINGAL, ASHWANI K;STEWART, CHRISTOPHER M
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:
Alcohol-associated liver disease (ALD) is a leading cause of liver-related mortality/morbidity and there is no FDA-approved therapy for any stage of ALD. Advanced ALD conditions including severe alcohol-associated hepatitis (sAH) have especially poor outcomes. Indeed the 90-day mortality for sAH is ~30%. Return to drinking impacts quality of life morbidity and mortality in these patients. There are limited drug therapies or well-studied behavior therapies in this patient population. An optimal approach would be the integration of AUD and ASLD care givers and therapies but there are no guidelines for this approach. Our proposed AUD/ALD team approach seeks to overcome the perceived stigma of alcohol misuse which can adversely affect treatment seeking quality of care and patient outcomes. The AlcHepNet RCT was stopped at the interim analysis because of the unexpected 90% 90-day survival in sAH patients treated with prednisone using the Lille stopping rule. These dramatic results need to be confirmed and novel therapies such as IL-22 need to be studied in sAH. Acamprosate appears to be the safest FDA-approved therapy for AUD in patients with ALD but safety and efficacy in severe ALD need to be evaluated. Motivational interviewing/enhancement therapy is well-suited behavioral therapy for patients with ALD. Based on preliminary data and knowledge gaps our overall hypothesis is that integrated management of ALD and AUD will improve clinical outcomes in patients with sAH and decompensated ALD. We will utilize the following AIMS:Aim 1. Perform a randomized controlled trial of treatment for steroid-eligible patients with severe AH. A SMART trial design will be used to compare daily prednisone for 28 days (with the 7-day Lille score-based stopping rule) vs IL-22 fusion protein (F-652) followed by randomization of each of these groups to receive motivational Interviewing/enhancement therapy combined with acamprosate vs usual care including referral to 12-step programs before discharge from the hospital. The primary endpoint of the trial will be a composite measure of mortality liver and alcohol use related outcomes at 6 months.AIM 2. Build a platform for biosamples data repositories and patient registries to support site-specific and network-wide ancillary studies.In summary these proposed studies will leverage the existing resources of the AlcHepNet to evaluate the clinical impact of integrated ALD/AUD treatment in a cohort of patients for whom there are limited treatment options.

project_terms:
Address;Affect;Alcohol consumption;Alcoholic Hepatitis;Alcoholic Liver Diseases;Ancillary Study;Antimicrobial Effect;Antioxidants;Apoptotic;Behavior Therapy;Biological Specimen Banks;Caregivers;Chimeric Proteins;Clinical;Clinical Treatment;Clinical Trials;Collection;Combined Modality Therapy;Compensation;Counseling;Data;Databases;Diagnosis;Eligibility Determination;Evaluation;FDA approved;Funding;Glucocorticoids;Guidelines;Health Personnel;Heavy Drinking;Hepatitis;Hospitals;Individual;Informatics;Interleukin-1 Receptors;Knowledge;Link;Liver;Liver diseases;Measures;Morbidity - disease rate;National Institute on Alcohol Abuse and Alcoholism;Observational Study;Outcome;Patient-Focused Outcomes;Patients;Pharmacotherapy;Phase;Physicians;Prednisone;Quality of Care;Quality of life;Randomized;Randomized Controlled Trials;Regression Analysis;Reporting;Research Design;Research Personnel;Resources;Safety;Site;Steroids;Systems Biology;Translational Research;Transplantation;Zinc;acamprosate;alcohol abstinence;alcohol abuse therapy;alcohol misuse;alcohol use disorder;anakinra;antagonist;behavioral study;care outcomes;catalyst;clinical center;cohort;data repository;drinking;healthy volunteer;improved;interleukin-22;longitudinal database;meetings;mortality;motivational enhancement therapy;new therapeutic target;novel;novel therapeutics;open label;optimal treatments;patient population;patient registry;primary endpoint;programs;prospective;social stigma;standard of care;translational study;treatment as usual;treatment strategy;trial design

public_health_relevance:
:Alcohol-associated liver disease (ALD) is a leading cause of mortality/morbidity and there is no FDA-approved therapy for any stage of ALD. Unfortunately patients with ALD rarely have their underlying alcohol use disorder (AUD) concomitantly addressed. This consortium links health providers with expertise in AUD and ALD in a unified treatment strategy to evaluate novel combined treatments for AUD/ALD in patients with advanced ALD. The exiting resources of the NIAAA-funded consortium are used for patient studies biospecimen collection and site-specific translational studies.


application_id: 11194265
project_number: 5U18FD006519-08
project_title: Assuring Radiation Protection
administering_ic: FDA
award_notice_date: 2025-09-23
opportunity_number: RFA-FD-23-018
application_type: 5
activity_code: U18
ic: FD
serial_number: 006519
program_official: MILLER, DONALD
project_start_date: 2018-09-01
project_end_date: 2028-08-31
study_section: ZFD1-CDRH-K(01)1
contact_pi_person_id: 80356231
contact_pi: BRUEDIGAN, LISA R
other_pis: Not Applicable
congressional_district: 01
department: Unavailable
primary_duns: 115963720
primary_uei: SBT5JJP6JP86
duns_number: 115963720
uei: SBT5JJP6JP86
fips: US
organization_id: 1565201
organization_name: CONFERENCE OF RADIATION CONTROL PROG DIR
organization_city: Frankfort
organization_state: KY
organization_type: Other Domestic Non-Profits
organization_zip: 406013717
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/AbstractThe objective of this cooperative agreement is to coordinate state and federal activities to achieveeffective solutions to present and future radiation control challenges. The Conference of RadiationControl Program Directors (CRCPD) a professional organization whose membership includesrepresentatives of state radiation control programs and whose mission is dedicated to radiationprotection will provide a forum for development of coordinated national radiation policy modelregulations guidance and procedures for the control of sources of radiation in the United States andwill coordinate the interchange of radiation protection experience among the states and between thestates tribes and the federal government. CRCPD will establish and maintain approximately 65committees other working groups and liaisons to other organizations made up of its state and localgovernment members to address specific radiation control problems in the application of radiation in thehealing arts education and industry; the control and mitigation of radiation exposure from all sourcesincluding radiation in the environment and as a result of licensed activities accidents and incidents; andpreparedness for radiological emergencies and homeland security. Work products of the committeeswith oversight by an elected Board of Directors will include updates to the Suggested StateRegulations for Control of Radiation protocols for evaluation of x-ray trends practice guidelines andother model procedures and reports for use by state and local government agencies in maintainingeffective radiation programs.CRCPD will also plan facilitate and provide travel assistance for state representatives for annualmeetings of the National Conference on Radiation Control as an opportunity for member States andother stakeholders to convene and exchange information on radiation issues and new technologies.The conference will include discussions lectures and workshops on radiation priorities as determinedby state and federal planners. CRCPD will also provide radiation protection training sessions inconjunction with the annual meeting and at other times outside of the annual meeting through state-federal workshops and web-based training sessions. CRCPD will also maintain various mechanismsfor access to information for the benefit of the States and other interested parties including: afrequently-updated website for posting of working group products meetings services and opportunitiesfor service as well as a secure site for committees and state agency members to access sensitiveinformation; a periodic newsletter; liaison with other related organizations; broadcast e-mails for time-sensitive information; and use of social media and video-conferencing for major concerns affecting amajority or all of the states.1

public_health_relevance:
Project NarrativeThe objective of this cooperative agreement is to coordinate Federal State and Tribal activitiesto achieve effective solutions to both current and future radiation control challenges. The effortsof volunteers across the nation plus the adoption and implementation of the guidancerecommendations and procedures provided under this project will provide for improved qualityin radiation protection programs throughout the United States. The overall impact of thesecooperative efforts will ultimately reduce the risk of illness and deaths associated withunnecessary radiation exposure from all sources and improve the quality of medical radiationimaging and therapy.


application_id: 11193966
project_number: 5R18HS030202-02
administering_ic: AHRQ
award_notice_date: 2025-09-29
opportunity_number: PA-18-793
application_type: 5
activity_code: R18
ic: HS
serial_number: 030202
program_official: PATEL, SHEENA
project_start_date: 2024-09-30
project_end_date: 2029-07-31
study_section: Healthcare Information Technology Research[HITR]
contact_pi_person_id: 12034450
contact_pi: ABRAHAM, OLUFUNMILOLA
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: 2025-08-01
project_title:
Disseminating and Implementing MedSMAT Families in Emergency Departments: A Randomized Control Trial to Assess Effectiveness of an Evidence-Based Gaming Intervention to Reduce Opioid Misuse

project_abstract:
Project Summary/AbstractAdolescents (ages 12-18) are uniquely at risk for prescription opioid misuse for a variety of reasons includinginadequate knowledge about safety risks easy access to opioids stored improperly in the home and limitedfamily communication about opioid safety in the home. Although adolescents identify parents as useful resourcesfor opioid safety information parents report they do not have the comfort or skills to talk to their children aboutopioid medication safety. Introducing an intervention at the point of care in emergency departments (EDs) (i.e.when an adult is prescribed an opioid prescription) is an accessible low-cost way to provide opioid educationand facilitate communication about opioid medication safety among youth and their families. Althoughadolescents represent a public health priority population no intervention has attempted to improve adolescentand parent knowledge attitudes and behaviors about opioid safety to prevent adolescent opioid misuse in EDs.Our transdisciplinary team with experts in community engagement dissemination and implementation scienceemergency medicine and pediatrics family medicine and community health addiction medicine and substanceuse adolescent and digital health game design biostatistics health economics and mixed-methods researchwill collaborate with a health system: UW Health. The collaboration will lead to the adaptation and evaluation ofa digital health intervention (MedSMAT Mobile) in health system EDs to improve medication safety amongadolescents and their parents thus reducing prescription opioid misuse. The MedSMAT Mobile interventionincorporates the evidence-based serious game  MedSMAT: Adventures in PharmaCity  and a personalizedfamily medication safety plan to promote opioid safety communication between youth and parents.We will use the Exploration Preparation Implementation Sustainment (EPIS) framework to ensure continualoptimization of MedSMAT Mobile in ED settings. Three aims support the goal of reducing opioid misuse foradolescents and their parents. First qualitative evaluation of adolescents parents and ED staff stakeholderswill generate feedback used to iteratively adapt MedSMAT Mobile for its maximal availability in ED settingswhile also informing an Implementation Package for more widespread ED adoption. Second a randomizedcontrolled trial will be used to evaluate effectiveness of MedSMAT Mobile to improve adolescent/parent opioidmisuse knowledge attitudes and behaviors over 9 months. Finally MedSMAT Mobile will be made availablein more EDs and interviews and a survey will be used to evaluate ED staff perceptions of sustainability andorganizational preparedness for sustainability while exploring health cost impact of increased opioid safety.Leadership from the health systems as well as their front-line ED staff are committed to promoting awarenessof this innovative intervention for families receiving an opioid prescription. This is the first preventativeintervention designed in direct response to an unmet critical need identified by the AHRQ Call for Proposals (PA-18-793) to design implement disseminate and spread and evaluate interventions to improve patient safety.

public_health_relevance:
Project NarrativeTeens are at risk for prescription opioid misuse due to easy access to opioids in the home seeing their friendsand parents using opioids incorrectly not talking to their parents about opioid safety and lack of educationalmaterials to prevent misuse. A game-based educational tool (MedSMAT Mobile) exists that helps teens andparents communicate about opioid medication safety and this project will make this tool more available inemergency departments (EDs) in Wisconsin and northern Illinois  by (1) changing MedSMAT Mobile to fit theneeds of individual EDs and their patients (2) testing whether the MedSMAT Mobile tool improves teen/parentopioid misuse knowledge attitudes and behaviors and (3) making the MedSMAT Mobile educational toolavailable in more EDs and getting staff feedback about whether EDs are able to continue to offer it to theirpatients while also showing some financial benefits to patient healthcare. This new evidence-based educationalgame will strengthen families knowledge of opioid medication safety risks while also helping them create apersonalized medication safety plan which can reduce teen opioid misuse.


application_id: 11193812
project_number: 5R44HL158430-03
administering_ic: NHLBI
award_notice_date: 2025-06-30
opportunity_number: PA-23-230
application_type: 5
activity_code: R44
ic: HL
serial_number: 158430
program_official: FENTON, KATHLEEN NELLE
project_start_date: 2021-04-01
project_end_date: 2027-06-30
study_section: Special Emphasis Panel[ZRG1-IVBH-V(11)B]
contact_pi_person_id: 11058700
contact_pi: TOPAZ, STEPHEN R
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 832402486
primary_uei: RK1ZDCXE3LJ7
duns_number: 832402486
uei: RK1ZDCXE3LJ7
fips: US
organization_id: 10024870
organization_name: W-Z BIOTECH, LLC
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 405060286
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2025-07-01
project_title:
Development of a Minimally Invasive Single Cannulation Compact Single Port Pulsatile Ventricular Assist Device (sppVAD) for Total LV Support

project_abstract:
Cardiogenic shock (CS) is a serious condition of low cardiac output with a 40-50% mortality. In severe CShypoperfusion causes multi-organ failure and high left ventricle (LV) preload/wall stress exacerbates cardiacinjury/prevents recovery. Temporary mechanical circulatory support (MCS) is needed to restore perfusion andunload the LV bridging the CS patient to recovery long-term LV assist device (LVAD) or heart transplant.Venoarterial extracorporeal membrane oxygenation is most often used in severe CS but it fails to unload LVin > 50% of these patients with no improved outcomes. Minimally invasive percutaneous MCS devices also donot improve severe CS outcomes since they do not completely restore the circulation. Non-percutaneous MCSdevices provide total support but require open chest surgery and are not ambulation friendly. Impella 5.5 hasbecome the preferred MCS device for CS. Yet patients with an Impella 5.5 must stay in ICU with very limitedambulation. Thus a big market gap exists for an ideal temporary MCS device that: 1) is minimally invasive 2)provides total LV support and 3) enables easy ambulation. Our goal is to develop a new temporary MCSsystem that provides total LV support via a minimally invasive technique with easy ambulation enabling patientdischarge for at-home MCS. Our device will provide one month MCS (potential for up to 3 months) to bridgesevere CS patient to further treatment recovery durable VAD or heart transplant. Our enabling technologyis a single port pulsatile ventricular assist device (sppVAD) system that includes valved single lumen cannula(VSLC) valveless single port diaphragm displacement pump (spDDP) and compact/portable console. OursppVAD system has following novel design:1) One VSLC for withdrawal and infusion; 2) single lumen designdoubles usable area to reduce circuit blood resistance for >6 L/min pumping; 3) One transapical to aortacannulation for minimally invasive installation; 4) Only one port reduces pump size for easy ambulation; 5)Simple valveless pump geometry for better durability and 1-month MCS. In the Phase I SBIR our sppVADsystem achieved >6 L/min pulsatile flow in bench test and 6 hr total LV unloading in sheep. Specific Aim 1:Optimize and fabricate VSLC valveless spDDP and compact/portable console for the sppVAD system.The VSLC will be made of reinforced polyurethane (PU). Inlet valves will be in LV for blood withdrawal. A tri-leaflet outlet valve on VSLC tip will be in aorta for blood delivery. The spDDP will be made of polycarbonatewith a PU diaphragm. A compact/portable console will also be developed. Specific Aim 2: Bench test thesppVAD system for performance durability and hemocompatibility. The sppVAD system will be tested inmock loop for performance/durability and in an in vitro loop with bovine blood to quantify hemolysis. SpecificAim 3: Perform 4-week preclinical testing of sppVAD system in sheep. A near commercial quality sppVADsystem will be tested in sheep (n=10) for safety/biocompatibility/reliability. Our novel sppVAD system fills alarge unmet need for ambulatory at-home temporary total LV support to improve patient outcomes.

project_terms:
Aorta;Apical;Area;Biotechnology;Blood;Cannulas;Cannulations;Cardiac;Cardiogenic Shock;Cattle;Circulation;Clinical;Dedications;Development;Devices;Drainage procedure;Engineering;Ensure;Extracorporeal Membrane Oxygenation;Failure;Friends;Geometry;Goals;Heart;Heart Injuries;Heart Transplantation;Hemolysis;Home;Housing;In Vitro;Infusion procedures;Kentucky;Laboratory Animal Production and Facilities;Left ventricular structure;Life;Low Cardiac Output;Lung;Marketing;Multiple Organ Failure;Organ;Outcome;Patient Discharge;Patient-Focused Outcomes;Patients;Performance;Perfusion;Phase;Polyurethanes;Preclinical Testing;Pulsatile Flow;Pump;Recovery;Resistance;Respiratory Diaphragm;Safety;Scientist;Self-Help Devices;Sheep;Small Business Innovation Research Grant;Stress;Support System;Surgeon;System;Techniques;Technology;Testing;Thoracic Surgical Procedures;Universities;Withdrawal;ascending aorta;bench testing;biomaterial compatibility;commercialization;design;experience;fabrication;flexibility;hemocompatibility;hypoperfusion;implantation;improved;improved outcome;in vivo;innovation;invention;mechanical circulatory support;minimally invasive;mortality;multidisciplinary;myocardial injury;novel;polycarbonate;portability;prevent;purge;research and development;restoration;usability;ventricular assist device

public_health_relevance:
We are proposing to develop a single port pulsatile ventricular assist device (sppVAD) for total leftventricle (LV) support that employs a minimally invasive single cannulation technique for implantation andfeatures a compact size/easy ambulation for patient discharge/at-home mechanical circulatory support. Ourenabling technologies that form the sppVAD system are a valved single lumen cannula (VSLC) a valvelesssingle port diaphragm displacement pump (spDDP) and a compact/portable console. Our sppVAD system is anovel invention that fills a large unmet clinical need for a minimally invasive ambulatory at-home temporarytotal LV support to improve patient outcomes.


application_id: 11192863
project_number: 5R00DE031825-04
project_title: The Role of SoxE Transcription Factors in Neural Crest Cell Specialization
administering_ic: NIDCR
award_notice_date: 2025-07-23
opportunity_number: PA-20-188
application_type: 5
activity_code: R00
ic: DE
serial_number: 031825
program_official: SAIFUDEEN, ZUBAIDA
project_start_date: 2024-09-16
project_end_date: 2027-08-31
study_section: NSS
contact_pi_person_id: 12157988
contact_pi: SCHOCK, ELIZABETH (BETSY)
other_pis: Not Applicable
congressional_district: 06
department: BIOCHEMISTRY
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/AbstractNeurocristopathies are a class of syndromes that are predominately characterized by malformations in thecraniofacial complex. These defects are caused by aberrant development of the neural crest a stem cellpopulation unique to vertebrates. One distinctive feature of the neural crest is their ability to give rise to bothectomesenchymal (bone/cartilage) and non-ectomesenchymal (melanocytes and peripheral neurons/glia)derivatives. SoxE transcription factors play important roles in both the formation and the diversification of theneural crest. All three SoxE factors (Sox8 Sox9 and Sox10) function redundantly to promote neural crestformation. Interestingly individual SoxE factors direct the differentiation of the neural crest into distinct lineages.Sox9 promotes chondrogenesis while Sox10 supports both the melanocyte and peripheral neuron/glial fates. Anoutstanding question is how these highly similar SoxE factors lead to neural crest specialization. This proposalutilizes omics-based approaches gain and loss of function experiments and Sox9-Sox10 chimera constructs toassess how and when SoxE-mediated neural crest specialization occurs. Furthermore mutations in SOX9 andSOX10 are causative for Campomelic dysplasia and Waardenburg syndrome respectively. The syndromespresent with very different craniofacial phenotypes which are reflective of SOX9/SOX10 specific defects duringneural crest specialization. Work from this study will lead to the identification of novel SoxE transcriptional targetsdetermine when SoxE factors begin to promote neural crest specialization and determine how specific patientvariants for Campomelic dysplasia/Waardenburg syndrome cause disease phenotypes. Overall this work is ofhigh clinical significance and will provide evolutionary insights into the molecular origins of neural crestdiversification. My primary goal for the mentored phase of this proposal is to identify when SoxE factors begin topromote lineage specialization within the neural crest and determine the functional domains that contribute toSoxE family subfunctionalization. I plan to use my remaining time as a postdoctoral fellow to master newexperimental techniques and develop robust computational analyses. I will capitalize on the rich academicenvironment of Northwestern University especially the expertise in NSF-Simons Center for Quantitative Biology.My long-term career goal is to establish an independent research program that uses multiple model systems toinvestigate the cellular and molecular origins of syndromes characterized by craniofacial phenotypes. I plan touse Sox transcription factors (and associated syndromes) as a starting point in my career but then extend myresearch interests to other gene families through collaboration with clinicians. My measurable experience withvarious model organisms will allow me to investigate biochemical molecular cellular and morphological aspectsof developmental disorders by exploiting the benefits of each model system.

project_terms:
ATAC-seq;Biochemical;Biological Models;Biology;Brightfield Microscopy;Cartilage;Cell Culture Techniques;Cells;ChIP-seq;Chick;Chimera organism;Chimeric Proteins;Chondrogenesis;Chromatin;Collaborations;Computer Analysis;Congenital Abnormality;Coupled;Craniofacial Abnormalities;DNA Binding Domain;Data Analyses;Defect;Development;Disease;Dominant-Negative Mutation;Embryo;Environment;Etiology;Face;Family;Future;Gene Activation;Gene Family;Genes;Genetic Transcription;Genome;Genotype;Global Change;Goals;Heterogeneity;Human;Individual;Lead;Link;Measurable;Mediating;Mentors;Molecular;Morphology;Mutation;Neural Crest;Neural Crest Cell;Neuroglia;Neurons;Patients;Peripheral;Peripheral Nervous System;Phase;Phenotype;Pigments;Play;Population;Postdoctoral Fellow;Proteins;Research;Role;SOX8 gene;Specificity;Stains;Syndrome;Tadpoles;Techniques;Tertiary Protein Structure;Time;Universities;Variant;Vertebrates;Waardenburg syndrome;Work;Xenopus;Xenopus laevis;bone;campomelic dysplasia;career;cell type;clinically significant;craniofacial;craniofacial complex;craniofacial development;craniofacial disorder;developmental disease;directed differentiation;disease phenotype;experience;experimental study;gain of function;insight;interest;loss of function;malformation;melanocyte;migration;model organism;neurodevelopment;novel;programs;screening;stem cell population;transcription factor;transcriptome sequencing;work-study

public_health_relevance:
Project NarrativeCraniofacial defects are among the most common of all congenital abnormalities. An embryonic population ofcells called the neural crest gives rise to a significant portion of the craniofacial complex including bone andcartilage of the face pigment cells and components of the peripheral nervous system. My work seeks tounderstand how a subfamily of transcription factors (SoxE) help the neural crest form the diversity of cell typesin the face and how patient specific SOXE mutations cause Campomelic dysplasia and Waardenburg syndrome.


application_id: 11192378
project_number: 5R01AR070313-07
project_title: Deciphering how tissue resident macrophages regulate musculoskeletal regeneration in spiny mice
administering_ic: NIAMS
award_notice_date: 2025-08-15
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: AR
serial_number: 070313
program_official: BELKIN, ALEXEY
project_start_date: 2017-03-13
project_end_date: 2029-07-31
study_section: Surgery, Anesthesiology and Trauma Study Section[SAT]
contact_pi_person_id: 10345749
contact_pi: SEIFERT, ASHLEY WINN
other_pis: Not Applicable
congressional_district: 06
department: BIOLOGY
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:
One path towards generating new therapeutic avenues to induce regeneration is understanding fundamentaldifferences between a regenerative and scarring response to injury. When tissue regeneration in spiny mice(Acomys) is studied in parallel with rodent models of scarring (e.g. laboratory mice - Mus) this comparativeapproach can uncover fundamental cell states and molecular signals that explain how identical injuries followone healing trajectory instead of the other. At the outset of either healing type tissue trauma stimulates sterileinflammation that first protects and then resolves the injury. Inflammation is orchestrated by macrophageswhose phenotypic states can have diverse functions. While current data supports that macrophages arerequired for proper wound healing whether macrophages specifically regulate musculoskeletal regeneration ispoorly understood. The long-term goal of our research is to uncover key molecular signals and cell states thatdirect mammalian musculoskeletal injuries towards regenerative healing. The objective of this proposal is tounderstand how tissue resident macrophages (TR-MFs) and their secreted products specifically regulateregeneration in spiny mice and to manipulate the wound microenvironment in laboratory mice to enhanceregenerative healing. The central hypothesis we will test is that TR-MFs are required separately during thewound healing and tissue generation stages of regeneration to first regulate inflammatory magnitude andoxidative stress and then to facilitate cell proliferation. This hypothesis is based upon our published andpreliminary studies demonstrating that when spiny mouse TR-MFs are depleted prior to injury regeneration isinhibited and Acomys TR-MFs uniquely produce secreted molecules such as VEGFc and lactoferrin (LTF)that are important for regeneration. Guided by strong preliminary data this hypothesis will be tested bypursuing the following three specific aims: (1) Asses how TR-MFs separately regulate cellular inflammationand new tissue formation during regeneration by depleting TR-MFs in spiny mice and using establishedassays to assess re-epithelialization inflammation extracellular matrix production and proliferation. Single cellRNA-sequencing will also be deployed to analyze how loss of TR-MFs alters resident cell states and behavior.(2) Define the species-specific epigenetic and transcriptional landscape of TR-MFs during regeneration(Acomys) versus scar formation (Mus) to discover the genetic program controlling TR-MF identity in spiny miceand (3) functionally assess if exogenous lactoferrin delivered to Acomys injuries in the absence of TR-MFs cancontrol inflammation and permit cell proliferation and when delivered to mouse injuries enhance healing. Theapproach is innovative in the applicants opinion because it explicitly focuses on understanding how complextissue regeneration occurs naturally in an adult mammal. The proposed research is significant because it isexpected to provide new and fundamental insight into how TR-MFs regulate musculoskeletal healing andbecause our discoveries can inform novel clinical interventions to reduce fibrosis and stimulate regeneration.

project_terms:
Acomys;Adult;Behavior;Biological Assay;Cell Aging;Cell Cycle Progression;Cell Proliferation;Cell Senescence Induction;Cells;Chromatin;Cicatrix;Clinical Treatment;Complement;Complex;Data;Dichloromethylene Diphosphonate;Drug or chemical Tissue Distribution;Ear;Epigenetic Process;Extracellular Matrix;Fibrosis;Gene Expression;Generations;Genetic;Genetic Transcription;Goals;Human;Infiltration;Inflammation;Inflammatory;Injury;Laboratory mice;Lactoferrin;Leucocytic infiltrate;Liposomes;Macrophage;Mammals;Molecular;Mus;Musculoskeletal;Natural regeneration;Oxidative Stress;Phase;Phenotype;Production;Proliferating;Public Health;Publishing;Research;Resolution;Rodent;Rodent Model;Signal Transduction;Spatial Distribution;Sterility;Stress;Stromal Cells;Testing;Tissue atlas;Tissues;VEGFC gene;Work;cell type;comparative;cytokine;disability;external ear auricle;healing;improved;injured;innovation;insight;multiple omics;musculoskeletal injury;novel;novel therapeutics;programs;re-epithelialization;regenerative;regenerative healing;regenerative tissue;repaired;response;response to injury;single nucleus RNA-sequencing;single-cell RNA sequencing;tissue regeneration;tissue trauma;transcriptome sequencing;wound;wound healing

public_health_relevance:
PROJECT NARRATIVESpiny mice naturally regenerate complex musculoskeletal tissues whereas other mammals use scar tissue torepair identical injuries. Thus the proposed research is relevant to public health because discovering the celltypes and molecules that permit and direct this unique example of mammalian regeneration is expected togenerate novel clinical interventions to reduce fibrosis and enhance healing in humans. Stimulating tissueregeneration greatly improves the functionality of injured tissue and will help reduce the burden humandisability.


application_id: 11192351
project_number: 5R01HL158779-04
project_title: Low Density Neutrophils Link Inflammation and Coagulopathy in COVID-19
administering_ic: NHLBI
award_notice_date: 2025-09-08
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: HL
serial_number: 158779
program_official: AGRAWAL, NITIN
project_start_date: 2022-09-23
project_end_date: 2026-08-31
study_section: Innate Immunity and Inflammation Study Section[III]
contact_pi_person_id: 6983402
contact_pi: YAN, JUN
other_pis: HUANG, JIAPENG ;URIARTE, SILVIA M
congressional_district: 03
department: SURGERY
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 Coronavirus disease 2019 (COVID-19) is a potentially life threatening disease caused by the novel viralpathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of COVID-19patients experience severe disease typically presenting with bilateral pneumonia and about 5% progress toacute respiratory distress syndrome (ARDS). ARDS results from a combination of virally induced lung injury andthe rapid influx of immune cells that release inflammatory mediators leading to a hyper-activated state known ascytokine storm. COVID-19 ARDS is further exacerbated by a unique diffuse coagulopathy leading to thrombusformation in the venous and arterial circulations and microthrombi in capillaries of the lungs. Predisposing factorsfor this coagulopathy include increased fibrinogen activated coagulation cascade platelet activation hyper-inflammation neutrophil extracellular trap (NET) formation and endothelial cell damage. Understanding thepathophysiology of COVID-19 coagulopathy and ARDS is critical to finding effective therapeutic interventions.Accumulating evidence indicates critical roles of neutrophils in both ARDS and immunothrombosis in COVID-19.Our preliminary studies identified a novel population of low-density neutrophils (LDN) which expressesintermediate levels of CD16 (CD16Int LDN) in COVID-19 patients. The number of CD16Int LDN correlated withdisease severity levels of inflammatory cytokines IL-6/TNF-a D-dimer levels and clinical outcomes. In additionCD16Int LDN showed spontaneous NET formation and evidence of in vivo platelet activation and granuleexocytosis. Based on these findings we postulate that CD16Int LDN play a critical role in the induction ofcoagulopathy and pulmonary inflammation in severe and critical COVID-19 patients. Three specific Aimsare proposed to further dissect the underlying mechanisms. Aim 1 will comprehensively characterize LDNsubsets using proteomics and transcriptomics approaches. The information gained from those studies will beused to refine our CyTOF antibody panel. We will use this panel to track differential neutrophil clusters inlongitudinal patient samples. Aim 2 will determine LDN subsets functional changes during disease progressionand their contributions to dysregulated inflammatory response and coagulopathy in severe and critical COVID-19 patients. Neutrophil degranulation NET formation phagocytosis chemotaxis apoptosis and cytokinerelease will be examined. We will also determine if LDN promote coagulopathy in COVID-19 patients. Aim 3 willdetermine whether inhibition of neutrophil granule exocytosis using our novel TAT-fusion protein inhibitorsprevents activated neutrophil-mediated functional changes and hypercoagulation. We will also use a hACE2 Tgmouse model to determine the in vivo efficacy of TAT-fusion proteins on lung inflammation and impaired function.Successful completion of this proposal will provide novel insights into COVID-19 pathophysiology by defining therole of a unique subset of neutrophils and by establishing neutrophil degranulation as a therapeutic target forinhibiting inflammatory lung injury and immunothrombosis in COVID-19.

project_terms:
2019-nCoV;Acute Lung Injury;Acute Respiratory Distress Syndrome;Alpha Granule;Antibodies;Apoptosis;Arteries;Bilateral;Blood Coagulation Disorders;Blood capillaries;Blood specimen;Bronchoalveolar Lavage Fluid;COVID-19;COVID-19 patient;COVID-19 severity;COVID-19/ARDS;Cells;Chemotaxis;Chimeric Proteins;Circulation;Clinical;Coagulation Process;Cytoplasmic Granules;Data;Diffuse;Disease;Disease Outcome;Disease Progression;Economics;Endothelial Cells;Exocytosis;Exocytosis Inhibition;FCGR3B gene;Fibrin fragment D;Fibrinogen;Functional disorder;Gene Expression;Hemorrhage;Histologic;Hypoxia;Immune;Impairment;In Vitro;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;Interleukin-6;Life;Link;Lower respiratory tract structure;Lung;Lymphocyte;Measures;Mediating;Modeling;Neutrophil Infiltration;Outcome;Patients;Pattern;Perfusion;Phagocytosis;Plasma;Platelet Activation;Platelet Count measurement;Play;Pneumonia;Population;Predisposing Factor;Proteome;Proteomics;Pulmonary Inflammation;Reactive Oxygen Species;Respiratory Burst;Role;SARS-CoV-2 negative;Sampling;Severity of illness;Structure of parenchyma of lung;Surface;T-Lymphocyte;TNF gene;Therapeutic;Therapeutic Intervention;Thrombus;Time;Venous;Viral;antimicrobial;cell injury;cytokine;cytokine release syndrome;cytotoxic;density;design;exhaustion;experience;extracellular;immune activation;immunoregulation;immunothrombosis;in vivo;inhibitor;insight;lung injury;mouse model;neutrophil;novel;novel marker;novel therapeutic intervention;pandemic disease;pathogenic virus;peripheral blood;prevent;respiratory pathogen;response;therapeutic target;therapeutically effective;transcriptome sequencing;transcriptomics;treatment effect;ventilation

public_health_relevance:
Project NarrativeSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and has resulted inongoing pandemic tragic loss of life and dire economic consequences. COVID-19 patients with severeand critical disease also develop pulmonary inflammation and abnormal bleeding problems. We proposeto study the mechanisms underlying these problems and develop a novel therapeutic approach; this willhelp us achieve rapid progress toward overcoming the challenges of COVID-19.


application_id: 11190450
project_number: 4UH3NS134920-03
project_title: Long-acting aldicarb hydrolase as a medical countermeasure for aldicarb poisoning
administering_ic: NINDS
award_notice_date: 2025-08-28
opportunity_number: PAR-22-209
application_type: 4
activity_code: UH3
ic: NS
serial_number: 134920
program_official: SPRIGGS, SHARDELL M
project_start_date: 2023-09-01
project_end_date: 2028-08-31
study_section: Special Emphasis Panel[ZRG1-KUDS-F(50)]
contact_pi_person_id: 10880007
contact_pi: ZHENG, FANG
other_pis: ZHAN, CHANG-GUO
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
project_abstract:
As one of the Chemicals of Concern (CoC) identified by the US Department of Homeland Security aldicarbbelongs to the Cholinergic Warfare and Pesticides category. As the most toxic carbamate pesticide  a potentfast-acting inhibitor of acetylcholinesterase (AChE) aldicarb is readily absorbed from all routes of exposureincluding oral and dermal exposure. In all species tested the acute oral toxicities of aldicarb are similar. Due toits physical properties documented in literature aldicarb could be used by terrorists to cause mass casualty.Organophosphorus (OP) warfare/pesticides and carbamate pesticides have a common mode of action for theirneurotoxicity as AChE inhibitors. Currently available options for treating this type of poisoning such asadministration of atropine or co-administration of atropine and pralidoxime (2-PAM) have limited efficacy. Therehave been extensive efforts in development of improved options for treatment of OP poisoning. Relatively lessstudies have been carried out in development of aldicarb poisoning treatment. Reported studies indicated that2-PAM had neither positive nor negative effects on survival in animal studies on aldicarb intoxication. Thisoutcome is understandable as 2-PAM was developed to reactivate phosphorylated AChE (an intermediateformed from the inhibition reaction of AChE with an OP) but not carbamylated AChE (an intermediate formedfrom the reaction of AChE with a carbamate like aldicarb). It is highly desired to develop a new effective post-exposure treatment option for aldicarb poisoning. This investigation will focus on rational design and discoveryof an engineered enzyme capable of rapidly and efficiently detoxifying aldicarb as a catalytic aldicarbbioscavenger for aldicarb poisoning. As an effective bioscavenger it must be able to react with aldicarb morerapidly than AChE so as to protect AChE from reaction (carbamylation) with aldicarb. In preliminary studies wehave demonstrated that an Fc-fused cocaine hydrolase (Fc-CocH) developed previously in our lab for treatmentof cocaine use disorders (CUDs) can more potently bind with aldicarb than with AChE and wild-typebutyrylcholinesterase (BChE) and can also catalyze aldicarb hydrolysis. In further in vivo rescue experiment thisFc-CocH protein powerfully rescued all mice that had been injected intraperitoneally (IP) with a lethal dose (~2 LD50) of aldicarb. With the encouraging preliminary data taking advantage of our positive experience inpreclinical and clinical development of Fc-CocHs we propose to first evaluate an in-house library of Fc-CocHsfor their activities with aldicarb in order to select the one with the highest catalytic activity for aldicarb hydrolysisand the best overall in vivo profiles followed by lead optimization to optimize its catalytic activity against aldicarbsubstrate selectivity post-exposure in vivo efficacy and toxicity/immunogenicity profiles. Accomplishment of thisinvestigation will deliver a couple of safe highly efficient aldicarb hydrolases that are promising for treatment ofaldicarb poisoning. The one with the best overall in vivo profiles will serve as a clinical candidate and the secondbest will serve as a backup for further preclinical and clinical development in the future.

project_terms:
Acetylcholinesterase;Acetylcholinesterase Inhibitors;Acute;Aerosols;Aftercare;Air;Aldicarb;Animal Model;Animals;Atropine;Binding;Biological Assay;Brain;Butyrylcholinesterase;Carbamates;Categories;Cavia;Chemical Warfare;Chemicals;Clinical;Cocaine;Cocaine use disorder;Computer Models;Control Groups;Convulsions;Corn Oil;Data;Development;Dose;Drug Metabolic Detoxication;Engineering;Enzymes;Evaluation;Exposure to;Future;Hour;Human Engineering;Hydrolase;Hydrolysis;Hyperactivity;In Vitro;Intoxication;Investigation;Lead;Lethal Dose 50;Libraries;Literature;Molecular;Mus;Oral;Organophosphorus Compounds;Outcome;Oximes;Paraoxon;Pesticides;Phosphorylation;Poisoning;Polymers;Proteins;Rattus;Reaction;Reporting;Research;Safety;Sarin;Security;Soman;Talc;Testing;Toxic effect;absorption;acute toxicity;aged;bioscavenger;blood-brain barrier crossing;cholinergic;clinical candidate;clinical development;computer studies;cyclosarin;dermal exposure;drug candidate;experience;experimental study;exposure route;immunogenicity;improved;in vivo;intraperitoneal;lead optimization;mass casualty;medical countermeasure;mortality;nerve agent;neurotoxicity;novel;pharmacokinetics and pharmacodynamics;physical property;preclinical development;programs;rational design;success;tabun

public_health_relevance:
This investigation may lead to discovery of a promising protein drug candidate to be developed for treatment ofaldicarb poisoning in the future.


application_id: 11189664
project_number: 5K99AA031309-02
administering_ic: NIAAA
award_notice_date: 2025-08-27
opportunity_number: PA-20-187
application_type: 5
activity_code: K99
ic: AA
serial_number: 031309
program_official: HAGMAN, BRETT THOMAS
project_start_date: 2024-09-15
project_end_date: 2026-08-31
study_section: Clinical, Treatment and Health Services Research Study Section[AA-3]
contact_pi_person_id: 78770053
contact_pi: RZESZUTEK, MARK JUSTIN
other_pis: Not Applicable
congressional_district: 06
department: FAMILY 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
budget_start_date: 2025-09-01
project_title:
Examining the Relationship Between Ongoing Alcohol Use Suicidal Thoughts and Behaviors and Related Constructs and Behavioral Economic Decision-Making

project_abstract:
PROJECT SUMMARY Factors that lead to suicidal thoughts and behaviors (STBs; i.e. passive or active suicidal ideationbehaviors plans gestures or attempts) are complex. An important factor in suicide deaths and attempts isalcohol use; up to 36% of completed suicides involve acute alcohol use while those with AUD may account forup to 20-40% of suicides. Despite this relationship processes that may underlie the two are unclear. Acommon variable between alcohol use and STBs appears to be behavioral economic decision-making such asdelay discounting (i.e. devaluing a commodity as a function of time). However other forms of discounting (i.e.probability; devaluing an outcome based on its likelihood social; devaluing an outcome based on thecloseness of another) have not been explored. Other behavior economic decision-making such as demand foralcohol (i.e. continued purchasing and consumption a commodity as prices increase) has been related toincreased discounting. Furthermore losses of close social supports through suicide or overdose death couldresult in allocation towards further alcohol use which could affect decision-making and therefore affect suiciderisk. Together excessive discounting and demand with losses of social reinforcers might be markers forsuicide risk for those with excessive alcohol use. Behavioral economic decision-making has also beenpredictive of engagement and success of substance use treatment. The contextualized reinforcer pathologymodel allows for integration of these different factors to help better understand how alcohol use could influencesuicide risk as well as who might engage in treatment for alcohol use. Therefore the purpose of this proposedK99/R00 is to determine relationships between alcohol use behavioral economic decision-makingbereavement and STBs within a contextualized reinforcer pathology framework. In Study 1 (K99) this will firstbe assessed within a group of adults with risky alcohol use (n = 100) to determine cross-sectional associationsprevalence of STBs in this sample and determine factors that predict engagement with a remote interventionfor alcohol and its effects on alcohol use. Participants will complete a baseline assessment and be givenaccess for remote self-guided CBT4CBT modules for alcohol use. Participants will also complete three follow-up assessments over three months to determine engagement with CBT4CBT and changes in alcohol use. InStudy 2 (R00) adults with risky alcohol use without current STBs (n = 100) and with current STBs (n = 100) willbe compared using a 2x2 design to further determine relationships between alcohol use and STBs (Study2/R00). Half will be randomized to immediate access to CBT4CBT while the other will be waitlist controls andreceive access 28 days later with remaining procedures being similar to Study 1. This allows for determinationof predictors of engagement and efficacy of a remote intervention for alcohol use as a function of STBs. Thiswill allow the candidate to develop skills in alcohol use and STB research and initiate an independent careerpath uncovering factors that underly the relationship between alcohol use and suicide risk.

