# projects

application_id: 10973604
project_number: 5R01ES033767-04
project_title: Phthalate-Induced Dysregulation of Prostaglandin and Angiogenic Function During Ovulation in Women
administering_ic: NIEHS
award_notice_date: 2024-11-05
opportunity_number: RFA-ES-21-001
application_type: 5
activity_code: R01
ic: ES
serial_number: 033767
program_official: SCHUG, THADDEUS
project_start_date: 2022-01-01
project_end_date: 2026-10-31
study_section: ZES1-LAT-S(R1)
contact_pi_person_id: 12252020
contact_pi: HANNON, PATRICK RYAN
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/ABSTRACTThis ONES award will elucidate the mechanisms by which phthalates a class of endocrine-disrupting chemicalsdisrupt prostaglandin and angiogenic function during the critical period of ovulation. Further rescue approacheswill be investigated to alleviate phthalate-induced inhibition of ovulation and fertility which is crucial forenvironmental and reproductive health as exposure to phthalates is unavoidable. Phthalates are incorporated inseveral common consumer medical housing and personal care products leading to daily human exposure.However little is known about the effects of environmentally relevant levels and mixtures of phthalates onovulation especially in women. This is alarming because defects in ovulation are the leading cause of femaleinfertility. The abundant increase of prostaglandins in the ovary and the surge of new vasculature formation viaangiogenesis are vital for ovulation and fertility. Preliminary data for this proposal are the first to show that anenvironmentally relevant phthalate mixture decreases the levels of prostaglandins and factors that driveangiogenesis in human and mouse ovarian samples. Further the phthalate mixture decreased ovulation ratesby 96% in mouse samples. These findings suggest that environmentally relevant phthalate exposure targetsovulatory prostaglandin and angiogenic action which may cause infertility. Our compelling preliminary data alsosuggest that supplementation with cyclic adenosine monophosphate a common cell signaling molecule tohuman ovarian cells may rescue the phthalate-induced decreases in ovulatory prostaglandin and angiogenicfactor levels. A major strength of this proposal is our ability to mimic human exposure to phthalates by the useof environmentally relevant phthalate mixtures and human ovarian models. These models as well as in vivo andin vitro mouse models will be used to test the hypothesis that phthalates inhibit ovulatory prostaglandinproduction and function leading to impaired angiogenesis and ovulatory failure/infertility. Specific Aim 1 willelucidate the mechanism by which phthalates decrease ovulatory prostaglandin levels. Specific Aim 2 willdetermine the deficiencies in angiogenesis ovulation and fertility caused by phthalates. Specific Aim 3 will defineapproaches to alleviate phthalate toxicity. These findings will advance environmental health sciences byproviding mechanistic data establishing the impact of environmentally relevant phthalate mixture exposure onprostaglandin and angiogenic function which are essential mediators for fertility. Thus these findings will revealnovel actions of phthalates on infertility and reproductive dysfunction. Additionally the use of human samplesand the establishment of rescue approaches provide a translational approach to understanding and mitigatingphthalate toxicities. Infertility in women seeking to conceive leads to a decreased quality of life includingincreased levels of stress diminished social functioning and mental and physical health issues. By delineatingthe detrimental impacts of phthalate exposure on ovulation and fertility the overarching goal of this proposal isto provide a foundation to benefit womens reproductive and general healthcare.

project_terms:
Agonist;Angiogenesis Inhibition;Angiogenic Factor;Animal Model;Award;Biological Assay;Blood capillaries;Cell Proliferation;Cell model;Cells;Chemicals;Couples;Cyclic AMP;Cyclooxygenase Inhibitors;Data;Defect;Dose;Endocrine Disruptors;Endothelial Cells;Ensure;Environment;Environmental Health;Exhibits;Exposure to;FGF2 gene;Failure;Female infertility;Fertility;Fertility Rates;Foundations;Functional disorder;Goals;Health Care;Housing;Human;Impairment;In Vitro;Infertility;Link;Literature;Mediator;Medical;Mental Health;Metabolism;Modeling;Mus;Nature;Non-Steroidal Anti-Inflammatory Agents;Oocytes;Outcome;Ovarian;Ovarian Follicle;Ovarian Granulosa Cell;Ovary;Ovulation;Ovulation Inhibition;PTGS2 gene;Parents;Pathway interactions;Pregnant Women;Prevalence;Process;Production;Proliferating;Prostaglandin Inhibition;Prostaglandin Production;Prostaglandin-Endoperoxide Synthase;Prostaglandins;Public Health;Quality of life;Reproductive Health;Research;Rodent Model;Sampling;Signal Transduction;Signaling Molecule;Social Functioning;Societies;Stress;Supplementation;Testing;Time;Toxic effect;VEGFA gene;Woman;Women's Health;Women's prevalence;Work;angiogenesis;cost;critical period;exposed human population;granulosa cell;human model;in vivo;migration;mouse model;novel;personal care products;phthalates;physical conditioning;prevent;receptor;reproductive;translational approach;urinary

public_health_relevance:
PROJECT NARRATIVEExposure to phthalates a class of chemicals that humans are unavoidably exposed to on a daily basis isincreasingly being recognized as contributing to the prevalence of infertility in which defects in ovulation are theleading cause of infertility in women. The proposed research will address this public health concern by providinga more complete understanding of how phthalates inhibit prostaglandins and angiogenesis which are essentialfor ovulation and fertility in women. Because infertility in women seeking to conceive leads to impairments intheir physical and mental health the overarching goal of this proposal is to establish novel rescue approachesto alleviate phthalate-induced reproductive dysfunction and infertility.


application_id: 10973593
project_number: 5R25ES027684-08
project_title: Summer Research in Environmental Health Sciences
administering_ic: NIEHS
award_notice_date: 2024-11-22
opportunity_number: PAR-21-168
application_type: 5
activity_code: R25
ic: ES
serial_number: 027684
program_official: HUMBLE, MICHAEL C
project_start_date: 2017-05-01
project_end_date: 2028-10-31
study_section: ZES1-LKB-S(SR)1
contact_pi_person_id: 1883439
contact_pi: SWANSON, HOLLIE ISABEL
other_pis: PEARSON, KEVIN JOSEPH
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 SUMMARYThe Summer Undergraduate Research in Environmental Health Sciences (SURES) program at the University ofKentucky is designed to introduce students to the highly interdisciplinary and collaborative nature ofenvironmental health science (EHS) research that is focused on solving key global health problems. Anadditional focus is to prepare underprivileged and under-represented students for successful careers in relevantfields. This is a competitive renewal application seeks support to continue our 10-week summer program andsupport fellowships for 10 students. The SURES program leverages the substantial and ongoing efforts at theUniversity of Kentucky driven to enhance the undergraduate research experience with the robust environmentalhealth science research programs of involved faculty mentors. The specific aims are to 1) enhance studentunderstanding and interest in EHS and 2) improve student scientific and career skills. Towards this end studentswill be recruited from the Commonwealth of Kentucky with an emphasis on those from the Appalachian regionas well as from a variety of undergraduate institutions in order to create a cohort of participants representingdiverse populations. The SURES program will commence with a week-long session that introduces students toresearch laboratory safety and scientific ethics. The students will then experience hands-on research byperforming experiments in the laboratories of their chosen mentors. Professional development and a sense ofbelonging to the EHS community will be built via student participation in weekly lunches with EHS researchersand professionals net-working opportunities and tours of research facilities. In addition students will be pairedwith a near-peer mentor and engage in weekly activities that include a citizen science lead collection groupexercise a theatre improvisation workshop community-building circle on mentoring painting their projects andviewing a discussing a film on climate change. Each participant will create an EHS-relevant podcast. TheSURES program will culminate in a campus-wide poster session attended by the faculty staff students andstudent family members. Success of the program is indicated by the engagement of prior participants in careersin university research (13%) industry (16%) government/nonprofits (11%) and pursuing graduate (16%)/professional (37%) education. Dissemination of the approaches used in this program and their outcomes willbuild upon the expansion of the traditional environmental health sciences research training from the graduateand post-doctoral level to the undergraduates at a national level.