project_terms:
Acute;Adherence;Adult;Affect;Alcohol consumption;Alcohols;Behavior;Behavioral;Bereavement;Career Choice;Cessation of life;Cognitive;Complex;Consumption;Control Groups;Data;Decision Making;Dose;Exposure to;Feeling suicidal;Gestures;Heavy Drinking;Individual;Literature;Measures;Mediating;Mental Health;Methods;Modeling;Outcome;Overdose;Participant;Pathology;Pathway interactions;Patient Self-Report;Persons;Pharmaceutical Preparations;Population;Predictive Factor;Prevalence;Price;Probability;Procedures;Process;Randomized;Recording of previous events;Research;Research Personnel;Rewards;Risk;Role;Sampling;Self Direction;Self-control as a personality trait;Series;Severities;Social support;Suicide;Suicide attempt;Time;Training;Uncertainty;Waiting Lists;addiction;alcohol abuse therapy;alcohol demand;alcohol intervention;alcohol measurement;alcohol risk;alcohol use disorder;behavioral economics;completed suicide;cost;design;discounting;economic behavior;efficacy evaluation;experience;experimental study;follow up assessment;overdose death;prospective;reinforcer;remote intervention;skills;social;substance use treatment;success;suicidal behavior;suicidal morbidity;suicidal risk;suicide rate

public_health_relevance:
PROJECT NARRATIVE Alcohol use and suicidal thoughts and behaviors are strongly related but the exact relationship betweenalcohol and suicide risk is poorly understood. Behavioral economic decision-making such as rapid devaluingof delayed rewards (i.e. delay discounting) appears to be a common factor for increased alcohol use andsuicidal thoughts and behaviors. The proposed research is to better understand how behavioral economicdecision-making differs between individuals who use alcohol and those who use alcohol and have suicidalthoughts and behaviors.


application_id: 11189002
project_number: 5R01DK124619-05
administering_ic: NIDDK
award_notice_date: 2025-07-14
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: DK
serial_number: 124619
program_official: NIHALANI, DEEPAK
project_start_date: 2024-05-01
project_end_date: 2027-06-30
study_section: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]
contact_pi_person_id: 10526655
contact_pi: CHHABRA, KAVALJIT H
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
budget_start_date: 2025-07-01
project_title:
Role of Hypothalamic MC4R in Glucose Homeostasis via a Novel Neuroendocrine Circuit involving the Kidneys and Adrenal Glands

project_abstract:
We recently identified the contribution of hypothalamic MC4R in regulating blood glucose levels by influencing glycosuria through epinephrine and renal GLUT2. Moreover we have demonstrated previously that diabetes decreases the hypothalamic Mc4r expression that consequently leads to defective counterregulatory response (CRR) to glucose deficits in mice. The molecular and integrative mechanisms underlying these clinically significant observations remain unknown. Specifically how does hypothalamic MC4R regulates plasma epinephrine levels? Does a neural crosstalk between the hypothalamic MC4R and kidney GLUT2 coordinate the regulation of systemic glucose homeostasis via epinephrine? In our Preliminary Studies we observed that MC4R restoration selectively in the corticotropin releasing hormone (CRH) neurons normalized plasma epinephrine levels in otherwise MC4R-deficient mice indicating the role of MC4R- expressing CRH neurons in regulating plasma epinephrine levels. Unexpectedly kidney-specific Glut2 knockout mice are protected from diabetes-mediated defective CRR to hypoglycemia and the mice show increased Mc4r and Crh mRNA levels in the hypothalamus suggesting the influence of renal GLUT2 on the hypothalamic melanocortin system. Our Preliminary Data also indicate the contribution of renal but not liver gluconeogenesis toward restoration of normal blood glucose levels following hypoglycemia in the kidney-specific Glut2 knockout mice. Based on these preliminary findings we hypothesize that hypothalamic MC4R-expressing CRH neurons are activated by the afferent renal nerves in response to glucose deficits to enhance plasma epinephrine which in turn increases renal gluconeogenesis and restores blood glucose levels. Moreover elevated kidney GLUT2 levels in diabetes compromises this activation of MC4R-expressing CRH neurons to impair counterregulatory response to hypoglycemia. We will test the hypotheses with the following Aims Aim1: Determine the role of hypothalamic MC4R-expressing CRH neurons in integrating signals from renal afferent nerves to increase plasma epinephrine in response to hypoglycemia. Aim2: Identify the molecular and integrative (central versus peripheral) mechanisms  chronically elevated renal GLUT2 decreased renal afferent nerve activity and/or blunted activation of hypothalamic MC4R-expressing CRH neurons - through which diabetes compromises the bodys ability to defend against hypoglycemia. Aim3: Establish the contribution of renal gluconeogenesis as a source of glucose to defend against hypoglycemia and identify the renal adrenergic receptors through which epinephrine increases glucose reabsorption and renal gluconeogenesis. Altogether this project will likely identify a novel neuroendocrine circuit underlying the crosstalk between the hypothalamus kidney and adrenal gland to coordinate systemic glucose homeostasis. This integrative circuit will probably inform the molecular basis of how diabetes compromises the bodys ability to increase plasma epinephrine in the face of glucose deficits leading to hypoglycemia-associated autonomic failure a life- threatening condition in patients with type 1 or late-stage type 2 diabetes.

project_terms:
Ablation;Adrenal Glands;Adrenergic Receptor;Affect;Bilateral;Blood Glucose;Cause of Death;Chronic;Corticotropin-Releasing Hormone;Data;Defect;Diabetes Mellitus;Enzymes;Epinephrine;Epithelial Cells;Event;Excision;Exhibits;Failure;GLUT-2 protein;Genes;Gluconeogenesis;Glucose;Glycosuria;Goals;Hypoglycemia;Hypothalamic structure;Impairment;Kidney;Knock-out;Knockout Mice;Life;Link;Longitudinal Studies;Mediating;Melanocortin 4 Receptor;Messenger RNA;Molecular;Mus;Nerve;Neurons;Neurosecretory Systems;Non-Insulin-Dependent Diabetes Mellitus;Pathway interactions;Patients;Peripheral;Pilot Projects;Plasma;Plasma Enhancement;Population;Pro-Opiomelanocortin;Probability;Proximal Kidney Tubules;Publishing;Reagent;Regulation;Reporting;Research Project Grants;Role;SLC2A1 gene;Signal Transduction;Source;System;Testing;Work;absorption;afferent nerve;beta-adrenergic receptor;blood glucose regulation;clinically significant;defined contribution;innovation;knock-down;mad itch virus;mouse model;neural;novel;response;restoration;small hairpin RNA

public_health_relevance:
Diabetes affects nearly 10% of US population. It is the seventh leading cause of death in the US. In this research project we will define the contribution of a novel neuroendocrine circuit involved in glucose homeostasis. The results of this study may help us mitigate fatal events of hypoglycemia in patients with diabetes.


application_id: 11184222
project_number: 5U24GM146576-04
project_title: University of Kentucky SuRE Resource Center
administering_ic: NIGMS
award_notice_date: 2025-09-15
opportunity_number: PAR-21-227
application_type: 5
activity_code: U24
ic: GM
serial_number: 146576
program_official: BASKIR, RUBIN SAM
project_start_date: 2022-09-05
project_end_date: 2027-08-31
study_section: ZGM1-RCB-4(RC)
contact_pi_person_id: 1879406
contact_pi: SPEAR, BRETT
other_pis: MURPHY, MICHAEL PAUL
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:
SUMMARYThe overarching goal of the University of Kentucky SuRE Resource Center (UK-SuRE) supported by anNIGMS U24 grant is to assist faculty and Office of Sponsored Project (OSP) staff at SuRE-eligibleinstitutions (<$6 million in NIH funding >25% PELL eligible students) prepare and submit competitive NIHgrants applications with an emphasis on SuRE and SuRE-First awards. To accomplish this goal UK facultyand research support staff with experience in all aspects of NIH grant applications will share theirknowledge with those at SuRE-eligible institutions through a series of webinars workshops and directconsultation. Three regional coordinators will provide vital links between faculty and OSP staff at SuRE-eligible institutions and faculty and research support staff at UK-SuRE. This center will also coordinatebiennial SuRE Conferences and oversee a competitive seed grant program that will provide funds forSuRE-eligible institutions to establish or grow OSPs. Specifically four aims are proposed: (1) Assist SuRE-eligible faculty write grants and manage research programs with success being measured by number ofgrants submitted scored and funded; number of publications seminars; and meeting presentations; andtenure and promotion outcomes; (2) Assist SuRE-eligible institutions to establish and grow OSPs andresearch infrastructure with success being measured by growth/establishment of OSPs in SuRE-eligibleinstitutions number of research grants received and overall research funding at these institutions andquestionnaires for SuRE faculty regarding the quality of in-house OSP services; (3) Grow the number ofinstitutions that participate in the SuRE Program and establish an interactive community of SuRE-eligibleinstitutions with success being measured by the number of institutions that participate in webinars attendthe biennial conference and submit NIH grants (with an emphasis on SuRE applications) as well as theamount of peer-to-peer faculty mentoring and social media engagement; and (4) Enhance the researchexperience for students who are working in NIH-funded labs in SuRE-eligible institutions with successbeing measured by student conference presentations authorship on publications degrees earned andpost-graduate employment. Taken together these activities will enhance the research capacity at SuRE-eligible institutions and promote high-quality student-centric biomedical research. In the process theseoutcomes will contribute to diversifying and strengthening the nations research enterprise.

project_terms:
Applications Grants;Area;Authorship;Award;Biomedical Research;Communication;Communities;Consultations;Data;Educational workshop;Eligibility Determination;Employment;Ensure;Face;Faculty;Feedback;First Independent Research Support and Transition Awards;Fostering;Funding;Goals;Grant;Growth;Individual;Infrastructure;Institution;Kentucky;Knowledge;Link;Marketing;Measures;Mentors;Methods;Minority-Serving Institution;Modality;National Institute of General Medical Sciences;Outcome;Population;Preparation;Process;Publications;Questionnaires;Research;Research Infrastructure;Research Personnel;Research Project Grants;Research Support;Resources;Schools;Science;Series;Services;Site;Students;Training;United States;United States National Institutes of Health;Universities;Writing;career;college;expectation;experience;faculty mentor;faculty support;human disease;meetings;next generation;peer;programs;skills;social media platform;social media use;student conference;student mentoring;student research;success;symposium;webinar

public_health_relevance:
NARRATIVEThe overarching goal of the University of Kentucky (UK) SuRE Resource Center is to build research capacityat SuRE-eligible institutions recognizing the vital contribution these colleges and universities make to thenation's research enterprise. Through a series of webinars and other training modalities direct consultation acompetitive seed grant program to create or enhance offices of sponsor projects (OSPs) and biennialconferences experienced UK faculty and research support staff will assist faculty and OSP staff at SuRE-eligible institutions prepare and submit competitive NIH grants applications with an emphasis on SuRE andSuRE-First awards. Multiple methods will be used to collect and analyze data to measure the success of thiscenter.


application_id: 11184175
project_number: 5R01HL160910-04
project_title: Platelet Metabolism in Diabetes Mellitus
administering_ic: NHLBI
award_notice_date: 2025-07-08
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: HL
serial_number: 160910
program_official: GOLDBERG, ILANA GRACE
project_start_date: 2022-09-20
project_end_date: 2027-06-30
study_section: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]
contact_pi_person_id: 8688832
contact_pi: WANG, QINGJUN
other_pis: Not Applicable
congressional_district: 06
department: OPHTHALMOLOGY
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 Heart disease and stroke are the No. 1 and 5 causes of deaths in the US. Type 1 diabetes mellitus (T1DM)significantly increases the risk for heart attacks and strokes. Intense glycemic control has been reported toreduce major cardiovascular events by >30% suggesting that hyperglycemia is one of the major contributors toT1DM-associated heart attack and stroke risk escalation. However how T1DM and hyperglycemia exacerbatesuch risk is unclear. Platelets are vascular first-responders that activate for hemostasis upon blood vesseldamage; whereas pathogenic platelet activation leads to spurious thrombosis and acute vascular obstruction.T1DM and hyperglycemia lead to platelet hyperactivity and increased propensity to form thrombi. This proposalsaims to understand how hyperglycemia causes platelet hyperactivity and thrombosis in T1DM and to developnew therapeutic strategies to mitigate T1DM-associated heart attacks and strokes. Utilizing an integratedmetabolism toolkit including state-of-the-art Stable Isotope Resolved Metabolomics (SIRM) we demonstratedcritical role of altered platelet metabolism in thrombin-induced platelet activation. Specifically thrombinstimulation alters platelet metabolism that is centered on glycogen metabolism pentose phosphate pathway(PPP) and fructose 16-bisphosphate (F16BP) namely the glycogen-PPP-F16BP axis modulating energyredox and calcium homeostasis in platelets and leading to their activation. Literature and our compellingpreliminary data further reveal that hyperglycemia increases glycogen storage and its mobilization that generatesATP PPP inhibition reactive oxygen species and intracellular calcium all of which are in line with increasedpropensity for platelets to activate. Therefore our overarching hypothesis is that hyperglycemia changes theglycogen-PPP-F16BP axis in platelets to drive platelet hyperactivity and thus thrombotic risk in T1DM. In Aim 1we will delineate these hyperglycemia-induced changes in the glycogen-PPP-F16BP axis in platelets isolatedfrom T1DM patients and normal healthy platelets subject to acute hyperglycemia in vitro. In Aim 2 we willdetermine how modulation of the glycogen-PPP-F16BP axis by pharmacological and genetic means suppresseshyperglycemia-induced platelet hyperactivity in vitro. In Aim 3 we will determine how modulation of the glycogen-PPP-F16BP axis by pharmacological and genetic means reduces hyperglycemia-exacerbated thrombosis andstroke in animal models. Our team is in a unique position to address our hypothesis as we possess recognizedexpertise in metabolism and metabolomics (Qingjun Wang PhD and Matthew Gentry PhD) platelet biology(Sidney Whiteheart PhD) T1DM (Lisa Tannock MD) and stroke (Justin Fraser MD and Jill Roberts PhD) andwe have strong partnership with the University of Kentucky Metabolomics Redox Metabolism and RodentSurgery Cores. Upon completion of the proposed project we will have presented a novel mechanism formetabolic dysregulation in platelets to mediate hyperglycemia-induced platelet hyperactivity and thrombosis inT1DM and will have identified new therapeutic targets for mitigating T1DM-associated heart attacks and strokes.

project_terms:
Acute;Address;Affect;Animal Model;Binding;Biological Assay;Biology;Blood Glucose;Blood Platelets;Blood Vessels;Blood coagulation;Buffers;Calcium;Carbon;Cardiovascular system;Carotid Artery Injuries;Cause of Death;Chelating Agents;Citric Acid Cycle;Clot retraction;Coagulation Process;Consumption;Data;Development;Diabetes Mellitus;Doctor of Philosophy;Enzymes;Event;Fibrin;Fructose;Genetic;Gluconeogenesis;Glucose;Glucose Transporter;Glucosephosphate Dehydrogenase;Glycogen;Glycogen Phosphorylase;Glycolysis;Heart Diseases;Hemostatic function;Homeostasis;Human;Hyperactivity;Hyperglycemia;Impairment;In Vitro;Incidence;Insulin-Dependent Diabetes Mellitus;Kentucky;Kinetics;Knowledge;Lead;Learning;Literature;Mediating;Metabolic;Metabolic Pathway;Metabolism;Middle Cerebral Artery Occlusion;Modeling;Morbidity - disease rate;Mus;Myocardial Infarction;NADP;Obstruction;Operative Surgical Procedures;Outcome;Oxidation-Reduction;Pathogenicity;Pathway interactions;Patients;Pentosephosphate Pathway;Phosphoric Monoester Hydrolases;Phosphorylases;Platelet Activation;Positioning Attribute;Production;Protein Dephosphorylation;Pulmonary Embolism;Reactive Oxygen Species;Reduced Glutathione;Regulation;Reporting;Rest;Risk;Risk Reduction;Rodent;Role;Source;Streptozocin;Stroke;Testing;Thrombin;Thrombosis;Thrombus;Universities;chelation;diabetic patient;first responder;glucose metabolism;glucose uptake;glycemic control;glycogen metabolism;in vivo;inhibitor;inorganic phosphate;metabolomics;mortality;mouse model;new therapeutic target;novel;novel therapeutic intervention;pharmacologic;platelet function;stable isotope;stroke risk;thrombotic;tool

public_health_relevance:
Project Narrative Type 1 diabetes mellitus (T1DM) a condition of high blood glucose greatly increases the risk of heartattacks and strokes; yet how T1DM exacerbates heart attacks and strokes is unclear. This proposal looks intohow high blood glucose alters glucose-related metabolic pathways in platelets making them more prone toactivation and blood clot formation. The knowledge gained from our studies will facilitate development of newtherapeutic strategies to reduce the risk of heart attacks and strokes in diabetic patients.


application_id: 11183528
project_number: 7K25AI177810-02
project_title: Understand the mechanism of SARS-CoV-2 entry by single-molecule approaches
administering_ic: NIAID
award_notice_date: 2024-11-12
opportunity_number: PA-24-254
application_type: 7
activity_code: K25
ic: AI
serial_number: 177810
program_official: PLIMACK, MARY KATHERINE BRADFORD
project_start_date: 2024-07-11
project_end_date: 2029-07-31
study_section: Microbiology and Infectious Diseases Advisory Committee[MID]
contact_pi_person_id: 15362631
contact_pi: SHRESTHA, PRAKASH
other_pis: Not Applicable
congressional_district: 06
department: CHEMISTRY
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:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its transmission across theworld was the cause of the COVID-19 pandemic. The CoV entry is mainly initiated by the binding of furincleavage activated spike (S) protein with ACE2 receptor protein on the surface of host cell. Next S2cleavage by transmembrane protease serine 2 (TMPRSS2) on the cell surface induce the conformationalchange of S2 subunit to activate the membrane fusion and entry of virus genetic material. Therefore Sprotein has been the major target to design the vaccines and therapeutics. While a handful ofinvestigations have been reported about the structure of S protein:ACE2 complex critical questions aboutthe detachment of S1/S2 subunits structural changes in S2 and their dynamics to activate the membranefusion remain. These answers will help to improve the current understanding of the mechanism of virusentry and should be highly significant for the development of effective preventions and therapeutics. I propose to combine novel DNA nanoswitch calipers (DNC) single-molecule fluorescence integratedoptical tweezers and high-throughput magnetic tweezers to study the dynamics of the molecular eventsassociated with the membrane fusion process of viral entry and analyze the heterogeneity of neutralizingantibodies (nAbs). Using DNC that I developed we showed the measurement of multiple distances within atarget biomolecule at angstrom level precision. Next we showed the high-throughput measurements inmagnetic tweezers to analyze the heterogeneous mixture of peptides. Therefore DNCs are useful to studymulticomponent protein-protein interactions and simultaneously monitor the structural changes associated withthe process. By executing these projects I will have the following three important answers. First I will measurebinding dynamics of full-length S protein and monomer/dimer ACE2 receptor proteins to understand the entireenergy landscape governing the interaction of these proteins. Second I will measure the detachment kineticsof S1/S2 subunits induced by TMPRSS2 and determine the change in conformation of S2. These reactionsare critical to understand the membrane fusion process. Third I will utilize the similar approach to measure thebinding dynamics of nAbs with S protein. By high-throughput measurements in magnetic tweezers I willanalyze the efficacy and heterogeneity of nAbs to understand the immune response of the patients andvaccinated individuals and also validate DNC assay with a cell-based pseudovirus neutralization assay. Hence the proposed work will provide detailed insight into understanding the mechanism of SARS-CoV-2 entry and rapid analysis of immune response of the patients. My quantitative approaches and advancedsingle-molecule approaches will bring insights into the field of virology and immunology. This study will alsogive me firsthand experience in biochemistry molecular biology virology and immunology enabling me tobetter apply my quantitative and physical training to more topics in biological research in the future.

public_health_relevance:
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) the causative agent of the Covid-19pandemic infects the host cell by binding its spike protein with the angiotensin-converting enzyme 2 (ACE2) onthe host receptor cells. Structurally spike protein has two subunits S1 and S2 and is a trimer while the ACE2protein is a homodimer; however critical questions about the dynamics of the molecular interactions to activatethe membrane fusion remain. This project will determine the dynamics of each molecular interactionassociated with the SARS-CoV-2 entry thus helping to design more effective countermeasures.


application_id: 11182570
project_number: 5R34CA287718-02
project_title: A Motivation-Based Adolescent Vaping Typology to Inform Cessation Interventions
administering_ic: NCI
award_notice_date: 2025-08-25
opportunity_number: RFA-CA-22-042
application_type: 5
activity_code: R34
ic: CA
serial_number: 287718
program_official: RODITIS, MARIA LEIA
project_start_date: 2024-09-04
project_end_date: 2027-08-31
study_section: ZCA1-RPRB-6(M2)R
contact_pi_person_id: 10361270
contact_pi: MCLEISH, ALISON C
other_pis: HART, JOY L.
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_abstract:
PROJECT SUMMARY/ABSTRACTSince the introduction of e-cigarettes in the U.S. in 2007 there has been a dramatic increase in the prevalenceof e-cigarette use among adolescents. These high prevalence rates have been driven in part by beliefs that e-cigarettes are less harmful than combustible cigarettes. Unfortunately mounting evidence indicates that e-cigarettes pose significant health risks. E-cigarettes also contain nicotine which can interfere with normal braindevelopment. Because it is still developing the adolescent brain is more vulnerable to the negative effects ofnicotine exposure putting adolescent e-cigarette users at greater risk of nicotine dependence as well asreduced impulse control and deficits in attention and cognition. Thus although many had hoped that e-cigarettes would serve as a smoking cessation tool they may in fact be ushering in a new generation ofindividuals dependent on nicotine. Therefore we face an urgent need to promote e-cigarette cessation amongadolescents. Unfortunately the empirical literature on e-cigarettes has not been able to keep pace with theirrapid increase in popularity. These knowledge gaps combined with the unique challenges of working withadolescent e-cigarette users have hindered the development of empirically supported e-cigarette cessationinterventions for this population and we currently lack targeted e-cigarette cessation interventions that aredevelopmentally appropriate grounded in empirically supported theories of behavior change and acceptableto adolescents. To create such interventions formative research is needed to better understand the differenttypes of adolescent e-cigarette users based on their motivations for use rather than patterns of use.Identification of such a typology is critical as each type will have distinct cues use patterns beliefs andpreferences resulting in the need for type-specific interventions. Moreover greater adolescent engagement isneeded to ensure that the content of these interventions as well as the messaging surrounding them areacceptable to adolescents and take into account their perceptions of their own use. A mixed methods approachwill be utilized to gather formative data on types of adolescent e-cigarette users and interventional targetsspecific to each type to inform the development of tailored cognitive behavioral e-cigarette cessationinterventions for each type. A sample of 1200 high school students who have used an e-cigarette in the pastmonth will be recruited. Self-report data will be used to identify e-cigarette user types based on motivations foruse as well as cognitive and behavioral correlates of each type. Focus groups with users of each type as wellas students who have successfully quit using e-cigarettes will provide further information about cognitive andbehavioral intervention targets and cessation needs and preferences. The findings of this project will fill criticalknowledge gaps that will result in the development of cognitive behavioral e-cigarette cessation treatmentprotocols specifically designed for adolescent e-cigarette users and tailored to their specific use type that willbe evaluated in future clinical trials.

project_terms:
Address;Adolescent;Attention;Behavior Therapy;Behavioral;Belief;Brain;Cardiovascular Diseases;Cigarette Smoker;Clinical Trials;Cognition;Cognitive;Cues;Data;Data Reporting;Development;Electronic cigarette;Ensure;Face;Focus Groups;Future;Generations;Health;Heterogeneity;High Prevalence;High School Student;Individual;Intervention;Knowledge;Language;Literature;Methods;Motivation;Nicotine;Nicotine Dependence;Patient Self-Report;Pattern;Perception;Population Intervention;Prevalence;Psychopathology;Reporting;Research;Research Personnel;Respiratory Disease;Risk;Sampling;Students;Tobacco;Tobacco use;Treatment Protocols;Typology;Youth;alcohol tobacco and other drug use;behavior change;cognitive development;combustible cigarette;comparative efficacy;design;e-cigarette cessation;electronic cigarette use;electronic cigarette user;flexibility;interest;nicotine exposure;nicotine use;peer;preference;psychosocial;recruit;smoking cessation;social;theories;therapy development;tobacco control;tobacco products;tool;uptake;vaping

public_health_relevance:
PROJECT NARRATIVEDue to the dramatic rise in adolescent e-cigarette use we face an urgent need to promote e-cigarettecessation among adolescents; unfortunately although most adolescent e-cigarette users are interested inquitting and have made at least one quit attempt no empirically validated e-cigarette cessation interventionsare available. For such interventions formative research is needed to develop (1) a motivation-based typologyof adolescent e-cigarette users in order to identify the cognitive and behavioral intervention targets specific toeach type of user and (2) an understanding of adolescent views to further inform intervention content (e.g.examples of type-specific cues and maladaptive cognitions) and ensure maximal acceptability engagementand efficacy of the resulting interventions. The data from this project will inform the creation of subsequentadolescent e-cigarette cessation interventions that are targeted to specific use motivations developmentallyappropriate grounded in cognitive behavioral principles and highly engaging and acceptable to users.


application_id: 11182527
project_number: 4RF1AG084688-02
project_title: Metabolic regulation of myocardial perfusion in the aging heart
administering_ic: NIA
award_notice_date: 2025-09-18
opportunity_number: PA-20-185
application_type: 4
activity_code: RF1
ic: AG
serial_number: 084688
program_official: GAO, HONGWEI
project_start_date: 2024-09-15
project_end_date: 2029-08-31
study_section: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]
contact_pi_person_id: 9543696
contact_pi: HILL, BRADFORD GUY
other_pis: NYSTORIAK, MATTHEW A
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 SUMMARYAdvanced age is the leading risk factor for all chronic diseases. It is associated with a host of geneticimmunologic and physiologic changes that contribute to progressive tissue dysfunction and an increased risk ofmortality. Although many hallmarks of aging have been identified a key physiological feature of aging isdecreased tissue perfusion and an inability to match perfusion to the metabolic requirements of organ function.The impacts of such deficits in perfusion are more pronounced in tissues with high oxygen demand; hence dueto its high energy demand the heart is particularly vulnerable to perfusion deficits. Acute increases in myocardialdemand such as those due to increased physical activity are met by an increase in perfusion (i.e. hyperemia).This increase in myocardial perfusion is triggered by metabolic signals that evoke coronary vasodilation. Ourrecent work shows that increases in O2 demand in cardiomyocytes modify the pyridine nucleotide redox potential(i.e. elevates NADH:NAD) in coronary arterial smooth muscle cells which stimulates voltage-gated K+ (Kv)channel activity to promote vasodilation. Inhibition of this heterocellular signaling results in hypoperfusion andacute pump failure during stress. We propose that disruption to this signaling is the key mechanism underlyingthe progressive age-dependent loss of coupling between myocardial metabolism and coronary vascular tone.Moreover because cardiac output is essential for adequate perfusion and function of all peripheral tissuesdiminished cardiac function at high workloads (e.g. during exercise) likely contributes to widespread dysfunctionand could explain the pervasive deleterious effects of aging. Our preliminary data show that aged mice havereduced myocardial perfusion impaired diastolic and systolic function and lower exercise capacity comparedwith sex-matched young mice. Consistent with cardiac metabolic remodeling as an underlying cause of thesechanges recapitulating the metabolic profile of the aged significantly blunts work-dependent paracrine redoxsignals to the vasculature and suppresses the hyperemic response consistent with a loss of redox-dependentKv channel stimulation. Furthermore acute interventions that decrease cardiomyocyte carbohydrate metabolism(ketone body infusion) rescue myocardial perfusion in aged mice. Based on these preliminary data wehypothesize that age-dependent changes in myocardial metabolism suppress pyridine nucleotide redox-dependent K+ efflux in vascular smooth muscle leading to progressive uncoupling of coronary perfusion frommyocardial workload. Accordingly our specific aims are to: (1) delineate age-dependent changes in cardiacmetabolism myocardial perfusion and left ventricular function; (2) assess the impact of changes in myocardialglucose metabolism on redox-dependent myocardial hyperemia; and (3) determine the efficacy of myocardialmetabolic interventions to prevent age-dependent exercise intolerance and cardiac remodeling. This project willelucidate the mechanism underlying a key physiological defect associated with aging and provide new insightsinto how this defect could be attenuated to prolong cardiovascular health and function over the lifespan.

project_terms:
Acute;Affect;Aging;Atherosclerosis;Attenuated;Blood Vessels;Blood flow;Carbohydrates;Cardiac;Cardiac Myocytes;Cardiac Output;Cardiovascular Physiology;Catabolism;Chronic;Chronic Disease;Clinical;Contrast Echocardiography;Coronary;Coronary artery;Coupling;Data;Defect;Dementia;Diabetes Mellitus;Elderly;Etiology;Exercise;Exercise Tolerance;Failure;Fatty Acids;Functional disorder;Genetic;Genetic Models;Glucose;Heart;Hyperemia;Immunologics;Impairment;In Vitro;Infusion procedures;Intervention;Ketone Bodies;Knowledge;Left Ventricular Function;Link;Longevity;Measures;Metabolic;Metabolism;Modeling;Mus;Myocardial;Myocardial perfusion;NADH;Organ;Oxidation-Reduction;Oxygen;Perfusion;Peripheral;Physical activity;Physiological;Play;Pump;Radiolabeled;Regulation;Risk Factors;Role;Signal Transduction;Smooth Muscle;Smooth Muscle Myocytes;Stress;Structure;Testing;Tissues;Vascular Smooth Muscle;Vasodilation;Work;Workload;active lifestyle;age effect;age related;age related changes;age related decline;age-related disease;aged;carbohydrate metabolism;cardiac aging;cardiovascular health;coronary perfusion;efficacy evaluation;exercise capacity;exercise intolerance;fatty acid metabolism;flexibility;glucose metabolism;hallmarks of aging;heart function;heart metabolism;hypoperfusion;improved;in vivo;insight;life span;metabolic profile;mortality risk;novel strategies;old mice;oxidation;paracrine;pathological aging;preservation;pressure;prevent;pyridine nucleotide;response;restoration;sex;stable isotope;voltage

public_health_relevance:
PROJECT NARRATIVEAdvanced age is the leading risk factor for all chronic diseases. Although many hallmarks of aging have beenidentified a key physiological feature of aging is decreased blood flow and an inability to match blood flow toorgan requirements. This project will elucidate the metabolic mechanisms by which aging impairs blood flow inthe heart and identify interventions to improve blood flow heart function and exercise tolerance over the lifespan.


application_id: 11181739
project_number: 1R41AG090217-01A1
project_title: Trans Spinal Delivery of Targeted Exosomal Formulation of Curcuminoids to Treat AD
administering_ic: NIA
award_notice_date: 2025-09-15
opportunity_number: PAS-22-197
application_type: 1
activity_code: R41
ic: AG
serial_number: 090217
suffix: A1
program_official: MARTIN, ZANE
project_start_date: 2025-09-15
project_end_date: 2026-08-31
study_section: Special Emphasis Panel[ZRG1 AN-P (11)]
contact_pi_person_id: 8240457
contact_pi: GUPTA, RAMESH C
other_pis: Not Applicable
congressional_district: 04
department: Unavailable
primary_duns: 831172668
primary_uei: HSCNW2K7VN97
duns_number: 831172668
uei: HSCNW2K7VN97
fips: US
organization_id: 10023330
organization_name: 3P BIOTECHNOLOGIES, INC.
organization_city: PROSPECT
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 400598574
organization_country: UNITED STATES
project_abstract:
TECHNICAL ABSTRACT Neurodegenerative disorders affect over 40 million people worldwide and most are mediated by inflammation.Even though several drugs are approved by the FDA for treating neurological disorders such as Alzheimersdisease (AD) their efficacy as AD therapeutics has not been realized as extremely low levels of the drug reachthe brain. The goal of this Phase I project is to develop a targeted delivery system for the bioactive curcuminoidscurcumin (CUR) and bisdemethoxycurcumin (BDMC) to treat and mitigate the progression of neuroinflammatorydiseases specifically AD. We will apply our extensive experience in exosomes drug delivery plant therapeuticsand inflammatory responses for efficient targeted delivery of bioactive curcuminoids to the microenvironment ofthe brain where progressive increase in inflammation amyloid plaque formation and neurofibrillary tanglesultimately leads to manifestation of AD. We hypothesize that the combined CUR and BDMC will be highly effectiveat ameliorating neuroinflammation and aberrant AD-related gene expression returning these biomarkers to pre-disease levels due to synergistic action via different mechanisms. We also hypothesize that rabies virusglycoprotein (RVG)- and folic acid (FA)-functionalized exosomal formulations administered using a novel topicaltrans-spinal (t.s.) route will provide enhanced targeting to AD-related regions of the brain including the cortex andhippocampus. Exosomes cross the BBB efficiently and areas of the brain associated with AD have high levels offolate receptors (FRs). Thus t.s.-administered RVG/FA-ExoCUR/BDMC will deliver higher payload to the brainvs. conventional routes. Our hypotheses are supported by 1) effective drug loading of curcuminoids onto bovinecolostrum exosomes 2) Higher levels (>14-fold) of curcuminoids in the mouse brain after FA-ExoCUR/BDMC t.s.than p.o. 3) FA-exosomes can increase drug delivery to the brain which contains >20-fold higher expression ofFR than other tissues 4) reduced NFB accumulation and decreased abundance of phosphorylated Tau (pTau)and amyloid precursor protein (APP) expression in brain lysates of mice treated orally with ExoCUR/BDMC inconcurrence with increased expression of brain-derived neurotrophic factors (BDNF) comparable to levels in age-matched untreated WT mice while free CUR/BDMC was ineffective and 5) higher brain accumulation of labeledexosomes in mice treated via t.s. vs. i.v. route. Investigators experienced in exosomes drug delivery planttherapeutics and animal models leveraging experience of the neurologist Dr. Robert Friedland in AD researchwill pursue the following specific aims: Aim 1. Optimize ExoCUR/BDMC formulations in vitro and determinebiodistribution in WT mice. Aim 2. Determine efficacy toxicity and tissue levels of curcuminoids forExoCUR/BDMC formulations in AD mice. This project will provide proof-of-principle for the effectiveness of t.s.-delivered RVG/FA-ExoCUR/BDMC on the modulation of key molecular targets and behavioral tests with ADprogression. In Phase II we will conduct dose-finding and longer-term intervention using multiple rodent ADmodels chronic toxicity etc. The t.s.-brain delivery could ultimately lead to the development of t.s. patches for AD.

project_terms:
3xTg-AD mouse;Affect;Aftercare;Age;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease therapeutic;Alzheimers disease biomarker;Amyloid beta-Protein Precursor;Animal Model;Animals;Anti-Inflammatory Agents;Area;Atrophic;Attenuated;Biodistribution;Biological Availability;Biological Markers;Brain;Brain region;Brain-Derived Neurotrophic Factor;Cattle;Cervical spine;Chronic;Clinical;Clinical Research;Colostrum;Curcumin;Data;Development;Disease;Disease Marker;Disease Progression;Dose;Drug Delivery Systems;Drug or chemical Tissue Distribution;Effectiveness;Electrophoretic Mobility Shift Assay;Enzymes;Euthanasia;Exhibits;FDA approved;Folic Acid;Formulation;Gene Expression;Glycoproteins;Goals;Hepatic;Hippocampus;Histologic;Image;Immunoassay;In Vitro;Individual;Inflammation;Inflammation Mediators;Inflammatory Response;Intervention;Label;Lead;Mediating;Metabolism;Minor;Molecular Target;Mus;Neck;Nervous System Disorder;Neurodegenerative Disorders;Neurofibrillary Tangles;Neurologist;Neurons;Oral;Oxidative Stress;Persons;Pharmaceutical Preparations;Phase;Plants;Powder dose form;Property;Rabies;Regional Disease;Renal function;Research;Research Personnel;Rodent;Route;Senile Plaques;Spinal;Standardization;System;Testing;Therapeutic;Tissues;Toxic effect;Transgenic Mice;Viral;abeta accumulation;abeta deposition;behavior test;beta-site APP cleaving enzyme 1;blood-brain barrier crossing;brain tissue;cognitive function;cognitive testing;demethoxycurcumin;donepezil;efficacy evaluation;efficacy study;ex vivo imaging;exosome;experience;folate-binding protein;imager;improved;in vivo;liver function;nanoformulation;nanoparticle;neuroinflammation;novel;preclinical study;protein expression;public health relevance;rabies virus glycoprotein G;receptor;rivastigmine;standard of care;success;targeted delivery;tau-1;treatment response

public_health_relevance:
Narrative (Public Health Relevance Statement) In the proposed project we will use a novel nano formulation of curcuminoids to mitigateneuroinflammation and attenuate neurological diseases with emphasis on Alzheimer's disease (AD). In ourapproach curcuminoids known for their potent anti-inflammatory activity and activities inhibiting early brainmarkers of AD including neurofibrillary tangles and amyloid plaque formation will be sequestered in exosomes(natural nanoparticles) isolated from standardized bovine colostrum powder to increase bioavailability. Theexosomes will be decorated with folic acid whose receptors are expressed in high levels in the AD-relatedregion of brain to target sub tissues such as cortex and hippocampus and the formulation is delivered by anovel trans-spinal (t.s.) topical route for targeted brain delivery and the efficacy assessed using transgenicmouse model of AD.


application_id: 11180966
project_number: 5R01AR083375-02
project_title: Mechanistic Assessment of NMES to Rescue Localized Neuromuscular Disruption after ACL Injury
administering_ic: NIAMS
award_notice_date: 2025-07-30
opportunity_number: PA-20-183
application_type: 5
activity_code: R01
ic: AR
serial_number: 083375
program_official: WASHABAUGH, CHARLES H
project_start_date: 2024-08-30
project_end_date: 2029-07-31
study_section: Special Emphasis Panel[ZRG1-MSOS-C(05)M]
contact_pi_person_id: 11267737
contact_pi: FRY, CHRISTOPHER
other_pis: NOEHREN, BRIAN
congressional_district: 06
department: MISCELLANEOUS
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: UNIVERSITY-WIDE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project SummaryAnterior Cruciate Ligament (ACL) injury and subsequent reconstruction result in disrupted neuromuscularpathways which have been linked to protracted quadriceps weakness and atrophy. There is a significant gap inknowledge concerning the signaling cascades that precipitate peripheral quadriceps deficits limiting progressin the field to address the inceptive events underlying poor functional recovery. Lacking mechanistic evidencehinders the development of targeted rehabilitation protocols to address quadriceps atrophy and weakness thatoften persist far beyond return to activity. Pilot data in this proposal has identified a molecular signature ofquadriceps neuromuscular dysfunction that appears following the initial ACL injury and is further exacerbatedby reconstruction. Early molecular changes following ACL reconstruction culminate in local quadricepsdenervation and weakness. Additionally provided data show this molecular signature to be responsive toneuromuscular electrical stimulation (NMES) providing a heretofore previously unknown mechanistic target ofNMES. Conflicting results from studies lacking rigor and mechanistic insight have limited the efficacy andutilization of NMES following ACL injury hindering its therapeutic potential. The overarching hypothesis of thisproposal is that ACL injury results in rapid quadriceps neuromuscular remodeling and local denervation whichresults in subsequent quadriceps atrophy and weakness. Further NMES is hypothesized to mitigatedenervation-induced molecular signaling within the quadriceps providing critical mechanistic insight. Threeinterconnected but independent aims will address the overarching hypothesis. Specifically innovative pre-clinical gain and loss of function experiments will establish causative roles for specific signaling cascadeswithin the quadriceps that are critical for responsiveness to NMES. Additionally a rigorous and targeted clinicaltrial will address gaps in knowledge surrounding NMES that have previously limited acceptance and utilization.Results of the current study will provide necessary mechanistic insight to overcome a critical barrier in thedevelopment of evidence-based guidelines. Results from this work will directly lead to new testable treatmentsto advance the care of individuals with ACL injuries that will remedy the pervasive issue of protractedquadriceps weakness.

project_terms:
Address;Atlases;Atrophic;Biological;Biopsy;Caring;Cell Nucleus;ChIP-seq;Clinical Practice Guideline;Clinical Trials;Data;Deacetylase;Denervation;Development;Etiology;Event;Fiber;Functional disorder;Genetic;HDAC4 gene;Histone Deacetylase Inhibitor;Impairment;Individual;Injury;Knockout Mice;Knowledge;Link;Measures;Modeling;Molecular;Molecular Profiling;Molecular and Cellular Biology;Morphology;Mus;Muscle;Muscle Weakness;Muscle function;Muscular Atrophy;Neuromuscular Junction;Nuclear;Nuclear RNA;Operative Surgical Procedures;Orthopedic Surgery;Outcome;Participant;Pathway interactions;Peripheral;Phenotype;Physical therapy;Positioning Attribute;Postoperative Period;Protocols documentation;Randomized;Reconstructive Surgical Procedures;Recovery;Recovery of Function;Rehabilitation therapy;Resolution;Role;Signal Transduction;Skeletal Muscle;Testing;Therapeutic;Time;Torque;Translations;Work;anterior cruciate ligament injury;anterior cruciate ligament reconstruction;anterior cruciate ligament rupture;defined contribution;evidence based guidelines;experimental study;gain of function;gene induction;gene induction/repression;human data;improved outcome;innovation;insight;loss of function;molecular targeted therapies;multidisciplinary;muscle strength;neural;neuromuscular;neuromuscular stimulation;novel;pharmacologic;pre-clinical;preclinical study;quadriceps muscle;reconstruction;regenerative rehabilitation;response;single nucleus RNA-sequencing;statistics;transcriptional reprogramming;transcriptome;transcriptome sequencing

public_health_relevance:
Project NarrativeAnterior cruciate ligament tears are a common injury and in spite of surgical reconstruction and rehabilitationthere remain significant impairments in the quadriceps muscle which contribute to poor long term outcomes.This project has identified a molecular signature of quadriceps neuromuscular dysfunction that contributes tothe initial loss of quadriceps muscle strength. An innovative combination of pre-clinical studies and amechanistic clinical trial will determine the ability of neuromuscular electrical stimulation to mitigate this earlymolecular signature and restore quadriceps strength.


application_id: 11180387
project_number: 5R01AG084180-02
project_title: Impacting Inflammation through Mechanistic Target of Rapamycin (imTOR)
administering_ic: NIA
award_notice_date: 2025-07-15
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: AG
serial_number: 084180
program_official: TILAHUN, MULUALEM ENYEW
project_start_date: 2024-09-01
project_end_date: 2028-05-31
study_section: Special Emphasis Panel[ZRG1-EMS-D(02)M]
contact_pi_person_id: 6409370
contact_pi: NIKOLAJCZYK, BARBARA
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:
Inflammatory diseases limit healthspan defined as the length of ones life spent in good health. We propose anancillary study to an NIA-funded trial U01AG076941 (EVERLAST) that we call Impacting inflammation throughmechanistic Target Of Rapamycin (imTOR). The EVERLAST parent trial will test the ability of low/intermittentdoses of the rapamycin analogue everolimus to selectively inhibit mTORC1 but not mTORC2 and thusimprove multiple indicators of healthspan while avoiding the undesirable side-effects of rapamycin. Analysis ofimmune cells as major sources of mTOR-regulated inflammation coupled with analysis in the context of parenttrial outcomes would significantly enhance the value of EVERLAST without changing subject burden. imTORthus responds to NOT-AG-23-020 Maximizing the Scientific Value of Secondary Analysis of Existing Cohortsand Datasets in Order to Address Research Gaps and Foster Additional Opportunities in Aging Research.EVERLAST is enrolling middle-aged to older adults who are generally healthy but are overweight/obese andinsulin resistant to take placebo or everolimus daily (0.5mg) or everolimus once weekly (5mg) for 24 wks.EVERLAST will determine the impact of this intervention on fundamental hallmarks of aging including changesin metabolism muscle function brain health senescence and frailty. imTOR will expand the scope ofEVERLAST beyond flu vaccine-generated immune responses by quantitating the impact of everolimus onchronic inflammation a key cause of age-related health declines generated mainly by immune cells. imTORwill focus mainly on CD4+ T cells based on our data showing these cells are dominant sources of inflammationin healthy and obesity-associated aging. imTOR is designed to test the overall hypothesis that everolimuslowers the risk of age-related health problems by reducing chronic inflammation through mechanisms thatinclude improved bioenergetics and redox balance in immune cells. We will complement primary focus on Tcells with analyses of myeloid cells the latter a secondary source of systemic inflammation. Mechanisticinsights into everolimus action on immune cells will be analyzed relative to changes in hallmarks of agingcollected for EVERLAST. We will compare mitochondrial outcomes between immune cells and skeletal muscleto challenge the assumption of similar everolimus impacts on distinct tissue types. Parallel ex vivomanipulations will establish cause/effect relationships amongst everolimus mTORC1/2 function cellphysiology cytokine profiles and the frequency of polyfunctional T cells a newly appreciated modulator ofinflammatory disease. Success with the proposed project coupled with EVERLAST outcomes will determinesafety and efficacy of everolimus for promoting healthspan in our ever-aging population.

project_terms:
Address;Age of Onset;Aging;Ancillary Study;Animals;Bioenergetics;Blood;CCI-779;CD4 Positive T Lymphocytes;Cardiac;Cell Physiology;Cells;Chronic;Clinical Trials;Cognition;Cognitive;Compensation;Complement;Complex;Confocal Microscopy;Coupled;Data;Data Set;Disease;Dose;Effectiveness;Enrollment;Equilibrium;FRAP1 gene;Fostering;Frequencies;Funding;Health;Human;Immune;Immune response;Immunosuppression;In Vitro;Infection;Inflammaging;Inflammation;Inflammatory;Institution;Insulin Resistance;Intervention;Lead;Length;Life;Link;Lysosomes;Mediator;Metabolic;Metabolism;Mitochondria;Muscle function;Myeloid Cells;Obesity;Outcome;Outcome Study;Overweight;Oxidation-Reduction;Parents;Pathway interactions;Persons;Pharmaceutical Preparations;Placebos;Positioning Attribute;Process;Production;Proteomics;Regimen;Research;Resources;Risk;Risk Management;SDZ RAD;Safety;Sampling;Shipping;Signal Transduction;Sirolimus;Skeletal Muscle;Source;T-Lymphocyte;Testing;Tissues;Weight;age related;age related decline;age-related disease;aging biomarker;aging population;aging related;animal data;anti aging;brain health;clinical practice;cohort;cytokine;design;drug action;extend lifespan;frailty;gain of function;geroprotector;hallmarks of aging;healthspan;healthy aging;immunoregulation;improved;influenza virus vaccine;inhibitor;innovation;insight;intervention effect;lens;loss of function;middle age;mitochondrial metabolism;muscle aging;older adult;pharmacologic;predictive modeling;prevent;promote healthspan;secondary analysis;senescence;side effect;success;systemic inflammatory response;vaccine response

public_health_relevance:
Numerous studies support the premise that inflammation rises in aging. Drugs with immunomodulatory actionssuch as mechanistic Target of Rapamycin (mTOR) inhibitors may promote healthspan the length of ones lifespent in good health especially if given prior to onset of age-related declines. We will analyze deidentifiedsamples from an NIA-funded clinical trial to test the possibility that the mTORC inhibitor everolimus is a safeand effective option to ameliorate age-related inflammation and sequelae thereof.


application_id: 11180300
project_number: 5R16AI177410-02
project_title: Role of epigenetic changes in intracellular survival and replication of Legionell pneumophila
administering_ic: NIAID
award_notice_date: 2025-08-20
opportunity_number: PAR-21-173
application_type: 5
activity_code: R16
ic: AI
serial_number: 177410
program_official: ERNST, NANCY L
project_start_date: 2024-09-01
project_end_date: 2028-08-31
study_section: ZAI1-SPJ-D(M1)
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:
1 Legionella pneumophila is an opportunist pathogen that infects an immune-compromised host and causes2 inflammatory pneumonia in the lungs termed as legionnaires disease. L. pneumophila infects alveolar 3 macrophages within the lungs and using a type IV secretion system discharges an array of more than 300 4 proteins called effectors that interfere with the cells biochemical pathways to prepare a cozy niche for the 5 bacterial replication. Several recent studies also indicate that L. pneumophila infections in primary mouse 6 macrophages and protozoan cells manipulate host transcriptome and result in differential gene expression in the 7 infected host cell to facilitate their survival and evasion of the immune mechanisms. However the mechanisms 8 involved in gene expression alterations are not clear and undefined. A comprehensive localization analysis of 9 Legionella effectors using GFP-tag revealed that a few of these Legionella effectors translocate into the nucleus10 of the cell. An effector protein with an objective localization into the nucleus to modulate gene expression of the11 host is called nucleomodulin. Recent studies indicate that several bacterial pathogens produce nucleomodulins12 that aid in survival and pathogenesis through transient or long-term epigenetic modifications. In our prior work13 we identified five Legionella nucleomodulins with unknown function and the purpose of this study is to elucidate14 the role of the Legionella nucleomodulins in understanding the pathogenesis of L. pneumophilia.15 To better understand the effect of Legionella nucleomodulins on the host cells and determine their function16 during the growth of Legionella pneumophila we examined the differential gene expression pattern by17 performing RNA sequence analysis on RNA extracted from mammalian cells expressing Legionella18 nucleomodulin. The pathways and genes identified through functional analysis of RNA-seq data support19 epigenetic modifications of host cells through methylation and histone modifications. The first objective of this20 study is to examine the DNA methylation pattern on macrophages infected with L. pneumophila using Bisulfite21 sequencing and methylation assays in comparison to uninfected macrophages. The second objective examines22 interaction of Legionella nucleomodulin with histone and non-histone proteins by using chromatin23 immunoprecipitation sequencing and co-immunoprecipitation assays.24 The proposed research aims to detect transcriptional responses of a cell to its environmental influence such25 as infections and understand how bacterial nucleomodulins mediate regulatory control through epigenetic26 changes during an infection by intracellular pathogens to trigger altered gene expression patterns in the host cell27 and manipulate cellular processes. As these mechanisms are ambiguous this study will contribute to better28 understanding of bacterial nucleomodulins and their role in bacterial pathogenesis which can help in designing29 new therapeutic approaches. Additionally this project will expand research and education experience for30 undergraduate students at Western Kentucky University.

project_terms:
Alveolar;Alveolar Macrophages;Antibodies;Bacteria;Binding;Biochemical Pathway;Biological Assay;Biomedical Research;Cell Nucleus;Cell Physiology;Cells;Cellular biology;Centers for Disease Control and Prevention (U.S.);ChIP-seq;Chromatin;Co-Immunoprecipitations;Cytoplasm;DNA;DNA Methylation;DNA analysis;Data;Data Analyses;Disease Outbreaks;Education;Engineering;Environment;Epigenetic Process;Eukaryotic Cell;European;Event;Exclusion;Functional disorder;Gene Expression;Gene Expression Alteration;Gene Expression Profile;Gene Expression Regulation;Genes;Genetic Transcription;Growth;Histones;Host Defense Mechanism;Immune;Immune Evasion;Immune response;Immunoprecipitation;Infection;Inflammatory;Kentucky;Legionella;Legionella pneumophila;Legionnaires' Disease;Lung;Macrophage;Mammalian Cell;Mediating;Medicine;Methods;Methylation;Microbiology;Modification;Molecular Biology;Mus;Normal Cell;Notification;Nuclear Extract;Nuclear Proteins;Organ;Pathogenesis;Pathway interactions;Pneumonia;Population;Preventive measure;Process;Proteins;Public Health;RNA;RNA Sequence Analysis;RNA analysis;Research;Role;Signal Transduction;Sorting;Structure of parenchyma of lung;System;Testing;Tissue-Specific Gene Expression;Tissues;Type IV Secretion System Pathway;United States;United States National Academy of Sciences;Universities;Upregulation;Work;bisulfite;design;differential expression;emerging pathogen;experience;experimental study;histone modification;methylation pattern;mutant;next generation sequencing;non-histone protein;novel therapeutic intervention;pathogen;pathogenic bacteria;protein expression;protein protein interaction;response;therapeutically effective;transcriptome;transcriptome sequencing;undergraduate student

public_health_relevance:
Project NarrativeEmerging pathogens are continuously evolving their infective mechanisms to alter host cellular responses toestablish a niche and successful infection. In the wake of increase in Legionnaires outbreaks the ability ofLegionella pneumophila to modulate diverse number of eukaryotic cell processes to survive and multiply inmacrophages is of public health concern. Thus in-depth understanding of infection strategies from Legionellastudies can help to design effective therapeutic strategies and preventive measures against intracellular bacterialpathogens.


application_id: 11179279
project_number: 5R25CA221765-08
project_title: Appalachian Career Training in Oncology (ACTION) Program
administering_ic: NCI
award_notice_date: 2025-09-11
opportunity_number: RFA-CA-21-020
application_type: 5
activity_code: R25
ic: CA
serial_number: 221765
program_official: CALZOLA, JESSICA MARIE
project_start_date: 2018-09-18
project_end_date: 2028-08-31
study_section: Institutional Training and Education Study Section (F)[NCI-F]
contact_pi_person_id: 11045331
contact_pi: VANDERFORD, NATHAN LANE
other_pis: Not Applicable
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
arra_indicator: N
project_abstract:
The rural Appalachian Kentucky region has the highest cancer incidence and mortality rates in the United States and it is also one of the most economically distressed medically deprived and poorly educated regions of the country. These characteristics reveal a critical need for educational and scientific workforce preparedness intervention strategies targeted to this population. Through a Cancer Center Support Grant supplement in 2016 the research clinical care educational and outreach strengths of the University of Kentuckys Markey Cancer Center were leveraged to create the Appalachian Career Training In ONcology (ACTION) Program which has been funded as a Youth Enjoy Science education intervention since 2018. In this renewal each year the ACTION Program will immerse 20 high school and 20 undergraduate students from Appalachian Kentucky in mentored cancer research cancer care observation experiences cancer education and career development activities as well as hands-on outreach activities. The goal of the program is to enhance the biomedical workforce by preparing Appalachian Kentucky high school and undergraduate students for biomedical careers while also increasing individuals understanding of cancer thereby addressing the cancer and education discrepancies in Appalachian Kentucky and beyond. Impacts of the program will include: 1) supporting students matriculation into post-secondary professional and/or graduate biomedical degree programs; 2) instilling in students a lifelong commitment to research education/outreach and/or health care careers focused on the cancer burden and unique challenges in Appalachian Kentucky and beyond; and 3) enhancing Appalachian Kentuckys understanding of cancer cancer research and clinical care and linking these facets to the benefits of science education. The overarching goal and the program impacts will be accomplished through three Specific Aims: 1) to develop students cancer research knowledge and skills through cross-disciplinary faculty- and peer-mentored research training experiences; 2) to enhance students career preparation by providing cancer education and career development curriculum through faculty- and peer-led courses workshops seminars and career coaching and mentoring; and 3) to increase the understanding of the research and clinical aspects of cancer and the importance of science education among students and teachers parents/caregivers and families of ACTION students and the general public through impactful outreach activities in students counties. New features of the program will include virtual research education experiences that complement hands-on research and education activities a multi-institutional virtual outreach program and a cancer curriculum outreach program for middle and high school students and teachers. With significant momentum achieved since its creation the ACTION Program will continue having a transformational impact on Appalachian Kentucky students their families and their counties.

project_terms:
Academic achievement;Achievement;Address;Appalachian Region;Area;Bachelor's Degree;Cancer Burden;Cancer Center;Cancer Center Support Grant;Cancer Research Project;Caregivers;Characteristics;Clinical;Complement;Country;County;Death Rate;Degree Completion;Degree program;Distress;Doctor's Degree;Early Intervention;Economics;Education;Education and Outreach;Educational Activities;Educational Curriculum;Educational Intervention;Educational workshop;Faculty;Family;Funding;General Population;Goals;Health;Health Care;Health behavior;High School Student;Home;Incidence;Income;Individual;Institution;Intervention;Intervention Strategies;Kentucky;Knowledge;Link;Malignant Neoplasms;Medical;Mentors;Mentorship;Middle School Student;National Cancer Institute;Oncology;Parents;Population;Poverty Areas;Preparation;Readiness;Research;Research Activity;Research Training;Rest;Rural;Rural Appalachia;Science;Students;Target Populations;Training;Training and Education;United States;Universities;Youth;anti-cancer research;burden of illness;cancer care;cancer education;career;career development;career preparation;clinical care;curriculum development;economic indicator;education research;experience;faculty mentor;hands on research;health difference;high school;high school degree;higher education;matriculation;oncology program;outreach;outreach program;peer;peer coaching;peer networks;programs;research education experience;science education;skills;social;social health determinants;student retention;teacher;training opportunity;undergraduate student;virtual

public_health_relevance:
The renewal of the University of Kentucky Markey Cancer Centers Appalachian Career Training In ONcology (ACTION) Program will continue a cancer education and training opportunity for students from rural disease-burdened low economic and low education-attainment Appalachian Kentucky. The program will enhance the biomedical workforce by preparing Appalachian Kentucky high school and undergraduate students for biomedical careers. ACTION will also increase individuals understanding of cancer thereby addressing the cancer and education discrepancies in Appalachian Kentucky and beyond.


application_id: 11178504
project_number: 5R25GM155474-02
project_title: Quantitative Team Science (QuanTS) Program
administering_ic: NIGMS
award_notice_date: 2025-08-14
opportunity_number: PAR-21-196
application_type: 5
activity_code: R25
ic: GM
serial_number: 155474
program_official: STAMM, JOYCE CHIN-CHIN NG
project_start_date: 2024-09-01
project_end_date: 2029-08-31
study_section: ZGM1-TWD-V(IP)
contact_pi_person_id: 11929653
contact_pi: SLADE, EMILY
other_pis: POMANN, GINA-MARIA
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:
PROJECT SUMMARYAs the demand for data-intensive interdisciplinary research increases so does the demand for quantitativescientists who excel not only at working with data but also at collaborating effectively within research teamsacross all fields of medicine. Despite the integral role that quantitative scientists play on these teams theytypically receive very basic if any targeted team science training during their graduate studies or in theworkplace. We propose the creation of the Quantitative Team Science (QuanTS) Program to provide scalablemethods for training and mentoring quantitative scientists who are currently working within the biomedicalresearch community to foster the knowledge attitudes and behaviors inherent to effective team science.Relying on our teams past work our innovative approach focuses on competencies and skills that are specificto quantitative team scientists. We will first create a series of online educational modules to train quantitativeteam scientists in ten key collaborative skills. These modules including both didactic training materials and anaccompanying mentor guide are designed to be asynchronous and self-paced allowing for a flexibleaccessible and sustainable modality that can be easily scaled and utilized by a broad range of learners. Nextwe will implement a small-group synchronous mentorship program for quantitative team scientists to gainmore experiential training and focused mentorship in ten key collaborative skills. In this seven-month programparticipants will benefit from a three-pronged mentorship approach including program mentorship peermentorship and home institution mentorship. Throughout the development and deployment of the onlineeducational modules and the focused mentorship program we will integrate a mixed-methods evaluationprocess that examines the facilitators barriers and outcomes of the QuanTS Program in practice includingexamining changes for quantitative scientists their mentors and their domain collaborators as a result of theprogram. This will provide directly actionable information to inform processes for sustaining/expanding theQuanTS Program and will also provide guidance for future quantitative team science trainings. Thecomprehensive QuanTS Program will grow the workforce of highly-skilled quantitative team scientists who canintegrate diverse scientific perspectives into data analyses communicate results to a range of audiences andcultivate positive interpersonal relationships within the biomedical research environment. Quantitative scientistsare integrated within research teams across all disciplines and phases of biomedical research. Improving theway in which quantitative scientists collaborate with biomedical investigators (e.g. clinicians bench scientistsdomain experts) to conduct interdisciplinary research not only enhances the efficiency and rigor of dataanalyses but also holds the potential to accelerate the translation of research findings into tangible clinicalapplications thereby advancing the frontiers of medical knowledge and patient care.

project_terms:
Acceleration;Address;Biomedical Research;Clinical;Collaborations;Communication;Communities;Competence;Data;Data Analyses;Development;Discipline;E-learning;Education;Educational process of instructing;Educational workshop;Environment;Evaluation;Feedback;Fostering;Future;Goals;Health Knowledge Attitudes Practice;Home;Institution;Interdisciplinary Study;Interpersonal Relations;Knowledge;Leadership;Learning Module;Medical;Medicine;Mentors;Mentorship;Methods;Modality;Occupations;Outcome;Output;Participant;Patient Care;Phase;Play;Principal Investigator;Process;Program Development;Research;Research Personnel;Role;Running;Science;Scientist;Series;Structure;Technical Expertise;Training;Training Programs;Translational Research;Work;Workplace;career;clinical application;cohort;complex data;design;education research;experience;flexibility;graduate school;improved;innovation;novel;peer;programs;skills;success;uptake;virtual

public_health_relevance:
PROJECT NARRATIVEThe Quantitative Team Science (QuanTS) Program will provide training and mentorship in collaborative skillsto equip quantitative scientists to work effectively on research teams across all fields of medicine. Toaccomplish this goal we will create online didactic training materials that are broadly accessible to thequantitative science community facilitate an experiential small-group mentorship program focused on teamscience skills for early-career quantitative scientists and provide guidance and training materials for mentors.We will also integrate novel evaluation processes within the program to examine facilitators barriers andoutcomes of the proposed methods for training and mentoring quantitative team scientists.


application_id: 11178457
project_number: 5R01AG072797-05
project_title: Novel precision medicine approach to treatment of osteoporosis based on bone turnover
administering_ic: NIA
award_notice_date: 2025-08-12
opportunity_number: PA-20-183
application_type: 5
activity_code: R01
ic: AG
serial_number: 072797
program_official: NELLISSERY, MAGGIE JACOB
project_start_date: 2021-09-30
project_end_date: 2026-08-31
study_section: Special Emphasis Panel[ZRG1-MOSS-S(02)M]
contact_pi_person_id: 7705149
contact_pi: RAO, MADHUMATHI
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:
1. Project Summary/AbstractOsteoporosis is a health problem of major proportions. It affects more than 40 million Americans and results inmore than 2 million fractures annually among Medicare patients alone. Hospital admissions for osteoporoticfractures exceed those of heart attacks strokes and breast cancer combined. Osteoporosis is commonlyconsidered a disease associated with menopause. This estrogen deficiency related bone loss is characterizedby high bone turnover with increased resorption without commensurate changes in bone formation. It is incontrast to age-related bone loss which starts as early as in the fourth decade of life and continues withincreasing age. Age-related bone loss is usually associated with lower bone turnover and decreased boneformation is the main abnormality. Current therapies do not address age-related bone loss and the special needsof the age-related osteoporosis population is currently ignored. This is to a great degree due to difficultiesassociated with the bone biopsy necessary for determination of bone turnover status. Thus the current standardof care relies on starting with an antiresorber which is less effective in age-related osteoporosis and in factimpedes the effectiveness in this population of the appropriate anabolic medication.Our study seeks to achieve two specific aims: Aim 1) to establish a novel precision medicine approach totreatment of age-related osteoporosis based on recognition of low bone turnover and initial treatment withanabolics and Aim 2) to find a non-invasive method for diagnosing low bone turnover in osteoporotic patientsby measurements of serum carboxylated osteocalcin (1-43/49) with validation via the gold standard bonebiopsy and histomorphometry.Our approach will be to enroll female patients who have been diagnosed with osteoporosis in a prospectiveproof of concept study. Patients will undergo bone biopsy and blood draws at baseline. Bone turnover status willbe assessed employing histomorphometry. In addition blood levels of carboxylated osteocalcin (1-43/49) will bemeasured in order to determine their validity - alone or in combination with other bone markers - for diagnosinglow bone turnover prevailing in age-related bone loss.Patients will be grouped according to turnover status. Low-turnover patients will be randomized (1:1) either totreatment with the anabolic teriparatide (Group 1) or with the standard of care antiresorber alendronate (Group2) for one year. In order to provide the necessary comparison group for the non-invasive assessment of turnovernormal-high turnover patients (Group 3) will be treated with standard of care alendronate for one year. At baselineand at one-year bone mineral density measurements will be performed by DXA and 1-year changes in BMD willbe compared between groups. Our central hypothesis is that low turnover age-related osteoporosis needs to bediagnosed and treated differently from estrogen deficiency related osteoporosis. The results will provide aparadigm shift in the treatment of osteoporosis.

project_terms:
Achievement;Adult;Affect;Age;Age-Related Bone Loss;Age-Related Osteoporosis;Alendronate;American;Anabolic Agents;Biological Assay;Biopsy;Blood;Bone Density;Bone Resorption;Bone marrow biopsy;Complement;Data;Diagnosis;Disease;Dual-Energy X-Ray Absorptiometry;Effectiveness;Elderly;Enrollment;Estrogen deficiency;Familiarity;Forteo;Fracture;Health;Hematologist;Histology;Hospitalization;Life;Malignant Breast Neoplasm;Measurement;Measures;Medicare;Menopause;Methods;Myocardial Infarction;Osteocalcin;Osteogenesis;Osteoporosis;Outcome;Patients;Pharmaceutical Preparations;Physicians;Population;Quality of life;Randomized;Regimen;Serum;Societies;Special needs;Stroke;Techniques;Testing;Therapeutic;Training;Treatment Protocols;Validation;Woman;age related;aging population;bisphosphonate;bone;bone loss;bone mass;bone turnover;burden of illness;carboxylate;comparison group;design;improved;individualized medicine;mortality;normal aging;novel;osteoporosis diagnosis;osteoporosis patients;osteoporosis with pathological fracture;personalized approach;precision medicine;prospective;standard of care;success;tool;women patients

public_health_relevance:
8. Project NarrativeOsteoporosis affects 24.5% of women over 65 and results in fracture-related hospital admissions exceedingthose of heart attacks strokes and breast cancer combined. Current treatment options do not account fordifferences between age-related and estrogen deficiency related osteoporosis because of the need for bonebiopsies for determination. This study will establish a paradigm-shifting individualized treatment protocol for age-related osteoporosis and a non-invasive method for its determination thereby reducing the major healthproblems and enormous burden on society and the elderly related to this disease.


application_id: 11178360
project_number: 5R01DE033702-02
project_title: Pathoadaptive Modulation of Porphyromonas gingivalis Lipopolysaccharide Structure and Function
administering_ic: NIDCR
award_notice_date: 2025-07-25
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: DE
serial_number: 033702
program_official: MCNEALY, TAMARA L
project_start_date: 2024-09-01
project_end_date: 2029-08-31
study_section: Special Emphasis Panel[ZRG1-MSOS-L(03)M]
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
arra_indicator: N
project_abstract:
Project SummaryPeriodontitis is a polymicrobial-driven and prevalent inflammatory disease of the tissues supporting the teethin adults. Studies revealed highly active biosynthesis of the lipopolysaccharide (LPS) components of theGram-negative bacteria and also components of cyclic di-3' 5'-adenylic acid (c-di-AMP) second messengersignaling in the periodontal pockets of the periodontitis subjects. Findings from our laboratory demonstratedfor the first time that the LPS structure and function is regulated by c-di-AMP signaling in Porphyromonasgingivalis (Pg) strongly implicated in the onset and development of periodontitis. Our studies indicate that c-di-AMP regulation of LPS structure and therefore function is an essential aspect of the pathogenesis of theperiodontal pathogens. We have identified genes encoding some of the key components constituting the c-di-AMP signaling pathway in Pg including the essential c-di-AMP synthase gene (dacpg; PGN_0523) the c-di-AMPphosphodiesterase gene (pdepg; PGN_0521) and the predicted regulatory gene cdaR (PGN_1486) all of whichregulate Pg LPS structure and function. However we do not yet know the mechanisms of the regulation of LPSstructure and function by c-di-AMP signaling and its contribution to the pathogenesis of the periodontalpathogens and periodontitis progression. We will investigate these mechanisms in Pg in molecular detail throughthese aims: Specific Aim 1: We will conduct a comprehensive analysis of structural differences in LPSsynthesized by WT (strain 381) the strain lacking the c-di-AMP phosphodiesterase gene (pdepg) and a regulatorof c-di-AMP levels (cdaR) mutants. This will involve large-scale LPS purification followed by chromatographicfractionation and thorough characterization of LPS constituents using FLATn MALDI-ToF MS and NMRtechniques. Specific Aim 2: We will determine the protein interaction network of the c-di-AMP-regulated LPSstructure and function and identify c-di-AMP receptors and effectors through various genetic and biochemicalapproaches. The significance of the interactome will be demonstrated by creating mutations in the correspondinggenes in Pg and determining their effect on LPS structure and function. Specific Aim 3: We will use highlypure individual lipid A/LPS fractions isolated from WT pdepg and cdaR mutants purified throughchromatographic fractionation to test their immunostimulatory activities in relation to the TLR4 signalingpathway the complement system and cytokine production. These assessments will involve cell culture assayshuman whole blood studies and an animal model of inflammation. Upon completion of the proposedstudies we will learn how c-di-AMP signaling controls LPS structure-function impacts immunostimulatorypotential of LPS variants and subsequently host defense responses. Since c-di-AMP signaling does not exist inmammals our findings will inform about a novel druggable target.

project_terms:
Adenosine Monophosphate;Adult;Affect;Anabolism;Animal Model;Applications Grants;Biochemical;Biological;Biological Assay;Cell Culture Techniques;Cell model;Chromatography;Chronic;Communities;Data;Defense Mechanisms;Development;Dinucleoside Phosphates;Disease;Disease Progression;Environment;Enzymes;Exhibits;Fractionation;Generations;Genes;Genetic;Goals;Gram-Negative Bacteria;Host Defense;Human;In Situ;In Vitro;Individual;Infection;Inflammation;Inflammatory;Investigation;Laboratories;Learning;Light;Link;Lipid A;Lipids;Lipopolysaccharide Biosynthesis Pathway;Lipopolysaccharides;Mammals;Mediating;Methodology;Methods;Modification;Molecular;Mutation;Oligosaccharides;Organism;Pathogenesis;Pathogenicity;Pathway interactions;Periodicity;Periodontal Pocket;Periodontitis;Phenotype;Play;Polysaccharides;Population;Porphyromonas gingivalis;Preparation;Production;Protein Biosynthesis;Protein Isoforms;Proteins;Regulation;Regulator Genes;Research;Role;Second Messenger Systems;Signal Pathway;Signal Transduction;Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization;Structure;System;Systemic disease;TLR4 gene;Techniques;Testing;Time;Tissues;Tooth structure;United States;Variant;Whole Blood;chronic infection;complement system;cytokine;defense response;economic impact;immunoregulation;in vivo;in vivo evaluation;microorganism;mouse model;mutant;new therapeutic target;novel;novel strategies;pathogen;periodontopathogen;phosphoric diester hydrolase;receptor;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 thelipopolysaccharide driven pathoadaptation and pathogenesis of Pg contributing to periodontitisprogression.


application_id: 11177696
project_number: 5R01MH129357-03
project_title: Anxiety and Interoception Risk for Eating Disorders in Childhood
administering_ic: NIMH
award_notice_date: 2025-09-09
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: MH
serial_number: 129357
program_official: THOMAS, LAURA ANDERSON
project_start_date: 2023-09-15
project_end_date: 2028-08-31
study_section: Child Psychopathology and Developmental Disabilities Study Section[CPDD]
contact_pi_person_id: 10775786
contact_pi: LEVINSON, CHERI ALICIA
other_pis: BUFFERD, SARA J
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_abstract:
PROJECT SUMMARY/ABSTRACTOut of 100000 children and adolescents 120 will have Down Syndrome 56 will die fromsudden infant death syndrome 15 will be diagnosed with cancer 12 will develop Type IIdiabetes and 2900 will have an eating disorder (ED). Although the age of onset for EDs wastraditionally observed in adolescence onset is occurring younger with many childrendeveloping EDs by age 12. Estimates suggest there will be 1.9 million new cases of youth EDsby 2024. Despite the high prevalence costs impairment and deaths from EDs there is verylittle knowledge on what predisposes children to develop EDs. Importantly early detection andintervention is crucial: problematic eating behaviors can damage developing brains and bodiesand untreated EDs carry significant risk for becoming lifelong chronic health conditionsassociated with high mortality rates societal and personal burden. Our scientific premisedeveloped from our past work is that anxiety and interoceptive deficits (inaccuracy identifyingbodily sensations heightened or blunted sensitivity to these sensations) as well as deficits infear learning underlying anxiety and interoceptive deficits will predict common problematiceating behaviors and cognitions (e.g. restriction body dissatisfaction cognitive restraint) aswell as clinical EDs. Our study goals are to (1) test if childhood anxiety and interoceptive deficitsare risk factors for problematic eating behaviors and cognitions and EDs and (2) test if deficits infear learning are a mechanism by which anxiety and interoceptive deficits contribute to risk.These goals will ultimately lead to (a) tools that can better detect childhood risk factors for EDsand (b) prevention efforts directly targeting mechanisms predictive of ED onset. The proposedresearch uses innovative parent-report momentary assessment combined with well-establisheddiagnostic behavioral observational and physiological assessment. We will recruit a sample of400 girls across two age cohorts (6-8; 10-12 years old) enriched for interoceptive deficitsanxiety and EDs; 75% (n=300) will be recruited based on maternal history of EDs or anxietyand 25% (n=100) will make up the control group. This study will for the first time allow us tobegin to quantify how early symptoms of ED develop. The specific aims are to test (1) multi-modal aspects of anxiety and (2) characteristics of interoceptive deficits that may prospectivelypredict problematic eating behaviors and cognitions and EDs and (3) mechanisms of predictionamong anxiety and interoceptive deficits. The proposed research has clinical impact: ultimatelythis study will lead to early detection and prevention of EDs in childhood and beyond avertingthe large personal and societal costs associated with both childhood onset and chronic EDs.

project_terms:
12 year old;Adolescence;Adolescent;Age;Age of Onset;Anxiety;Anxiety Disorders;Behavior;Behavioral;Body Size;Brain;Cessation of life;Characteristics;Child;Childhood;Chronic;Clinical;Cognition;Cognition Disorders;Cognitive;Control Groups;Data;Death Rate;Development;Diagnosis;Diagnostic;Down Syndrome;Early Diagnosis;Early Intervention;Early identification;Eating;Eating Behavior;Eating Disorders;Esthesia;Etiology;Exhibits;Extinction;Family;Fasting;Female;Fright;Goals;Health;High Prevalence;Hyperphagia;Hypersensitivity;Impairment;Individual;Interoception;Knowledge;Lead;Learning;Link;Literature;Malignant Neoplasms;Mental Depression;Mental disorders;National Institute of Mental Health;Non-Insulin-Dependent Diabetes Mellitus;Occupations;Onset of illness;Parents;Pathology;Physiological;Population;Predisposing Factor;Prevention;Prevention program;Recording of previous events;Reporting;Research;Risk;Risk Factors;Sampling;Societies;Sudden infant death syndrome;Symptoms;Testing;Time;Traction;United States;Work;Youth;bodily sensation;body dissatisfaction;childhood anxiety;cohort;cost;design;dieting;early adolescence;early childhood;early onset;experience;follow-up;gastrointestinal system;girls;high risk;improved;innovation;insight;maternal anxiety;multimodality;negative affect;novel;opioid use;prospective;public health relevance;recruit;restraint;social anxiety;societal costs;standard care;theories;tool

public_health_relevance:
PROJECT NARRATIVEThis project will collect data on early childhood risk factors for eating disorders in femalechildren ages 6-12. The proposed research has significant public health relevance as it willenhance our understanding of how eating disorders develop and for whom leading to earlydetection and prevention efforts. The proposed research is relevant to NIMHs strategic aim 3.1.A to strive for prevention based on an understanding of risk as it will lead to tools that canbetter identify early risk factors as well as prevention efforts directly targeting mechanismspredictive of the onset of early eating disorders and related pathology.


application_id: 11177227
project_number: 5P20GM130456-05
project_title: Novel therapeutics for controlling antibiotic-resistant Salmonella infections in humans
administering_ic: NIGMS
award_notice_date: 2024-02-28
opportunity_number: PAR-18-266
application_type: 5
activity_code: P20
ic: GM
serial_number: 130456
program_official: FRINCU, CRINA
project_start_date: 2024-08-26
project_end_date: 2025-07-31
study_section: ZGM1-RCB-9(C1)
subproject_number: 7760
contact_pi_person_id: 78775561
contact_pi: HELMY, YOSRA A.
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
project_abstract:
SUMMARY: Salmonella is the leading cause of bacterial foodborne poisoning with significant public health implications worldwide. Poultry products (eggs and poultry meat) are humans' main source of Salmonella infections. Human Salmonella serotypes do not cause disease in birds which serve as the reservoir but colonize their intestines. Salmonella can enter the human food chain during processing and humans can be exposed to infection through direct contact with infected poultry carcasses. Currently Salmonella infections are controlled by antibiotics and/or vaccination; however the emergence of antibiotic-resistant Salmonella strains is a growing source of concern. Additionally live Salmonella vaccines are not effective at reducing food poisoning and they raise the risk of live bacteria entering the human food chain. Untreated Salmonella infections have been linked to a variety of chronic health issues such as colon and gallbladder cancers. According to the American Cancer Society gallbladder and colon cancers have been associated with infections with two Salmonella serovars S. Typhi and S. Enteritidis respectively. Therefore there is a critical need for antibiotic alternatives to control Salmonella infection in poultry and to mitigate the risk of Salmonella food poisoning antimicrobial resistance and cancer in humans. Quorum sensing autoinducer-2 (QS AI-2) plays a critical role in the pathogenicity virulence biofilm formation motility genetic competence sporulation and antibiotic production of several bacteria including Salmonella. Therefore inhibition of QS AI-2 activity using QS inhibitors (QSI) is a potentially novel strategy for antibacterial development. Since QSIs do not interfere with the metabolic processes of a bacterial cell such as protein synthesis DNA metabolism and cell wall formation which are the targets for the development of drug resistance QSIs will not exert selection pressure on the bacteria during treatment thus bacteria are less likely to develop resistance. We hypothesize that breaking the bacterial conversation by using QSIs makes pathogens less virulent and thus more susceptible to host immune responses. Through the screening of 1900 compounds to identify the QS/AI-2 inhibitors against S. Typhimurium we identified 10 compounds that inhibited the QS/AI-2 production of S. Typhimurium (95%; at 10M final concentration) without affecting bacterial growth. We compared the efficacy of these 10 compounds to the benchmark QSIs identified in previous studies and found that our compounds are more effective at lower concentrations. In this proposal we will (Aim 1) identify and evaluate the efficacy of the selected QSIs in vitro (Aim 2) evaluate the efficacy of the lead QSIs in infected 3D human intestinal pluripotent stem cell-derived organoids and in the reservoir animal host (chickens) and (Aim 3) identify the drug target(s) of the selected leads using drug-target binding studies. Completion of these aims will contribute towards our long-term objective of developing new anti-Salmonella therapeutics that control the emergence of antibiotic-resistant Salmonella associated with poultry production and mitigate the risk of food poisoning and gallbladder and colon cancers in humans.