project_terms:
Address;Affect;Appalachian Region;Area;Collection;Communities;Critical Thinking;Development;Doctor's Degree;Economics;Education;Educational workshop;Elevator;Engineering;Environment;Environmental Exposure;Environmental Health;Environmental Science;Ethics;Evaluation;Exercise;Faculty;Family member;Fellowship;Film;Funding;Future;Goals;Government;Health Professional;Individual;Industry;Institution;Interview;Kentucky;Laboratories;Lead;Life;Measures;Mentors;Mission;National Institute of Environmental Health Sciences;Nature;Oral;Outcome;Paint;Participant;Personal Satisfaction;Persons;Play;Population Heterogeneity;Positioning Attribute;Postdoctoral Fellow;Poverty Areas;Professional Competence;Publications;Questionnaires;Reporting;Research;Research Personnel;Research Project Grants;Research Training;Role;STEM field;Safety;Science;Scientist;Speech;Students;Surveys;Technology;Training;Training Programs;Underrepresented Students;United States;Universities;Work;career;citizen science;climate change;cohort;college;community building;design;experience;experimental study;faculty mentor;global health;hands on research;health science research;improved;interest;member;multidisciplinary;novel;outreach;patient engagement;peer;peer coaching;podcast;posters;programs;recruit;research facility;skills;social;student mentoring;student participation;student retention;success;summer program;summer research;supportive environment;undergraduate education;undergraduate research;undergraduate research experience;undergraduate student;undergraduate summer research

public_health_relevance:
NARRATIVEThe overall objective of the Summer Undergraduate Research Experience in EnvironmentalHealth Sciences (SURES) program is to use a research-intensive approach for introducingstudents from the impoverished region of Appalachia to the multidisciplinary nature ofenvironmental sciences and opportunities for pursuing relevant careers. Exceptional training ina wide variety of research areas working with interdisciplinary collaborative research groupswho are housed in multiple departments and colleges is provided. In addition seminarsoutreach opportunities and interactive workshops are designed to prepare students forsuccessful environmental health related careers.


application_id: 10953880
project_number: 3P20GM103436-24S1
administering_ic: NIGMS
award_notice_date: 2024-08-29
opportunity_number: PA-20-272
application_type: 3
activity_code: P20
ic: GM
serial_number: 103436
suffix: S1
program_official: ZHOU, YANG
project_start_date: 2001-09-30
project_end_date: 2029-04-30
study_section: ZGM1(IN)
contact_pi_person_id: 1871981
contact_pi: BICKFORD, MARTHA E
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_title:
KY INBRE NOSI Supplement: Identification of Personalized Treatment Targets in Pregnant and Postpartum Women

project_abstract:
Project Summary AbstractOne in 20 pregnant women in the United States have clinically severe disordered eating (DE)symptoms during pregnancy such as intentional vomiting food restriction and binge eating. DEduring pregnancy is related to serious mental emotional and physical impairments as well aspregnancy complications. Specifically DE greatly increases the risk of miscarriagehemorrhage severe/prolonged vomiting preterm birth low birth weight birth defectsimpairments and death and doubles risk of severe anxiety and depression. DEdisproportionally impacts women during reproductive years and pregnant and postpartumwomen face unique challenges in this period such as societal pressures (e.g. fear of gainingtoo much baby weight pressure to lose weight quickly after pregnancy) along with pregnancysymptoms (e.g. difficulty eating bodily changes morning sickness). These vulnerabilitiesexacerbate DE and risk of devastating health and pregnancy outcomes for mothers and infants.This proposal will modify our personalized self-guided system to identify treatment targets toultimately address the unique presentation of the symptoms that drive DE in pregnant andpostpartum women. There are currently no personalized digital self-guided interventions for thishigh-risk population. Thus this supplement is to develop and modify a personalized self-guided digital intervention to address DE in pregnant and postpartum women. First usingidiographic models we aim to identify the frequency of the most problematic symptoms thatdrive DE in this high-risk population (N=60). Second we aim to modify and test if our digitaltherapeutic to address treatment targets personalized for pregnant and postpartum womenreduces DE and increases their quality of life. Our highly novel methods are packaged within adigitalized program delivered directly to these high-risk women to intervene on the mostproblematic symptoms in a personalized manner within their day-to-day life to improve accessto care. This proposal is in-line with the parent grant to provide the growth of our currentmentorship training and research experiences for students and support three early careerresearchers to be competitive for further independent funding. We aim to provide relevant andpersonalized DE interventions for pregnant and postpartum women to reduce the risk forimpairment and mortalities for both mother and infant.

project_terms:
Address;Algorithms;Anemia;Anxiety;Anxiety Disorders;Automobile Driving;Binge Eating;Birth;Caring;Cellular Phone;Cessation of life;Chronic;Clinical;Computer software;Congenital Abnormality;Data;Death Rate;Defect;Depressive disorder;Disproportionately impacts women;Eating;Eating Disorders;Emotional;Evidence based intervention;Face;Frequencies;Fright;Funding;Growth;Health;Health Services Accessibility;Hemorrhage;High Prevalence;High Risk Woman;Impairment;Improve Access;Infant;Infant Health;Insurance;Intervention;Life;Low Birth Weight Infant;Mental Depression;Mental Health;Mental disorders;Mentorship;Methods;Modeling;Monitor;Morning Sickness;Mothers;Pathological anxiety;Pathology;Population;Postpartum Period;Postpartum Women;Precision therapeutics;Pregnancy;Pregnancy Complications;Pregnancy Outcome;Pregnant Women;Premature Birth;Provider;Psyche structure;Quality of life;Randomized Controlled Trials;Recommendation;Reporting;Research;Research Personnel;Risk;Risk Reduction;Sleep disturbances;Spontaneous abortion;Students;Symptoms;System;Testing;Therapeutic;Training;Treatment Efficacy;United States;United States National Institutes of Health;Vomiting;Weight;Weight Gain;Woman;Women's Health;Work;associated symptom;body dissatisfaction;career;community intervention;cost;digital;digital intervention;digital treatment;experience;food restriction;health care availability;high risk;high risk population;improved;infant outcome;maternal outcome;mortality;novel;parent grant;personalized intervention;personalized medicine;physical conditioning;physical impairment;post pregnancy;postpartum complications;postpartum outcome;pressure;programs;public health relevance;purge;recruit;reduce symptoms;reproductive;response;smartphone based assessment;societal costs;symptom treatment;user friendly software

public_health_relevance:
Project NarrativeFive percentage of pregnant women have clinically severe disordered eating symptoms withdevastating consequences for both mother and infant and high societal cost. This proposedresearch will identify which disordered eating symptoms are most problematic and frequent fordriving disordered eating in pregnant and postpartum women and develop and test interactiverelevant personalized digital interventions for this high-risk population. This research hassignificant public health relevance to provide the first highly accessible digital personalized self-guided therapeutic to address the unique challenges that pregnant and postpartum women withdisordered eating face and is relevant to NIHs and IDeA strategic initiatives to developpersonalized intervention and treatments and to provide better healthcare access for womenand infants.


application_id: 10953652
project_number: 3R01GM150200-02S1
project_title: Diversity Supplement for Haley Stanczyk
administering_ic: NIGMS
award_notice_date: 2024-06-13
opportunity_number: PA-23-189
application_type: 3
activity_code: R01
ic: GM
serial_number: 150200
suffix: S1
program_official: SALAZAR, DESIREE LYNN
project_start_date: 2023-06-01
project_end_date: 2025-03-31
study_section: Cellular Signaling and Regulatory Systems Study Section[CSRS]
contact_pi_person_id: 7353657
contact_pi: GAO, TIANYAN
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
project_abstract:
ABSTRACT Protein phosphorylation defines one of the most important and pervasive regulatory mechanisms in cellsignaling. A precise control of the balance between phosphorylation and dephosphorylation is crucial for livingorganisms to maintain normal physiological functions. While protein kinases have attracted a significant amountof attention given the promise of developing inhibitors for targeted therapies significant knowledge gaps existon the opposing actions of protein phosphatases. The overall objective of this study is to investigate themolecular mechanisms by which PTPRF a receptor-type tyrosine phosphatase regulates Wnt signaling andnormal intestinal homeostasis. A large body of evidence indicates that Wnt signaling is required for themaintenance of normal intestinal stem cells; and dysregulation of Wnt signaling is often the first step leading tothe development of colorectal cancer. In our efforts to investigate the regulatory mechanisms of Wnt signalingwe identified PTPRF a receptor protein tyrosine phosphatase as a novel positive regulator in the Wnt pathwaythat promotes the activation of Wnt signaling upstream of the -catenin destruction complex. To further determinethe functional importance of PTPRF we utilized Ptprf knockout mice to investigate if Ptprf-loss alters Wntsignaling and the proliferation and differentiation of intestinal stem cells in vivo. Our exciting new data showedthat intestinal crypts isolated from Ptprf knockout mice have reduced ability to form organoids which coincideswith decreased expression of Wnt target genes. In addition we found that PTPRF interacts and co-localizes withLRP6 and caveolin upon Wnt stimulation; and CRISPR/Cas9-mediated knockout of PTPRF in 293T cellsattenuates Wnt-stimulated TOP-Flash reporter activity as well as LRP6 phosphorylation. Moreover we identifiedNEDD4L as a novel E3 ligase that controls PTPRF ubiquitination and degradation. The following specific aimsare proposed: 1) to delineate the molecular mechanisms underlying PTPRF-mediated regulation of Wntsignaling; 2) to determine the role of NEDD4L in controlling PTPRF protein stability; and 3) to define the functionalimportance of PTPRF in regulating the proliferation and differentiation of intestinal stem cells in vivo. Resultsfrom our studies will fill an important knowledge gap on how protein phosphatases are involved in regulatingcomplex biological processes. This supplement will allow Ms. Haley Stanczyk to receive further training inconducting basic research in cell signaling. Her results will assist in determining the role of PTPRF in regulatingWnt signaling and intestinal stem cell functions. She will examine the molecular mechanisms by which PTPRFregulates caveolin-mediated endocytosis of Wnt receptors. Moreover she will investigate if loss of PTPRFexpression reduces the stemness of intestinal stem cells using organoid and mouse models. Ultimately byproviding new insights into PTPRF-dependent regulation of Wnt signaling our findings will help identify newstrategies for treating Wnt-driven diseases by using PTPRF as a target.

project_terms:
3-Dimensional;Attention;Attenuated;Automobile Driving;Basic Science;Bioinformatics;Biological Process;CRISPR/Cas technology;Caveolins;Cell Differentiation process;Cell Proliferation;Cell membrane;Cells;Cellular biology;Colon;Colon Carcinoma;Colorectal Cancer;Complex;Data;Development;Disease;Endocytosis;Ensure;Epithelium;Equilibrium;Genes;Goals;Human;Human body;In Vitro;Internal Ribosome Entry Site;Intestines;Investigation;Knock-out;Knockout Mice;Knowledge;LGR5 gene;Maintenance;Mediating;Modeling;Molecular;Mus;Mutation;Oncogenic;Organism;Organoids;PTPRR gene;Pathway interactions;Phosphoric Monoester Hydrolases;Phosphorylation;Physiological;Physiology;Play;Process;Proliferating;Protein Dephosphorylation;Protein Kinase;Protein Tyrosine Phosphatase;Protein phosphatase;Proteins;Regulation;Reporter;Role;Sampling;Signal Transduction;System;Technology;Testing;Tissues;Training;Ubiquitination;Villus;WNT Signaling Pathway;beta catenin;cancer cell;colon cancer patients;colon tumorigenesis;in vivo;inhibitor;insight;intestinal crypt;intestinal epithelium;intestinal homeostasis;knock-down;mouse model;novel;novel therapeutic intervention;receptor;self-renewal;single-cell RNA sequencing;stem cell fate;stem cell function;stem cell proliferation;stem cells;stemness;success;targeted treatment;tumor growth;ubiquitin-protein ligase

public_health_relevance:
PROJECT NARRATIVE Wnt signaling is a rapidly evolving and important field of investigation and new regulators involved in thiscascade are continuously being identified. Our study focuses on developing a mechanistic understanding ofPTPRF-mediated regulation of Wnt signaling and intestinal stem cell function. Results from our studies will helpidentify new therapeutic strategies for treating Wnt-driven diseases by using PTPRF as a target.


application_id: 10950843
project_number: 4R42MH135825-02
administering_ic: NIMH
award_notice_date: 2024-07-19
opportunity_number: PA-22-178
application_type: 4
activity_code: R42
ic: MH
serial_number: 135825
program_official: GRABB, MARGARET CHRISTINE
project_start_date: 2024-08-01
project_end_date: 2026-07-31
study_section: Special Emphasis Panel[ZRG1-ISB-Z(10)B]
contact_pi_person_id: 8252681
contact_pi: YU, GUOQIANG
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 078515036
primary_uei: HSZNRZ4JS954
duns_number: 078515036
uei: HSZNRZ4JS954
fips: US
organization_id: 10032228
organization_name: BIOPTICSTECHNOLOGY, LLC
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 405131245
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-08-01
project_title:
Time-resolved laser speckle contrast imaging of resting-state functional connectivity in neonatal brain