project_terms:
3-Dimensional;Affect;American Cancer Society;Animals;Anti-Bacterial Agents;Antibiotic Resistance;Antibiotics;Antimicrobial Resistance;Bacteria;Benchmarking;Binding;Birds;Cell Wall;Cells;Centers of Research Excellence;Chickens;Chronic;Colon Carcinoma;Competence;DNA metabolism;Development;Disease;Domestic Fowls;Drug Targeting;Drug usage;Exposure to;Food Chain;Food Poisoning;Genetic;Growth;Health;Human;Immune response;In Vitro;Infection;Intestines;Lead;Link;Malignant Neoplasms;Malignant neoplasm of gallbladder;Meat;Metabolism;Microbial Biofilms;Motility;Pathogenicity;Pharmacologic Substance;Play;Pluripotent Stem Cells;Poisoning;Poultry Products;Predisposition;Production;Protein Biosynthesis;Public Health;Research;Resistance development;Risk;Role;Salmonella;Salmonella Vaccines;Salmonella food poisoning;Salmonella infections;Salmonella typhi;Salmonella typhimurium;Serotyping;Source;Therapeutic;VAI-2;Vaccination;Virulence;Virulent;comparative efficacy;drug resistance development;efficacy evaluation;egg;foodborne;inhibitor;innovation;novel strategies;novel therapeutics;pathogen;pressure;quorum sensing;risk mitigation;screening;stem cell organoids


application_id: 11177065
project_number: 5R01EY035523-03
project_title: The Influence of the Pretectum on the Visual Thalamus
administering_ic: NEI
award_notice_date: 2025-08-25
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: EY
serial_number: 035523
program_official: FLANDERS, MARTHA C
project_start_date: 2023-09-01
project_end_date: 2026-07-31
study_section: Special Emphasis Panel[ZRG1-ICN-U(02)M]
contact_pi_person_id: 1871981
contact_pi: BICKFORD, MARTHA E
other_pis: BORGHUIS, BART GERARD
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 / ABSTRACTThe pretectum (PT) is a relatively unexplored brain area in mammals and it is currently unknownhow the PT affects the visual properties of thalamic neurons that underly the complex integrationof vision and movement. Here a team of investigators propose a multifaceted approach - fromsynapse to behavior  to answer fundamental questions regarding PT circuits (Aim 1) the visualand/or motor response properties of identified PT neurons (Aim 2) the effects of PT input on theresponse properties of thalamic neurons (Aim 3) and the effects of the PT on visual behavior(Aim 4). Each aim will utilize a combination of novel intersectional circuit labeling techniquesneuronal activation and recording strategies to probe two identified PT pathways: a GABAergicpathway to the lateral geniculate nucleus (LGN) and the visual sector of the thalamic reticularnucleus (vTRN) and a nonGABAergic pathway to the pulvinar nucleus (PUL) from PT neuronsthat contain parvalbumin. Aim 1 will use cre-dependent monosynaptic rabies tracing to inducethe expression of the calcium indicator GCaMP to classify using 2P imaging the receptive fieldproperties and morphology of retinal ganglion cells that innervate PT-LGN/TRN and PT-PULneurons. Monosynaptic rabies tracing will also be used to characterize cortical and subcorticalbrain inputs to PT-LGN/TRN and PT-PUL cells; identified PT inputs will subsequently be studiedusing electron microscopy and in vitro whole cell recordings paired with optogenetic activation tocharacterize their ultrastructure and synaptic properties. Aim 2 will use in vivo extracellularrecordings in awake animals paired with opto-tagging to determine the response properties ofPT-LGN/TRN and PT-PUL neurons. Aim 3 will use in vivo extracellular recordings from awakeanimals paired with optogenetic activation of PT inputs to determine the effects of the PT inputson LGN vTRN and PUL response properties. Finally Aim 4 will use cre- and flp-dependentchemogenetic activation of PT-LGN/TRN or PT-PUL neurons to determine if these cells affectstereopsis and/or optokinetic responses. Collectively these 4 lines of inquiry will provide keyinformation regarding the role of the PT in active vision.

project_terms:
Address;Affect;Amblyopia;Animals;Area;Behavior;Behavioral;Brain;Butyric Acids;Calcium Signaling;Cell Nucleus;Cells;Classification;Complex;Darkness;Depth Perception;Diagnosis;Disease;Disinhibition;Dorsal;Dyslexia;Electron Microscopy;Eye Movements;Felis catus;Fluorescence;Genetic;Glutamates;Image;In Vitro;Injections;Interneurons;Knowledge;Label;Lasers;Lateral Dorsal Nucleus;Lateral Geniculate Body;Light;Link;Mammals;Mediating;Medical;Methods;Miosis disorder;Modeling;Morphology;Motion;Motion Perception;Motor;Movement;Mus;Neurons;Neurotransmitters;Ocular Motility Disorders;Parvalbumins;Pathologic Nystagmus;Pathway interactions;Pattern;Perception;Play;Population;Property;Pulvinar structure;Research;Research Personnel;Retina;Retinal Ganglion Cells;Role;Running;Saccades;Schizophrenia;Sensory;Shapes;Signal Transduction;Source;Speed;Strabismus;Synapses;Techniques;Testing;Thalamic structure;Transgenic Organisms;Viral;Viral Vector;Vision;Visual;Visual Motion;Whole-Cell Recordings;active vision;area striata;awake;calcium indicator;cell type;extracellular;ganglion cell;gaze;in vivo;insight;monocular;novel;optogenetics;rabies viral tracing;receptive field;response;retinogeniculate;spatiotemporal;tool;transmission process;two-photon;visual stimulus;visual tracking

public_health_relevance:
PROJECT NARRATIVEThe proposed research will investigate brain circuits involved in active vision (circuits that link visualmotion perception and gaze shifts). This research should provide information relevant to the treatmentof disorders in which visual motion processing is compromised such as dyslexia and schizophreniaand may provide insight into the use of eye tracking as a tool for medical diagnoses and/or eyemovement disorders such as nystagmus strabismus and amblyopia.


application_id: 11177008
project_number: 5R01NS132773-02
administering_ic: NINDS
award_notice_date: 2025-08-15
opportunity_number: PAR-22-181
application_type: 5
activity_code: R01
ic: NS
serial_number: 132773
program_official: BAMBRICK, LINDA LOUISE
project_start_date: 2024-09-01
project_end_date: 2029-07-31
study_section: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]
contact_pi_person_id: 11253032
contact_pi: METCALFE, MARIAJOSE
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
budget_start_date: 2025-08-01
project_title:
Regulated PTEN expression to overcome barriers to corticospinal tract regeneration after spinal cord injury

project_abstract:
Project Summary: 30 lines of text (Currently 28):Spinal cord injuries (SCI) disrupt the communication pathways in the spinal cord leading to paralysis primarilyaffecting the corticospinal tract (CST) responsible for voluntary movements. Unfortunately damaged CSTaxons have limited regrowth capacity due to intrinsic and extrinsic factors. Efforts to address intrinsic factorshave focused on targeting proteins like PTEN which inhibits neuronal growth. In addition there has been afocus on targeting extrinsic molecules such as chondroitin sulfate proteoglycans (CSPGs) throughchondroitiase ABC (chABC) digestion which hinder axon growth. Despite progress in individually targetingthese factors overall growth remains limited posing a significant challenge. Adeno-associated virus (AAV)-based delivery of growth-promoting molecules has shown promise but permanent expression can have off-target effects. Our recent findings demonstrated that permanent AAV-driven PTEN deletion resulted insignificant functional recovery after SCI albeit with pathophysiology at 2 months post-SCI.The long-term goal of this project is to develop effective therapeutic strategies for SCI by evaluating controlledPTEN deletion and CSPGs degradation in promoting axon regeneration and functional recovery. The followingthree specific aims are proposed: 1) Temporal evaluation of PTEN knockdown after SCI without developmentof pathophysiologies; 2) Determine the role of CST in PTEN-deletion induced recovery of function; 3) Examinethe role of CSPGs in growth impairment of PTEN deleted axons. For the first aim our approach involvesregulating PTEN deletion using a regulatory system within our AAVs. This system enables the activation ofPTEN deletion in the presence of an inducer drug enabling us to pinpoint the crucial temporal window for CSTregeneration while avoiding the development of pathophysiologies. In the second aim our approach is tointerrupt PTEN-deleted CSTs to assess the extent to which CST regeneration contributes to the observedrecovery of function in PTEN-deleted mice after SCI. Lastly for the third aim our approach entails testingwhether CSPGs are the main impediment for the growth of PTEN-deleted axons by temporally regulating thedigestion of CSPGs using chondroitinase ABC (chABC). The proposed studies are innovative as they aim todetermine the optimal timing for PTEN deletion to maximize regeneration while avoiding adverse effectsinvestigate the mechanistic link between PTEN deletion in the CST and functional recovery and examine therole of CSPGs in inhibiting axonal growth of PTEN-deleted axons. This project is significant as it addresses thecritical challenge of limited axon regeneration following spinal cord injury and seeks to identify effectivestrategies for promoting functional recovery. The completion of the proposed research will establish newknowledge and approaches to enhance axon regeneration and improve outcomes for individuals with SCI.

project_terms:
Address;Adult;Adverse effects;Affect;Axon;Bilateral;Cells;Central Nervous System;Cervical spinal cord injury;Chondroitin ABC Lyase;Chondroitin Sulfate Proteoglycan;Communication;Corticospinal Tracts;Dependovirus;Development;Digestion;Doxycycline;Environment;Evaluation;FRAP1 gene;Functional disorder;Genes;Goals;Growth;Homologous Gene;Impairment;Individual;Injections;Injury;Interruption;Intrinsic factor;Knowledge;Lesion;Link;MT3 gene;Mediating;Movement;Mus;Natural regeneration;Nervous System Disorder;Neurons;Paralysed;Pathway interactions;Pharmaceutical Preparations;Play;Proteins;Proto-Oncogene Proteins c-akt;Recovery of Function;Research;Rodent Model;Role;Site;Spinal Cord;Spinal cord injury;Structure of rubrospinal tract;System;Testing;Text;Time;Transgenes;Upper limb movement;Variant;adenovirus mediated delivery;axon growth;axon injury;axon regeneration;combinatorial;designer receptors exclusively activated by designer drugs;functional improvement;genetic approach;healing;improved;improved outcome;innovation;inorganic phosphate;insight;knock-down;motor recovery;neural repair;neuronal growth;novel therapeutic intervention;promoter;retrograde transport;small hairpin RNA;spinal tract;tensin;therapeutically effective;transgene expression

public_health_relevance:
Project Narrative: Three sentences.Damage to the spinal cord doesnt heal because regrowth of injured axons is limited by the lackof growth capacity of adult neurons and by the inhibitory environment in the injury site. We userodent models to test controlled delivery of treatments to promote axonal regeneration afterinjury avoiding off-target effects and study the role of the inhibitory environment when injuredaxons are prompted to grow. These studies are relevant as they could open the field to explorecombinatorial strategies to promote optimal axonal regrowth after spinal cord injury.


application_id: 11176927
project_number: 5R44CA295197-02
administering_ic: NCI
award_notice_date: 2025-08-29
opportunity_number: PA-23-231
application_type: 5
activity_code: R44
ic: CA
serial_number: 295197
program_official: LI, MELISSA WANLING
project_start_date: 2024-09-01
project_end_date: 2027-08-31
study_section: Special Emphasis Panel[ZRG1-CTH-T(10)B]
contact_pi_person_id: 12334483
contact_pi: ABRAMOV, VASILIY
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 786659719
primary_uei: CBL5M5DKH3K7
duns_number: 786659719
uei: CBL5M5DKH3K7
fips: US
organization_id: 10021015
organization_name: CREOSALUS, INC.
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 402046033
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2025-09-01
project_title:
Comparison of convection enhanced delivery systems in a randomized controlled clinical study of recurrent Grade 3-4 glioma patients

project_abstract:
Project AbstractSignificance: The devasting outcomes for glioblastoma (GBM) patients remain despite the advances incancer therapy. Improved GBM therapy as a critical unmet need requires new intervention capabilities and thelikely integration of innovative GBM interventions as proposed with this research. The premise of this project isthat one of the challenges to improving GBM patient lives can be overcome by increased therapeutic coverageof GBM tumors using an innovative convection enhanced delivery (CED) catheter. Innovations: Theproposed SBIR Direct to Phase II research offers the innovations of (1) improved GBM therapeutic agentdelivery obtained with the CED Porous Brain Infusion Catheter (PBIC) when combined with a more accurateMolecular Flow Simulations (MFS) software  as the PBIC System and (2) a novel approach to evaluate CEDdrug delivery catheters with a randomized controlled trial. Preliminary Data: PBIC has demonstratedpreclinical in vivo increased volume of infused brain distribution. The MFS infusion planning software hasdemonstrated robust correlation of actual and simulated human brain tumor infusions and has obtained FDA510k marketing clearance. Comparative GBM tumor infusion simulations using the FDA cleared MFS softwareindicate PBIC can increase therapeutic coverage of GBM tumors. Hypothesis: The PBIC will have equivalentor improved safety profile and significantly greater percentage of enhancing tumor coverage than an end portCED catheter. Overall Project Objective: Accelerate CED research with the clinical safety and infusiondistribution evaluation of the PBIC System in Aim 1 research. Specific Aim 1: First-In-Human study toevaluate PBIC safety and recurrent GBM tumor infusion distribution efficacy. CreoSalus will manufacture PBICtest devices and provide physician placement training. Duke investigators with Therataxis support will evaluatethe PBIC to treat recurrent WHO grade 3 or 4 malignant glioma (rGBM) patients using an existing Dukeclinical trial of intratumoral therapeutic infusion via CED of D2C7-IT and 2141-V11 (NCT04547777 IND151390). A total of 24 patients (12 patients per catheter group) will be randomized to either the PBIC or thecurrent Duke CED end port catheter. Safety analysis will be based on catheter related adverse events.Infusion distribution in enhancing tumor will be evaluated with co-infused PET imaging tracers (124I-humanserum albumin (HSA)) same as used in prior Duke Brain Tumor Center and Therataxis CED distributionstudies. Aim 1 Milestone: Compared to the control end port catheter the PBIC will demonstrate (a)equivalent or better safety and (b) significantly improved (p<.05) 124I-HSA distribution in enhancing tumor.Research Impact: Improved drug distribution using a catheter specifically designed for CED to improve GBMand other brain disease/injury patient outcomes.

project_terms:
Acceleration;Acute;Adoption;Adverse event;Biopsy;Brain;Brain Diseases;Brain Neoplasms;Catheters;Chronic;Clinical;Clinical Research;Clinical Trials;Complex;Computer software;Convection;Data;Devices;Diagnosis;Drug Delivery Systems;Evaluation;FDA approved;Family suidae;Future;Glioblastoma;Glioma;Hospitals;Human;Infusion procedures;Injury;Institutional Review Boards;Intervention;Joints;Letters;Magnetic Resonance Imaging;Malignant Glioma;Manufacturer;Marketing;Medical Device;Methods;Molecular;Neurosurgeon;Outcome;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phase;Physicians;Porosity;Positron-Emission Tomography;Procedures;Product Approvals;Protocols documentation;Qualifying;Randomized;Randomized Controlled Trials;Readiness;Recurrence;Research;Research Personnel;Safety;Sales;Sample Size;Serum Albumin;Small Business Innovation Research Grant;Study Section;System;Technology;Testing;Therapeutic;Therapeutic Agents;Time;Tracer;Training;Tumor Subtype;Tumor Volume;cancer therapy;commercial application;commercialization;comparative;comparison control;design;drug distribution;first-in-human;human study;improved;in vivo;innovation;manufacture;molecular imaging;neuro-oncology;neurosurgery;novel strategies;pre-clinical;pre-clinical research;provider adoption;randomized controlled study;simulation;simulation software;tumor

public_health_relevance:
Narrative Many of the primary and metastatic brain tumor subtypes present enormously complex diagnosis andtherapy challenges with dismal outcomes that have not changed for several decades. The proposed researchis for combining two drug delivery technologies that have demonstrated feasibility into an innovativecommercial system and then evaluated for a first time in a clinical study for improved brain tumor drug delivery.


application_id: 11176529
project_number: 3K12DA035150-13S1
administering_ic: NIDA
award_notice_date: 2024-09-12
opportunity_number: PA-20-272
application_type: 3
activity_code: K12
ic: DA
serial_number: 035150
suffix: S1
program_official: FALCON-MORALES, EDGARDO
project_start_date: 2022-08-01
project_end_date: 2027-07-31
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
arra_indicator: N
budget_start_date: 2024-08-01
project_title:
Supplement for Kentucky BIRCWH Program: Training the Next Generation of Women's Health Scholars: Dr. Conner

project_abstract:
AbstractThe BIRCWH program at the University of Kentucky (UK) has been extremely successful in creatinga research environment to prepare early career scientists with necessary skills to becomeindependent NIH-supported researchers dedicated to improving womens health. This supplement willcontinue the training of a 4th BIRCWH scholar Dr. Laneshia Conner who is from an underrepresentedracial minority group with the goal of developing research skills necessary to become an independentresearcher engaged in intervention development for older Black women in real world settings. HIVremains a major public health issue with adults aged 50 and older experiencing an increase in HIVdiagnoses over the past two decades and 82% of HIV infections transmitted through heterosexualcontact. Black women continue to be disproportionately impacted by HIV making up less than 15% ofthe female population yet accounting for half of new HIV infections in women in the U.S. Older Blackwomen are often overlooked when it comes to HIV prevention services due to ageism and stigmaabout high-risk behaviors among older adults and lack of an empirical base about older Blackwomen. Dr. Conner will continue to acquire skills to launch her research program in three areas:intervention development developing sustainable community programs for older adults andexpanding methodological skills for a future RCT research. The proposed project will develop aculturally relevant Woman 2 Woman (W2W) intervention that has been adapted to address uniquegaps in HIV prevention that target older Black women and provide data on the feasibility andacceptability of the intervention in addition to the measuring behavioral and knowledge outcomes.Working with two low-income housing complexes for adults over the age of 50 older Black womenwill be recruited to participate in a multisession group-level behavioral intervention adapted toaddress both physiological risk as well as low perception of risk. High unknown serostatus suggestthat HIV prevalence may be higher than reported among older adults. Implementation assessmentprocedures and protocols will inform a subsequent full-scale randomized clinical trial. The objectiveof this innovative project is to develop and test the feasibility acceptability usability and preliminaryefficacy of Woman to Woman (W2W) using a mixed methods approach. Specific aims are: (1) Adaptthe group-level intervention (W2W) focused on reducing HIV risk and increasing decision makingskills in older Black women to include reproductive health histories in exploring the impact on sexualdecision making and risk behaviors and (2) Conduct a pilot study of the revised W2W intervention intwo community sites to evaluate acceptability and feasibility.

project_terms:
AIDS prevention;Accounting;Address;Adult;Age;Ageism;Area;Behavior Therapy;Communities;Complex;Data;Decision Making;Dedications;Environment;Female;Future;Goals;HIV;HIV Infections;HIV diagnosis;HIV risk;Heterosexuals;Housing;Intervention;Kentucky;Knowledge;Low income;Methodology;Methods;Outcome;Physiological;Pilot Projects;Population;Prevalence;Procedures;Protocols documentation;Public Health;Recording of previous events;Reporting;Reproductive Health;Research;Research Personnel;Risk;Risk Behaviors;Scientist;Site;Training;United States National Institutes of Health;Universities;Woman;Women's Health;acceptability and feasibility;aged;base;behavior measurement;black women;career;experience;feasibility testing;high risk behavior;improved;innovation;next generation;older adult;prevention service;programs;racial minority population;randomized clinical trials;recruit;risk perception;skill acquisition;skills;social stigma;therapy development;transmission process;usability

public_health_relevance:
Project NarrativeThere are no known evidence-based interventions targeting the prevention of HIV transmissionamong older Black women in the U.S. which is a major public health concern as there is a growingaging Black American population living with HIV. The objective of this innovative project is to developand test the feasibility acceptability usability and preliminary efficacy of Woman to Woman (W2W)an HIV intervention for older Black women. The mentorship and training activities combined with theimplementation of the feasibility trial within this BIRCWH supplement will provide the needed skillsand data for the BIRCWH scholar Dr. Laneshia Conner to address comments for her competitiveK01 to conduct a large scale randomized controlled trial to assess the impact of the W2W interventionin reducing HIV risk among older Black women.


application_id: 11176231
project_number: 5R44CA295373-02
administering_ic: NCI
award_notice_date: 2025-09-03
opportunity_number: PA-23-230
application_type: 5
activity_code: R44
ic: CA
serial_number: 295373
program_official: ZHAO, MING
project_start_date: 2024-09-01
project_end_date: 2026-08-31
study_section: Special Emphasis Panel[ZRG1-ISB-Z(10)B]
contact_pi_person_id: 10810394
contact_pi: MOLLOY, JANELLE ARLENE
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 093718777
primary_uei: L8D1CH5FK9X3
duns_number: 093718777
uei: L8D1CH5FK9X3
fips: US
organization_id: 10052089
organization_name: WILD DOG PHYSICS, LLC
organization_city: NICHOLASVILLE
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 403568039
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2025-09-01
project_title:
Improving allocation of scarce medical physics resources through a novel comprehensive quality assurance device.

project_abstract:
RT is an effective component of the treatment strategy for patients suffering from many types of cancer. Advanced techniques such as intensity modulated radiation therapy (IMRT) image-guided RT (IGRT) stereotactic body RT (SBRT) and stereotactic radiosurgery (SRS) improve outcomes and are delivered using medical linear accelerators (i.e. linacs). SBRT is especially appealing in modern settings given that the precise treatments are delivered in 1-5 daily treatment fractions as opposed to the 20-40 fractions required for conventional techniques. This improvement in treatment efficiency can positively impact delivery of care and the financial viability of providers of RT. The quality assurance (QA) that medical physicists provide is critical for safe treatments yet there is a shortage of qualified medical physicists (QMPs) both in the US and globally. At the same time more centers are introducing modern techniques that are more precise but intrinsically have more risk due the high doses and geometric precision required. There is widespread noncompliance with industry standard QA protocols in the US and internationally. Existing QA devices have not evolved sufficiently to provide the precision versatility and efficiency that is needed for high precision RT. Given these exacerbated safety risks the market needs a paradigm shift in how QA is performed in modern RT. Wild Dog Physics (WDP) proposes to design and test a new-generation QA device that addresses these unmet medical needs. We have trademarked this device the RetrieverTM. When complete it will be more precise efficient and comprehensive than any QA solution currently on the market. The proposed project seeks to develop a clinical prototype to be tested in the Radiation Therapy clinic at the University of Kentucky as well as partner organizations seeking to improve operational efficiency. Having proven feasibility in our feasibility study we seek to advance this innovation to commercial viability in Phase 2 through three specific aims: 1) hardware refinement to allow measurement of machine performance metrics to within 0.5 mm and 1% relative does; 2) software development to allow real-time data analysis real-time compliance assessment and analytical tools that can monitor long-term trends abrupt shifts and inter-machine and inter-institutional comparisons and; 3) clinical testing to validate the sensitivity and specificity of the Retriever to shifts in machine characteristics. We will work with key academic and clinical partners in the design and testing phases including private practice medical physics groups for which operational efficiency and data integrity are paramount.

project_terms:
Address;Adoption;Advocate;Assessment tool;Benchmarking;Canis familiaris;Characteristics;Clinic;Clinical;Collection;Computer software;Coupled;Data;Data Analyses;Dependence;Devices;Dose;Feasibility Studies;Funding;Future;Generations;Image;Industry;Industry Standard;Intensity-Modulated Radiotherapy;International;Kentucky;Linear Accelerator Radiotherapy Systems;Longitudinal trends;Marketing;Measurement;Mechanics;Medical;Medical Device;Methods;Modernization;Monitor;Optics;Patients;Peer Review;Performance;Phase;Physics;Positioning Attribute;Private Practice;Process;Protocols documentation;Provider;Qualifying;Quality Control;Radiation;Radiation therapy;Radiosurgery;Resources;Risk;Safety;Sensitivity and Specificity;Specific qualifier value;System;Techniques;Technology;Testing;Time;Trademark;Universities;Validation;Visible Radiation;Work;analytical tool;cancer type;care delivery;commercialization;cost;data integrity;design;dosimetry;image guided;imaging system;improved;improved outcome;innovation;inter-institutional;machine vision;manufacture;non-compliance;novel;peer support;product development;prototype;quality assurance;research clinical testing;software development;transmission process;treatment strategy

public_health_relevance:
The pervasive shortage of Qualified Medical Physicists is compelling the medical device industry to provide enhanced solutions for efficient quality assurance (QA) in radiation therapy. To date the market has failed to yield a disruptive QA solution. We propose to design and test a new-generation QA device capable of improving quality and efficiency across a wide range of clinical settings.


application_id: 11175525
project_number: 5R01HD115554-02
project_title: The Impact of Leukocyte-derived Cytokines on Ovulation in Humans
administering_ic: NICHD
award_notice_date: 2025-04-18
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: HD
serial_number: 115554
program_official: TAYMANS, SUSAN
project_start_date: 2024-08-22
project_end_date: 2029-05-31
study_section: Special Emphasis Panel[ZRG1-EMS-C(02)M]
contact_pi_person_id: 14509280
contact_pi: CHOI, YOHAN
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
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT Mid-cycle gonadotropin-induced ovulation a pivotal event in female reproductive physiology sharesmany features with an acute inflammatory response notably marked by a substantial influx of leukocytes intothe dominant follicle. Despite this the precise impact of leukocytes on the ovulatory process remains largelyuncharted territory. This knowledge gap serves as the foundation of the proposed study which endeavors toelucidate the role of leukocytes in facilitating ovulation and luteinization in the human ovary. Our preliminaryfindings derived from single-cell RNA sequencing (scRNA-seq) analysis using follicular aspirates obtainedfrom in vitro fertilization patients (due to male factor or egg donation) have revealed the presence of tendistinct leukocyte subpopulations. Furthermore based on the single-cell transcriptomic datasets we found thatinflammatory cytokines are exclusively expressed in leukocytes while the expression of their correspondingreceptors is abundantly detected in follicular (granulosa and theca) cells. Therefore we hypothesize that thesecytokines and their receptors play a pivotal role in ovulatory changes including steroid hormone andprostaglandin production as well as cell metabolic shifts in the human periovulatory follicle. In Specific Aim 1we will comprehensively delve into characterizing the expression profile of these cytokines and theircorresponding receptors in dominant follicles throughout the ovulatory period analyzing samples obtained fromregularly cycling women before and at defined hours after human chorionic gonadotropin (hCG) administrationto understand spatiotemporal dynamics of leukocyte-derived cytokines and their corresponding receptors. Alsowe will determine the regulatory mechanisms by which hCG increases the expression of the receptors for theleukocyte-derived cytokines using primary human granulosa/lutein cells (hGLCs). Specific Aim 2 focuses onelucidating the impact of these leukocyte-derived cytokines and their corresponding receptors in granulosacells on the ovulatory process. By treating hGLCs with hCG cytokines and/or receptor antagonists we aim touncover the underlying signaling pathways and associated functional changes facilitating ovulation and lutealformation in the human ovary. The implications of this proposed study extend beyond advancing ourunderstanding of normal ovulation; it also holds significant promise for addressing female infertility caused byinflammation-related ovarian conditions. By shedding light on these intricate mechanisms our research has thepotential to provide invaluable insights into the development of innovative therapeutic strategies aimed atimproving womens reproductive health and fertility.

project_terms:
Acute;Address;Anabolism;Animal Model;Anti-Inflammatory Agents;Bioinformatics;Cell Cycle;Cell Physiology;Cell Proliferation;Cells;Chronic;Cytokine Receptors;Data;Data Set;Development;Dinoprostone;Endometriomas;Etiology;Event;Female;Female infertility;Fertility;Fertilization in Vitro;Foundations;Gene Expression;Gene Expression Profiling;Gonadotropins;Hour;Human;Human Chorionic Gonadotropin;IFNGR1 gene;IFNGR2 gene;IL10RB gene;IL16 gene;IL1R1 gene;IL6ST gene;In Situ;Infertility;Inflammation;Inflammatory;Inflammatory Response;Interferon Type II;Interleukin-10;Interleukin-16;Knowledge;Leucocytic infiltrate;Leukocytes;Ligands;Light;Luteal Cells;Luteinization;MAPK3 gene;Malignant Neoplasms;Mediator;Messenger RNA;Metabolic;Metabolism;Micro Array Data;Mitochondria;Ovarian;Ovary;Ovulation;Ovulation Induction;Ovulation Inhibition;PTGS2 gene;Patients;Persons;Pharmaceutical Preparations;Phase;Phosphopeptides;Phosphorylation;Play;Polycystic Ovary Syndrome;Process;Production;Progesterone;Prostaglandin Production;Proteins;Proteomics;Recombinant Human Chorionic Gonadotropin;Reproductive Physiology;Research;Role;STAT3 gene;Sampling;Signal Pathway;Signal Transduction;Specific qualifier value;Steroid biosynthesis;Supplementation;TNF gene;TNFRSF1A gene;Techniques;Therapeutic;Therapeutic immunosuppression;Tissue-Specific Gene Expression;Tissues;Western Blotting;Woman;antagonist;aspirate;cytokine;cytokine therapy;egg;female fertility;granulosa cell;improved;in vivo;innovation;insight;male;oncostatin M;receptor;receptor expression;single-cell RNA sequencing;spatiotemporal;steroid hormone;tandem mass spectrometry;theca cell;transcriptome sequencing;transcriptomics;women's reproductive health

public_health_relevance:
PROJECT NARRATIVEThe gonadotropin surge-induced ovulatory changes include the infiltration of leukocytes into the dominantfollicle implying a significant role of leukocytes in the ovulatory process; however underlying mechanismsremain elusive. Our pilot single-cell transcriptomic data using human follicular aspirates revealed specificcytokines produced by leukocytes and their corresponding receptors in follicular cells indicating a collaborativerole of leukocytes and follicular cells in successful ovulation. Consequently the proposed study willcharacterize leukocyte-derived cytokines and their receptors in the human dominant follicle and elucidate theiractions and roles in periovulatory granulosa cells thereby better understanding the mechanisms of howleukocytes facilitate the ovulatory process and luteal formation in the human ovary and its impact on femalefertility.


application_id: 11175234
project_number: 5U54OH007547-24
project_title: Southeast Center for Agricultural Health and Injury Prevention
administering_ic: NIOSH
award_notice_date: 2025-08-21
opportunity_number: PAR-15-353
application_type: 5
activity_code: U54
ic: OH
serial_number: 007547
program_official: DEARWENT, STEVE
project_start_date: 2022-09-30
project_end_date: 2027-09-29
study_section: ZOH1-EHG(01)
contact_pi_person_id: 8433958
contact_pi: SANDERSON, WAYNE 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:
Southeast Center for Agricultural Health and Injury PreventionProject Summary/AbstractThe Southeast Center for Agricultural Health and Injury Prevention (SCAHIP) at the Universityof Kentucky proposes to continue its long history of serving as one of the NIOSH Centers forAgricultural Safety and Health for 2022-2027. The Center founded in 1992 on a land-grantuniversity campus provides multidisciplinary collaboration from colleges of agricultureengineering public health education medicine nursing and the Cooperative Extension Servicefrom universities in the Southeast. We propose 6 Research Core projects: Postsecondary-Community Safe Farm Steward & Advocate Program; Timber Safe Resource Center: Reductionof Central Appalachian Logging Hazards through the Implementation and Diffusion of a TestedLogging Operations Safety and Health Management System; Farmer Mental Health in theSoutheast Region: Community Networking Access and Support for Farmer Well-being;Exposure Risk Assessment and Respiratory Disease Prevention Associated with GrainProduction; Vector-borne Disease Assessment and Prevention among Farmers and ForestryWorkers; and a Pilot/Feasibility Program. The Centers theme Multidisciplinary partnerships toimprove agricultural safety and health in the Southeast is distinguished by our emphasis onserving vulnerable farm populations while addressing persistent and emerging agriculturalsafety concerns. The region served by the Center will continue to be 9 southeastern states ofAL GA KY MS NC SC TN VA and WV. The Center will evaluate its impact on the followingpriorities and NIOSH Strategic Goals in the agriculture and forestry sector: prevention of injuriesfrom unsafe equipment and work practices on farms; a reduction in logging injuries andfatalities; providing training and information on resources and support for mental health amongthe agriculture population; reduction in exposures and risks for respiratory diseases from graindust exposure; and surveillance and risk reduction for vector-borne diseases. Through ourPilot/Feasibility Outreach and Emerging Issues program we will work with our manyinterdisciplinary partners to continue address a wide variety of problems in our regions. TheCenter benefits from strong institutional support from multiple colleges within the University ofKentucky and collaboration with researchers and partners at many other universitiesprofessional organizations and farm and forestry families in the Southeast. A major goal of theSCAHIP leaders is to prepare the next generation for enjoying safer and healthier work on ourregions farms and forests.

public_health_relevance:
Southeast Center for Agricultural Health and Injury PreventionProject NarrativeIn collaboration with regional stakeholders and our multidisciplinary team of investigators theSoutheast Center for Agricultural Health and Injury Prevention (SCAHIP) has developed acomprehensive plan which includes surveillance measurement and assessment trainingintervention and translational research projects that target important continuing problems in theagricultural and forestry sectors in the Southeastern US. The SCAHIP has invited a greatnumber of collaborators to work together to produce measureable improvements towards saferand healther agriculture and forstry work practices and outcomes.


application_id: 11174954
project_number: 3R01MH129357-02S1
project_title: Anxiety and Interoception Risk for Eating Disorders in Childhood
administering_ic: NIMH
award_notice_date: 2024-08-28
opportunity_number: PA-23-189
application_type: 3
activity_code: R01
ic: MH
serial_number: 129357
suffix: S1
program_official: THOMAS, LAURA ANDERSON
project_start_date: 2023-09-15
project_end_date: 2025-04-24
study_section: Child Psychopathology and Developmental Disabilities Study Section[CPDD]
contact_pi_person_id: 10775786
contact_pi: LEVINSON, CHERI ALICIA
other_pis: BUFFERD, SARA J
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
project_abstract:
PROJECT SUMMARY/ABSTRACTOut of 100000 children and adolescents 120 will have Down Syndrome 56 will die fromsudden infant death syndrome 15 will be diagnosed with cancer 12 will develop Type IIdiabetes and 2900 will have an eating disorder (ED). Although the age of onset for EDs wastraditionally observed in adolescence onset is occurring younger with many childrendeveloping EDs by age 12. Estimates suggest there will be 1.9 million new cases of youth EDsby 2024. Despite the high prevalence costs impairment and deaths from EDs there is verylittle knowledge on what predisposes children to develop EDs. Importantly early detection andintervention is crucial: problematic eating behaviors can damage developing brains and bodiesand untreated EDs carry significant risk for becoming lifelong chronic health conditionsassociated with high mortality rates societal and personal burden. Our scientific premisedeveloped from our past work is that anxiety and interoceptive deficits (inaccuracy identifyingbodily sensations heightened or blunted sensitivity to these sensations) as well as deficits infear learning underlying anxiety and interoceptive deficits will predict common problematiceating behaviors and cognitions (e.g. restriction body dissatisfaction cognitive restraint) aswell as clinical EDs. Our study goals are to (1) test if childhood anxiety and interoceptive deficitsare risk factors for problematic eating behaviors and cognitions and EDs and (2) test if deficits infear learning are a mechanism by which anxiety and interoceptive deficits contribute to risk.These goals will ultimately lead to (a) tools that can better detect childhood risk factors for EDsand (b) prevention efforts directly targeting mechanisms predictive of ED onset. The proposedresearch uses innovative parent-report momentary assessment combined with well-establisheddiagnostic behavioral observational and physiological assessment. We will recruit a sample of400 girls across two age cohorts (6-8; 10-12 years old) enriched for interoceptive deficitsanxiety and EDs; 75% (n=300) will be recruited based on maternal history of EDs or anxietyand 25% (n=100) will make up the control group. This study will for the first time allow us tobegin to quantify how early symptoms of ED develop. The specific aims are to test (1) multi-modal aspects of anxiety and (2) characteristics of interoceptive deficits that may prospectivelypredict problematic eating behaviors and cognitions and EDs and (3) mechanisms of predictionamong anxiety and interoceptive deficits. The proposed research has clinical impact: ultimatelythis study will lead to early detection and prevention of EDs in childhood and beyond avertingthe large personal and societal costs associated with both childhood onset and chronic EDs.

project_terms:
12 year old;Adolescence;Adolescent;Age;Age of Onset;Anxiety;Anxiety Disorders;Behavior;Behavioral;Body Size;Brain;Cessation of life;Characteristics;Child;Childhood;Chronic;Clinical;Cognition;Cognition Disorders;Cognitive;Control Groups;Data;Death Rate;Development;Diagnosis;Diagnostic;Down's Syndrome;Early Diagnosis;Early Intervention;Early identification;Eating;Eating Behavior;Eating Disorders;Esthesia;Etiology;Exhibits;Extinction;Family;Fasting;Female;Fright;Goals;Health;High Prevalence;Hyperphagia;Hypersensitivity;Impairment;Individual;Interoception;Knowledge;Lead;Learning;Link;Literature;Malignant Neoplasms;Mental Depression;Mental disorders;National Institute of Mental Health;Non-Insulin-Dependent Diabetes Mellitus;Occupations;Onset of illness;Parents;Pathology;Physiological;Population;Predisposing Factor;Prevention;Prevention program;Recording of previous events;Reporting;Research;Risk;Risk Factors;Sampling;Societies;Sudden infant death syndrome;Symptoms;Testing;Time;Traction;United States;Work;Youth;bodily sensation;body dissatisfaction;childhood anxiety;cohort;cost;design;dieting;early adolescence;early childhood;early onset;experience;follow-up;gastrointestinal system;girls;high risk;improved;innovation;insight;maternal anxiety;multimodality;negative affect;novel;opioid use;prospective;public health relevance;recruit;restraint;social anxiety;societal costs;standard care;theories;tool

public_health_relevance:
PROJECT NARRATIVEThis project will collect data on early childhood risk factors for eating disorders in femalechildren ages 6-12. The proposed research has significant public health relevance as it willenhance our understanding of how eating disorders develop and for whom leading to earlydetection and prevention efforts. The proposed research is relevant to NIMHs strategic aim 3.1.A to strive for prevention based on an understanding of risk as it will lead to tools that canbetter identify early risk factors as well as prevention efforts directly targeting mechanismspredictive of the onset of early eating disorders and related pathology.


application_id: 11174553
project_number: 5R21AI178108-02
project_title: Role of putative cytotoxins in Chlamydia infection
administering_ic: NIAID
award_notice_date: 2025-06-13
opportunity_number: PA-20-195
application_type: 5
activity_code: R21
ic: AI
serial_number: 178108
program_official: VINCENT, LEAH REBECCA
project_start_date: 2024-08-21
project_end_date: 2026-06-30
study_section: Bacterial Virulence Study Section [BV]
contact_pi_person_id: 7726964
contact_pi: FIELDS, KENNETH A
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:
ABSTRACT Chlamydia species are important pathogens that represent a paradigm for understandingsuccessful obligate intracellular parasitism. C. trachomatis is a prevalent human pathogenswhereas C. muridarum is a murine-specific pathogen often used to study chlamydial disease ina small animal model. Species-specific variability in coding capacity within the so-calledplasticity zone of the chlamydial chromosome is thought to be one source dictating differencesin infection biology. The presence/absence of genes encoding glycosyltransferases designatedas putative cytotoxins represents an intriguing example of this diversity. C. muridarum expressmultiple homologous proteins that also show similarity to a family of larger cytotoxins. Theplasticity zone of common urogenital C. trachomatis serovars express a truncated protein whileocular serovars of members of the lymphogranuloma venereum (LGV) biovar lack the toxingenes completely. These cytotoxins have been proposed to mediate immediate toxicity in highlyinfected epithelial cells by interfering with actin polymerization. Lack of tractable genetics in Cmuridarum and urogenital C. trachomatis in particular has previously confounded definitivestudies leading to a paucity in details regarding molecular mechanisms of infection. We haveovercome this barrier by deletion of putative cytotoxin genes in C. muridarum. Our dataindicated that these proteins were dispensable for immediate toxicity. Combined with analysis ofC. trachomatis CT166 our data implicate an alternative function for these proteins. We proposeto apply genetic and biochemical approaches to delineate molecular function(s) of theseputative glycosyltransferases and address their contribution(s) to species-specific infectionbiology.