project_abstract:
ABSTRACTContinuous monitoring of neonatal brain development is crucial for effective management of brain injury andassociated complications thus reducing healthcare burden and costs. One rapidly developing method for earlycharacterization of abnormal brain development is to map resting-state functional connectivity (rs-FC) acrossdistinct regions of the brain. However currently available neuroimaging technologies are either expensive anddifficult to use continuously (fMRI and PET) or lack the combination of temporal-spatial resolution and large field-of-view (FOV) to image distributed rs-FC (EEG and near-infrared spectroscopy and tomography). In collaborationwith University of Kentucky inventors Bioptics Technology is developing validating and commercializing arevolutionary time-resolved laser speckle contrast imaging (TR-LSCI) technology that enables noncontact fasthigh-resolution imaging of cerebral blood flow (CBF) over a large FOV. TR-LSCI illuminates picosecond-pulsedwidefield coherent near-infrared light onto the brain and synchronizes a newly developed picosecond-gatedhigh-resolution single-photon avalanche diode (SPAD) camera for 2D mapping of cerebral blood flow (CBF) atdifferent depths into the head. By applying the time-gated strategy TR-LSCI differentiates short and long photonpaths through the layered head tissues at different depths thus eliminating the need for time-consuming complex3D reconstruction in near-infrared diffuse optical tomography technologies. In preliminary studies continuousmapping of CBF at different depths has been demonstrated by a lab-made benchtop TR-LSCI prototype in flow-simulating phantoms and in vivo rodents. In this Fast Track STTR proposal through two phases we will developoptimize validate and commercialize a user-friendly portable TR-LSCI device for fast high-solution andmultiscale imaging of CBF and rs-FC in neonatal rodents (Phase 1) and neonatal piglets (Phase 2). SpecificallyPhase 1 will optimize and assess the benchtop TR-LSCI prototype for imaging CBF and extracting rs-FC (derivedfrom time-course CBF images) in neonatal rodents with perinatal hypoxic-ischemic encephalopathy (HIE).Neonatal rats are used in this Phase 1 feasibility test to de-risk the TR-LSCI before its full-scale development inneonatal piglets during Phase 2. HIE is selected to study as it affects 2-9 babies per 1000 term births and isassociated with severe neurodevelopmental problems and mortality. Phase 2 will develop optimize and assessa user-friendly portable TR-LSCI device for continuous imaging of CBF and rs-FC in neonatal piglets with HIE.Neonatal piglets are selected to study as their head size and post-HIE pathology are analogous to humanneonates. TR-LSCI results will be correlated with MRI results and clinical outcomes to identify biomarkers forassessing neonatal brain injury after HIE. While this proposal tests it on HIE models of neonatal rats and pigletsas the first step for preclinical commercialization the TR-LSCI device is broadly applicable to investigate manyneurovascular diseases beyond HIE occurring in human neonates thereby providing a significant opportunityfor future clinical development and commercialization.

project_terms:
3-Dimensional;Affect;Algorithms;Animal Model;Biological Markers;Brain;Brain Injuries;Brain imaging;Brain region;Calibration;Cerebrovascular Circulation;Clinical;Collaborations;Complex;Consumption;Development;Diffuse;Diffusion;Disease;Early Diagnosis;Electroencephalography;Functional Magnetic Resonance Imaging;Future;Head;Health;Human;Image;Imaging Device;Imaging technology;Infant;Investigation;Kentucky;Laboratories;Laser Speckle Imaging;Light;Magnetic Resonance Imaging;Maps;Methods;Modality;Modeling;Monitor;Near-Infrared Spectroscopy;Neonatal;Neonatal Brain Injury;Neonatal Intensive Care Units;Neurodevelopmental Problem;Neurosciences Research;Noise;Operating System;Outcome;Pathology;Perinatal anoxic ischemic brain injury;Phase;Photons;Physiologic pulse;Positron-Emission Tomography;Property;Rattus;Resolution;Rest;Risk;Rodent;Scalp structure;Signal Transduction;Small Business Technology Transfer Research;Statistical Models;System;Technology;Term Birth;Testing;Time;Tissues;Universities;Variant;biomarker identification;brain abnormalities;care costs;cerebral hemodynamics;clinical application;clinical development;commercialization;cost;cranium;denoising;design;diffuse optical tomography;experimental study;feasibility testing;healthcare burden;high resolution imaging;imager;improved;in vivo;lens;mortality;neonatal brain;neonatal brain development;neonatal hypoxic-ischemic brain injury;neonate;neuroimaging;neurovascular;operation;porcine model;portability;pre-clinical;prevent;prototype;reconstruction;tomography;user-friendly

public_health_relevance:
PROJECT NARRATIVEContinuous monitoring of neonatal brain development is crucial for effective management of brain injury andassociated complications thus reducing healthcare burden and costs. Bioptics Technology is developingvalidating and commercializing a revolutionary time-resolved laser speckle contrast imaging (TR-LSCI)technology that enables noncontact fast high-resolution imaging of cerebral blood flow and resting-statefunctional connectivity across distinct regions of the brain for noninvasive and continuous assessment ofneonatal brain development to prevent brain injury. While the proposal tests this imaging technology in perinatalhypoxic-ischemic encephalopathy models of neonatal rats and piglets as the first step for preclinicalcommercialization the TR-LSCI device is broadly applicable to investigate many neurovascular diseases beyondHIE occurring in human neonates thereby providing a significant opportunity for future clinical development andcommercialization.


application_id: 10950495
project_number: 3R01AI145910-06S1
project_title: Dysregulation of maternal immunity during pregnancy by pregravid obesity
administering_ic: NIAID
award_notice_date: 2024-08-27
opportunity_number: RFA-AI-18-023
application_type: 3
activity_code: R01
ic: AI
serial_number: 145910
suffix: S1
program_official: PRABHUDAS, MERCY R
project_start_date: 2019-09-01
project_end_date: 2026-08-31
study_section: ZAI1-NVM-I(M1)
contact_pi_person_id: 8774042
contact_pi: MESSAOUDI, ILHEM
other_pis: Not Applicable
congressional_district: 06
department: MICROBIOLOGY/IMMUN/VIROLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
Successful pregnancy requires carefully coordinated changes in the immune system that facilitate placentationpromote fetal tolerance and growth and induce labor. Deviations from this tightly regulated pregnancyimmunological clock can lead to as pre-eclampsia and complications during labor. The rates of obesity amongstwomen of childbearing age have increased at an alarming rate making it one of the most common comorbiditiesduring pregnancy. Previously published studies and our preliminary data indicate an enhancement of monocyteresponse to LPS between 12 and 37 weeks of gestation Importantly our preliminary analyses indicate thatmaternal pregravid body mass index (BMI) >30 abrogates this pregnancy-associated monocyte activation. Thisobservation provides a potential explanation for the increased susceptibility to infections and poor wound healingoutcomes observed in obese pregnant women. We hypothesize that chronic low grade inflammationinduced by pregravid obesity disrupts the gestational age dependent monocyte activation skewing themto an immunotolerant phenotype. Additionally given that macrophages in the decidua are recruited fromcirculating monocytes we will investigate the burden of obesity on phenotype and function of decidualmacrophages. We further hypothesize that pregravid obesity results in a hyper-inflammatory phenotypewithin decidual macrophages. We will employ a multi-dimensional approach to test these hypotheses. Thenovelty of this application lies in the systems biology approach that integrates phenotypic functional andgenomic readouts longitudinally in peripheral blood and at term in the placenta. Completion of the proposedexperiments will reveal the molecular mechanisms that explain progressive changes in monocyte activation overthe course of healthy pregnancy and how that is disrupted with obesity.