project_terms:
Actins;Address;Affect;Animal Model;Antibodies;Applied Genetics;Biochemical;Biological Assay;Biology;Caspase;Cell Culture Techniques;Cells;Cellular biology;Chlamydia;Chlamydia Infections;Chlamydia muridarum;Chlamydia trachomatis;Chlamydiaceae;Chlamydiales;Chlamydophila pneumoniae;Chromosomes;Chronic;Code;Cytoskeleton;Cytotoxin;Data;Disease;Engineering;Epithelial Cells;Eukaryotic Cell;Exhibits;Family;Family member;Foundations;Gene Order;Genes;Genetic;Genitourinary system;Goals;Guanosine Triphosphate Phosphohydrolases;Homologous Protein;Human;Infection;Inflammation;Invaded;Longitudinal Studies;Lymphogranuloma Venereum;Mediating;Modeling;Molecular;Mucous Membrane;Mus;Outcome;Pathogenesis;Pathology;Pathway interactions;Polymers;Protein Truncation;Proteins;Reproducibility;Research Design;Role;Source;Surface;Testing;Time;Toxic effect;Toxin;Virulence;Work;cell type;comparative;design;experience;genital infection;glycosyltransferase;human disease;human pathogen;in vivo;intracellular parasitism;member;mouse model;mutant;obligate intracellular parasite;pathogen;polymerization;protein function;reproductive tract;respiratory pathogen;rho;spatiotemporal;success;tissue tropism

public_health_relevance:
Chlamydia species infect a wide range of mammalian hosts and deploy an array of anti-hostproteins to promote the ability to cause disease. While many of these proteins are conservedacross species some have diverged and are likely to contribute to species-specific differencesin infection. This proposal contains work designed to characterize a group of those variableproteins and elucidate specific contributions to chlamydial disease.


application_id: 11173897
project_number: 5R01CA272669-03
project_title: Targeting the Immunosuppressive Tumor Microenvironment for Colorectal Cancer Treatment
administering_ic: NCI
award_notice_date: 2025-08-28
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: CA
serial_number: 272669
program_official: XI, DAN
project_start_date: 2023-09-01
project_end_date: 2028-08-31
study_section: Tumor Host Interactions Study Section[THI]
contact_pi_person_id: 10125947
contact_pi: WANG, QINGDING
other_pis: EVERS, BERNARD MARK
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
arra_indicator: N
project_abstract:
Project Summary/Abstract Despite notable improvements in colorectal cancer (CRC) treatment the prognosis of patients withmetastatic CRC (mCRC) remains poor with a median overall survival of approximately 30 months.Immunotherapy such as immune checkpoint blockade (ICB) represents a novel therapeutic approach for avariety of cancers including mCRC with microsatellite instability-high (MSI-H). However ICB therapy shows littleor no clinical activity in approximately 95% of patients with microsatellite-stable (MSS) mCRC. We and othershave shown that administration of either a ketogenic diet (KD) or the ketone body -hydroxybutyrate (HB)enhances the anticancer effects of ICB for CRC in mouse tumor models. However whether KD/HB can improveICB therapy for CRCs with MSS is not known. Moreover the impact of altered ketogenesis on theimmunosuppressive tumor microenvironment (TME) remains to be defined and represents a major gap in ourunderstanding of tumor immunoresistance. Cancer associated fibroblasts (CAFs) the major component of tumor stromal cells play a critical role in thetumor suppressive TME. We have shown that downregulated ketogenesis is a hallmark in CRC TME. Activationof oncogenic signaling (e.g. WNT and KRAS) decreases ketogenesis in CRCs. Restoration of ketogenesisinhibits aerobic glycolytic activity in CAFs and inhibits histone deacetylase 1 (HDAC1)/KLF5 dependent CAFproliferation and cytokine expression and secretion. Importantly we showed that KD improves theimmunosuppressive TME as noted by increased CD8+ T cell and NK cell infiltration and decreased M2macrophage populations and enhances the efficacy of ICB. Our findings demonstrate a previously unknownassociation of downregulated de novo ketogenesis metabolic alteration and CAF functions in the TME and haveidentified cancer ketogenesis as a potential immunotherapeutic target. Based on these novel findings wehypothesize that downregulated ketogenesis contributes to the proliferation and immunosuppressive effects ofCAFs and thus reprograms the CRC TME which leads to ICB resistance and CRC progression. Our long-termgoal is to identify aberrant metabolism within the cancer and/or stromal compartments that can be used toimprove the treatment of patients with mCRC. To examine our central hypothesis we have assembled a highlycollaborative team with significant expertise in CRC progression and treatment tumor metabolism tumorimmunity and neoplastic ketogenesis and planned experiments which will determine the impact of alterations ofketogenesis on the immunosuppressive TME in CRC delineate ketogenic control of CAF metabolismproliferation and functional potency in the TME and define the impact of targeting ketogenic metabolism on theefficacy of ICB for CRC. Ultimately our findings will: i) revolutionize our concept of CRC TME andimmunoresistance; ii) significantly advance paradigms regarding the effects of KD/HB; and iii) may provide anovel CRC treatment strategy by targeting dysregulated ketogenic metabolism.

project_terms:
3-hydroxy-3-methylglutaryl-coenzyme A;Aerobic;Biological Models;CD34 gene;CD8-Positive T-Lymphocytes;CXCL6 gene;Cancer Control;Cancer Etiology;Carbohydrates;Cessation of life;Characteristics;Clinical;Colorectal Cancer;Cytotoxic T-Lymphocytes;Down-Regulation;Enzymes;Fatty acid glycerol esters;Fibroblasts;Genetically Engineered Mouse;Glycolysis;Glycolysis Inhibition;Goals;Growth;HDAC1 gene;Histone Deacetylase;Histone Deacetylase Inhibitor;Human;Immune response;Immunosuppression;Immunotherapeutic agent;Immunotherapy;In Vitro;Infiltration;KRAS oncogenesis;KRAS2 gene;Ketone Bodies;Macrophage;Malignant Neoplasms;Mediating;Metabolic;Metabolism;Metastatic Neoplasm to the Lung;Microsatellite Instability;Microsatellite Repeats;Modeling;Molecular;Mus;Natural Killer Cells;Oncogenes;Oncogenic;PD-1 blockade;PPAR gamma;Patients;Play;Population;Production;Proliferating;Publishing;Repression;Resistance;Role;Signal Transduction;Stromal Cell-Derived Factor 1;Stromal Cells;Stromal Neoplasm;Techniques;Technology;Testing;Therapeutic;Treatment Protocols;Tumor Immunity;Tumor Tissue;United States;anti-PD1 therapy;anti-cancer;beta catenin;beta-Hydroxybutyrate;c-myc Genes;cancer cell;cancer therapy;chemokine;colon cancer patients;colorectal cancer progression;colorectal cancer treatment;cytokine;experimental study;immune checkpoint blockade;immune resistance;improved;in vivo;innovation;ketogenesis;ketogenic diet;ketogentic;metabolomics;metastatic colorectal;mouse model;multidisciplinary;neoplastic;novel;novel therapeutic intervention;patient derived xenograft model;patient prognosis;programs;restoration;single-cell RNA sequencing;stable isotope;therapeutically effective;treatment strategy;tumor;tumor metabolism;tumor microenvironment;tumor-immune system interactions;tumorigenesis

public_health_relevance:
Project NarrativeColorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States; alteredcellular metabolism drives tumorigenesis and progression and promotes resistance to immune checkpointblockade. Our proposed study will define the metabolic adaptations associated with decreased ketogenesis andwill significantly improve the efficacy of immunotherapy for advanced CRC by targeting the dysregulatedketogenesis.


application_id: 11172682
project_number: 5F99CA294265-02
administering_ic: NCI
award_notice_date: 2025-07-22
opportunity_number: RFA-CA-23-042
application_type: 5
activity_code: F99
ic: CA
serial_number: 294265
program_official: ODEH, HANA M
project_start_date: 2024-09-01
project_end_date: 2026-08-31
study_section: ZCA1-RTRB-U(M1)
contact_pi_person_id: 79493459
contact_pi: OZA, VIRAL
other_pis: Not Applicable
congressional_district: 06
department: BIOCHEMISTRY
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: 2025-09-01
project_title:
Harnessing Extracellular Vesicles to Overcome Radiation Resistance in Pediatric Diffuse Midline Glioma

project_abstract:
PROJECT SUMMARY Diffuse midline gliomas with H3K27M alteration (DMG-H3K27M) are the leading cause of pediatricbrain tumor-associated deaths. All DMG-H3K27M becomes resistant to radiation the standard of care andmost children succumb to their disease within two years of diagnosis. New treatment options are urgentlyneeded. The applicant's long-term goal is to combine engineering and cancer cell biology to lead a researchgroup that advances extracellular vesicle (EV)-based drug delivery for central nervous system diseases likeDMG-H3K27M. EVs are potent signaling vehicles in the tumor microenvironment and are understudied inDMG-H3K27M. The overall objectives are to define how DMG-H3K27M derived EVs contribute to radiationresistance within a heterogenous tumor and to develop EVs as a delivery vehicle for brain-penetrantradiosensitizers while equipping the applicant with the skills to become a strong independent cancerresearcher. Preliminary data show that some subclones within DMG-H3K27M are inherently radiation resistantand can release EVs readily taken up by radiosensitive cells in a receptor-mediated manner. These EVsprotect the recipient tumor cells from radiation-induced cell death. Therefore the central hypothesis is that thecargo of DMG-H3K27M extracellular vesicles particularly microRNAs drives radiation resistance within thesetumors and that targeting these factors can sensitize DMG-H3K27M cells to radiotherapy. Additionally theselective uptake of EVs by DMG-H3K27M cells suggests that EVs can be exploited as a drug delivery tool. Therationale is that this research will provide novel insights into mechanisms of radioresistance in DMG-H3K27Mand may result in new approaches to target this cancer. The hypothesis will be tested by pursuing two specificaims: 1) Determine the mechanism of EV-mediated radioresistance in DMG-H3K27M and 2) Engineerextracellular vesicles to selectively target brain tumor cells and deliver radiosensitizers. The first aim will becarried out as part of the dissertation research and will use patient-derived DMG-H3K27M cells proteomicsapproaches and chemical inhibitors to define the mechanism of EV uptake. miRNA mimics and antagomirs willalso be used to overexpress and silence miRNAs found in EV cargo released from radioresistant cells toidentify miRNAs that confer enhanced radioresistance in DMG-H3K27M. Targets will be validated usingzebrafish xenograft models. The second aim will encompass the post-doctoral research and focus on usingsingle-cell microfluidic methods to engineer non-tumor extracellular vesicles for specificity towards brain tumorcells and assessing their capability to cross the blood-brain barrier to deliver radiosensitizers. The researchproposed in this application is significant because it will provide new insights into the role of tumorheterogeneity in driving therapy resistance. This project will also identify new mechanisms of DMG-H3K27Mradioresistance and develop an innovative strategy for drug delivery to optimize the therapeutic efficacy ofradiosensitizers in the brain potentially improving treatment outcomes for children with DMG-H3K27M.

project_terms:
Address;Affect;Automobile Driving;Biodistribution;Biology;Brain;Brain Neoplasms;Cancer Biology;Cancer Model;Cell Death Induction;Cells;Cellular biology;Central Nervous System Diseases;Cessation of life;Chemicals;Child;Childhood;Childhood Brain Neoplasm;Clinic;Clinical;Communication;Communities;Creativeness;DNA Repair;Data;Development;Diagnosis;Diffuse intrinsic pontine glioma;Disease;Drug Delivery Systems;Drug Targeting;Electroporation;Engineering;Ensure;Fostering;Fractionated radiotherapy;Gene Expression;Genes;Genetic;Glioma;Goals;Health;Histones;Human;In Vitro;Individual;Investigation;Knowledge;Label;Link;Malignant Neoplasms;Malignant neoplasm of brain;Mediating;Methods;MicroRNAs;Microfluidic Microchips;Microfluidics;Mission;Modeling;Mutation;Outcome;Pathway interactions;Patients;Penetrance;Pharmaceutical Preparations;Phase;Population;Postdoctoral Fellow;Process;Proteomics;Public Health;Radiation;Radiation Tolerance;Radiation therapy;Radiation-Sensitizing Agents;Research;Research Personnel;Research Project Grants;Research Training;Resistance;Role;Scientist;Signal Transduction;Specificity;Surface;Testing;Therapeutic;Training;Treatment Efficacy;Treatment outcome;Tumor-Derived;Xenograft Model;Xenograft procedure;Zebrafish;antagonist;blood-brain barrier crossing;blood-brain barrier penetration;cancer cell;cancer therapy;cell type;combinatorial;delivery vehicle;diffuse midline glioma;extracellular vesicles;improved;inhibitor;innovation;insight;knock-down;machine learning model;multidisciplinary;neoplastic cell;new therapeutic target;next generation;novel;novel strategies;novel therapeutic intervention;on a chip;overexpression;radiation resistance;radioresistant;receptor;skills;standard of care;success;therapy resistant;tool;treatment strategy;tumor;tumor heterogeneity;tumor microenvironment;tumor progression;uptake;vesicular release

public_health_relevance:
PROJECT NARRATIVEThe investigation of Diffuse Midline Glioma-derived extracellular vesicles and their impact on tumorradioresistance is relevant to public health as it addresses the leading cause of pediatric brain tumor-relateddeaths and seeks to provide new insights into overcoming treatment resistance. By focusing on the functionaleffects of extracellular vesicles and their potential as drug-delivery agents this research is relevant to NCIsmission of understanding cancer mechanisms and developing innovative treatment strategies.


application_id: 11172582
project_number: 5F30HL165813-03
project_title: Fibroblast TAK1 signaling in cardiac fibrosis
administering_ic: NHLBI
award_notice_date: 2025-09-02
opportunity_number: PA-21-050
application_type: 5
activity_code: F30
ic: HL
serial_number: 165813
program_official: MEADOWS, TAWANNA
project_start_date: 2023-09-30
project_end_date: 2026-12-30
study_section: Special Emphasis Panel[ZRG1-F10A-K(20)L]
contact_pi_person_id: 78328337
contact_pi: NGUYEN, DANIEL
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:
AbstractCardiovascular diseases share fibrosis as a common characteristic. Fibrosis is caused in large part by activationof cardiac fibroblasts which change their phenotype in response to insults such as pressure overload ormyocardial infarction and contribute to excessive deposition of extracellular matrix (ECM) in the myocardialinterstitium and perivascular space. Previous studies in models of cardiac fibrosis demonstrate that elevatedlevels of paracrine factors such as TGF- are fundamental in fibroblast activation. In particular activation of thecanonical TGF-/Smad pathway is known to play a prominent role in cardiac fibrosis; however the response ofcardiac fibroblasts to stress also involves paracrine signaling by other ligands elevated in the injured or stressedheart. Indeed inflammatory cytokines such as TNF- and IL-1 also contribute to changes fibroblast phenotype.Signaling elicited by these ligands appear to target signaling pathways that converge on TGF--activated kinase1 (TAK1) which is known to integrate signals from not only TNF- and IL-1 receptors but TGF- receptors aswell. Our preliminary data suggest that TAK1 is abundant in cardiac fibroblasts and that its inhibition influencesthe expression of key markers of the myofibroblast phenotype. Moreover our data suggest that deletion of TAK1in cardiac fibroblasts influences the secretion of profibrotic cytokines and proteins which further intimates acritical role of TAK1 in fibroblast phenotype and fibrosis. Guided by these findings we hypothesize that TAK1integrates cytokine and growth factor signaling to modulate the response of cardiac fibroblasts to insult or injury.Although it is likely that fibroblast TAK1 signaling plays a major role in cardiac fibrosis there have been nodetailed studies that elucidate its influence on fibroblast-mediated myocardial responses to stress. Thisknowledge is important because it could be used to develop targeted strategies to lessen fibrotic burden in theheart for which there are currently no approved therapies. To test our hypothesis we will: (1) assess theinfluence of TAK1 on cardiac fibroblast phenotype; and (2) elucidate the role of fibroblast-specific TAK1 onpressure overload-induced cardiac remodeling. Completion of this project will delineate how non-canonicalfibrotic signaling through TAK1 influences cardiac remodeling and fibrosis in models of fibroblast activation andpressure overload. We expect to find that TAK1 acts as a central nexus that integrates profibrotic signals topromote cardiac fibrosis. Such knowledge is important because it will not only enhance our understanding ofmechanisms of cardiac fibrosis but also could be used to develop new therapeutic avenues to diminish fibroticburden in the heart. Working with my sponsors and clinical mentors I will develop a better understanding of themechanisms that promote cardiac fibrosis and refine my critical thinking skills which will enhance my successin biomedical research and as a clinician.

project_terms:
Atomic Force Microscopy;Biochemical;Biomedical Research;Blood Vessels;Breeding;Cardiac;Cardiovascular Diseases;Cells;Characteristics;Clinical;Collagen;Critical Thinking;Cues;Data;Deposition;Development;Echocardiography;Exposure to;Extracellular Matrix;Fibroblasts;Fibrosis;Genetic Transcription;Growth Factor;Heart;Heart failure;Inflammatory;Injury;Interleukin-1 beta;Knowledge;Ligands;MAP3K7 gene;Mechanics;Mediating;Mentors;Metabolism;Modeling;Mus;Myocardial;Myocardial Infarction;Myofibroblast;Paracrine Communication;Pathologic;Pathology;Pathway interactions;Peptide Initiation Factors;Phenotype;Play;Profibrotic signal;Proliferating;Protein Secretion;Proteins;Role;Signal Pathway;Signal Transduction;Stress;Structure;TNF gene;Testing;Transforming Growth Factor beta;Transforming Growth Factor beta Receptors;aorta constriction;coronary fibrosis;cytokine;indexing;injured;novel;novel therapeutics;paracrine;pharmacologic;pressure;profibrotic cytokine;programs;receptor;response;skills;success;transdifferentiation

public_health_relevance:
PROJECT NARRATIVECardiac fibrosis is a common contributing factor to heart failure. This project will test novel mechanisms by whichpressure overload influences cardiac fibrosis which could be leveraged to develop new therapies to diminishthe burden of heart failure.


application_id: 11172557
project_number: 5R01AR081002-03
project_title: Muscle and physical function recovery after acute critical illness
administering_ic: NIAMS
award_notice_date: 2025-08-25
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: AR
serial_number: 081002
program_official: LINDHURST, MARJORIE JEAN
project_start_date: 2023-09-18
project_end_date: 2028-08-31
study_section: Musculoskeletal Rehabilitation Sciences Study Section[MRS]
contact_pi_person_id: 1884084
contact_pi: DUPONT-VERSTEEGDEN, ESTHER E
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:
Many patients who survive critical illness including sepsis and acute respiratory failure have arduousrecoveries plagued by an inability to recover muscle and physical function after hospital discharge resulting inlower quality of life inability to return to work and disability. The number of patients surviving critical illnesses inthe United States continues to rise each year and therefore it is critically important to develop interventions thatwill support their recovery. Clinical and muscle cellular factors driving skeletal muscle dysfunction are relativelyunknown after an acute critical illness but are necessary to inform intervention development. We will addressthis knowledge gap by studying myofibrillar and collagen protein turnover cellular signaling pathways andmarkers of damage inflammation and immune response in the first year of recovery. The unique aspect of thisproposal is the serial intra-patient muscle tissue sampling paired with simultaneously obtained clinicalfunctional parameters over the first year of recovery post hospital discharge. Physical function and quality oflife outcomes will be assessed to understand why some patients recover muscle function yet others developsevere disability. The overall goal of this clinical observational study is to elucidate the cellular environmentand the patients clinical characteristics contributing to failed muscle recovery and physical disability insurvivors of critical illness. Our central hypothesis is that alterations in myofibrillar mitochondrial and collagenprotein homeostasis are underlying muscle and physical dysfunction in patients surviving critical illness. In Aim1 we will identify trajectory of recovery for muscle strength and power as well as physical function in patientssurviving ICU-related critical illness including pneumonia sepsis and COVID-19 etiologies. We hypothesizethat patients with a higher initial severity of illness will show poor recovery of muscle strength and physicalfunction during the first year of recovery. In Aim 2 we will determine mechanisms of skeletal muscledeficiencies contributing to disparate recovery in patients surviving ICU-related COVID-19 or other acute lunginjury etiologies. We hypothesize that patients with longer ICU durations will show poor recovery of muscle sizeand increased collagen deposition during the first year of recovery. In addition we hypothesize that patientswith persistent weakness and fatigue have prolonged impairments in mitochondrial function compared topatients who recover their muscle function. Finally we hypothesize that patients with long-term disability havean inability to recover muscle function due to a cellular environment of that is not permissive to a positiveprotein balance. We will use stable isotope mass spectroscopy measurements of muscle biopsies to determinesynthesis of myofibrillar mitochondrial and collagen protein. Findings from this study will inform why somepatients develop persistent disability and others gradually improve. The results from this research will guidefuture development of therapeutic interventions that are specific to skeletal muscle deficits with considerationfor patient related factors such as age and co-morbid burden.

project_terms:
Acceleration;Acute;Acute Lung Injury;Acute Respiratory Distress Syndrome;Acute respiratory failure;Adult;Age;Area;Attention;Automobile Driving;Awareness;Biopsy;COVID-19;Cells;Characteristics;Chronic disability;Clinical;Collagen;Communities;Critical Illness;Data;Deposition;Deuterium Oxide;Development;Disparate;Environment;Equilibrium;Etiology;Extracellular Matrix;Fatigue;Fibrosis;Functional disorder;Future;Goals;Growth;Hospitalization;Hospitals;Immune;Immune response;Impairment;Inflammation;Inflammatory;Influenza;Intensive Care Units;Intervention;Knowledge;Label;Lifelong disability;Long-term disability;Long-term physical disability;Mass Spectrum Analysis;Measurement;Measures;Metabolic;Mission;Mitochondria;Muscle;Muscle Fibers;Muscle Weakness;Muscle function;National Institute of Arthritis and Musculoskeletal and Skin Diseases;Nutrition;Observational Study;Outcome;Patients;Pattern;Pharmacotherapy;Phenotype;Physical Function;Pneumonia;Proteins;Quality of life;Recovery;Recovery of Function;Rehabilitation therapy;Research;Research Project Grants;Respiration;Sepsis;Severity of illness;Signal Pathway;Skeletal Muscle;Survivors;Therapeutic Intervention;Time;Tissue Sample;Tissues;United States;Work;comorbidity;disability;disabled;evidence base;improved;interest;muscle progenitor cell;muscle strength;participant enrollment;patient subsets;pharmacologic;physical impairment;physically handicapped;predictive modeling;protein biomarkers;protein degradation;proteostasis;response;sepsis induced ARDS;severe disability;skeletal muscle wasting;stable isotope;therapeutic development;therapy development

public_health_relevance:
Patients who survive an acute critical illness including sepsis COVID-19 influenza and acute respiratorydistress syndrome often develop physical disability that can persist for years after hospital discharge. Theplanned proposal will determine cellular and clinical parameters responsible for the reduced or inability torecover muscle and physical function after critical illness. The findings of this study will inform the developmentof future therapeutic interventions that mitigate long-term impairments and stimulate muscle and physicalrecovery after critical illness.


application_id: 11172529
project_number: 5R01EY035110-03
project_title: Functions of chromatin remodeler Chd7 in retinal cell development
administering_ic: NEI
award_notice_date: 2025-08-28
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: EY
serial_number: 035110
program_official: NEUHOLD, LISA
project_start_date: 2023-09-30
project_end_date: 2027-07-31
study_section: Special Emphasis Panel[ZRG1-CDB-M(02)M]
contact_pi_person_id: 10184513
contact_pi: MORRIS, ANN C
other_pis: MARTIN, DONNA M.;MEYER, JASON STEPHEN
congressional_district: 06
department: BIOLOGY
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:
CHD7 (Chromodomain helicase DNA-binding 7) is an ATP-dependent chromatinremodeling protein that has critical functions in neurogenesis and neural crest celldevelopment. Pathogenic variants in CHD7 are the most common cause of CHARGEsyndrome or CHD7 disorder a complex genetic syndrome characterized by ocularcoloboma heart abnormalities choanal atresia retardation of growth genitourinarydefects and hearing loss as well as other developmental defects. Although somestudies have examined the molecular basis for the early ocular defects (such ascoloboma) resulting from CHD7 pathogenic variants it is not known whether there is acontinuing requirement for CHD7 in the developing retina once ocular morphogenesis iscomplete. We have recently shown that CHD7 is robustly expressed in subsets of newlydifferentiated retinal cell types including rod and cone photoreceptors as well as inproliferating retinal progenitor cells. Furthermore zebrafish and mouse Chd7 mutantsdisplay reductions in cone photoreceptor number and abnormally small photoreceptorouter segments suggesting a critical role for CHD7 in photoreceptor differentiation andouter segment morphogenesis. We hypothesize that the chromatin remodeling functionof CHD7 is necessary for the transcriptional activation of genes promoting retinal celltype differentiation and genes involved in photoreceptor outer segment morphogenesis.In this proposal we will test this hypothesis through a combination of zebrafish andmouse genetics transcriptomic and epigenomic analyses and studies of human retinalorganoids and human retinal imaging. Results from these studies will contribute to ourunderstanding of the genetic and epigenetic regulation of retinal cell type developmentas well as the pathogenesis of visual system defects associated with CHD7 disorder.

project_terms:
ATAC-seq;Applications Grants;Blindness;Brain;CHARGE syndrome;CHD7 gene;Cells;Childhood;Choanal Atresia;Chromatin;Chromatin Remodeling Factor;Coloboma;Complex;Congenital Abnormality;DNA Binding;Data;Data Set;Defect;Development;Disease;Ear;Embryonic Development;Epigenetic Process;Event;Eye;Eye Abnormalities;Eye Development;Functional disorder;Gene Activation;Gene Expression;Genes;Genetic;Genetic Diseases;Genetic Transcription;Genitourinary system;Germ Lines;Growth;Heart;Heart Abnormalities;Human;Image;Individual;Knock-out;Knowledge;Mediating;Molecular;Morphogenesis;Mus;Mutagenesis;Mutation;Neural Crest Cell;Nose;Organoids;Pathogenesis;Pathogenicity;Phenotype;Photoreceptors;Process;Proliferating;Proteins;Retina;Retinal Cone;Role;Structure;Syndrome;Testing;Transcriptional Activation;Variant;Vertebrate Photoreceptors;Vision;Visual System;Visual impairment;Zebrafish;cell type;chromatin remodeling;epigenetic regulation;epigenomics;experience;experimental study;eye formation;gene regulatory network;hearing impairment;helicase;improved;mouse genetics;mouse model;mutant;neurogenesis;novel;retinal imaging;retinal progenitor cell;transcriptome sequencing;transcriptomics

public_health_relevance:
Disruptions to the process of eye formation can result in ocular birth defects andpediatric blindness; although some of the genetic causes of ocular birth defects havebeen identified we still dont have a good understanding of exactly how mutations inthese genes cause visual system dysfunction. In this grant proposal we will study thefunction of the chromatin remodeling factor CHD7 during eye development; thesestudies are important because loss of expression of CHD7 causes CHARGE syndrome(also known as CHD7 disorder) a genetic disorder that results in defects in the eyesears heart brain nose and genitourinary system. The results of our experiments willhelp us better understand the chain of events that leads to abnormal eye formationduring embryonic development and this knowledge may improve the identificationmanagement and treatment of congenital sight-threatening diseases.


application_id: 11172233
project_number: 5F31AA031600-02
administering_ic: NIAAA
award_notice_date: 2025-08-12
opportunity_number: PA-23-271
application_type: 5
activity_code: F31
ic: AA
serial_number: 031600
program_official: LIN, LI
project_start_date: 2024-08-12
project_end_date: 2027-08-11
study_section: ZAA1-GG(32)L
contact_pi_person_id: 78768031
contact_pi: BLANTON, MADISON BROOKE
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: 2025-08-12
project_title:
Uncovering the functional and mechanistic dysregulation of monocytes after abstinence and post-abstinence drinking

project_abstract:
Over 85% of individuals 18 years and older within the United States (US) consume alcohol. More importantly astaggering 25.8% and 6.3% are classified by the National Institute on Alcohol Abuse and Alcoholism criteria asbinge or heavy drinkers respectively making alcohol the 3rd leading cause of preventable death. Chronic heavydrinking (CHD) increases the incidence of heart disease stroke cancer and alcoholic liver disease. CHD is alsoassociated with heightened susceptibility to bacterial/viral pathogens and tissue repair mechanisms suggestingalcohol consumption negatively impacts the immune system. Indeed studies from our group and others havereported functional transcriptional and epigenetic modifications in peripheral monocytes and tissue-residentmacrophages with CHD skewing them toward a hyper-inflammatory phenotype while impairing pathogendefense mechanisms. Despite the significant contribution of aberrant monocyte/macrophage responses to CHD-induced organ injury no studies to date have investigated the effects of abstinence and post-abstinence drinkingon these critical cells. Organs and organ systems after alcohol consumption (brain liver lung) are challengingto interrogate throughout repeated bouts of abstinence and post-abstinence drinking. Since circulatingmonocytes are precursors of some tissue-resident macrophages investigating the effects of abstinence andrelapse on circulating monocytes will provide greater insight into how CHD dysregulates organs and organsystems. In this application we will leverage a rhesus macaque model of voluntary ethanol self-administrationto test the hypothesis that CHD induces persistent functional transcriptional and epigenetic changes inperipheral monocytes that are not reversed by short periods of abstinence and are exacerbated byrepeated bouts of abstinence and post-abstinence drinking. This hypothesis will be tested using a multi-pronged approach using multiplex ELISA flow cytometry single cell omics and metabolic assays after a 28-dayabstinence and post-abstinence drinking episodes. These experiments will provide deeper insight into thepersistence of CHD-induced immune modifications in complex organs and organ systems. This understandingcould identify novel druggable targets that decrease alcohol cravings or organ damage/opportunistic infectionsthat occur after CHD.

project_terms:
Abstinence;Activities of Daily Living;Address;Adult;Affect;Alcohol consumption;Alcohol-Induced Disorders;Alcoholic Liver Diseases;Alcoholic beverage heavy drinker;Alcohols;Alveolar Macrophages;Automobile Driving;Bacterial Infections;Biological Assay;Biological Response Modifiers;Body System;Brain;Cardiovascular Diseases;Cell Physiology;Cells;Chromatin;Chronic;Classification;Complex;Consumption;Cryopreservation;Defense Mechanisms;Energy-Generating Resources;Enzyme-Linked Immunosorbent Assay;Epigenetic Process;Ethanol;Flow Cytometry;Functional disorder;Gene Expression Profile;Genetic;Genetic Transcription;Genus Hippocampus;Glucose Transporter;Glycolysis;Glycolysis Inhibition;Heart Diseases;Heavy Drinking;Human;Immune;Immune system;Impaired wound healing;Impairment;Incidence;Individual;Inflammatory;Inflammatory Response;Knowledge;Kupffer Cells;Liver;Longitudinal Studies;Lung;Macaca mulatta;Macrophage;Malignant Neoplasms;Mediating;Metabolic;Microglia;Modeling;Modification;Myeloid Cells;National Institute on Alcohol Abuse and Alcoholism;Opportunistic Infections;Organ;Oxidative Phosphorylation;Pathology;Pathway interactions;Peripheral;Phagocytes;Phenotype;Physiological;Predisposition;Production;Reactive Oxygen Species;Relapse;Reporting;Role;Self Administration;Stroke;Surveys;Techniques;Testing;Therapeutic Intervention;Tissues;Training;United States;Viral;Withdrawal;Woman;alcohol craving;alcohol misuse;alcohol use disorder;anti-microbial peptide;binge drinker;binge drinking;chronic alcohol ingestion;drinking;drinking behavior;epigenome;experimental study;glucose uptake;histone modification;insight;men;metabolic phenotype;monocyte;new therapeutic target;novel;organ injury;pathogen;pathogenic virus;peripheral blood;preventable death;response;single cell ATAC-seq;single-cell RNA sequencing;tissue repair;transcriptome

public_health_relevance:
Chronic alcohol consumption (CHD) has been shown to poise myeloid cells towards a hyper-inflammatoryphenotype and impair key pathogen defense mechanisms. Aberrant myeloid cell responses specifically tissue-resident macrophages have been shown to significantly contribute to the pathophysiology of CHD-inducedorgan damage and alcohol use disorder. Since monocytes are precursors to tissues resident macrophages andtissue-resident macrophages in organs and organ systems affected by CHD are hard to study longitudinally thisproposal seeks to gain insight into changes that occur in complex organs subsequent to CHD by investigatingthe effects of repeated bouts of abstinence and post-abstinence drinking on the functional transcriptionalmetabolic and epigenetic profiles of circulating monocytes.


application_id: 11171359
project_number: 5K99ES036286-02
project_title: Unraveling the molecular link between heavy metal exposure and triple-negative breast cancer
administering_ic: NIEHS
award_notice_date: 2025-08-22
opportunity_number: PA-20-188
application_type: 5
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: ZES1-LWJ-W(K9)1
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 TNBC in their lifetimes compared to the rest of the population. However roughly eighty percent of TNBC cases cannot be explained by germline mutations. TNBC disproportionately affects populations that live in closer proximity to areas contaminated with heavy metals including cadmium (Cd). Cd is a heavy metal group 1 carcinogen that has a long biological half-life in the human body. Epidemiological studies demonstrate that Cd exposure increases breast cancer risk and in vitro studies determined that Cd exposure promotes TNBC initiation in normal human breast cells. Cd is known to displace zinc (Zn) from Zn coordinating proteins and several Zn coordinating 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 pathway inhibition. Whether Cd promotes TNBC initiation and progression by disruption of DSB signaling and repair including direct inhibition of RAD50 or BRCA1 remains to be established. The experiments proposed to test the hypothesis that Cd exposure promotes TNBC initiation and progression by disruption of multilateral DSB signaling and repair will be conducted in two phases. During the mentored K99 phase mass spectrometry single-molecule imaging using isolated recombinant proteins and DNA curtain assays and CRISPR-based editing will be employed to determine how Cd directly targets DSB repair proteins to disrupt DSB Repair pathway choice. While in the mentored phase the candidate will take advantage of career development resources made available by the University of Louisville Center for Integrative Environmental Health Sciences and will apply research and career development skills to didactic lecturing mentoring writing and presentation opportunities. In the non-mentored R00 phase of the project technical skills gained from the K99 phase will be used for mechanistic studies to interrogate the role of Cd-induced fusion genes in TNBC development (Aim 2). These experiments will provide data needed for initial independent publications and preliminary data for R-series grants and will establish an independent direction for the candidate from her mentor.Modified

project_terms:
Affect;Anchorage-Independent Growth;Area;BRCA mutations;BRCA1 gene;Binding;Biological;Biological Assay;Biophysics;Breast;Breast Cancer Patient;Breast Cancer Risk Factor;Breast Cancer gene;Breast Epithelial Cells;Cadmium;Carcinogens;Cell Separation;Cells;Chronic;Clonal Expansion;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Cysteine;DNA;DNA Adducts;DNA Double Strand Break;DNA Repair;Data;Development;Double Strand Break Repair;Environmental Exposure;Environmental Health;Exposure to;Gene Deletion;Gene Fusion;Gene Mutation;Genetic;Genetic Predisposition to Disease;Germ-Line Mutation;Goals;Grant;Half-Life;Heavy Metals;Hispanic Women;Human;Human body;Immunocompromised Host;In Vitro;Incidence;Individual;Lateral;Link;Malignant - descriptor;Malignant Breast Neoplasm;Mass Spectrum Analysis;Measures;Mediating;Mentors;Metal exposure;Methods;Mind;Modeling;Molecular;Mus;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;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;public health relevance;recombinational repair;repaired;research and development;single molecule;skill acquisition;targeted treatment;triple-negative invasive breast carcinoma;tumor;tumor progression;tumorigenic

public_health_relevance:
Public Health Relevance Statement Disruption of DNA double-strand break (DSB) repair promotes triple-negative breast cancer (TNBC). The overarching goal of this study is to determine the molecular mechanisms responsible for disruption of DSB repair elicited by cadmium (Cd) exposure to promote TNBC. These studies will elucidate a fundamental mechanism not currently recognized that can explain TNBC arising in individuals without a genetic predisposition.


application_id: 11170636
project_number: 5R01ES030380-07
project_title: Radon on the RADAR
administering_ic: NIEHS
award_notice_date: 2025-06-13
opportunity_number: PAR-22-210
application_type: 5
activity_code: R01
ic: ES
serial_number: 030380
program_official: O'FALLON, LIAM
project_start_date: 2020-02-20
project_end_date: 2029-05-31
study_section: Community Influences on Health Behavior Study Section[CIHB]
contact_pi_person_id: 15382528
contact_pi: STANIFER, STACY
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
project_abstract:
ABSTRACT Lung cancer is the leading cause of cancer mortality yet the disease remains highly preventable byeliminating exposure to tobacco smoke and radon. As rural communities lead the nation in lung cancerincidence and mortality there is urgency to lower radon exposure in rural areas. Radon on the RADAR(Residents Acting to Detect and Alleviate Radon) 1.0 uncovered disparities in access to and affordability ofradon mitigation and low testing and mitigation rates despite access to radon detectors in public librariesand geologic impacts on home radon exposure that warrant further investigation to reduce exposure to thedeadly gas in rural areas. RADAR 2.0 will strengthen partnerships with citizen scientists public libraries andlocal radon coalitions to increase access to affordable radon mitigation develop effective radon riskcommunication messaging automate report-back using a novel website platform and translate geologicand residential data to builders and policymakers to educate and inform radon resistant new constructionpolicy. Aim 1 will evaluate the reach effectiveness adoption implementation and maintenance of a radonmeasurement and mitigation curriculum developed and implemented by Kentucky Community and TechnicalCollege System Construction Technology faculty and students. Aim 2 will develop and test the effects of radonrisk messages with rural homeowners who have never tested for radon and those with high radon who havenot mitigated. Aim 3 will design and test the effects of My Radon Report a novel automated personalizedradon report-back tool on intention to test and mitigate for radon environmental health literacy and efficacyfor radon testing and mitigation among rural homeowners and track usage and website metrics for scalability.Aim 4 will examine the association among geologic soil and residential characteristics and indoor radonvalues to guide education and better inform radon resistant new construction policy. RADAR 2.0 is innovativein several ways: 1) partnering with the community college system to build capacity for certified radon mitigatorsin rural Kentucky by offering and evaluating a radon measurement and mitigation certification and trainingcurriculum; 2) evaluating radon testing and mitigation messages with key target groups; 3) developing andtesting a user-initiated personalized report-back website platform to accompany the radon detector library loanprogram; and 4) performing in-depth analyses of soil processes and characteristics that relate to elevatedindoor radon levels closing a critical gap in our understanding of the role of geologic factors on radon riskpotential. RADAR 2.0 will address gaps in radon risk reduction in rural communities by designing andevaluating a novel approach to increasing access to certified radon professionals expanding ourunderstanding of radon risk messaging and report-back and conducting in-depth geo-assessment to guideeducation and inform radon resistant new construction policy through citizen scientist engagement.

project_terms:
Address;Awareness;Back;Cancer Etiology;Certification;Cessation of life;Characteristics;Clinical Trials Cooperative Group;Collaborations;Communication;Communities;County;Data;Disease;Education;Educational Curriculum;Environmental Health;Exposure to;Faculty;Feedback;Funding;Gases;Geology;Health;Home;Incidence;Intention;Investigation;Kentucky;Lead;Libraries;Malignant neoplasm of lung;Measurement;Minerals;Participant;Policies;Policy Developments;Policy Maker;Process;Public Health;Radioactive;Radon;Reach Effectiveness Adoption Implementation and Maintenance;Reporting;Resistance;Risk;Risk Reduction;Risk Reduction Behavior;Role;Rural;Rural Community;Sampling;Soil;Source;Students;System;Techniques;Technology;Testing;Training;Translating;Uranium;Waiting Lists;access disparities;cancer risk;citizen science;community college;cost;design;detector;environmental tobacco smoke exposure;health literacy;innovation;mortality;novel;novel strategies;programs;risk prediction;rural area;scale up;success;technical college;theories;tobacco exposure;tool;uptake;usability;voucher;web site

public_health_relevance:
PROJECT NARRATIVE In the U.S. radon-induced lung cancer accounts for 21000 deaths annually yet the disease remainshighly preventable by eliminating exposure to the deadly gas. RADAR 2.0 will address community concernsabout high lung cancer rates by building capacity for radon mitigation in rural communities and discoveringradon risk messaging intended to prompt radon risk reduction behavior. Additionally we will support publichealth action by developing an automated report-back website and investigate the soil processes andcharacteristics to support pre-construction radon risk forecasting and radon resistant new construction policy.


application_id: 11170449
project_number: 5K23ES034462-03
project_title: Household Air Pollution Adiposity and Cardiorenal Disease Risk in Children
administering_ic: NIEHS
award_notice_date: 2025-08-15
opportunity_number: PA-20-206
application_type: 5
activity_code: K23
ic: ES
serial_number: 034462
program_official: QUINN, ASHLINN KO
project_start_date: 2023-09-01
project_end_date: 2028-08-31
study_section: ZES1-BWD-S(KS)1
contact_pi_person_id: 14132183
contact_pi: MURPHY, MARGARET O.
other_pis: Not Applicable
congressional_district: 06
department: PEDIATRICS
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:
ABSTRACTChildhood obesity is a major public health threat with rates increasing at an alarming rateworldwide. Currently 22.4% of children and adolescents are obese approximately 16.7 millionwith rates of obesity increasing in all age groups in the pediatric population. Obese children aremore likely to be diagnosed with several major morbidities (hypertension hyperlipidemiacoronary artery disease and diabetes). The estimated annual health care costs of obesity-related illness are a staggering $190.2 billion or nearly 21% of annual medical spending in theUnited States. Household air pollution (HAP) is a term that describes the health andenvironmental impacts of pollutants produced from incomplete combustion of solid fuels such aswood coal charcoal animal dung crop wastes burnt on open fires or wood-burning stoves inpoorly ventilated homes and releases suspended particulate matter (PM). There are few studiesexamining the role of household air pollution including PM2.5 in cardiovascular risk in the settingof pediatric obesity. An important component of cardiovascular health is a diurnal variation ofblood pressure where nocturnal levels are approximately 20% lower than daytime values. Theabsence of nocturnal BP-dipping in childhood may be an important indicator of early diseaserisks and our team has recently published evidence that childhood obesity is associated withnon-dipping. The specific project proposed here will test the hypothesis that exposure tohousehold air pollution increases cardiovascular risk in obese children through an inflammation-related disruption in diurnal BP regulation. This project will recruit patients aged 10-18 to definerelationships between at-home air quality and hypertension risk factors. A pilot study todetermine the impact of high efficacy particulate matter (HEPA) filtration units on air qualityexposure and health risks will be measured in these patients as well. This research addresses asignificant public health issue by understanding and identifying environmental exposures in avulnerable high-risk group of rural children in order to develop new treatments to improve theirhealth.

project_terms:
18 year old;Address;Adipocytes;Adolescent;Adolescent obesity;Adult;Adverse effects;Air;Animals;Appearance;Biological Markers;Biometry;Blood Pressure;Cardiorenal syndrome;Cardiovascular Abnormalities;Cardiovascular Diseases;Cardiovascular system;Charcoal;Child;Childhood;Chronic;Chronic Kidney Failure;Cities;Classification;Clinic;Clinical Research;Coal;Coronary Arteriosclerosis;Devices;Diabetes Mellitus;Diagnosis;Diameter;Disease;Diurnal Rhythm;Early Intervention;Environment;Environmental Exposure;Environmental Impact;Exposure to;Filtration;Fire - disasters;Goals;Health;Health Care Costs;High School Student;Home;Household;Household Air Pollution;Human;Hyperlipidemia;Hyperplasia;Hypertension;Hypertrophy;IL6 gene;Inflammation;Inflammatory;Intervention;Intervention Strategies;Investigation;Kentucky;Kidney;Left Ventricular Hypertrophy;Link;Literature;Measurement;Measures;Medical;Mentors;Morbidity - disease rate;Nephrology;Obesity;Participant;Particulate Matter;Patient Recruitments;Patients;Pediatric Hospitals;Pilot Projects;Population;Prevalence;Prevention strategy;Public Health;Publishing;Random Allocation;Research;Risk;Risk Factors;Role;Rural Population;Severities;Surveys;TNF gene;Testing;Training Programs;Translational Research;United States;Variant;Wood material;Wood stove;Youth;adipokines;adiponectin;age group;aged;ambient air pollution;blood pressure regulation;burden of illness;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;career;career development;circadian;coarse particles;cohort;disorder risk;fine particles;high body mass index;high risk;high risk population;improved;insight;instrumentation;intercellular cell adhesion molecule;low socioeconomic status;meter;mortality;obesity in children;pollutant;rational design;recruit;risk stratification;solid fuel;statistics;synergism;systemic inflammatory response;ultrafine particle;ventilation;wasting

public_health_relevance:
PROJECT NARRATIVEHousehold air pollution (HAP) describes the health and environmental impacts of pollutants produced fromincomplete combustion of solid fuels such as wood coal and charcoal that are burnt on open fires or wood-burning stoves in poorly ventilated homes and releases suspended particulate matter (PM). Exposure tohousehold air pollution is thought to be related to worse cardiovascular and kidney health beginning in childhoodand this study will examine how household air pollution increases risk for hypertension in obese children andadolescents. Understanding and identifying these children and adolescents at greatest risk for disease due tohousehold air pollution will develop new treatments to improve their health.


application_id: 11170040
project_number: 5R01DE031998-03
administering_ic: NIDCR
award_notice_date: 2025-06-03
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: DE
serial_number: 031998
program_official: LOPEZ, ORLANDO
project_start_date: 2023-08-01
project_end_date: 2028-07-31
study_section: Imaging Technology Development Study Section[ITD]
contact_pi_person_id: 14584136
contact_pi: ZHU, CAIGANG
other_pis: Not Applicable
congressional_district: 06
department: BIOMEDICAL ENGINEERING
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: BIOMED ENGR/COL ENGR/ENGR STA
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2025-08-01
project_title:
Point-of-care optical spectroscopy platform and novel ratio-metric algorithms for rapid and systematic functional characterization of biological models in vivo

project_abstract:
PROJECT SUMMARYCellular metabolism is highly dynamic and strongly influenced by its local vascular microenvironment gaining asystems-level view of tumor metabolism and vasculature in vivo is essential in understanding many criticalcancer biology questions. However there are surprisingly few techniques available that can quantify the keymetabolic and vascular endpoints together in vivo with easy access. The goal here is to fill this gap bydeveloping a point-of-care optical spectroscopy platform with a tumor-sensitive fiber probe and novel ratio-metric data processing techniques to quantify the major axes of tumor metabolism (glucose uptakemitochondrial membrane potential Bodipy) and the associated vasculature (oxygenation hemoglobin) onbiological models in vivo. For scientific validation and translational purposes we will compare our techniqueswith existing metabolic tools we will also integrate our optical strategies with the state-of-art metabolomicstechnique i.e. Stable Isotope-Resolved Metabolomics (SIRM) to provide a rapid and comprehensiveunderstanding in tumor metabolism. We will then demonstrate our synergistic approach through addressing acontemporary problem in cancer therapy for head and neck squamous cell cancer (HNSCC). Specifically wewill address the critical challenge of radio-resistance (RR) in HNSCC and test the hypothesis that radiotherapy(RT) induced HIF-1 and HIF-2 activation and the following metabolic changes are responsible for HNSCCRR and recurrence the tumor-specific in vivo genetic editing platform targeting on HIF-1 and HIF-2 canimprove RT efficacy. Our point-of-care optical spectroscopy along with novel ratio-metric algorithms make ourtechnologies easy to access easy to use and systematic which are all critical to maximizing its accessibilityfor cancer research. Our spectroscopy techniques and their integration with the SIRM will provide new ways ofstudying cancer biology and diseases and they will also impact the study of a wide array of other biomedicalproblems through the lens of tumor bioenergetics and vasculature. Our study on HNSCC RR mechanisms andthe demonstration of tumor-specific genetic editing platform in orthotropic HNSCC models will offer new waysfor targeted RT to improve HNSCC patient survival rates. The platforms and methodologies developed in thisproject will be applicable to the study of RR and recurrence in other types of human cancers.

project_terms:
Address;Algorithms;Animal Model;Animals;Benchmarking;Bioenergetics;Biological;Biological Assay;Biological Models;Blood Vessels;Cancer Biology;Cancer Model;Cancer Patient;Citric Acid Cycle;Development;Devices;Dimensions;Disease;Fiber;Genes;Genetic;Genus Hippocampus;Geometry;Glycolysis;Goals;Guidelines;Head and Neck Squamous Cell Carcinoma;Hemoglobin;Human;Immunohistochemistry;Lipids;Malignant Neoplasms;Measurement;Measures;Mediating;Membrane Potentials;Metabolic;Metabolic Pathway;Metabolism;Methodology;Modeling;Monitor;Optics;Outcome;Oxygen;Oxygen Consumption;Proteins;Publishing;Radiation Tolerance;Radiation therapy;Recurrence;Risk;Spectrum Analysis;Stains;Survival Rate;System;Targeted Radiotherapy;Techniques;Technology;Testing;Tissues;Treatment Efficacy;Tumor Biology;Validation;Viral;aerobic glycolysis;angiogenesis;anti-cancer research;cancer therapy;computerized data processing;extracellular;genome editing;glucose uptake;improved;in vivo;in vivo Model;insight;lens;metabolomics;mitochondrial membrane;mitochondrial metabolism;nanoparticle;novel;overexpression;point of care;prevent;radiation resistance;radioresistant;ratiometric;stable isotope;therapy design;tool;trend;tumor;tumor metabolism;vector

public_health_relevance:
PROJECT NARRATIVEThe goal of this project is to establish novel optical strategies for rapid systematic metabolic characterization ofbiological models in vivo to address questions in the field of HNSCC radio-resistance and recurrence usingorthotropic HNSCC models. We will also integrate our optical strategies with the state-of-art Stable Isotope-Resolved Metabolomics (SIRM) to provide rapid and comprehensive understanding in tumor metabolism thatrelates to radio-resistance. Our synergistic approach will provide the metabolic underpinnings of radio-resistance and recurrence and facilitate advances in the understanding of tumor biology assessment ofrecurrence risk and design of therapies that can mitigate radio-resistance and recurrence altogether.


application_id: 11170005
project_number: 5R21AA031563-02
project_title: RNA Modification Changes in Alcohol-Associated Liver Disease
administering_ic: NIAAA
award_notice_date: 2025-08-25
opportunity_number: PA-20-195
application_type: 5
activity_code: R21
ic: AA
serial_number: 031563
program_official: PERRUCCIO, ELIZABETH M
project_start_date: 2024-08-15
project_end_date: 2026-07-31
study_section: Biomedical Research Study Section[AA-1]
contact_pi_person_id: 14963272
contact_pi: HE, LIQING
other_pis: Not Applicable
congressional_district: 03
department: CHEMISTRY
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_abstract:
Abstract. Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases.The progressive nature of alcohol-associated liver disease (ALD) has been well described but the complexinteractions under which these pathologies evolve remain only partially elucidated. Based on our preliminarystudy free nucleosides and nucleosides hydrolyzed from total RNA are altered in mice treated with alcohol andin a human liver cell line HepaRG treated with acetaldehyde. We also observed significant changes in theserum and urine of patients with different stages of ALD. Therefore we hypothesize that alcohol consumptionaffects RNAs' chemical modification and contributes to ALD development and progression. To prove thishypothesis we will treat mice with alcohol and first map the chemical modifications on RNAs by isolating differenttypes of RNAs from mouse liver digesting them into nucleosides and oligonucleotides and detecting the site-specific modification on each RNA using comprehensive 2DLC-MS (Aim 1). And then RNA modification variationwill be studied between alcohol fed and normal fed mice at the RNA level and the underlying mechanism will beuncovered by detecting the expression of the corresponding enzymes (Aim 2).1

project_terms:
Acetaldehyde;Affect;Alcohol consumption;Alcoholic Liver Diseases;Alcohols;Aliquot;Back;Biological;Cell Line;Cells;Chemicals;Chronic;Complex;Data;Databases;Detection;Development;Ensure;Enzymes;Etiology;Exhibits;Feces;Genetic Transcription;Hepatocyte;Human;Immunohistochemistry;Laboratories;Liver;Liver Extract;Liver diseases;Location;Maps;Messenger RNA;Modification;Molecular;Mus;NMR Spectroscopy;National Institute on Alcohol Abuse and Alcoholism;Nature;Nuclear Magnetic Resonance;Nucleosides;Oligonucleotides;Organ;Pathogenesis;Pathogenicity;Pathology;Patients;Positioning Attribute;Procedures;Proteomics;RNA;RNA Degradation;RNA Sequences;Resolution;Ribonucleosides;Ribosomal RNA;Role;Serum;Site;Source;Techniques;Technology;Transfer RNA;Untranslated RNA;Urine;Variant;Western Blotting;alcohol effect;base;bioinformatics infrastructure;cell type;chronic alcohol ingestion;chronic liver disease;experience;feeding;gel electrophoresis;human disease;insight;liquid chromatography mass spectrometry;mouse model;nanopore;novel;transcriptome sequencing;two-dimensional

public_health_relevance:
Chronic alcohol consumption can cause alcohol associated liver disease (ALD) which is one of the leadingcauses of liver disease. We will use mouse models to explore the changes of RNA modification in the mouselivers to uncover the molecular mechanisms of ALD.


application_id: 11169978
project_number: 5R01HL163419-02
project_title: Role of carnosine in peripheral arterial disease
administering_ic: NHLBI
award_notice_date: 2025-06-30
opportunity_number: PA-20-183
application_type: 5
activity_code: R01
ic: HL
serial_number: 163419
program_official: REID, DIANE M
project_start_date: 2024-08-15
project_end_date: 2029-05-31
study_section: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]
contact_pi_person_id: 11110260
contact_pi: BABA, SHAHID P
other_pis: BHATNAGAR, ARUNI ;DWIVEDI, AMIT J
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:
AbstractPeripheral arterial disease is a serious manifestation of atherosclerosis in the lowerextremities. Current interventions approved by FDA are either ineffective or have amodest effect. Surgical revascularization is the only viable option for PAD subjects;however the stents can fail. Patients with PAD have marked defects in skeletal musclemetabolism where the aerobic and anaerobic metabolism are uncoupled increasedacidification of the skeletal muscle and decreased ATP synthesis. In glycolytically activetissue such as skeletal muscle there are present histidyl dipeptides such as carnosinewhich buffers intracellular pH under ischemic conditions and facilitate the utilization ofglucose during exercise and ischemia. Recent evidence from our laboratory shows thatin addition to buffering carnosine chelates first transition metals and improvesangiogenesis forms conjugates with reactive aldehydes derived from lipid peroxidationand regress atherosclerosis. Hence enhancing carnosine via supplementation whicheasily permeates through the ischemic muscle is easily could be a feasible therapeuticthat can target the underlying pathophysiological associated with PAD and increase limbfunction. To achieve this goal we will treat the PAD subjects with carnosine and examinewhether the carnosine supplementation improves the lower extremity function. Secondwe will perform extensive mechanistic studies to elucidate the mechanism by whichcarnosine improves the muscle function and finally we will follow these subjects anddetermine if carnosine has durable effects. Collectively our pilot clinical trial will help ustest the efficacy of carnosine as a low-cost therapeutic intervention for PAD patients andthe data generated will serve as a strong rationale to design large definitive Phase IIIclinical trial for carnosine.

project_terms:
ATP Synthesis Pathway;Aerobic;Affect;Aftercare;Aldehydes;American;Ankle;Arterial Fatty Streak;Arterial Occlusive Diseases;Arteries;Atherosclerosis;Attenuated;Binding;Biopsy;Blood flow;Buffers;Cardiac;Carnosine;Cell Therapy;Chronic;Clinical Management;Clinical Trials;Data;Defect;Dipeptides;Double-Blind Method;Effectiveness;Enrollment;Enzymes;Excision;Excretory function;Exercise;FDA approved;Female;Fibrosis;Food Supplements;Foundations;Functional disorder;Glucose;Goals;Growth;Hindlimb;Histidine;Impairment;Intermittent Claudication;Intervention;Ischemia;Isolated limb perfusion;Laboratories;Leg;Limb structure;Lipid Peroxidation;Lower Extremity;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Measures;Mediating;Medical;Metabolic;Metabolic dysfunction;Metabolism;Metals;Mitochondria;Morbidity - disease rate;Mus;Muscle;Muscle function;Obstruction;Operative Surgical Procedures;Outcome Study;Participant;Pathway interactions;Patients;Performance;Perfusion;Peripheral arterial disease;Persons;Pharmacotherapy;Phase III Clinical Trials;Placebos;Preclinical data;Process;Property;Proteomics;Quality of life;Randomized;Reperfusion Injury;Rest;Risk Factors;Role;Secondary to;Skeletal Muscle;Stenosis;Stents;Supplementation;Testing;Therapeutic;Therapeutic Intervention;Time;Tissues;Transition Elements;Walking;angiogenesis;blood perfusion;cardiovascular disorder risk;chelation;claudication;clinical efficacy;cost;design;efficacy testing;exercise capacity;feeding;follow-up;hemodynamics;improved;indexing;limb loss;male;metabolomics;mortality;muscle physiology;novel;pre-clinical;prevent;primary outcome;protein expression;revascularization surgery;secondary outcome;skeletal muscle metabolism;standard of care;success;treadmill;urinary;walking performance;-Alanine

public_health_relevance:
AbstractA food supplement carnosine can improve the walking ability of patients having legischemia.Project Narrative


application_id: 11168841
project_number: 5UG1HD107649-04
project_title: Neonatal Opioid Withdrawal Syndrome (NOWS) in Kentucky: Improving Outcomes for Infants
administering_ic: NICHD
award_notice_date: 2025-08-20
opportunity_number: RFA-HD-21-031
application_type: 5
activity_code: UG1
ic: HD
serial_number: 107649
program_official: CHAKHTOURA, NAHIDA ABDO
project_start_date: 2021-09-17
project_end_date: 2026-08-31
study_section: ZHD1-DSR-T(50)
contact_pi_person_id: 8880455
contact_pi: DEVLIN-PHINNEY, LORI ANN
other_pis: TELANG, SUCHETA
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/ABSTRACT The medical and non-medical use of opioids and other psychoactive drugs in women of childbearing age isa significant public health concern in the United States. Prolonged in utero exposure of the developing fetus tomaternal opioids often results in Neonatal Opioid Withdrawal Syndrome (NOWS) after delivery. Infants withNOWS may have mild signs of withdrawal that minimally impact their ability to function or they may havesignificant withdrawal that requires a prolonged course of pharmacologic therapy and a lengthy newborn hospitalstay which stresses families communities and the healthcare system. Prolonged hospitalization may result indecreased maternal and infant bonding and attachment and have a negative impact on neurodevelopmental andbehavioral outcomes of affected children. The prevalence of opioid use during pregnancy and the subsequentoccurrence of NOWS after delivery is disproportionately higher in rural and underserved areas. Kentucky is ahighly rural and underserved state and has an estimated rate of NOWS that is approximately three times thenational average. Despite the significance of this problem the clinical care for neonates with NOWS is complicated by a lackof nationally accepted standardized approaches which leads to significant site-to-site variation. Such variation isdue in part to a lack of generalizable evidence to inform clinical practice. Previous research has been limited byboth small sample sizes due to difficulty with recruitment and retention and inherent limitations in study designs.In order to identify the most effective treatment and thereby optimize the care of infants with NOWS a directcomparison of pharmacologic treatment regimens in a generalizable population is urgently needed. Collaboration with local community partners and with other clinical sites will be undertaken within theproposed research consortium to design implement and conduct a multicenter randomized controlled clinicaltrial. The goal of the trial is to provide a direct comparison of pharmacologic treatment for infants with NOWSaccount for confounding variables such as non-pharmacologic care and adjuvant medications and evaluateneurodevelopmental and behavioral outcomes in the first years of life. The anticipated results of this RCT will behighly generalizable to improve care for infants with NOWS in KY and throughout the nation.

project_terms:
Accounting;Address;Adjuvant Analgesic;Affect;Caring;Child;Childhood;Clinic;Clinical;Clinical Nursing Research;Clinical Pharmacology;Clinical Practice Guideline;Clinical Research;Clinical Trials;Clinical Trials Network;Collaborations;Communities;Confounding Factors (Epidemiology);Country;Data Analyses;Dedications;Development;Dose;Enrollment;Ensure;Evaluation;Family;Female of child bearing age;Fetal Development;Frequencies;Geography;Goals;Health;Health Care Systems;Health Personnel;Hospitalization;Hospitals;Infant;Infant Care;Infrastructure;Kentucky;Leadership;Length of Stay;Life;Medical;Medical Care Team;Mothers;Multi-Institutional Clinical Trial;Multi-site clinical study;Neonatal;Neonatal Abstinence Syndrome;Neonatal Intensive Care Units;Newborn Infant;Opioid;Outcome;Patient Recruitments;Patients;Pharmacotherapy;Play;Population;Population Heterogeneity;Pregnancy;Prevalence;Psychotropic Drugs;Public Health;Randomized Controlled Clinical Trials;Randomized Controlled Trials;Recording of previous events;Research;Research Design;Research Personnel;Role;Rural;Sample Size;Scientist;Site;Solid;Standardization;Stress;Treatment Protocols;United States;United States National Institutes of Health;Universities;Variant;Visit;Withdrawal;Work;behavioral outcome;care outcomes;clinical care;clinical practice;clinical research site;clinically relevant;community advisory board;community partners;comparative effectiveness trial;compare effectiveness;data sharing;design;effective therapy;evidence base;experience;follow-up;high risk;improved;improved outcome;infant outcome;member;neonate;opioid epidemic;opioid misuse;opioid use;opioid use in pregnancy;optimal treatments;outreach;pediatric department;pediatrician;pharmacologic;prenatal exposure;programs;prospective;recruit;rural area;rural underserved;standard of care;suburb;underserved area;urban underserved

public_health_relevance:
PROJECT NARRATIVEThe increased use and misuse of opioids during pregnancy and resulting Neonatal Opioid Withdrawal Syndrome(NOWS) are critical public health concerns in the United States. We will collaborate as a member of the proposedresearch group to design and conduct a multicenter clinical trial to directly compare the effectiveness ofpharmacologic treatments for infants with NOWS. We anticipate that our studies will identify the optimal treatmentfor NOWS to improve the care and overall health and neurodevelopmental outcomes of infants with NOWSthroughout the US.


application_id: 11168744
project_number: 5F31HL165826-04
project_title: Role of Pck2 in cardiac fibrosis
administering_ic: NHLBI
award_notice_date: 2025-08-07
opportunity_number: PA-21-051
application_type: 5
activity_code: F31
ic: HL
serial_number: 165826
program_official: CHEON, YEWON
project_start_date: 2022-09-01
project_end_date: 2026-08-31
study_section: Special Emphasis Panel[ZRG1-F10A-K(20)L]
contact_pi_person_id: 77801946
contact_pi: WELLS, COLLIN
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:
Project SummaryFibrotic remodeling after myocardial infarction involves temporal development of several fibroblast phenotypescharacterized by high proliferation rates differentiation into myofibroblasts and heightened extracellular matrixdeposition. These processes require large increases in metabolic demand to achieve or maintain the activatedfibroblast state. Nevertheless how fibroblasts meet these phases of high metabolic demand and whetherparticular metabolic steps could be antifibrotic targets remains unclear. Previous studies indicate that profibroticstimuli augment catabolic activity in fibroblasts and that lowering either glycolysis or oxidative phosphorylationdiminishes myofibroblast differentiation. These metabolic pathways are important not only for ATP productionbut also for their role in the synthesis of cellular building blocks and secreted proteins. In particular severalglycolytic intermediates serve as amphibolic metabolites capable of entering into pathways responsible for denovo nucleotide phospholipid and amino acid synthesis. These biosynthetic pathways could be particularlyimportant in the fibrotic response because activated fibroblasts require higher anabolic output to providebiomolecular building blocks for cell division and ECM secretion. Our preliminary data suggest that thegluconeogenic enzyme phosphoenolpyruvate carboxykinase 2 (Pck2) is upregulated in activated fibroblasts.This enzyme is positioned to coordinate anabolic processes because it can deliver carbon from the Krebs cycleintermediate pool to the 3-carbon glycolytic pool thereby increasing precursors for several biosyntheticpathways. We also find glutaminase to be upregulated in activated fibroblasts which could augment glutamine-derived carbon for the Krebs cycle pool which is then available to Pck2. Suggestive of its importance to fibroblastfunction Pck2 deletion decreases fibroblast proliferation and appears to affect markers of myofibroblastsindicating that it is a critical enzyme that may facilitate or uphold the activated fibroblast phenotype. We proposethat Pck2 is a fundamental regulator of fibrosis that regulates fibroblast activation by meeting the biosyntheticdemands required for proliferation or ECM deposition. Nevertheless virtually nothing is known about howbiosynthetic pathways change in fibroblasts in response to fibrogenic stimuli or how Pck2 influences fibroblastmetabolism and cardiac fibrosis. To address these gaps in knowledge we will: (1) elucidate how Pck2 influencescardiac fibroblast metabolism; and (2) determine the influence of Pck2 on fibroblast activation and MI-inducedcardiac remodeling. This project will yield fundamental knowledge necessary for understanding how fibroblastmetabolism modulates fibrotic remodeling after cardiac injury.

project_terms:
Address;Affect;Amino Acids;Anabolism;Biology;Blood Vessels;Carbon;Cardiac;Cardiovascular system;Cell division;Chronic;Citric Acid Cycle;Collagen;Data;Deposition;Development;Enzymes;Extracellular Matrix;Fibroblasts;Fibrosis;Genetic Transcription;Gluconeogenesis;Glucose;Glutaminase;Glutamine;Glycolysis;Heart;Heart Injuries;Infarction;Knowledge;Ligands;Metabolic;Metabolic Pathway;Metabolism;Myocardial Infarction;Myofibroblast;Nucleotides;Output;Pathology;Pathway interactions;Phase;Phenotype;Phosphoenolpyruvate Carboxylase;Phospholipids;Positioning Attribute;Process;Production;Proliferating;Protein Secretion;Role;Serine;Source;Stimulus;Testing;Transcript;Transforming Growth Factor beta;coronary fibrosis;diminished oxidative phosphorylation;extracellular;glucose metabolism;in vivo;meetings;mouse model;programs;response;therapeutic target;transcriptome sequencing;transdifferentiation;virtual

public_health_relevance:
Project NarrativeThe role of metabolism in the heart and in cardiovascular (patho)pathology is poorly understood. This project willdetermine how the gluconeogenic enzyme phosphoenolpyruvate carboxykinase 2 influences fibroblast biologyand affects cardiac remodeling after myocardial infarction.


application_id: 11167826
project_number: 5R24AI138963-08
administering_ic: NIAID
award_notice_date: 2025-08-14
opportunity_number: PAR-20-063
application_type: 5
activity_code: R24
ic: AI
serial_number: 138963
program_official: BREEN, JOSEPH J
project_start_date: 2018-07-23
project_end_date: 2027-08-31
study_section: ZAI1-SB-I(M1)
contact_pi_person_id: 10517640
contact_pi: WATSON, COREY TAYLOR
other_pis: SMITH, MELISSA LAIRD
congressional_district: 03
department: BIOCHEMISTRY
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
budget_start_date: 2025-09-01
project_title:
An ethnically diverse genomic reference resource for the human heavy and light chain immunoglobulin loci

project_abstract:
PROJECT SUMMARYThere is a fundamental gap in our understanding of how germline variation in the immunoglobulin (IG) heavy(IGH) and light chain (kappa IGK; lambda IGL) loci in the human population impacts the development of thefunctional antibody (Ab) response in health and disease. However there is growing appreciation for the fact thatIG polymorphism contributes to variability in the Ab repertoire indicating that the integration of IG genetic datain basic and biomedical research can inform our understanding of how IG gene regulation as well as Abrepertoire dynamics function in various clinical contexts. A critical barrier to progress has been that existinggenomic resources for the IG loci are incomplete and poorly represent diversity across human populationsparticularly those from non-European ancestries. Evidence continues to accumulate in support of the notion thatthe IG regions are among the most structurally complex and polymorphic regions of the human genome enrichedfor large structural variants (SVs) and single nucleotide variants (SNVs) resulting in extreme interindividualhaplotype variation. These complexities have long made the IG loci difficult to study using standard high-throughput methods with direct negative impacts on genetic disease association studies and more recently theanalysis of adaptive immune receptor repertoire sequencing (AIRR-seq) data. As a result knowledge of humanIG germline diversity particularly in populations underrepresented in genomics databases and its contributionto disease lags far behind that of other well-studied immune loci. This highlights a direct need for publiclyavailable well-characterized IG haplotype references and accurate variant catalogues from diverse ethnicbackgrounds to facilitate the design and integration of more accurate genotyping tools analysis pipelines andtheir interpretation. To meet these needs we have developed this renewal proposal which will build the mostcomprehensive IG genomic dataset to date with transformative potential impact for the fields of B cellimmunology and immunogenetics. The resource generated will: (i) shed light on the extent of IG diversityworldwide; (ii) establish a framework for linking genetic data to expressed antibody repertoire variation to informour understanding of V(D)J recombination and seed models of antibody repertoire dynamics; and (iii)substantially augment key databases and research initiatives pushing the frontiers of genomics and immunologyresearch. This renewal project will seamlessly build and expand upon the foundational IG genomics datagenerated in our initial proposal and continue to establish desperately needed genomic resources for the humanIG loci particularly in underrepresented populations and cohorts of immediate biomedical relevance which willserve the immunology and larger genomics communities for years to come.

project_terms:
2019-nCoV;Adaptive Immune System;Adult;Antibodies;Antibody Repertoire;Antibody Response;Antibody-mediated protection;Area;Autoimmunity;Award;B-Lymphocytes;Basic Science;Biomedical Research;Brazil;Catalogs;Clinical;Collaborations;Collection;Communities;Complex;Data;Data Set;Databases;Deposition;Development;Disease;Ensure;European;Genbank;Gene Expression Regulation;General Practitioners;Genes;Genetic;Genetic Diseases;Genetic Polymorphism;Genetic Variation;Genome;Genomics;Genotype;Genotype-Tissue Expression Project;Germ Lines;Germ-Line Mutation;HIV;Haplotypes;Health;Human;Human Genome;Human Resources;IGL@ gene cluster;Immune;Immunogenetics;Immunogenomics;Immunoglobulin A;Immunoglobulin G;Immunoglobulin Genes;Immunoglobulin M;Immunoglobulins;Immunologic Receptors;Immunology;Individual;Infection;International;Investigation;Knowledge;Light;Link;Malignant Neoplasms;Methods;Modeling;Nucleotides;Oceania;Outcome;Population;Population Heterogeneity;Positioning Attribute;Quantitative Trait Loci;Research;Resources;Rheumatic Heart Disease;Role;Sampling;Single Nucleotide Polymorphism;South African;Summary Reports;Uganda;Underrepresented Populations;V(D)J Recombination;Variant;analysis pipeline;cohort;data access;database of Genotypes and Phenotypes;dbSNP;design;ethnic diversity;frontier;genetic association;genome browser;genome resource;genomic data;high standard;immunoglobulin light chain locus;improved;long-read sequencing;novel;precision medicine;reference genome;response;structural mutation;tool;vaccine response

public_health_relevance:
PROJECT NARRATIVEGenomic resources for the human immunoglobulin loci poorly represent diversity among human populationslimiting our ability to resolve the role of antibody genetic variation in health and disease. This renewal project willbuild the most comprehensive immunoglobulin genomic dataset to date with transformative impact on the fieldsof B cell immunology and immunogenetics. The data generated will (i) shed light on the extent of immunoglobulindiversity worldwide; (ii) establish a framework for linking genetic data to expressed antibody repertoire variationto inform our understanding of V(D)J recombination and seed models of antibody repertoire dynamics in disease;(iii) and substantially augment key databases and research initiatives pushing the frontier of disease genomicsand immunology research.


application_id: 11167770
project_number: 5R01MH134859-02
project_title: Neural Mechanisms of Menstrual Cycle Effects on ADHD and Cognition
administering_ic: NIMH
award_notice_date: 2025-08-13
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: MH
serial_number: 134859
program_official: ZEHR, JULIA L
project_start_date: 2024-08-15
project_end_date: 2029-04-30
study_section: Child Psychopathology and Developmental Disabilities Study Section[CPDD]
contact_pi_person_id: 8204810
contact_pi: MARTEL, MICHELLE M
other_pis: Not Applicable
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 ARTS AND SCIENCES
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
ABSTRACTAttention-Deficit/Hyperactivity Disorder (ADHD) is increasingly recognized as a serious and debilitatingproblem in adolescent and adult females with impairment and comorbidity in female patients with ADHDincreasing dramatically around puberty. Given the deleterious consequences of ADHD and substantialcomorbidities in this group there is an urgent need to understand sex-specific factors contributing to symptomexpression in this understudied population. One promising but understudied factor is ovarian hormones whichbecome activated around puberty and fluctuate monthly in adulthood. To date no study outside of our lab hasexamined the effects of estrogen and progesterone changes on ADHD symptoms in female patients but basicscience data from animal studies provide a strong scientific premise for this work. These studies date back 20years and suggest that withdrawal fromand lower levels ofestradiol the predominant estrogen causecognitive and attention problems based on experimental work with ovariectomized rats. In fact we have pilotdata establishing the basic scientific premise and feasibility of this study design showing declines in estrogenpredict worsening response inhibition and working memory and increases in ADHD symptoms in a clinicalsample of female patients with ADHD. Yet it remains unclear what accounts for these effects at theneurobiological level in humans despite animal work showing estrogen effects on dopamine and human workin female heavy drinkers showing estrogen effects on insular brain activation patterns during responseinhibition tasks. The current project aims to use an innovative quasi-experimental and intensive longitudinalmenstrual cycle study design to elucidate the neurobiological mechanisms of estrogen effects on neuralmechanisms of cognition and ADHD symptoms in a clinical sample of 120 young adult female patients ages 18to 25 with ADHD. The project will evaluate whether menstrual cycle phase and hormonal effects on the neuralcircuitry involved in response inhibition and working memory predict short-term longitudinal change in ADHDsymptoms and medication response in young adult females with ADHD. This work is a critical extension of ourpreliminary data which found cycle phase and hormonal effects on ADHD and response inhibition and workingmemory but did not evaluate neural mechanisms or hormonal effects on treatment response. The long-termgoal of this project is to test whether medication titration or hormone stabilization across menstrual cycle phaseor reproductive phase improves ADHD symptoms and normalizes underlying neurocognitive and biologicalmechanisms in females. Such information is critical to advancing neurobiological theory of ADHD andsuggesting new avenues for personalized sex-specific assessment and psychopharmacological treatment ofADHD which may need to be targeted to cycle or reproductive phase hormonal profiles and impactedneurofunctional regions in pharmacotherapies.

project_terms:
Adolescence;Adolescent;Adult;Adult women;Age;Alcoholic beverage heavy drinker;Animals;Attention;Attention deficit hyperactivity disorder;Back;Basic Science;Biological;Brain;Childhood;Clinical;Cognition;Cognitive;Data;Dopamine;Estradiol;Estrogen decline;Estrogens;Feasibility Studies;Female;Goals;Gonadal Steroid Hormones;Hormonal;Hormones;Human;Impairment;Inferior;Link;Longitudinal Studies;Mediating;Menstrual cycle;Neurobiology;Neurocognitive;Neurophysiology - biologic function;Ovarian hormone;Ovariectomy;Participant;Pattern;Pharmaceutical Preparations;Pharmacotherapy;Phase;Population;Prevalence;Progesterone;Puberty;Quasi-experiment;Rattus;Research Design;Risk;Risk Factors;Sampling;Short-Term Memory;Symptoms;Testing;Titrations;Translating;Withdrawal;Work;animal data;caudate nucleus;cognitive task;comorbidity;design;hypothalamic pituitary gonadal axis;improved;innovation;longitudinal design;male bias;neural circuit;neurobiological mechanism;neuromechanism;perimenstrual;phase change;psychopharmacologic;psychostimulant;reproductive;response;sex;symptom treatment;theories;treatment response;women patients;young adult

public_health_relevance:
NarrativeThe current project will evaluate the neural mechanisms underlying menstrual cycle phase and hormonaleffects on response inhibition and working memory in females with ADHD. In addition the project willdetermine whether and how well cycle phase and hormonal effects on neural function during cognitive taskspredict ADHD symptoms and treatment response.


application_id: 11167065
project_number: 1R01HD116429-01A1
project_title: The role of glucocorticoid receptor in the ovary
administering_ic: NICHD
award_notice_date: 2025-07-08
opportunity_number: PA-20-185
application_type: 1
activity_code: R01
ic: HD
serial_number: 116429
suffix: A1
program_official: TAYMANS, SUSAN
project_start_date: 2025-07-15
project_end_date: 2030-05-31
study_section: Special Emphasis Panel[ZRG1 EMS-C (02)]
contact_pi_person_id: 8244639
contact_pi: JO, MISUNG
other_pis: HENNEBOLD, JON D
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:
Abstract Ovarian disorders in women including defects in ovulation and subsequent corpus luteum developmentaccount for up to 30% of all infertility cases. Understanding the mechanism underlying these processes iscritically important because this knowledge serves as a foundation for our ability to aid or manage femalefertility. Glucocorticoids (GCs) are potent hormones involved in various cellular functions includinginflammatory responses and cellular metabolism which are also hallmarks of the ovulatory process and lutealdevelopment. In the ovary the level of cortisol an active glucocorticoid dramatically increases in the follicularfluid after an ovulatory human chorionic gonadotropin (hCG) stimulation in women and monkeys whereas thelevel of cortisone an inactive form rapidly decreases. Our recent studies and preliminary data demonstratedthat the administration of an ovulatory bolus of hCG increased the expression of crucial components requiredfor cortisol production and action in granulosa cells of periovulatory follicles in normally cycling womenmonkeys and mice. Moreover our experimental data indicate that GCs/glucocorticoid receptor (GR) playscritical roles in cumulus expansion ovulation and luteal development. However little is known about themechanisms by which GCs/GR regulate these processes and their physiological significance in the ovary. Thepresent proposal will address these critical questions by utilizing experimental models from three key speciesto gain a comprehensive understanding of the role of GCs/GR in the pivotal process in the ovary. In Aim 1using transgenic mouse models in which GR expression is ablated in ovarian follicular cells we will determinethe physiological significance of GR and identify GR-mediated transcriptomic genomic and functional changesnecessary for successful ovulation and luteal development. In Aim 2 we will utilize adult female rhesusmonkeys to demonstrate that the inhibition of GR in preovulatory follicles negatively affects ovulation and lutealdevelopment and determine the specific function(s) and transcriptomic regulation affected by GR inhibition. InAim 3 using dominant preovulatory follicles obtained from normally cycling women across the ovulatory periodand primary human granulosa/lutein cells we will delineate the mechanisms by which GCs/GR signalingregulates ovulatory changes and luteinization by first identifying direct downstream target genes of GR inprimary human granulosa cells then characterizing their expression in dominant follicles during the ovulatoryperiod and lastly assessing functional impacts of GR inhibition. By demonstrating the physiologicalsignificance and identifying specific actions of GCs/GR in the periovulatory ovary across multiple species theproposed study will provide novel insights into the species-specific and -conserved mechanism controllingovulation and luteinization. This fundamental knowledge will be valuable for developing strategies to assistwomen experiencing infertility due to anovulatory disorders and luteal insufficiency.