project_terms:
37 weeks gestation;Address;Biology;Birth;Blood;Blood specimen;Body mass index;Categories;Cell Physiology;Cells;Cesarean section;Chronic;Data;Decidua;Dendritic Cells;Development;Dimensions;Epigenetic Process;Equilibrium;Exhibits;Female of child bearing age;Fetal Growth;Frequencies;Functional disorder;Genetic Transcription;Genomics;Gestational Age;Gestational Diabetes;Gravid;Growth;Growth and Development function;Health;Heterogeneity;Homeostasis;Host Defense;Immune;Immune system;Immunologics;Immunology;Impaired wound healing;Impairment;Induced Labor;Infection;Infiltration;Inflammation;Inflammation Mediators;Inflammatory;Innate Immune System;Investigation;Labor Complications;Laboratories;Ligands;Link;Macrophage;Macrophage Activation;Maintenance;Maternal-Fetal Exchange;Maternal-fetal medicine;Maternally-Acquired Immunity;Metabolic;Metabolism;Modeling;Molecular;Natural Killer Cells;Obesity;Outcome;Phagocytes;Phenotype;Placenta;Placentation;Play;Positioning Attribute;Pre-Eclampsia;Predisposition;Pregnancy;Pregnant Women;Premature Birth;Publishing;Risk;Role;Sampling;Statistical Models;Surgical Wound Infection;Systems Biology;Testing;Thinness;Third Pregnancy Trimester;Time;Tissues;Villous;Woman;adverse outcome;adverse pregnancy outcome;age related;antimicrobial;cell type;comorbidity;epidemiology study;epigenome;experimental study;fetal;healthy pregnancy;insight;intraamniotic infection;maternal outcome;monocyte;next generation sequencing;novel;obese mothers;peripheral blood;pregnancy hypertension;prepregnancy obesity;recruit;response;surgical risk;wound healing

public_health_relevance:
NARRATIVEPre-pregnancy obesity is associated with significant adverse health outcomes for the mother including increasedrisk of gestational diabetes and hypertension preeclampsia and infection. Recent studies from our laboratoryrevealed significant changes in immune cell function in blood samples collected from obese women at week 37of gestation. Since immune cells play a critical role in anti-microbial defense as well as the development ofchronic inflammation this application will carry out an in-depth investigation of maternal pre-pregnancy obesity-driven changes in the functional transcriptional and epigenetic landscape of blood immune cells.


application_id: 10950409
project_number: 1R25GM155474-01
project_title: Quantitative Team Science (QuanTS) Program
administering_ic: NIGMS
award_notice_date: 2024-08-28
opportunity_number: PAR-21-196
application_type: 1
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: Special Emphasis Panel[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;frontier;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: 10948698
project_number: 1R21AG088756-01
project_title: Therapeutic Value of BNC-1 in Addressing Tau Pathology in TBI
administering_ic: NIA
award_notice_date: 2024-09-03
opportunity_number: PA-20-195
application_type: 1
activity_code: R21
ic: AG
serial_number: 088756
program_official: RUNKO, ALEXANDER PETER
project_start_date: 2024-09-15
project_end_date: 2026-08-31
study_section: Special Emphasis Panel[ZRG1 AN-B (55)]
contact_pi_person_id: 10095513
contact_pi: BACHSTETTER, ADAM D
other_pis: LOVELL, MARK ANTHONY
congressional_district: 06
department: NEUROSCIENCES
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACTEach year approximately 200000 Americans aged 65 and older seek medical care for traumatic brain injuries(TBI) primarily from closed head injuries (CHI) from falls. Research shows that an individual suffering one TBIis at heightened risk for experiencing another. The ramifications extend beyond the immediate physicalconsequences: TBIs have been linked to an increased risk for all types of dementia and repetitive TBIs havebeen correlated with the accumulation of hyperphosphorylated tau (p-tau) which is a defining feature ofchronic traumatic encephalopathy (CTE). Our research and numerous other studies confirm the presence ofelevated p-tau levels in the aftermath of a TBI. However the precise mechanisms contributing to thesechanges are not fully understood. As we confront the complexities of these injuries and their long-term impactit becomes crucial to identify the underlying mechanisms that promote these tau-related pathological changes.Doing so could pave the way for targeted therapeutic interventions following a TBI reducing the risk ofdeveloping Alzheimers disease and related dementias. This study aims to examine the role of transforminggrowth factor-activated kinase 1 (TAK1) in tau pathology following a repetitive mild TBI in a humanized MAPTKI mouse model with the P301L risk variant of neuronal tauopathy. We found activated (phosphorylated) TAK1kinase (pTAK1) in neurons exhibiting substantial tau pathology in both Alzheimers disease and CTE brainsand developed a novel small molecule therapeutic BNC-1 that shows promising reductions in TAK1activation and p-tau accumulation in mouse models of tau pathology and wildtype mice with a CHI. Our goal isto determine an optimal BNC-1 dosage and treatment regimen that significantly reduces TAK1 phosphorylation(Aim 1) and an analysis of the ensuing tau pathology neuron degeneration and behavioral impairments (Aim2). Given the high prevalence of TBI in older adults the therapeutic advancement of BNC-1 could significantlyreduce the burden of TBI-induced cognitive impairments and risk for Alzheimers disease and relateddementias. Establishing the dose-response relationship and the optimal treatment schedule of BNC-1 is crucialdata for a preclinical R01 to validate target engagement understand the mechanism of action and conductpharmacokinetics/pharmacodynamics (PK/PD) testing of BNC-1. If supported by data our mid-term objectiveis to advance BNC-1 toward clinical research evaluation for TBI Alzheimers disease and other tauopathies.

project_terms:
Acute;Address;Adverse effects;Age;Age Months;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;American;Amyloid;Behavioral;Biochemical;Brain;Caring;Cell Count;Chronic;Clinical Research;Clinical Trials;Closed head injuries;DLG4 gene;Data;Dementia;Deterioration;Development;Diet;Dose;Drug Kinetics;Evaluation Research;Exhibits;Female;Future;Genetically Engineered Mouse;Goals;Head;High Prevalence;Impaired cognition;In Vitro;Incidence;Individual;Injury;Intervention;Knock-in Mouse;Lead;Legal patent;Link;Medical;Mus;Naphthyridines;Nerve Degeneration;Neurons;Older Population;Oral;PHF-1;Pathologic;Pathology;Pharmacodynamics;Phenotype;Phosphorylation;Phosphotransferases;Population;Predisposition;Process;Research;Risk;Risk Reduction;Role;Speed;Synapses;Synapsins;Synaptophysin;Tauopathies;Testing;Therapeutic;Therapeutic Intervention;Transforming Growth Factors;Traumatic Brain Injury;Treatment Protocols;Wild Type Mouse;behavioral impairment;carboxylate;chronic traumatic encephalopathy;dosage;drebrins;drug discovery;drug efficacy;experience;experimental group;fall injury;human old age (65+);hyperphosphorylated tau;injured;male;mild traumatic brain injury;mouse model;neuropathology;novel;older adult;optimal treatments;overexpression;pharmacokinetics and pharmacodynamics;pre-clinical;preclinical study;prevent;primary endpoint;response;risk variant;severe injury;small molecule therapeutics;targeted treatment;tau Proteins;tau aggregation;tau-1;therapeutic development;treatment effect

public_health_relevance:
PROJECT NARRATIVEThis study investigates the role of Transforming Growth Factor-Activated Kinase 1 (TAK1) in tau pathology after mildtraumatic brain injuries focusing on the potential of BNC-1 therapy to alleviate pathological tau andneurodegeneration in TBI and Alzheimer's disease. The research aims to deepen our understanding of themechanisms behind tau accumulation in conditions like TBI Alzheimer's disease and other related tauopathies.


application_id: 10948252
project_number: 3U44AA026126-05S1
administering_ic: NIAAA
award_notice_date: 2023-11-17
opportunity_number: PA-20-272
application_type: 3
activity_code: U44
ic: AA
serial_number: 026126
suffix: S1
program_official: SENEVIRATNE, CHAMINDI
project_start_date: 2017-08-25
project_end_date: 2025-08-31
contact_pi_person_id: 79171237
contact_pi: BURKLOW, CINDY ANN
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 196165877
primary_uei: N1NBJ43SQGX7
duns_number: 196165877
uei: N1NBJ43SQGX7
fips: US
organization_id: 10001163
organization_name: NAPROGENIX, INC
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 405060286
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2023-11-17
project_title:
Development of JR-220 (4-Chlorobenzylidenamino-guanidine hydrochloride) as a medication for alcohol dependence

project_abstract:
AbstractThe aim of phase I of the parent cooperative agreement (U44AA026126) was to generatesufficient data on the pharmacokinetics (PK) and toxicology (Tox) of JR-220 to support anapplication for a pre-IND meeting with the FDA. This aim has been successfully accomplished.The aim of phase II of the parent cooperative agreement is to expand the phase I studies with ratand a second species (canine) based upon the feedback of the FDAs pre-IND meeting responseto create a dossier that will be submitted to the FDA in support of IND status for JR-220 as amedication for treatment of alcohol use disorder (AUD). Neither of these aims has changed fromthe original funded application but the cost to support several GLP/GMP tasks related to theseaims have significantly increased for reasons outside the control of the company. All of thesetasks support the potential value of JR-220 as a medication for AUD and are required for INDsubmission. This administrative supplemental proposal is a request for additional funds to coverthe unanticipated increased cost of several key GLP/GMP tasks to be completed that are requiredby the FDA to submit the IND application. This administrative supplement proposal includes taskspreviously proposed and accepted by reviewers and NIAAA. The three key tasks with increasedcosts are 1) GLP CNS safety study (Neurotoxicity) in rat specifically requested by the FDA in thepre-IND meeting response 2) cGMP manufacturing of JR-220 (drug substance) and 3) cGMPmanufacturing of JR-220 capsules (drug product) for clinical trial. This administrativesupplemental request for additional funding under $100K to help cover the incrementalunanticipated cost increase from 2016 to completed these original scope tasks is important forthe successful completion of the overall goal of the parent cooperative agreement to submit theIND in support of JR-220 as medication for treatment for AUD.

project_terms:
Administrative Supplement;Alcohol dependence;Alcohols;Authorization documentation;Canis familiaris;Clinical;Clinical Trials;Cyclic GMP;Data;Dependence;Development;Dose;Drug Kinetics;Evaluation;Feedback;Financial Hardship;Formulation;Funding;Goals;Guanidines;Hour;Human;Investigation;Laboratories;Medical;Methods;Modification;National Institute on Alcohol Abuse and Alcoholism;Oral;Parents;Pharmaceutical Preparations;Phase;Rattus;Recommendation;Safety;Series;Toxicology;U-Series Cooperative Agreements;alcohol abuse therapy;alcohol use disorder;capsule;cost;manufacture;neurotoxicity;novel therapeutics;phase 1 study;pre-Investigational New Drug meeting;preclinical development;research clinical testing;response;safety study;validation studies

public_health_relevance:
Project NarrativeDependence on alcohol is a very serious problem in the US with a huge medical and financialburden. Current treatments are unsatisfactory and new medications are required. The applicantshave synthesized a novel drug that has shown great promise in preclinical development and thisproposal is to obtain the data necessary before investigation of the drug in the human.


application_id: 10945049
project_number: 1R01HL174922-01
project_title: Dual targeting chemokine receptors prevents chemotherapy-induced cardiotoxicity
administering_ic: NHLBI
award_notice_date: 2024-07-15
opportunity_number: PA-20-185
application_type: 1
activity_code: R01
ic: HL
serial_number: 174922
program_official: POIZAT, CORALIE ISABELLE
project_start_date: 2024-08-01
project_end_date: 2028-05-31
study_section: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]
contact_pi_person_id: 12101586
contact_pi: TAN, YI
other_pis: Not Applicable
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:
Doxorubicin (DOX) is an effective chemotherapeutic drug to treat cancer. However DOX-induced cardiotoxicity(DICT) has limited its use. Dexrazoxane is the only current FDA-approved agent for preventing DICT but itscardioprotective effect is incomplete and the side effects also limit its use. Thus the search for newcardioprotective agents for DICT continues. SDF-1 and its receptor CXCR4 play essential roles in cardiovasculardevelopment and diseases. Constitutive loss either one of them results in perinatal lethality partially due tocardiac septum defects. Myocardial supplement of SDF-1 attracts stem cells that express CXCR4 to the site ofinjury to promote cardiac regeneration and angiogenesis. However their roles in cardiovascular system remaincontroversial. For instance heterozygous deletion of CXCR4 in mice reduced infarct size and CXCR4overexpression increased infarct size and reduced cardiac function along with excessive cardiac inammatorycell infiltration. CXCR7 is a lately identified second receptor for SDF-1. CXCR7 binds SDF-1 with an affinity aboutten times higher than CXCR4 and it can either positively or negatively affect SDF-1/CXCR4 axis-mediatedfunctions. This raises a concern as to how to distinguish the roles of SDF-1/CXCR7 from SDF-1/CXCR4 incardiac protection. We showed that SDF-1 prevents cardiac lipotoxicity through CXCR7 but not CXCR4. A single-cell RNA-seq analysis revealed the most abundant expression of CXCR7 in cardiomyocytes and cardiomyocyte-specific CXCR7 deletion showed more prominent cardiac dysfunction after myocardial infraction suggesting anessential cardiac protection. Given the protective effects of CXCR7 in cardiomyocytes and the harmful effects ofCXCR4-mediated cardiac excessive inflammation we tested the protective effects of a dual targeting compoundwith specific antagonistic activity against CXCR4 and potent agonistic activity on CXCR7 against DICT. Wefound this compound treatment significantly prevented DOX-induced cardiac dysfunction cell deathinflammation and fibrosis along with upregulation of signals involving in cardiac energy reserve metabolicprocess and downregulation of signals involving in mast cell infiltration and activation but without affecting thesuppressive effects of DOX on tumor growth. We thus hypothesize that dual targeting compound preventsDICT by activating cardiac CXCR7 to reprogram cardiomyocyte metabolism and prevent cardiacdysfunction and by antagonizing CXCR4 to inhibit cardiac mast cell infiltration and activation but withoutaffecting the suppressive effects of DOX on tumor growth. This hypothesis will be tested through specificaims: 1) Optimizing the protective effects against DICT in tumor-free and tumor-bearing mice; 2) Determiningwhether it prevents DICT through activating CXCR7/AMPK and prevents cardiac cell death and dysfunction; 3)Determining whether it prevents DICT through inhibiting CXCR4-mediated cardiac mast cell infiltration andactivation. Successful completion of this project will reveal new insight into the underlying mechanisms behindand provide fundamental evidence for it as a novel approach for preventing DICT in future clinical studies.