project_terms:
ATAC-seq;Ablation;Address;Adult women;Affect;Aryl Hydrocarbon Receptor;Birth;Bolus Infusion;Cell Physiology;Cell Separation;Cells;ChIP-seq;Cholesterol;Cortisone;Data;Defect;Development;Embryonic Development;Essential Genes;Event;Experimental Models;Fertility;Follicular Fluid;Follicular Ovarian Cell;Foundations;Gene Expression;Genes;Genetic Models;Genomics;Glucocorticoid Receptor;Glucocorticoids;Hormones;Human;Human Chorionic Gonadotropin;Hydrocortisone;Impairment;Infertility;Inflammatory Response;Informatics;Knockout Mice;Knowledge;Luteal Cells;Luteinization;Macaca mulatta;Mediating;Metabolism;Molecular;Monkeys;Morphology;Multiomic Data;Mus;Mutant Strains Mice;NR3C1 gene;Names;Oocytes;Ovarian;Ovarian Diseases;Ovarian Follicle;Ovary;Ovulation;Ovulation Induction;Phenotype;Physiological;Play;Process;Production;Progesterone;Receptor Inhibition;Receptor Signaling;Regulation;Reproductive Health;Respiratory Failure;Role;Steroid biosynthesis;System;Time;Transgenic Mice;Woman;anovulatory disorder;antagonist;corpus luteum;experience;female fertility;granulosa cell;insight;knock-down;mouse genetics;mouse model;novel;receptor expression;receptor sensitivity;stem;steroid hormone;tacrolimus binding protein 4;transcriptome sequencing;transcriptomics

public_health_relevance:
Narrative Successful ovulation and subsequent corpus luteum development are essential for female fertility. In thepresent proposal we will demonstrate for the first time that glucocorticoids/glucocorticoid receptor plays criticalroles in ovulation and corpus luteum development in mice monkeys and humans. This fundamentalInformation will not only provide novel insights into the mechanism(s) underlying ovulation and luteal formationbut also be valuable for developing strategies to assist women with compromised reproductive health andinfertility stemming from defects in the ovulatory process and luteal development.


application_id: 11166637
project_number: 5R01HL170193-02
project_title: Targeting Lung Fibrosis Using Epigenetic Therapy
administering_ic: NHLBI
award_notice_date: 2025-08-15
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: HL
serial_number: 170193
program_official: VUGA, LOUIS J
project_start_date: 2024-08-15
project_end_date: 2028-07-31
study_section: Lung Injury, Repair, and Remodeling Study Section[LIRR]
contact_pi_person_id: 10317047
contact_pi: BRAINSON, CHRISTINE FILLMORE
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 Pulmonary fibrosis is a complex disease that limits lung function through development of collagen-richscar tissue. Although there are currently two FDA-approved therapies for fibrosis patients these drugs arecapable of extending life only months and do not reverse the progression of the disease. The research describedin this proposal would build upon evidence that reprogramming cellular fate through modulation of theepigenetic enzyme EZH2 can ameliorate several phenotypes of pulmonary fibrosis including aberrantalveolar cell fate and pro-fibrotic cytokine signaling. Specifically the aims will test if the FDA-approved EZH2inhibitor tazemetostat will allow for prevention or reversion of these cellular phenotypes. The model systems tobe used include both human and mouse organotypic cell cultures and two established in vivo models ofpulmonary fibrosis namely lung instillation of the chemotherapy bleomycin or adeno-associated virus (AAV)expressing TGF. For Aim 1 we will quantify the extent of aberrant basaloid/alveolar transition cells in lungepithelial cultures that are depleted for EZH2 activity genetically or pharmacologically and assess rescue of thisphenotype by deletion of the transcription factor FOXP2. FOXP2 deletion and knock-down will also be used tounderstand this important transcription factors role alveolar cell fate. We will also assess the down-regulation ofIL1 by EZH2 inhibition and its effects on both murine and human epithelial and fibroblast cells. The influenceof TGF on fibroblasts and epithelial cells in the presence of EZH2 inhibitor will be tested. In Aim 2 in vivo lunginjury models will be used to examine both prevention and treatment of lung fibrosis and to characterize specificchanges to the epithelial fibroblast and myeloid cell populations driven by EZH2 inhibition. Lung functiontesting histology scRNA-seq and flow cytometry will be used to characterize the lung phenotypes. Patienttissues will be used to understand if EZH2 activity is high and FOXP2 expression is low in aberrantbasaloid/alveolar transition cells in vivo. We expect that this research could validate the use of EZH2 inhibitionas a treatment for pulmonary fibrosis and will expand our knowledge in the field of lung epigenetics and stemcell biology.

project_terms:
Alveolar;Alveolar Cell;Attenuated;Biological Availability;Biological Models;Bleomycin;Cell Culture Techniques;Cell Lineage;Cell Reprogramming;Cells;ChIP-seq;Chromatin;Cicatrix;Collagen;Complex;Cytokine Signaling;Data;Dependovirus;Development;Disease;Disease Progression;Down-Regulation;EZH2 gene;Enzymes;Epigenetic Process;Epithelial Cells;Epithelium;FDA approved;FOXP2 gene;Fibroblasts;Fibrosis;Flow Cytometry;Gene Expression;Genes;Genetic Transcription;Harvest;Histologic;Histology;Histone H3;Human;Immune;Infection;Inflammatory;Injury;Interleukin-1 beta;Intervention;Knowledge;Laboratories;Life;LoxP-flanked allele;Lung;Lung Diseases;Lysine;Medicine;Mesenchymal;Methylation;Modeling;Mus;Mutation;Myeloid Cells;Oral;Organoids;Patients;Persons;Pharmaceutical Preparations;Phenotype;Polycomb;Population;Prevention;Pulmonary Fibrosis;Pulmonary function tests;Radiation;Repression;Research;Role;Sampling;Signal Transduction;Silicon Dioxide;Stains;Supporting Cell;System;Testing;Therapeutic;Tissues;Transforming Growth Factor beta;Upregulation;Viral;Western Blotting;allergic airway disease;cell type;chemotherapy;cytokine;derepression;epigenetic therapy;histone methyltransferase;improved;in vivo;in vivo Model;inhibitor;insight;knock-down;lung injury;lung repair;novel therapeutic intervention;overexpression;pharmacologic;prevent;profibrotic cytokine;promoter;pulmonary function;response;single-cell RNA sequencing;small molecule;stem cell biology;transcription factor;transcriptome sequencing

public_health_relevance:
PROJECT NARRATIVELung fibrosis is a progressive incurable disease with few treatment options. This proposal aims to define iftargeting the epigenetic enzyme EZH2 using an FDA-approved drug would be a viable therapeutic option forlung fibrosis patients. The proposed research will expand our knowledge about how epi-drugs can influenceimportant phenotypes of lung disease.


application_id: 11166632
project_number: 5R01MH131633-03
administering_ic: NIMH
award_notice_date: 2025-07-07
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: MH
serial_number: 131633
program_official: CHAVEZ, MARK RAY
project_start_date: 2023-09-01
project_end_date: 2028-06-30
study_section: Adult Psychopathology and Disorders of Aging Study Section[APDA]
contact_pi_person_id: 10775786
contact_pi: LEVINSON, CHERI ALICIA
other_pis: SMITH, APRIL ROSE
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
budget_start_date: 2025-07-01
project_title:
Longitudinal Personalized Dynamics Among Anorexia Nervosa Symptoms Core Dimensions and Physiology Predicting Suicide Risk

project_abstract:
PROJECT SUMMARY/ABSTRACTAnorexia nervosa (AN) is a severe mental illness with the highest mortality rate of any psychiatric disorder withsuicide as the second leading cause of death. Despite extremely high rates of suicide risk factors for suicidalideation (SI) and behaviors/attempts (SA) in this high-risk population are not well understood. While there isevidence that threat reactivity stress-response over-arousal emotion dysregulation and agitation contributeto suicide risk the dynamic relations among these processes have not been characterized on acomprehensive momentary basis. Our scientific premise developed from our past work is that the applicationof ideation-to-action and network theories will enable the identification of dynamic longitudinal interactionsamong core dimensions (e.g. arousal threat) AN symptoms and SI/SA both between and within individuals.Our study goals are to (1) identify symptom and dimension risk interactions of co-occurring AN and SI/SAbetween and within persons (2) differentiate which risk factors predict SI vs SA and (3) test if these risk factorspredict onset of SI/SA. These goals will ultimately identify which factors should be targeted in novel preventionand treatment efforts. We will use a multiple units of analysis approach combined with novel cutting-edgeadvances in suicide and network science. We will collect intensive real-time data on AN and suicide behaviorsanxiety over-arousal emotion regulation and agitation using mobile technology as well aspsychophysiological assessment of emotion regulation (via heart-rate variability) and arousal (viaelectrodermal activity characterizing over-arousal and acceleration characterizing the sleep-wake cycle) from230 individuals with a diagnosis of AN/Atypical AN (AAN). At 1-month 6-month and one year follow-up we willtest if individual risk factors predict SI/SA. We expect 35-58 participants will have SA across our study period.Specific aims are to (1) test which symptoms and dimensions across time and between-persons maintaincomorbid SI/SA and AN symptoms (2) develop personalized network models to identify which suicide and ANfeatures predict SI/SA within individuals and an exploratory aim (3) to test if there are differences between ANand AAN. The proposed research uses highly innovative methods combining intensive longitudinal datacollection methods measurement of physiological data via wearable sensor technology and novel advances innetwork science to answer previously unresolvable questions pinpointing which individual risk factorscontribute to suicide outcomes. The proposed research has clinical impact. If we identify patterns thatcontribute to suicide risk these data will provide a model of personalized medicine for the entire field ofpsychiatry as well as providing novel intervention targets to prevent and treat AN spectrum illnesses.Additionally the algorithms we develop can be used in both (a) clinician friendly software to identify treatmenttargets to prevent SI/SA and (b) in wearable alert devices that can disrupt SA before it occurs.

project_terms:
Acceleration;Accelerometer;Adult;Affect;Agitation;Algorithms;Anorexia Nervosa;Anxiety;Arousal;Behavioral;Cause of Death;Clinical;Computer software;Data;Data Collection;Death Rate;Devices;Diagnosis;Diagnostic;Dimensions;Distal;Eating Disorders;Ecological momentary assessment;Feeling suicidal;Female;Friends;General Population;Goals;Hour;Individual;Intervention;Interview;Life;Link;Measurement;Mediator;Mental Health;Mental disorders;Methodology;Methods;Modeling;Movement;Negative Valence;Outcome;Participant;Pathology;Pathway Analysis;Pathway interactions;Pattern;Persons;Physiological;Physiology;Population;Precision Medicine Initiative;Precision therapeutics;Predictive Factor;Prevention;Prevention program;Process;Psychiatry;Psychophysiology;Reporting;Research;Resistance;Risk;Risk Factors;Science;Shapes;Skin;Sleep Wake Cycle;Sleep disturbances;Suicide;Suicide attempt;Suicide prevention;Symptoms;Testing;Thinking;Time;United States National Institutes of Health;Variant;Weight;Work;biological adaptation to stress;comorbidity;dynamic system;emotion dysregulation;emotion regulation;follow-up;handheld mobile device;heart rate variability;high risk;high risk population;ideation;improved;indexing;individualized prevention;innovation;mobile computing;mobile sensing;network models;novel;personalized medicine;prediction algorithm;prevent;psychologic;public health relevance;restrictive eating;severe mental illness;suicidal;suicidal behavior;suicidal morbidity;suicidal risk;suicide rate;theories;user-friendly;wearable device;wearable sensor technology

public_health_relevance:
PROJECT NARRATIVEThis project will identify dynamic risk factors for suicidal ideation and behaviors withinindividuals with anorexia nervosa. The proposed research has significant public healthrelevance as it will lead to personalized novel preventative efforts that disrupt suicidalbehaviors before they occur in an extremely high-risk population. The proposed research isrelevant to NIHs precision medicine initiative as it will identify within-person risk factors acrossmultiple levels of analysis leading to user-friendly personalized prevention programs andtreatments which incorporate dynamic interactions among core dimensions symptoms andphysiology of individuals.


application_id: 11166442
project_number: 5R01ES029846-07
project_title: Urban Greenness and Cardiovascular Health
administering_ic: NIEHS
award_notice_date: 2025-07-21
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: ES
serial_number: 029846
program_official: JOUBERT, BONNIE
project_start_date: 2018-07-01
project_end_date: 2029-05-31
study_section: Social and Environmental Determinants of Health Study Section[SEDH]
contact_pi_person_id: 1885223
contact_pi: BHATNAGAR, ARUNI
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:
Although the results of many studies suggest that urban greenspaces have conducive effects of health from extant data it is difficult to isolate causal links or to identify the environmental and physiological processes that contribute to the health-promoting effect of greenery. A better understanding and assessment of the health effects of urban greenness is therefore needed to optimize its public health impact. To examine the effects of greenness directly we initiated the Green Heart Project which is a community based clinical trial to test the hypothesis that increasing neighborhood greenery diminishes the risk of cardiovascular disease (CVD) by decreasing the levels of local air pollutants. In the first phase of the phase of the project we acquired baseline data on neighborhood characteristics and community health from 8 control (C) and 8 adjacent target (T) clusters of neighborhoods in Louisville KY. We acquired aerial hyperspectral and LiDAR scans of the area and conducted stationary and mobile monitoring to develop high-resolution maps of local air pollution. We conducted in-person exams to acquire baseline physical and psychosocial data. After acquiring baseline data we planted mostly evergreen mature trees and upon completion of planting we evaluated changes in pollution and reacquired health data from in-person exams. We now plan to conduct follow-up studies to determine the long-term effects of the greening intervention on the levels of air pollutants and the health of individuals living in the neighborhood. For this we assess CVD risk and psychosocialcharacteristics and collect biospecimens from the cohort every 2 years for the next 4 years to quantify the impact of changes in greenery and greenness-related neighborhood characteristics on differences in cardiovascular health. Using high-resolution hyperspectral and LiDAR imagery we will determine the effects of the greening intervention on neighborhood greenery and measure changes in air pollution temperature and noise to evaluate whether the healthful effects of greenery are related to positive changes in neighborhood characteristics. To ensure sustainability we will identify barriers and facilitators including how urban greenness is perceived used and maintained and estimate the ecosystem services provided by the increase in greenery. Successful completion of the project will lead to a rigorous and direct evaluation of the link between greenspaces and cardiovascular health. Findings of the project will help delineate the contribution of environmental psychological social and physical factors to the beneficial effects of greenery and guide the development of new strategies for increasing sustainable healthfulness of urban neighborhoods. Lessons learned from implementation and sustainability and long-term cost benefit analyses of the greening intervention could inform the development of large-scale environmental interventions to promote community health. Collectively these results could inform new public health policies and facilitate evidence-based optimization of ongoing greening efforts worldwide.

project_terms:
Air Pollutants;Air Pollution;Ancillary Study;Area;Biological Markers;Biomass;Blood;Characteristics;Clinical Data;Clinical Trials;Communities;Community Health;Cost-Benefit Analysis;Data;Data Set;Databases;Development;Ecosystem;Ensure;Environment;Environmental Exposure;Environmental Impact;Evaluation;Exposure to;Follow-Up Studies;Green space;Hair;Health;Health Policy;Health Promotion;Heart;Human;Imagery;Immunity;Income;Individual;Interruption;Intervention;Link;Long-Term Effects;Longitudinal Studies;Maps;Measures;Monitor;Nature;Neighborhoods;Noise;Observational Study;Outcome;Ozone;Persons;Phase;Physiological Processes;Plants;Pollution;Population;Public Health;Questionnaires;Research Design;Resolution;Sampling;Scanning;Selection Criteria;Series;Services;Stress;Temperature;Testing;Time;Trees;Urine;Work;arterial stiffness;cardiovascular disorder risk;cardiovascular health;cohort;community engagement;criteria air pollutant;efficacy trial;environmental intervention;epidemiologic data;evidence base;follow-up;foot;health assessment;health data;implementation facilitators;intervention effect;member;psychologic;psychosocial;racial diversity;secondary analysis;social;systemic inflammatory response;ultrafine particle;volatile organic compound

public_health_relevance:
NARRATIVEThis project is to assess the impact of urban greenspaces on community health. For this assessment weacquired health data from individuals living in a low-to-middle income neighborhoods in Louisville KY beforeand after planting a large number of mature trees and shrubs in the area. We have also acquired data on airpollution before and after the planting. We now plan to study the long-term impact of this intervention oncommunity health and the levels of air pollution in the neighborhoods.


application_id: 11166299
project_number: 5U2FFD008043-03
project_title: Kentucky's Application for RRT
administering_ic: FDA
award_notice_date: 2025-06-24
opportunity_number: RFA-FD-23-019
application_type: 5
activity_code: U2F
ic: FD
serial_number: 008043
program_official: ANDREWS, THANH
project_start_date: 2023-09-01
project_end_date: 2026-06-30
study_section: ZFD1-ORA-J(06)1
contact_pi_person_id: 79080311
contact_pi: BELL, WILLIAM 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:
Kentucky Department for Public Health-Division of Public Health Protection & Safety Food Safety Branch Project Summary/AbstractRE: Development and Maintenance of Human and Animal Food Rapid Response Teams (U2F)Clinical Trials Not Allowed (Funding Opportunity Announcement (FOA) Number RFA-FD-23-019).Kentucky has seen a rise in the number of foodborne outbreaks activations and recalls (on a national level). Inorder to maintain our current RRT structure which is designed to rapidly detect and respond to foodborneoutbreaks and other activation events we are seeking continued funding to support maintenance andenhancement of our state RRT program. Specific priorities during the 2023-2026 Period of Performance will be toextend support and develop our efforts to rapidly detect outbreaks and respond to additional activation events inorder to protect public health. Maintain and further develop our states new food complaint system so our RRTprogram can effectively and comprehensively identify and respond to previously undetected outbreaks.Kentuckys RRT structure includes a multi-agency multi-disciplinary team that operates using Incident CommandSystem (ICS)/National Incident Management System (NIMS) principles and a Unified Command structure torespond to human and animal food emergencies. Our agency aims to maintain the written framework for KY RRTSOPs and MOUs update our sustainability assessment continue organizing meetings focused on improvementwith RRT team members and mentors and learn from outbreaks to better respond to future events. To furtherthe innovation integration and national capacity development the KY RRT Program will utilize federal funding tocontinue collaborating with state partners in the development of Food Complaint Systems (FCS) modeled after theKY FCS. The KY RRT Program also intends to schedule multiple training and outreach events with stakeholders inorder to increase our capability to respond to human and animal food emergencies.The KY RRT program will enhance data sharing capacities by gathering and sharing foodborne outbreak data withrelevant KY regulatory agencies and our state/federal partners in order to protect Public Health. Outbreak datawill also be shared with local health departments (LHDs) to heighten responsiveness. Funding from this grantopportunity is aimed at supporting state and national prevention efforts in that KY RRT will enter data obtainedfrom LHD investigations into the National Environmental Assessment Reporting System (NEARS) while ourEpidemiology partners enter data into the National Outbreak Reporting System (NORS). The KY RRT Program willcommunicate its impact through outreach by providing annual presentations at the local state and national levelto meet the requirements detailed in the Funding Opportunity Announcement.

public_health_relevance:
Kentucky Department for Public Health-Division of Public Health Protection & Safety Food Safety Branch Project Narrative/Intended OutcomesRE: Development and Maintenance of Human and Animal Food Rapid Response Teams (U2F)Clinical Trials Not Allowed (Funding Opportunity Announcement (FOA) Number RFA-FD-23-019).The primary goal of the Kentucky Rapid Response Team is to minimize exposure to foodborneillnesses in the population. To meet this goal the KY RRT will maintain and expand the currentmultiagency interdisciplinary team to assist in all hazard responses including continued upkeepand development of our state Food Complaint System. This team will continue supporting theframework by providing training to state and local partners to increase their proficiency inevent response.


application_id: 11164816
project_number: 5T32AG078110-04
project_title: Training in Translational Research in Alzheimer's and Related Dementias (TRIAD)
project_terms: Alzheimer's disease related dementia;Training;Translational Research
administering_ic: NIA
award_notice_date: 2025-08-22
opportunity_number: PAR-21-112
application_type: 5
activity_code: T32
ic: AG
serial_number: 078110
program_official: CHAKROBORTY, SHREAYA
project_start_date: 2022-08-01
project_end_date: 2027-07-31
study_section: ZAG1-ZIJ-2(M2)
contact_pi_person_id: 1870576
contact_pi: VAN ELDIK, LINDA J
other_pis: MURPHY, MICHAEL PAUL
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
project_abstract:
Our T32 training program entitled Training in Translational Research In Alzheimers and Related Dementias (TRIAD) aims to provide cross-disciplinary training from bench to bedside to produce a new translational workforce that is critically needed to advance effective treatments for Alzheimers disease and related dementias (ADRD). We will continue to support 4 predoctoral and 4 postdoctoral trainees who will receive rigorous training through a transdisciplinary and integrative mentoring program that spans the discovery continuum from molecular/ biochemical methods preclinical translational approaches and clinical research. The thematic focus is on major ADRD risk factors including cerebrovascular dysfunction neuroinflammation brain injury and genetic/lifestyle risks. The 23 faculty mentors include well-funded investigators with established and extensive collaborative relationships and successful track records in training. The faculty mentors encompass varied yet complementary areas of expertise along the translational continuum from cell and molecular biology genetics and data science through preclinical model systems therapeutic development neuroimaging biomarkers neuropathology clinical trials and longitudinal clinical studies. The majority (20) of these mentors are faculty in the University of Kentucky Sanders Brown Center on Aging which includes a long-standing NIA-funded Alzheimers Disease Research Center (ADRC). The two-year training plan will emphasize 1) experiential research and learning of core competencies required to become independent leaders in clinical/ translational research 2) a tailored educational plan that emphasizes the translational continuum from basic science to clinical to community and 3) multidisciplinary mentoring from highly committed program faculty. Each trainee will develop an individualized development plan to enable advancement to independent research and funding. Trainees will participate in a structured educational program that includes a dedicated AD101 course training in the responsible conduct of research Good Research Practice training data science and workshops and seminars. Trainees will gain career development experiences through the monthly trainee-organized team meeting presentations at the annual Markesbery Symposium on Aging and Dementia and grant writing workshops. Trainees will also have the opportunity to participate in an experiential learning externship which can include an off-site training course visiting a collaborators lab to develop additional research skills or visiting another ADRC to observe/shadow/learn specific aspects based on the trainees research interests. Quantitative and qualitative metrics for evaluation of trainees mentors and the training program will assure a high-quality and effective training experience. Overall this T32 program is uniquely positioned to fill a growing need for a multidisciplinary translational research workforce with the cross-disciplinary team science skills required to conduct rigorous and cutting-edge basic translational and clinical research to develop and advance effective interventions for ADRD.

public_health_relevance:
NARRATIVEOur training program for Translational Research In Alzheimers and Related Dementias (TRIAD) willprovide predoctoral and postdoctoral trainees with the cross-disciplinary knowledge and skills needed todiscover develop and advance new treatments for Alzheimers disease and related dementias. Trainees willbe provided with expertise in cutting edge approaches from molecular methods to preclinical approaches andtranslation to clinical research. Our highly collaborative interdisciplinary and supportive team-basedenvironment at the University of Kentucky will produce the skilled workforce that is critically needed to conductbasic translational and clinical research for Alzheimers disease and related dementias.


application_id: 11164473
project_number: 5F31MH135623-02
administering_ic: NIMH
award_notice_date: 2025-09-16
opportunity_number: PA-23-271
application_type: 5
activity_code: F31
ic: MH
serial_number: 135623
program_official: SWEENEY, MARY MARGARET
project_start_date: 2024-07-28
project_end_date: 2026-07-27
study_section: Special Emphasis Panel[ZRG1-F16-H(20)L]
contact_pi_person_id: 78001613
contact_pi: FRUHBAUEROVA, MARTINA
other_pis: Not Applicable
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 ARTS AND SCIENCES
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2025-07-28
project_title:
Randomized controlled trial of a single-session mechanism-focused intervention for suicidal thoughts and behaviors

project_abstract:
Suicide is a leading cause of death in the U.S. and worldwide. The number of people who experiencesuicidal thoughts and behaviors (STBs) is even larger. Although effective for treating suicidal behaviorstraditional outpatient treatments for suicidality are time intensive. Given that the average number ofsessions attended by an individual is five suicidal individuals are unlikely to receive an adequate dose ofthese treatments. Additionally there are too few mental health clinicians and many providers are unwillingto treat suicidal individuals. To address accessibility barriers a number of brief suicide-specificinterventions have been developed. Brief interventions including single sessions reduce future suicidalbehavior and increase the likelihood of attending outpatient appointments. Extant treatments (both briefand traditional) appear to have a limited impact on suicidal ideation. However suicidal ideation as anupstream target may have an impact on suicide attempts and deaths downstream. In line with NIMHsRDoC initiative focusing on the core mechanisms that give rise to suicidal ideation may represent a morepotent and parsimonious approach to care. Ideation-to-action theories outline specific mechanisms thatcontribute to the onset and maintenance of STBs. These mechanistic theories point to a limited number ofpotentially malleable processes (i.e. hopelessness perceptions of social relatedness) that can becomethe focus of intervention yet this empirical literature has not been incorporated into treatmentdevelopment. The proposed study will compare a novel mechanism-focused Single Session Interventionfor STBs (SSI-STB) to treatment as usual (TAU) on an inpatient psychiatric unit. We aim to test whethertargeting the putative processes (hopelessness and negative perceptions of social relatedness) thatmaintain STBs indeed engages those mechanisms and consequently prevents future STBs. Theapplicant will also examine whether patients who receive the SSI-STB are more likely to attend theirfollow-up mental health appointment relative to TAU. Participants admitted for suicidal ideation and/orsuicide attempt to the inpatient psychiatric unit will be randomized to the SSI-STB or TAU conditionsreceive the intervention that corresponds to their assigned condition and will complete a post-interventionself-report assessment directly after the intervention and follow-up assessments at one week and onemonth after discharge. Results will help us address the critical need of integrating established mechanismsthat maintain suicidality into a disseminable intervention for STBs. Moreover this application describes anexcellent research environment for the proposed work supported by a collaborative mentorship team withrelevant expertise. The applicant will learn new skills in mechanism-focused treatment development. Thisclinical trial research experience will be invaluable toward the applicants goal of becoming an independentphysician/scientist.

project_terms:
Acute;Address;Admission activity;Ambulatory Care;Appointment;Automobile Driving;Behavior;Belief;Caring;Cause of Death;Clinical;Clinical Trials;Coping Skills;Data;Development;Dimensions;Dose;Environment;Feeling;Feeling hopeless;Feeling suicidal;Future;Goals;Hospitals;Individual;Inpatients;Intervention;Learning;Length;Life;Link;Literature;Maintenance;Mental Health;Mentorship;National Institute of Mental Health;Outpatients;Participant;Patient Admission;Patient Self-Report;Patients;Persons;Physicians;Process;Provider;Public Health;Randomized;Randomized Controlled Trials;Research;Research Domain Criteria;Role;Safety;Scientist;Social Perception;Suicide;Suicide attempt;Suicide prevention;Testing;Theoretical model;Thinking;Time;Uncertainty;United States;Work;acceptability and feasibility;acute care;brief intervention;career;experience;follow up assessment;follow-up;high risk;ideation;implementation intervention;improved;novel;post intervention;prevent;preventive intervention;psychiatric inpatient;reducing suicide;research and development;skills;social;suicidal;suicidal act;suicidal behavior;suicidal individual;suicidal morbidity;suicidal risk;theories;therapy development;treatment as usual;treatment disparity;treatment effect;virtual

public_health_relevance:
Suicide is a leading cause of death in the U.S. and worldwide with an even larger number of peopleexperiencing suicidal thoughts and behaviors (STBs); however extant (brief and traditional) treatmentsappear to have a limited impact on suicidal ideation. Focusing on the core mechanisms that give rise tosuicidal ideation as an upstream target that may have an impact on suicide attempts and deathsdownstream may represent a more potent and parsimonious approach to care. The proposed project willaddress the critical need of integrating established suicide-specific mechanisms that maintain suicidalideation into a disseminable intervention for STBs.


application_id: 11164232
project_number: 1R01HD118715-01
project_title: Functional Characterization of Genetic Variants in Rare Disease Associated with Shoc2 scaffold
administering_ic: NICHD
award_notice_date: 2025-04-10
opportunity_number: PAR-21-229
application_type: 1
activity_code: R01
ic: HD
serial_number: 118715
program_official: TOYAMA, REIKO
project_start_date: 2025-05-01
project_end_date: 2030-01-31
study_section: Special Emphasis Panel[ZRG1 MGG-L (02)]
contact_pi_person_id: 8586925
contact_pi: GALPERIN, EMILIA
other_pis: Not Applicable
congressional_district: 06
department: BIOCHEMISTRY
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:
SummaryMutations in the Shoc2 gene result in a developmental disorder called Noonan syndrome with loose anagenhair (NSLH) a condition affecting craniofacial features the heart the digestive system and neuraldevelopment. The Shoc2 is essential for transmitting the ERK1/2 cascade signals that control themorphogenesis of neural crest-derived tissues. Shoc2 forms intricate protein complexes to amplify intracellularsignals regulate the distribution of signaling proteins and control gene expression programs during celllineage specification. This application is led by the notion that functional analyses of different Shoc2 variants ofunknown significance identified in patients with birth defects will give important insights into the mechanisms bywhich these pathogenic variants affect cell differentiation and how these alterations lead to the variety ofphenotypes observed in NSLH patients. We will use a zebrafish vertebrate model carrying patient variants togain insights into the molecular and cellular processes altered by Shoc2 variants in neural crest-derivedlineages. This study will also examine how these variants impact Shoc2's function by dissecting its interactionswith other proteins and its localization within cells using biochemical and biophysical approaches. Results fromthis work will fill an essential gap in our understanding of the fundamental principles by which alterations ofdifferent aspects of signal transmission result in human disease with variable phenotypic outcomes. This workwill also have a broader impact on elucidating the importance of cell signaling mechanisms in craniofacialmorphogenesis.

project_terms:
Affect;Attenuated;Automobile Driving;Biochemical;Biophysics;Birth;CRISPR/Cas technology;Cell Differentiation process;Cell Lineage;Cell Physiology;Cells;Cellular biology;Cephalic;Characteristics;Child;ClinVar;Clinical;Complex;Congenital Abnormality;Darkness;Defect;Development;Diagnosis;Diagnostic;Embryonic Development;Etiology;Exhibits;Fluorescence Microscopy;Forehead;Future;Gene Expression;Genes;Goals;Guanosine Triphosphate Phosphohydrolases;Guidelines;Hair;Heart;Hereditary Disease;In Situ Hybridization;Larva;Lead;MAPK3 gene;Macrocephaly;Mediating;Missense Mutation;Modeling;Molecular;Morphogenesis;Mutation;Neural Crest;Neural Crest Cell;Noonan Syndrome;Outcome;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Persons;Phenotype;Phosphoric Monoester Hydrolases;Post-Translational Protein Processing;Prognosis;Proteins;RAF1 gene;Rare Diseases;Regulation;Reporting;Scaffolding Protein;Signal Transduction;Signaling Protein;Skin Pigmentation;Sorting;Spatial Distribution;Specific qualifier value;Supportive care;Syndrome;Systems Development;Testing;Tissues;Ubiquitination;United States;Variant;Work;Zebrafish;base;biophysical techniques;cartilage development;craniofacial;developmental disease;embryo tissue;gastrointestinal system;genetic variant;genome editing;growth hormone deficiency;high throughput technology;human disease;in vivo;insight;malformation;multipotent;neurodevelopment;novel;programs;protein complex;public database;public health relevance;scaffold;spatiotemporal;transmission process;variant of unknown significance;zebrafish genome

public_health_relevance:
Public Health Relevance StatementRare diseases collectively affect approximately 25-30 million people in the United States anddisproportionally affect children. The proposed work will result in a novel vertebrate model insights into thepathogenesis of the rare developmental disorder associated with Shoc2 variants and paraments to assessthe pathogenicity of genetic variants associated with birth defects. Ultimately this work will provide a modelfor the future development of guidelines for the diagnosis and treatment of rare disease.


application_id: 11163574
project_number: 5U54DA058256-03
project_title: AppalTRuST Biostatistics and Informatics Core
administering_ic: NIDA
award_notice_date: 2025-08-08
opportunity_number: RFA-OD-22-004
application_type: 5
activity_code: U54
ic: DA
serial_number: 058256
project_start_date: 2023-09-30
project_end_date: 2028-08-31
study_section: Special Emphasis Panel[ZRG1-ICN-R]
subproject_number: 7558
contact_pi_person_id: 8672812
contact_pi: RAYENS, MARY KAY
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:
ABSTRACT  BIOSTATISTICS AND INFORMATICS CORE The Biostatistics and Informatics Core (BIC) will serve as the AppalTRUST hub for study design and all data-related activities including data collection linkage harmonization analysis sharing and security. The core will include biostatistics and informatics experts and staff with extensive experience developing surveys managing and analyzing data and ensuring ongoing data security. Leveraging technology resources available through UK Markey Cancer Center BIC will house all the biostatistical and informatics resources and expertise needed to support AppalTRUST projects and respond to additional needs arising from future TCORS priorities. BIC Aims include: (1) support the statistical planning and analysis data collection and data coordination needs of the AppalTRUST projects and cores; (2) collaborate with the Community Outreach & Participant Engagement (COPE) Core to develop data collection instruments harmonized across projects and data collection timelines; (3) create a secure standardized and integrated AppalTRUST Data Warehouse; and (4) Provide easy-to-use tools to ensure stakeholder access to the AppalTRUST Data Warehouse and other Center information. BIC will oversee and coordinate all aspects of research design as well as data collection harmonization and analyses for all projects and pilots. Data files including structured semi-structured and unstructured data along with data dictionaries and other documentation will be managed centrally for projects pilots and cores in BIC. To facilitate the generalizability of inferential statistical analyses BIC will also develop survey weights for all participants recruited to the AppalTRUST cohort. In collaboration with COPE BIC will assist each project and pilot with coordinated development of data collection instruments to support seamless data sharing limiting response burden for participants enrolled in more than one project and promoting synergy throughout the Center. BIC will also deploy informatics portals and reporting mechanisms to make data widely accessible to stakeholders with users able to access only the data they have been authorized for commensurate with their needs. The informatics portal will include dashboards and analytical and query tools which can be customized to coincide with the level of stakeholder data access needed. State-of-the-art analytical methods and information science will support and permeate all projects pilots and cores within AppalTRUST to ensure that the TCORS successfully meets its goal of investigating FDA CTP regulatory priorities in Appalachian Kentucky through collaboration education and pioneering regulatory science research.

project_terms:
Appalachian Region;Area;Authorization documentation;Biometry;Biostatistics Core;Cancer Center;Characteristics;Cities;Collaborations;Community Outreach;County;Data;Data Collection;Data Files;Data Mart;Data Security;Development;Documentation;Education;Ensure;Future;Goals;Informatics;Information Centers;Information Dissemination;Information Sciences;Kentucky;Measures;Participant;Patient Recruitments;PhenX Toolkit;Pilot Projects;Probability;Probability Samples;Reporting;Research;Research Design;Resource Informatics;Resources;Rural Community;Sampling;Science;Secure;Security;Staging;Standardization;Statistical Data Interpretation;Structure;Surveys;Technology;Weight;Work;analytical method;analytical tool;career;cohort;community collaboration;dashboard;data access;data dictionary;data format;data infrastructure;data integration;data sharing;data standards;data warehouse;experience;instrument;low socioeconomic status;participant enrollment;patient engagement;peri-urban;query tools;recruit;response;rural area;rural counties;structured data;synergism;timeline;tobacco products;tobacco regulatory science;tool;unstructured data;web site


application_id: 11163573
project_number: 5U54DA058256-03
project_title: AppalTRuST Community Outreach and Participant Engagement Core
administering_ic: NIDA
award_notice_date: 2025-08-08
opportunity_number: RFA-OD-22-004
application_type: 5
activity_code: U54
ic: DA
serial_number: 058256
project_start_date: 2023-09-30
project_end_date: 2028-08-31
study_section: Special Emphasis Panel[ZRG1-ICN-R]
subproject_number: 7557
contact_pi_person_id: 8310976
contact_pi: HULL, PAMELA CARMEN
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:
ABSTRACT  COMMUNITY OUTREACH AND PARTICIPANT ENGAGEMENT (COPE) CORE The Community Outreach and Participant Engagement (COPE) Core will recruit and retain the AppalTRUST Cohort of 2000 adults (ages 18+) in Appalachian Kentucky (KY) including a) an address-based probability sample (PS) of 1000 participants; and b) a quota-based non-probability sample (NPS) of 1000 participants. The Biostatistics and Informatics Core (BIC) will use statistical methods to combine them. Project 1 will use the full AppalTRUST Cohort (N=2000) providing an adequate sample to capture estimates of tobacco use behaviors (e.g. initiation switching transitions) over time among subpopulations of interest (e.g. young adults tobacco users). Project 2 (n=308 ages 18-24) and Project 3 (n=473 tobacco users ages 21+) will draw from the Cohort. All projects pilots and TCORS partners will have access to the Cohort data through our AppalTRUST Data Warehouse.  Using established rural/urban taxonomies we selected heterogeneous counties that make up a rural catchment of 5 counties and a peri-urban (i.e. intermediate and smaller cities and towns) catchment of 3 counties enabling projects to assess contextual- and individual-level effects of rurality on outcomes enhancing innovation and our ability to inform effective FDA regulations for these areas. COPE Aims are to: (1) develop and implement a culturally tailored community-engaged outreach campaign to promote participation in the AppalTRUST Cohort; (2) implement strategic recruitment and baseline data collection for the AppalTRUST Cohort (Project 1) and recruitment into the other projects and pilot studies; (3) implement strategic retention strategies and administer 6-month follow-up surveys; and (4) disseminate AppalTRUST research findings to the community to sustain support and retention.  COPE will co-design a community outreach campaign with two community advisory boards (one per catchment) with promotional materials tailored for Appalachian KY that are strategically disseminated to reach subpopulations of interest (e.g. tobacco users). COPE will hire train and monitor local field staff to recruit and enroll participants into the AppalTRUST Cohort and manage completion of 6-month follow-up surveys. Cohort participants will complete 3 to 8 surveys depending on time of enrollment in Project 1. Multiple strategies will maximize retention including our community outreach campaign and monthly contact between participants and field staff. Our community dissemination plan will report back AppalTRUST study findings to sustain community support and Cohort retention. The innovative approaches implemented by COPE will support AppalTRUST in closing a critical knowledge gap in rural tobacco use behaviors marketing and impact analysis to help shape effective FDA regulations for this region.