project_terms:
Affect;Affinity;Agonist;Binding;CXCR;CXCR4 Receptors;CXCR4 gene;Cancer Survivor;Cardiac;Cardiac Myocytes;Cardiometabolic Disease;Cardiotonic Agents;Cardiotoxicity;Cardiovascular Diseases;Cardiovascular system;Cell Death;Cells;Clinical Research;Development;Dexrazoxane;Disease;Dose;Down-Regulation;Doxorubicin;Etiology;FDA approved;Fibrosis;Functional disorder;Future;Genetic Transcription;Glucans;Glycogen;Health;Heart;Heart Septal Defects;Heart failure;Heterozygote;Immune;Immune response;Immunocompetent;Infarction;Infiltration;Inflammation;Inflammatory;Injury;Knockout Mice;Lymphoma;Malignant Neoplasms;Mediating;Metabolism;Mitochondria;Mus;Myocardial;Myocardial Infarction;Myocardial dysfunction;Myocarditis;Myocardium;Pathologic;Pathway interactions;Performance;Perinatal mortality demographics;Pharmaceutical Preparations;Play;Prevention approach;Refractory;Role;Series;Signal Transduction;Site;Stromal Cell-Derived Factor 1;Testing;Therapeutic;Up-Regulation;adenoviral mediated;antagonist;cardiac angiogenesis;cardiac regeneration;cardioprotection;cell mediated immune response;chemokine receptor;chemotherapy;clinical application;clinically relevant;heart defect;heart function;heart metabolism;improved;innovation;insight;mast cell;mouse model;myocardial injury;neovascularization;novel strategies;overexpression;postnatal;prevent;programs;protective effect;sensor;side effect;single-cell RNA sequencing;stem cells;treatment strategy;tumor;tumor growth;tumorigenesis

public_health_relevance:
The objective of this study is to validate an innovative concept that the unique dual TC14012 protects againstdoxorubicin-induced cardiotoxicity (DICT) by activating cardiac CXCR7 to reprogram cardiomyocytemetabolism and prevent cardiac dysfunction and by antagonizing CXCR4 to inhibit cardiac mast cell infiltrationand activation in multiple mouse models. We will first optimize the doses of TC14012 for protecting againstDICT in two tumor-free and tumor-bearing mouse models and then we will determine its direct effects andmechanisms on energy reserve metabolism and mitochondrial function in cardiomyocytes and on cardiac mastcell infiltration and degranulation. This project will reveal new insight into the underlying mechanisms behindand provide fundamental evidence for TC14012 as a novel approach for the prevention of DICT in futureclinical studies.


application_id: 10944269
project_number: 1R01MH137471-01
administering_ic: NIMH
award_notice_date: 2024-07-24
opportunity_number: PA-20-183
application_type: 1
activity_code: R01
ic: MH
serial_number: 137471
program_official: ANKUDOWICH, ELIZABETH
project_start_date: 2024-08-01
project_end_date: 2024-08-31
study_section: Adult Psychopathology and Disorders of Aging Study Section[APDA]
contact_pi_person_id: 10570976
contact_pi: ADAMS, THOMAS G
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: 2024-08-01
project_title:
Characterization and Modulation of Functional Connectivity and Fear Extinction Abnormalities in Obsessive-Compulsive Disorder

project_abstract:
ABSTRACTApproximately 60% of patients with obsessive-compulsive disorder (OCD) respond to the psychotherapy ofchoice exposure and response prevention (ERP). Unfortunately troubling symptoms persist for most patientseven treatment responders. ERP is believed to depend on safety learning and engagement of related braincircuitry. OCD patients have repeatedly demonstrated deficits in safety learning and memory processes butimportant gaps exist in this literature. In particular there are limited data on neural functions related to safetylearning and memory deficits in OCD. This is important as multiple studies have shown that OCD is associatedwith dysconnectivity in large-scale networks that are implicated in fear signaling and to safety learning namelythe default mode network (DMN) and salience network (SN). Preliminary research by the PI suggests that thatanodal (excitatory) frontopolar (over the anterior medial prefrontal cortex [mPFC]) multifocal transcranial directcurrent stimulation (tDCS) reduced resting functional connectivity between these networks and acceleratessafety learning in community volunteers. Preliminary research by the PI also suggests that frontopolar tDCSaccelerates safety learning during a single session of in vivo ERP with patients diagnosed with OCD. Theproposed R01 project would be the first to examine if OCD is associated with deficits in inhibitory safetylearning  fear extinction learning that is acquired after original fear conditioning has been consolidated intolong-term memory  and would be among the first to probe neural functions associated with extinction deficitsin OCD. The proposed R01 project would also replicate and extend the PIs exciting preliminary findings to testif frontopolar tDCS can normalize dysconnectivity and functional activity within and between the DMN and SNand recover safety learning deficits in patients with OCD. Results from this project would pave the way foradditional experimental therapeutics target engagement research; research that examine the effects offrontopolar tDCS on neural abnormalities and safety learning deficits in other anxious psychopathology (e.g.posttraumatic stress disorder) and clinical trials examining the interactive effects of frontopolar tDCS and ERPon brain dysconnectivity and symptoms of OCD.

project_terms:
Acceleration;Adult;Anodes;Anterior;Behavior Therapy;Brain;Clinical;Clinical Trials;Cognitive Therapy;Communities;Data;Diagnosis;Double-Blind Method;Expectancy;Exposure to;Extinction;Fright;Functional Magnetic Resonance Imaging;Galvanic Skin Response;Genetic Complementation Test;Insula of Reil;Investigational Therapies;Learning;Literature;Measures;Medial;Memory impairment;Methods;Neurophysiology - biologic function;Obsessive-Compulsive Disorder;Participant;Patients;Pattern;Persons;Post-Traumatic Stress Disorders;Prefrontal Cortex;Prevention;Procedures;Process;Psychopathology;Psychotherapy;Randomized;Recovery;Reinforcement Schedule;Reporting;Research;Rest;Safety;Sampling;Scanning;Shock;Signal Transduction;Standardization;Stimulus;Symptoms;Testing;Therapeutic;Training;anxious;brain circuitry;cingulate cortex;conditioned fear;conditioning;design;experimental study;functional MRI scan;in vivo;innovation;learning extinction;long term memory;memory process;neural;response;screening;signal processing;therapeutic target;transcranial direct current stimulation;treatment choice;treatment responders;volunteer

public_health_relevance:
The behavioral treatment of choice for obsessive-compulsive disorder (OCD) is exposure and response prevention (ERP) which depends on safety learning processes and large-scale brain networks that are aberrant in OCD. The proposed project would be among the first to characterize neural functions associated with safety learning and memory deficits in OCD. The target engagement aim of the proposed project would test the effects of frontopolar multifocal transcranial direct current stimulation (tDCS) on functional connectivity and functional activation of the default mode network (DMN) and salience network (SN) and on fearful responding during extinction training in patients with OCD.