project_terms:
Address;Adult;Age;Appalachian Region;Area;Back;Behavior;Biometry;Calibration;Cities;Communities;Community Outreach;County;Data;Data Collection;Devices;Electronic Mail;Electronics;Enrollment;Ensure;Fostering;Future;Goals;Heterogeneity;Home;Individual;Informatics;Interview;Kentucky;Knowledge;Libraries;Longitudinal Studies;Marketing;Mass Media;Monitor;Outcome;Participant;Pattern;Persons;Pilot Projects;Printing;Probability Samples;Regulation;Reporting;Research;Research Project Grants;Rural;Rural Appalachia;Rural Community;Rural Population;Sampling;Services;Shapes;Statistical Methods;Surveys;System;Taxonomy;Telephone;Text;Time;Tobacco use;Training;Trust;Update;Variant;Visit;Work;Writing;cohort;community advisory board;community engaged research;contextual factors;cost efficient;data resource;data warehouse;design;digital;eligible participant;follow-up;innovation;insight;interest;low health literacy;meetings;outreach;participant enrollment;participant retention;patient engagement;peri-urban;recruit;retention rate;rurality;social media;tobacco regulation;tobacco regulatory science;tobacco user;web site;young adult


application_id: 11163572
project_number: 5U54DA058256-03
project_title: AppalTRuST Career Enhancement Core
administering_ic: NIDA
award_notice_date: 2025-08-08
opportunity_number: RFA-OD-22-004
application_type: 5
activity_code: U54
ic: DA
serial_number: 058256
project_start_date: 2023-09-30
project_end_date: 2028-08-31
study_section: Special Emphasis Panel[ZRG1-ICN-R]
subproject_number: 7556
contact_pi_person_id: 9641889
contact_pi: ASHFORD, KRISTIN H.
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:
ABSTRACT  CAREER ENHANCEMENT CORE The need for researchers who understand Tobacco Regulatory Science (TRS) and can translate science to support effective regulatory policies is vital for rural communities which have some of the highest tobacco use and associated morbidity rates in the nation. The goal of the AppalTRUST Career Enhancement Core (CEC) is to create a transformative environment that provides mentored multidisciplinary and immersive career enhancement experiences to expand and support TRS scholars with a critical emphasis on the impact of regulatory policies in rural communities. The CEC will target inquisitive and dedicated scholars with varied professional and disciplinary backgrounds and high potential to become independent TRS researchers.  Building on Center expertise we will recruit two cohorts of AppalTRUST Scholars each consisting of two Faculty Scholars and two Postdoctoral Scholars. These AppalTRUST Scholars will be recruited for a two-year non-overlapping experience. Each scholar will work with a mentoring team and participate in multidisciplinary TRS enrichment activities enjoying close monitoring of progress toward scientific career independence. Specifically AppalTRUST Scholars will receive personalized mentoring and career enhancement experiences through cohort-building multidisciplinary TRS enrichment activities including weekly meetings seminars journal clubs and a NIH-modeled grant writing series of workshops. AppalTRUST Scholars will also receive hands-on experience in TRS research working as part of the research team of one of three AppalTRUST projects and then developing their own (Scholar-led) TRS pilot project. AppalTRUST Scholars will benefit from the Cross-TCORS Visiting Scholars Program that will introduce them to scientific domains outside of AppalTRUST and promote collaborative networks among other TCORS investigators. CEC will work closely with Project Leads the Administrative Core the Community Outreach and Participant Engagement Core (COPE) and the Biostatistics and Informatics Core (BIC) to ensure AppalTRUST Scholars have ample resources and opportunities to learn innovative methodologies applied to the rural context. Finally CEC will collaborate with the Administrative Core to sponsor an AppalTRUST TRS Seminar Series. Four times a year CEC will host these seminars to create collegial and collaborative networks. We will specifically invite FDA scientists and TCORS faculty and scholars from other TCORS to present and inform AppalTRUST researchers and the broader TRS community about synergistic opportunities methodologic advances and new research findings across the TCORS community. The seminars will be open to all as they will be streamed recorded and archived on the AppalTRUST website.

project_terms:
Address;Appalachian Region;Archives;Area;Behavior;Biometry;Charge;Collaborations;Communities;Community Outreach;Decision Making;Dedications;Development;Educational workshop;Ensure;Environment;Faculty;Foundations;Funding Mechanisms;Goals;Grant;Growth;Heterogeneity;Informatics;Journals;Lead;Learning;Marketing;Menthol;Mentors;Methodology;Modeling;Monitor;Morbidity - disease rate;Nicotine;Pilot Projects;Policies;Postdoctoral Fellow;Research;Research Design;Research Methodology;Research Personnel;Resources;Rural;Rural Appalachia;Rural Community;Scholars Program;Science;Science Enrichment;Scientist;Series;Stream;Talents;Tobacco;Tobacco use;Translating;Translations;United States National Institutes of Health;Work;Writing;behavioral economics;career;cohort;community partnership;design;experience;hands on research;innovation;interest;meetings;mortality;multidisciplinary;next generation;patient engagement;programs;recruit;rural area;skills;tobacco products;tobacco regulatory science;visiting scholar;web site


application_id: 11163571
project_number: 5U54DA058256-03
project_title: AppalTRuST Administrative Core
administering_ic: NIDA
award_notice_date: 2025-08-08
opportunity_number: RFA-OD-22-004
application_type: 5
activity_code: U54
ic: DA
serial_number: 058256
project_start_date: 2023-09-30
project_end_date: 2028-08-31
study_section: Special Emphasis Panel[ZRG1-ICN-R]
subproject_number: 7555
contact_pi_person_id: 7602351
contact_pi: HIMELHOCH, SETH S
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:
ABSTRACT  ADMINISTRATIVE CORE The Administrative Core (Admin Core) will provide leadership and communications infrastructure strategic planning and financial management to facilitate the work of all AppalTRUST components as well as advance collaboration with the wider TCORS community. AppalTRUSTs overarching goal is to investigate the impact of US Food and Drug Administration Center for Tobacco Products (FDA CTP) regulatory policies in rural communities through collaboration education and pioneering tobacco regulatory science (TRS). Specifically the Admin Core will provide scientific oversight by fostering shared knowledge and maximizing interactions to ensure scientific rigor and transparency. The Admin Core will lead an Executive Committee meeting twice per month with all Project PIs and Core Leaders. To ensure representation engagement and input from the study communities in Appalachian KY the Admin Core will collaborate with Community Outreach and Participant Engagement (COPE) Core to ensure our two Community Advisory Boards are fully engaged in Center decision-making. To advance educational collaboration and maximize interactions with the wider TCORS community and Federal partners the Admin Core will work with the Career Enhancement Core (CEC) to sponsor a quarterly AppalTRUST TRS Seminar Series to engage the TCORS community and share synergistic opportunities methodologic advances and new research findings. The Admin Core will also collaborate with the CEC to sponsor an AppalTRUST Visiting Scholar Program to allow faculty and/or trainees from other TCORS to participate in a one-week in-depth learning experience in rural TRS. To provide quality control and evaluation across projects and cores the Admin Core alongside the Biostatistics and Informatics Core (BIC) and COPE will oversee a monthly quality control and evaluation meeting to foster seamless tracking and coordinating of all activities recruitment participant flow data collection and data management. To provide administrative oversight the Admin Core will guide and coordinate internal and external communications and coordination financial planning and management as well as the research and grants administrative processes. An External Advisory Board made up of leading scientific experts will meet annually to provide critical counsel and ensure the Center is meeting its stated goals. An Internal Advisory Board of key University scientific and administrative stakeholders will meet annually to provide counsel and advice and ensure AppalTRUST is able to effectively leverage UK and community resources to meet its goals. Impact: The Admin Core will provide the necessary organization and leadership to ensure an efficient collaborative infrastructure that will enhance synergies across AppalTRUST as well as advance collaboration with the wider TCORS community. Given that Appalachia is a rural region disproportionately impacted by socioeconomic disadvantage and tobacco use the Admin Core will lead AppalTRUST in closing a critical knowledge gap in rural tobacco use behaviors marketing and impact analysis to help shape effective FDA regulations for these communities.

project_terms:
Address;Administrator;Appalachian Region;Applications Grants;Behavior;Behavioral;Biometry;Clinical;Collaborations;Communication;Communities;Community Outreach;Coordination and Collaboration;Counseling;Data Collection;Decision Making;Education;Electronic cigarette;Ensure;Environment;Evaluation;Faculty;Fostering;Funding;Goals;Grant;Informatics;Infrastructure;Kentucky;Knowledge;Lead;Leadership;Learning;Marketing;Medicine;Menthol;Methodology;Nicotine;Nicotine Dependence;Nursing Faculty;Occupational activity of managing finances;Oral;Paper;Participant;Pilot Projects;Policies;Process;Publishing;Quality Control;Recommendation;Regulation;Reporting;Research;Research Personnel;Resources;Rural;Rural Community;Scholars Program;Science;Series;Shapes;Strategic Planning;Structure;Tobacco;Tobacco use;United States Food and Drug Administration;United States National Institutes of Health;Universities;Variant;Water;Work;Writing;career;cigarette smoking;college;combustible tobacco;community advisory board;community collaboration;data management;design;experience;improved;innovation;low nicotine content cigarette;meetings;novel;operation;patient engagement;polytobacco use;programs;recruit;rural area;rurality;scientific atmosphere;skills;socioeconomic disadvantage;synergism;tobacco products;tobacco regulatory science;visiting scholar


application_id: 11163568
project_number: 5U54DA058256-03
administering_ic: NIDA
award_notice_date: 2025-08-08
opportunity_number: RFA-OD-22-004
application_type: 5
activity_code: U54
ic: DA
serial_number: 058256
project_start_date: 2023-09-30
project_end_date: 2028-08-31
study_section: Special Emphasis Panel[ZRG1-ICN-R]
subproject_number: 7554
contact_pi_person_id: 10316536
contact_pi: KOFFARNUS, MIKHAIL NIKOLAAS
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: 2025-09-01
project_title:
AppalTRuST Project 3: Impact of proposed tobacco product rules in Appalachia on consumption and product switching with the Experimental Tobacco Marketplace

project_abstract:
ABSTRACT  Project 3 Our overall goal reflecting AppalTRUSTs Integrative Theme of investigating the effects of regulatory changes on tobacco product use in Appalachian KY is to assess the impact of proposed tobacco product regulations using behavioral economic methods that we have developed and refined in past years to characterize the consumption of tobacco products within the complex nicotine marketplace of Appalachian KY a rural region that would greatly benefit from focused tobacco regulatory science research. This project primarily falls under the Regulatory Scientific Domain of Impact Analysis. In 2009 the US Food and Drug Administration (FDA) was granted authority to regulate tobacco products to benefit public health. In the years since the FDA has proposed potential regulatory actions that may benefit public health including regulating the maximum nicotine content in combustible cigarettes and restricting flavors of combusted and noncombusted tobacco products. Estimating the impact of any proposed regulatory action is complicated by the existence of a complex tobacco marketplace containing multiple products that are economic substitutes for one another and the frequent introduction of new tobacco products by manufacturers. Furthermore when compared to more urban non-Appalachian communities rural Appalachian communities often have 1) higher rates of tobacco product use overall 2) different use patterns that include more combusted tobacco products and 3) different product availability in tobacco stores. It is therefore important to estimate any differential impact of proposed tobacco-product regulations in Appalachia. Using an Experimental Tobacco Marketplace (ETM) model where product availability is manipulated across groups and demand elasticity and substitution is measured across tobacco products we will estimate the impact of regulating 1) nicotine content of combusted cigarettes 2) menthol flavor restrictions in combustible cigarettes and 3) flavor additive restrictions in noncombusted nicotine/tobacco products including ENDS. Across two aims we will assess the impact of these three regulations within Appalachia (Aim 1) and the effect of rurality on impact of these proposed regulations in Appalachia (Aim 2).

project_terms:
Appalachian Region;Behavior;Biometry;Catchment Area;Cigarette;Cities;Communities;Community Outreach;Complex;Consumption;Data;Economics;Elasticity;Environment;Goals;Grant;Heterogeneity;Informatics;Manufacturer;Measures;Menthol;Methods;Modeling;Nicotine;Participant;Pattern;Policies;Price;Public Health;Randomized;Recommendation;Regulation;Research;Rural;Rural Appalachia;Rural Community;Sampling;Taxation;Tobacco;Tobacco use;United States Food and Drug Administration;Variant;abuse liability;authority;behavioral economics;combustible cigarette;design;falls;low nicotine content cigarette;nicotine user;patient engagement;peri-urban;prospective;recruit;rural area;rurality;tobacco products;tobacco regulation;tobacco regulatory science;urban area


application_id: 11163566
project_number: 5U54DA058256-03
administering_ic: NIDA
award_notice_date: 2025-08-08
opportunity_number: RFA-OD-22-004
application_type: 5
activity_code: U54
ic: DA
serial_number: 058256
project_start_date: 2023-09-30
project_end_date: 2028-08-31
study_section: Special Emphasis Panel[ZRG1-ICN-R]
subproject_number: 7553
contact_pi_person_id: 11156218
contact_pi: ROSE, SHYANIKA W
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: 2025-09-01
project_title:
AppalTRuST Project 2: Exposure to tobacco marketing for novel tobacco products and associations with future tobacco use in Appalachian young adults: tobacco regulatory science implications

project_abstract:
ABSTRACT  Project 2 FFederal tobacco regulatory policies enacted by the US Food and Drug Administration (FDA) are critical to curb the tobacco epidemic in rural Appalachia and reduce cancer burden. Kentucky (KY) is 50th in the nation for adult smoking rates with 21.4% of KY adults smoking cigarettes a rate not seen nationally in 20 years. Kentucky also has wide geographic differences between rural and urban residents particularly in Appalachian KY an area characterized by low SES. In this context Federal policies can be particularly influential in areas with weak tobacco control policies and high rates of tobacco use. In particular (1) the introduction of novel non-combustible products (2) product standards on flavored cigars/menthol cigarettes and (3) lowering nicotine in cigarettes have great potential to shift the tobacco marketplace moving rural Appalachian residents to quit smoking switch to potentially less harmful products or never initiate tobacco use at all. Project 2 seeks to expand the evidence base about the extent to which marketing exposure tobacco use behaviors and attitude towards tobacco products differ across rural communities and the extent to which regulatory actions by the FDA can potentially reduce use of tobacco among young adults in these areas. Additionally few studies examine how the retail environment novel products and potential policies could interact to reduce tobacco-related health problems among young adult populations by rurality. Tobacco retailer density is higher in rural areas by population but little is known about how retailers market in stores in this region. The purpose of the study is to examine how marketing and product availability of such novel tobacco products may change over time and how these patterns may influence tobacco use attitudes and patterns in rural communities providing guidance on future policy targets. To accomplish the study purpose we will conduct several aims. (1) We will assess marketing trends over time in retail store and digital audits (store websites and social media) in tobacco retailers in 2 rural catchment areas of KY. (2) We will compare marketing exposure to and appeal and harm perceptions of novel products in young adults through ecological momentary assessment (EMA) evaluating differences by rurality at the individual and census tract level. (3) Finally among EMA participants we will assess the predictive validity of exposure to novel product marketing exposure on use of tobacco at 6-month and 12-month follow-up and evaluate whether these outcomes are associated with rurality. For all of these activities we will partner closely with the AppalTRUST team cores and local community advisory boards to disseminate lessons learned to communities about industry actions and potential regulatory policies. Achieving the aims of this Project will expand the evidence base of the potential impacts of FDA policies on reducing tobacco use and potential geographic impact of these policies to reduce tobacco use and ultimately reduce cancer and other tobacco-related diseases.

project_terms:
Adult;Advertising;Affect;Age;Appalachian Region;Area;Attitude;Authorization documentation;Baseline Surveys;Behavior;Cancer Burden;Catchment Area;Censuses;Cigar;Cigarette;Cities;Communities;County;Data;Disease;Ecological momentary assessment;Electronic cigarette;Environment;Epidemic;Exposure to;Frequencies;Future;Geography;Goals;Health;Individual;Industry;Influentials;Kentucky;Link;Malignant Neoplasms;Marketing;Menthol;Modified Risk Tobacco Product;Nicotine;Outcome;Participant;Patient Self-Report;Pattern;Perception;Persuasive Communication;Policies;Population;Population Density;Predisposition;Prevalence;Price;Regulation;Reporting;Research;Risk;Rural;Rural Appalachia;Rural Community;Rural Population;Sampling;Smokeless Tobacco;Smoking;Source;Time;Time trend;Tobacco;Tobacco use;United States Food and Drug Administration;Work;age group;community advisory board;density;digital;electronic liquid;evidence base;experience;federal policy;follow-up;geographic difference;innovation;low nicotine content cigarette;low socioeconomic status;novel;peri-urban;public policy on tobacco;reduce tobacco use;response;rural area;rural counties;rurality;smoking cessation;social media;theories;tobacco advertising;tobacco exposure;tobacco flavor;tobacco products;tobacco regulation;tobacco regulatory science;tobacco user;urban area;web site;young adult


application_id: 11163563
project_number: 5U54DA058256-03
project_title: AppalTRuST Project 1: Population based Cohort study of tobacco use prevalence in Appalachian KY
administering_ic: NIDA
award_notice_date: 2025-08-08
opportunity_number: RFA-OD-22-004
application_type: 5
activity_code: U54
ic: DA
serial_number: 058256
project_start_date: 2023-09-30
project_end_date: 2028-08-31
study_section: Special Emphasis Panel[ZRG1-ICN-R]
subproject_number: 7552
contact_pi_person_id: 8672812
contact_pi: RAYENS, MARY KAY
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:
ABSTRACT  PROJECT 1 Rural populations which use tobacco at almost double national rates have largely been omitted from studies of the potential impact of tobacco regulations. AppalTRUSTs overarching goal is to investigate the impact of US Food and Drug Administration Center for Tobacco Products (FDA CTP) regulatory changes on tobacco product use in rural communities and examine variation based on relative rurality. The FDA regulatory policies have an outsized potential to reduce tobacco use in rural Appalachia and the rest of rural America given the relatively limited disincentives for use in these areas (i.e. few smoke-free laws and low tobacco taxes). The goal of Project 1 (P1) is to close the rural tobacco use knowledge gap by documenting tobacco use behaviors and related factors over time among Appalachian KY adults (18+ years) to inform current and future FDA regulations. P1 addresses the Scientific Domain of Behavior and will be guided by the Health Belief Model (HBM). The HBM provides a framework to evaluate associations of knowledge attitudes perceptions and external cues with tobacco use behaviors. P1 will use the AppalTRUST Cohort to enroll 2000 participants using a longitudinal cohort design that will collect participant data every 6 months for four years. We will recruit adults 18+ years from two catchment areas comprising 8 Appalachian KY counties; these two areas represent a range of rurality and will allow us to make not only catchment comparisons between a rural area and peri-urban one (i.e. partly urbanized rural areas) but also to assess for associations between tobacco use indicators and relative rurality within each catchment area. In addition 40 participants from the Cohort per year will complete key informant interviews to assess opinions about tobacco products and regulations and allow us to make annual updates to the survey. We will address the following aims: (1) evaluate baseline prevalence and longitudinal trends in the use of conventional (cigarettes smokeless tobacco hookah cigars/cigarillos and pipes) and novel (e-cigarettes nicotine pouches heated tobacco products and very low nicotine [VLN] cigarettes) tobacco products including initiation continuation switching cessation and dual/poly-use among Appalachian adults testing for the effect of rurality and controlling for individual- and county-level demographics; (2) assess changes over time in knowledge attitudes and perceptions relative to tobacco product characteristics (including flavors/menthol and VLN) among Appalachian KY adults while evaluating the effect of rurality and controlling for demographics; and (3) explore perceived benefits risks and intentions to use novel tobacco products among current tobacco product users and individuals susceptible to initiating novel product use with annual key informant interviews to capture reaction to changes in the product and regulatory landscape. We will evaluate the effects of the introduction of novel products and potential restrictions on flavored and high-nicotine products in rural communities so that regulatory decisions will be effective in these communities and be guided by a definition of rurality that is heterogeneous.

project_terms:
Address;Adult;Appalachian Region;Area;Attitude;Behavior;Catchment Area;Censuses;Characteristics;Cigar;Cigarette;Cities;Cohort Studies;Communities;County;Cues;Data;Disincentive;Electronic cigarette;Enrollment;Funding;Future;Geographic Locations;Goals;Health;Heterogeneity;Income;Individual;Interview;Kentucky;Knowledge;Longitudinal Studies;Longitudinal cohort;Longitudinal trends;Marketing;Masks;Measures;Menthol;Methods;Modeling;Nicotine;Participant;Pattern;Perception;Policies;Positioning Attribute;Predisposition;Prevalence;Productivity;Publications;Reaction;Recording of previous events;Regulation;Research;Resources;Rest;Risk;Rural;Rural Appalachia;Rural Community;Rural Population;Shapes;Smokeless;Smokeless Tobacco;Surveys;Taxes;Testing;Time;Tobacco;Tobacco use;United States Food and Drug Administration;United States National Institutes of Health;Update;Urbanization;Variant;Visit;cigarette smoking;cigarillos;cohort;demographics;density;design;electronic cigarette use;health belief;heated tobacco products;hookah;informant;innovation;insight;low nicotine content cigarette;multidisciplinary;novel;peri-urban;policy implication;population based;recruit;reduce tobacco use;residence;rural America;rural area;rurality;smoke-free policy;tobacco products;tobacco regulation;tobacco regulatory science;urban area


application_id: 11163562
project_number: 5U54DA058256-03
project_title: Appalachian Tobacco Regulatory Science Team (AppalTRuST)
administering_ic: NIDA
award_notice_date: 2025-08-08
opportunity_number: RFA-OD-22-004
application_type: 5
activity_code: U54
ic: DA
serial_number: 058256
program_official: CREAMER, MELISA RAY
project_start_date: 2023-09-30
project_end_date: 2028-08-31
study_section: Special Emphasis Panel[ZRG1-ICN-R(50)R]
contact_pi_person_id: 11156218
contact_pi: ROSE, SHYANIKA W
other_pis: HIMELHOCH, SETH S;KOFFARNUS, MIKHAIL NIKOLAAS
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
project_abstract:
Our overall goal reflecting AppalTRUSTs Integrative Theme of investigating the effects of regulatory changes on tobacco product use in Appalachian KY is to assess the impact of proposed tobacco product regulations using behavioral economic methods that we have developed and refined in past years to characterize the consumption of tobacco products within the complex nicotine marketplace of Appalachian KY a rural region that would greatly benefit from focused tobacco regulatory science research. This project primarily falls under the Regulatory Scientific Domain of Impact Analysis. In 2009 the US Food and Drug Administration (FDA) was granted authority to regulate tobacco products to benefit public health. In the years since the FDA has proposed potential regulatory actions that may benefit public health including regulating the maximum nicotine content in combustible cigarettes and restricting flavors of combusted and noncombusted tobacco products. Estimating the impact of any proposed regulatory action is complicated by the existence of a complex tobacco marketplace containing multiple products that are economic substitutes for one another and the frequent introduction of new tobacco products by manufacturers. Furthermore when compared to more urban non-Appalachian communities rural Appalachian communities often have 1) higher rates of tobacco product use overall 2) different use patterns that include more combusted tobacco products and 3) different product availability in tobacco stores. It is therefore important to estimate any differential impact of proposed tobacco-product regulations in Appalachia. Using an Experimental Tobacco Marketplace (ETM) model where product availability is manipulated across groups and demand elasticity and substitution is measured across tobacco products we will estimate the impact of regulating 1) nicotine content of combusted cigarettes 2) menthol flavor restrictions in combustible cigarettes and 3) flavor additive restrictions in noncombusted nicotine/tobacco products including ENDS. Across two aims we will assess the impact of these three regulations within Appalachia (Aim 1) and the effect of rurality on impact of these proposed regulations in Appalachia (Aim 2).

project_terms:
Appalachian Region;Behavior;Biometry;Catchment Area;Cigarette;Cities;Collaborations;Communities;Community Outreach;Complex;Consumption;Data;Disparity;Economics;Education;Elasticity;Environment;Future;Goals;Grant;Heterogeneity;Informatics;Knowledge;Manufacturer;Measures;Menthol;Methods;Modeling;Nicotine;Participant;Pattern;Policies;Price;Public Health;Randomized;Recommendation;Regulation;Research;Rural;Rural Appalachia;Rural Community;Sampling;Shapes;Taxation;Tobacco;Tobacco use;United States Food and Drug Administration;Variant;abuse liability;authority;behavioral economics;combustible cigarette;design;falls;low nicotine content cigarette;nicotine user;patient engagement;peri-urban;prospective;recruit;rural area;rurality;tobacco products;tobacco regulation;tobacco regulatory science;urban area

public_health_relevance:
The Appalachian Tobacco Regulatory Research Team (AppalTRUST) will investigate the impact of US Food and Drug Administration Center for Tobacco Products (FDA CTP) regulatory policies in rural communities through collaboration education and pioneering regulatory scientific research. Our three projects and four cores are designed to bridge the knowledge gap in rural tobacco use behaviors guided by a definition of rurality that accounts for heterogeneity. Our approach is designed to inform the shaping of current proposed and future FDA regulatory actions to reduce rural tobacco use disparities.


application_id: 11163439
project_number: 5R01AI167297-05
project_title: HDAC6 regulation of myeloid cell responses in sepsis
administering_ic: NIAID
award_notice_date: 2025-08-25
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: AI
serial_number: 167297
program_official: MINNICOZZI, MICHAEL
project_start_date: 2021-09-17
project_end_date: 2026-08-31
study_section: Special Emphasis Panel[ZRG1-IDIA-E(02)M]
contact_pi_person_id: 8693493
contact_pi: FU, JIAN
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 SummarySepsis is a life-threatening disease caused by dysregulated host responses to infection. Sepsisremains a major health problem worldwide with high mortality. Myeloid cell responses such asendotoxin tolerance epigenetic modification metabolic failure and apoptosis are profoundlyaffected in sepsis which leads to systemic dysfunction of immune cells and progenitor cells. Theregulation of myeloid cell responses in sepsis remains largely unknown. The histone deacetylaseHDAC6 regulates a variety of cellular responses. However HDAC6 regulation of myeloid cellresponses in sepsis has not been investigated. Our preliminary studies indicate that HDAC6 is akey mediator of cell signaling in myeloid cells. Myeloid-specific HDAC6 deletion reduces themortality in septic mice. Furthermore selective HDAC6 inhibition can modulate myeloid cellresponses in the mouse models of sepsis. In the proposed studies we will test the hypothesisthat HDAC6 activation mediates myeloid cell dysfunction in sepsis and HDAC6 inhibition couldimprove myeloid cell function and survival rate in sepsis.

project_terms:
Acetylation;Affect;Apoptosis;Bacteria;Cell Differentiation process;Cell Physiology;Cell Survival;Cells;Clinical Trials;Cytoskeleton;Deacetylation;Development;Disease;Endotoxins;Epigenetic Process;Failure;Functional disorder;Future;Generations;Genetic Transcription;HDAC6 gene;Health;Histone Deacetylase;IRF1 gene;Immune;Immune System Diseases;Immune response;Infection;Inflammation;Inflammatory;Interferons;Life;Macrophage;Mediating;Mediator;Metabolic;Microtubule Stabilization;Microtubules;Modification;Mus;Myelogenous;Myeloid Cells;Myeloid Progenitor Cells;Myeloid-derived suppressor cells;Pathway interactions;Phenotype;Play;Regulation;Reporting;Role;STAT1 gene;Sepsis;Signal Transduction;Suppressor-Effector T-Lymphocytes;Survival Rate;Testing;Therapeutic;Therapeutic Effect;hematopoietic stem cell expansion;immunoregulation;improved;mortality;mouse model;novel;response;septic;stem cells;transcriptomics; Tubulin

public_health_relevance:
Project NarrativeSuccessful completion of the proposed studies will reveal a novel role of HDAC6 in the regulationof myeloid cell immune responses in sepsis. The studies will validate the therapeutic potential ofHDAC6 inhibition to improve myeloid cell function in sepsis. The proposed studies will provideimportant information for future clinical trials.


application_id: 11163298
project_number: 5R00AI166116-05
project_title: Bacterial anti-inflammatory lipid mediators
administering_ic: NIAID
award_notice_date: 2025-08-21
opportunity_number: PAR-19-343
application_type: 5
activity_code: R00
ic: AI
serial_number: 166116
program_official: GONDRE-LEWIS, TIMOTHY A
project_start_date: 2022-02-17
project_end_date: 2026-08-31
study_section: NSS
contact_pi_person_id: 14354764
contact_pi: RADKA, CHRISTOPHER DAVID
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 SummaryThe rapid response of the innate immune system to infections relies on the detection of pathogen-associatedmolecular patterns (PAMPs) such as lipopolysaccharides that activate a robust inflammatory response toinvading organisms. My research program focuses on an unappreciated countermeasure deployed bycommensal bacteria and pathogens that attenuates the immune response to PAMPs. Oleate hydratase (OhyA)is an enzyme that is expressed in commensal bacteria and the important human pathogen Staphylococcusaureus. OhyA stereospecifically hydrates the 9-cis double bond of unsaturated fatty acids to produce 10-hydroxy-fatty acids (hFAs); however bacteria expressing OhyA do not synthesize unsaturated fatty acids.OhyA substrates are only encountered at the interface of host tissues where unsaturated fatty acids areabundant. I hypothesize that hFAs produced by commensal or pathogenic organisms serve as signalingmolecules that blunt the innate immune response to PAMPs. Indeed S. aureus ohyA knockouts fail toestablish infections in mice illustrating the importance of OhyA and hFAs to S. aureus virulence. Thus hFAswhich were first discovered in the gut microbiome may provide an important mechanism for commensalbacteria to attenuate gastrointestinal inflammation and create tolerant symbiotic environments. My pilotexperiments and some previous reports provide preliminary evidence for the anti-inflammatory action of hFAsbut the mechanism(s) of immune suppression by hFAs are unknown. To address this shortcoming I willreceive formal immunology instruction through coursework and hands-on training in the laboratory of Dr. PaulThomas an expert immunologist during the K99 phase. We will determine whether hFAs directly antagonizeextracellular PAMP binding to immune cell receptors bind to CD1 lipid-presenting molecules for T-cell receptorrecognition to antagonize T cell activation or intercept signaling downstream of PAMP-receptor activation bystimulating G-protein coupled receptors and/or PAPR. The results of these experiments will uncover themechanistic basis for hFA modification of immune cell responses. OhyA has no mammalian homolog andvalidating the importance of OhyA for virulence coupled with the X-ray structures of OhyA will provide the keyinformation required to determine whether OhyA is a candidate target for antimicrobial drug discovery. Duringthe R00 phase I will test the hypothesis that OhyA is packaged into extracellular vesicles released by S.aureus to interact with surrounding host tissues to form a halo of hFA mediators around the infection site. Myfindings will provide an atomistic mechanistic understanding of how OhyA binds to and influences membranestructure to promote vesicle formation. The K99/R00 research plan is designed to leverage my expertise inbiochemistry and structural biology while receiving new training in immunology to advance the understandingof immune regulation by bacteria and launch a productive and successful career in which I will lead a researchprogram to elucidate the role bacteria lipid products play in controlling host responses.

project_terms:
Address;Anti-Inflammatory Agents;Area;Arrestins;Attenuated;Bacteria;Bacterial Infections;Bifidobacterium;Binding;Biochemical;Biochemistry;Biological Assay;CD1 Antigens;Cell Culture Techniques;Cells;Complement;Coupled;Cryoelectron Microscopy;Encapsulated;Environment;Enzymes;Fatty Acids;Flow Cytometry;Foundations;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Genetic Transcription;Goals;Homologous Gene;Hydration status;Hydroxylation;Immune;Immune Evasion;Immune response;Immune signaling;Immunologics;Immunologist;Immunology;Immunosuppression;Infection;Infectious Skin Diseases;Inflammation;Inflammatory Response;Innate Immune Response;Innate Immune System;Instruction;Intercept;Intestines;Invaded;Investigation;Knock-out;Laboratories;Lead;Life;Ligand Binding;Lipids;Lipopolysaccharides;Lipoproteins;Luciferases;Mammalian Cell;Measures;Mediating;Mediator;Membrane;Mentors;Modeling;Modification;Molecular;Molecular Conformation;Mus;Oleates;Organism;Pathogen detection;Pathogenesis;Pathogenicity;Pathway interactions;Pattern;Pertussis Toxin;Phase;Phospholipids;Play;Productivity;Receptor Activation;Receptor Cell;Receptor Signaling;Reporter;Reporting;Research;Roentgen Rays;Role;Signal Pathway;Signal Transduction;Signaling Molecule;Site;Soft Tissue Infections;Staphylococcus aureus;Structure;Symbiosis;System;T cell response;T-Cell Activation;T-Cell Receptor;TLR2 gene;Techniques;Testing;Tissues;Toll-like receptors;Training;Unsaturated Fatty Acids;Vesicle;Virulence;anti-microbial drug;biophysical techniques;career;commensal bacteria;cytokine;design;drug discovery;experimental study;extracellular;extracellular vesicles;gastrointestinal;gut inflammation;gut microbiome;human pathogen;hydroxy fatty acid;immunoregulation;inhibitor;interest;lipid mediator;lipid metabolism;multidisciplinary;novel;pathogen;pathogenic bacteria;pi bond;programs;receptor;recruit;response;structural biology;vesicular release

public_health_relevance:
Project NarrativeLipid mediators are major signaling molecule constituents in all kingdoms of life and bacteria producebioactive lipid mediators that are not made by mammalian cells. Inflammation in the intestine or sites ofbacterial infections exemplifies the immune response to agonistic bacterial lipid mediators but some bacteriaalso produce lipid countermeasures such as hydroxy fatty acids that can suppress the inflammatoryresponse. This project will elucidate the immune signaling pathways that respond to hydroxy fatty acids tosuppress immune responses and the biosynthetic pathways by which commensal and pathogenic bacteriarelease hydroxy fatty acids.


application_id: 11163274
project_number: 5K12DA035150-14
project_title: Kentucky BIRCWH Program: Training the Next Generation of Women's Health Scholars
administering_ic: NIDA
award_notice_date: 2025-08-22
opportunity_number: RFA-OD-21-006
application_type: 5
activity_code: K12
ic: DA
serial_number: 035150
program_official: FALCON-MORALES, EDGARDO
project_start_date: 2022-08-01
project_end_date: 2027-07-31
study_section: Special Emphasis Panel[ZRG1-PSE-W(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
arra_indicator: N
project_abstract:
The University of Kentuckys (UK) BIRCWH program is built around three pillars: mentoring interdisciplinary research and career development. Given the significant health challenges in Kentucky we focus on three areas of important health disparity for Appalachian Kentuckians: 1) substance use 2) violence against women and 3) lifespan changes in health with aging. UK BIRCWH objectives are: 1) to provide the environment mentorship and facilities to enhance the ability of BIRCWH scholars to compete for NIH research grants in diverse areas of womens health research 2) to deepen our understanding of the unique role of sex in the manifestation of health and disease 3) to develop and implement new communication and social networking technologies to address sex differences and improve womens health 4) to personalize prevention diagnostics and therapeutics to address health disparities 5) to stimulate new collaborations in focused interdisciplinary and interactive research areas that are essential for uncovering sex differences and improving womens health; and 6) to use a thematic multidisciplinary focus as a platform for enhancing translational research between basic clinical and public health scientists. Our formal framework for growing the next generation of womens health and sex differences researchers includes a mentoring team for each Scholar composed of: 1) experienced faculty members (Mentors) and 2) a former BIRCWH scholar (Coach). This mentoring team will collectively provide in-depth research experience and didactic training to assistant professor tenure-track faculty. Career development will also include mechanisms for accountability for manuscript submissions workshops on grant development and aspects of academic development such as personnel management negotiation skills self-care and promotion. UK BIRCWH Scholar appointments will be 2 years for PhD and 3 years for MD scholars. Based on our prior experience we anticipate training 8 scholars over 5 years of funding. Outcomes: Since 2000 40 Scholars have completed BIRCWH training (17 MDs 23 PhDs) who have produced 1712 peer-reviewed publications secured $41636782 in NIH funding as PI and $239982415 as Co-I or PI from other external sources. UK has retained 57% of our BIRCWH graduates who continue active research programs and support BIRCWH as Coaches and Mentors. Given this success why should UKs BIRCWH funding continue? Succinctly Kentuckys need continues. Our rates of substance use violence and chronic disease (3 foci) are among this nations highest. With BIRCWH funding we can support those who will address the health inequities Kentuckians and others across the nation still face.

project_terms:
Accountability;Address;Aging;Appalachian Region;Appointment;Area;Chronic Disease;Clinical;Collaborations;Communication;Development;Diagnostic;Disease;Doctor of Philosophy;Educational workshop;Environment;Face;Faculty;Funding;Grant;Health;Interdisciplinary Study;Kentucky;Manuscripts;Mediation;Mentors;Mentorship;Outcome;Peer Review;Personnel Management;Public Health;Publications;Research;Research Personnel;Research Project Grants;Role;Scientist;Secure;Self Care;Sex Differences;Social Network;Source;Technology;Therapeutic;Training;Translational Research;United States National Institutes of Health;Universities;Violence;Women's Health;career development;experience;health difference;health disparity;health inequalities;improved;individualized prevention;life span;member;multidisciplinary;next generation;professor;programs;research and development;sex;skills;substance use;success;tenure track;violence against women

public_health_relevance:
Finding and addressing sex and differences in effective health care research and treatment are critical actions toward the goal of improving the health and wellbeing of all Americans. To achieve this goal the UK BIRCWH seeks to continue training and supporting our next generation of academic researchers to recognize sex differences in conditions that disproportionately affect Kentuckians. In this training and mentoring program for emerging researchers we focus on 3 health concerns that disproportionately affect Appalachian Kentuckians: Substance use violence against women and lifespan changes.


application_id: 11163256
project_number: 5U2FFD008077-03
administering_ic: FDA
award_notice_date: 2025-06-11
opportunity_number: RFA-FD-23-027
application_type: 5
activity_code: U2F
ic: FD
serial_number: 008077
program_official: BUTLER, JENICE
project_start_date: 2023-09-15
project_end_date: 2026-06-30
study_section: ZFD1-ORA-J(13)
contact_pi_person_id: 79080311
contact_pi: BELL, WILLIAM 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
budget_start_date: 2025-07-01
project_title:
Kentucky's Application for MFRPS Dietary Supplements Food Protection Task Force and Special Projects

project_abstract:
Kentucky Department for Public Health-Division of Public Health Protection & Safety Food Safety Branch Project Summary/AbstractRE: Flexible Funding Model-Infrastructure Development and Maintenance for StateManufactured Food Regulatory Programs (U2F) Clinical Trials Not Allowed (FundingOpportunity Announcement (FOA) Number RFA-FD-23-027).The goal of this project over the 2023-2026 three-year Period of Performance is to maintainour agencys full conformance with each of the 10 Manufactured Food Regulatory ProgramStandards by continuing to actively participate and advance state/federal efforts for anationally integrated food protection system. Previous Cooperative Funding Agreements since2011 have allowed our agency to build and maintain a quality state program for theregulation of our manufactured food industry. In addition to MFRPSmaintenance/conformance this project will utilize Cooperative Agreement funding toexpand our current regulatory foundation incorporating Dietary Supplements as part of ourManufactured Foods Regulatory Program.In an effort to better prioritize and direct our regulatory activities at reducing foodborne illnessoutbreaks our agency further intends to maintain and expand the framework and networkrelative to our Food Protection Task force. Funding under a Special Projects add-on will alsobe utilized to enhance our current food manufacturing database to enable quicker access toinspectional information along with bidirectional data sharing. In order to enhanceresponsiveness in terms of reducing food safety risks and prevention of foodborne outbreaksdata sharing with our FDA partners will promote faster communication relative to violativeconditions observed during manufactured food firm inspections.Continuing our agencys partnership with FDA under this Cooperative Agreement is essentialfor building a solid regulatory foundation maintaining and sustaining consistency in ouragencys inspectional approach supporting a framework aimed at reducing foodborne illnessand contribute to projects which support and enhances an IFSS.

public_health_relevance:
Kentucky Department for Public Health-Division of Public Health Protection & Safety Food Safety BranchFlexible Funding Model-Infrastructure Development and Maintenance for State ManufacturedFood Regulatory Programs (U2F) Clinical Trials Not Allowed (Funding OpportunityAnnouncement (FOA) Number RFA-FD-23-027).Project Narrative:The intended outcome of this Cooperative Agreement Funding Application for the 2023-2026Period of Performance is to maintain and further advance efforts for a Nationally IntegratedFood Safety System (IFSS) by utilizing available FDA funding assistance to allow The KentuckyDepartment for Public Health-Division of Public Health Protection and Safety-Food SafetyBranchs Manufactured Food Regulatory Program to maintain full conformance with theManufactured Food Regulatory Program Standards (MFRPS). This funding will allow the MFRPSprogram to maintain current staffing levels (including a MFRPS Coordinator) recruit and retaina highly trained/qualified inspection team review and update program SOPs assist our federal(FDA) partners in establishing a uniform basis for measuring and improving the performance ofmanufactured food regulatory programs and enhance our Regulatory Foundation to ensurethat Kentuckys Manufactured Food Regulatory Program develops and maintains best practicesfor a high-quality regulatory program. Kentuckys continued with these program standards willhelp Federal and State programs better direct their regulatory activities at reducing foodborneillness hazards in plants that manufacture process pack or hold foods.