application_id: 10940564
project_number: 1R15AG078992-01A1
administering_ic: NIA
award_notice_date: 2024-09-18
opportunity_number: PAR-22-060
application_type: 1
activity_code: R15
ic: AG
serial_number: 078992
suffix: A1
program_official: BAKOS, ALEXIS DIANE
project_start_date: 2024-09-19
project_end_date: 2027-08-31
study_section: Aging Systems and Geriatrics Study Section[ASG]
contact_pi_person_id: 1978589
contact_pi: SIMM, MALGORZATA
other_pis: Not Applicable
congressional_district: 05
department: NONE
primary_duns: 072667546
primary_uei: DKDHA3G4YCQ6
duns_number: 072667546
uei: DKDHA3G4YCQ6
fips: US
organization_id: 3496901
organization_name: UNIVERSITY OF PIKEVILLE
organization_city: PIKEVILLE
organization_state: KY
organization_type: SCHOOLS OF OSTEOPATHIC MEDICINE
organization_zip: 415019118
organization_country: UNITED STATES
arra_indicator: N
project_title:
The anatomical and functional study of the thymus - defining the milestones of the thymic aging in the elderly human population

project_abstract:
The concept of this program derives from our observations that the involution of the human thymus doesnot follow linear kinetics and is tailored to each individual. In most humans the involution processgradually shuts down the thymic T cell output until about the age of fifty. Still in some cases the structureand function of this primary lymphatic organ are preserved in elderly subjects until they are about 100years old. Our research plan asks how often we can find a functional thymus in the elderly and wepropose a qualitative and quantitative study of the thymic structure using cadavers in the Gross Anatomycourse at KYCOM. Applying immunohistochemistry techniques we will determine the degree of thymicinvolution and rank it by preserving the thymic epithelial space the symmetry of the involution in boththymic lobes and the presence of the T cells. To determine whether the thymus was functional at thetime of death we will apply molecular biology techniques to amplify the FoxN1 mRNA in thymic tissueand TREC (T cell receptor rearrangement excision circles) DNA in the splenocytes. Based on preliminarydata we expect to find four stages of thymic involution in elderly: (i) functional thymus with activethymopoiesis [TEC+/CD3+/FoxN1+/TREC+] (ii) functional thymus with no thymopoiesis [TEC+/CD3-/FoxN1+/TREC-] (iii) structural thymic support with no thymopoiesis and no FoxN1 activity [TEC+/CD3-/FoxN1-/TREC-] and (iv) silent involuted thymus [TEC-/CD3-/FoxN1-/TREC-]. We shall apply descriptivestatistics to find the central tendency or a typical element of the preserved thymic function in our samplein the context of the donors age and COD. We will apply inferential statistics to establish relationshipsbetween characteristics within the data sample. If we detect the functional thymus we will correlate itwith the degree of the structural preservation of the organ and the cause of death (COD). In the long-term plan we will apply the results generated from this application to predict the longevity of the immunesystem based on markers of the thymic function established in this study. This research proposal servestwo functions: (1) to meet the research goals and (2) through this REAP funding mechanism to providethe Kentucky College of Osteopathic Medicine students much-needed exposure to basic biomedicalresearch. To ensure the feasibility of the proposed work we formed an interdisciplinary team of expertsin immunology molecular biology gross anatomy and statistics. Over three years we will offer sixteenresearch Fellowships to Osteopathic Medical students to provide much-needed exposure to basicbiomedical research.

project_terms:
Age;Aging;Anatomy;Antibodies;Antigens;Biomedical Research;CD14 gene;CD3 Antigens;CD8B1 gene;Cadaver;Categories;Cause of Death;Cells;Centenarian;Cessation of life;Characteristics;Classification;DNA;Data;Diameter;Disease;Elderly;Elements;Ensure;Epithelium;Excision;Exposure to;Failure;Fellowship;Funding Mechanisms;Gender;Goals;Grant;Harvest;Height;Human;Human body;Immigrant;Immune system;Immunohistochemistry;Immunology;Individual;Kentucky;Kinetics;Learning;Lobe;Longevity;MS4A1 gene;Medical Students;Messenger RNA;Microanatomy;Molecular Biology;Molecular Biology Techniques;Organ;Organ Preservation;Osteopathic Medicine;Output;Phenotype;Population;Process;Property;Publishing;Race;Research;Research Proposals;Sampling;Sorting;Specific qualifier value;Spleen;Splenocyte;Stains;Statistical Data Interpretation;Structure;Students;Study Subject;T-Cell Receptor;T-Cell Receptor-Rearrangement Excision DNA Circles;T-Lymphocyte;Techniques;Thick;Thymic Tissue;Thymus Gland;Time;Weight;Work;age group;aged;capsule;college;end of life;human old age (65+);inferential statistics;predictive marker;preservation;primary lymphoid organ;programs;recruit;sex;statistics;student participation;thymocyte

public_health_relevance:
The concept of this program derives from our observations that the involution of the human thymusdoes not follow linear kinetics and is tailored to each individual. We ask how often we can find afunctional thymus in the elderly population and find predictors of the thymic function longevity in theelderly. The preliminary results strongly support our hypothesis that the thymus or part of the organmay function into old age. In this research proposal we aim (1) to meet the research goals specified inthree research aims and (2) to provide the Kentucky College of Osteopathic Medicine students withmuch-needed exposure to basic biomedical research through this REAP funding mechanism.


application_id: 10939536
project_number: 1R35GM155281-01
project_title: Cellular and Molecular Determinants of Post-Burn Myopathy
administering_ic: NIGMS
award_notice_date: 2024-07-18
opportunity_number: PAR-23-145
application_type: 1
activity_code: R35
ic: GM
serial_number: 155281
program_official: CHAO, CHIEN-CHUNG
project_start_date: 2024-08-01
project_end_date: 2029-05-31
study_section: Maximizing Investigators' Research Award - D Study Section[MRAD]
contact_pi_person_id: 12654514
contact_pi: OWEN, ALLISON M.
other_pis: Not Applicable
congressional_district: 06
department: OTHER CLINICAL SCIENCES
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCH ALLIED HEALTH PROFESSIONS
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
ABSTRACTSevere burn trauma triggers profound muscle atrophy and weakness which persists for years post- injury. Todate research efforts have predominantly explored hypermetabolic and catabolic signaling within muscle cellsresulting from burn injuries with limited attention to other contributing factors.. The intricate processes ofmuscle regeneration and remodeling involve multiple cell types within the muscle niche including fibroblastsand immune cells. We propose that burn injuries disrupt crucial cell-to-cell signaling pathways resulting inmuscle dysfunction that cannot be solely attributed to hypermetabolism. We are uniquely positioned to pursueour long-term goal of unveiling cellular and molecular drivers of burn-induced myopathy with the aim ofidentifying innovative therapeutic targets that preserve muscle size and function. Over the next five years wewill pursue four interconnected yet distinct projects. Project 1 will identify cellular determinants of musclefibrosis after severe burn injury. Recent findings indicate significant collagen deposition post-murine burninjury indicative of unresolved fibrosis which may increase tissue stiffness and reduce strength. We willemploy a comprehensive multi-omic (transcriptomic and proteomic) approach to unveil cellular and moleculardeterminants of burn-induced fibrosis. Identified pathological mediators will be studied through transgenic andpharmacological interventions. Various techniques will assess collagen dynamics including architectureorientation and cross-linking to comprehend ECM remodeling potential post-burn injury. Project 2 willdetermine the impact of burn injury on immune cell function and its consequence on muscle wastingand weakness. We will assess immune cell abundance and phenotype in muscle in the days to monthsfollowing burn injury. Additionally we will investigate how burn injury epigenetically metabolically andfunctionally reprograms immune cells. Upon identification of cellular perpetuators of muscle dysfunction afterburn we may pursue cell depletion strategies to directly examine their role. Project 3 will elucidate effect ofimmunomodulation on muscle physiology after burn injury. We will explore whether modifyingmacrophage phenotype using Toll-like receptor (TLR) agonists can promote healthy ECM turnover andimproves muscle mechanics and strength. Project 4 will fill the knowledge gap regarding the role of muscleMyD88 in burn-induced cachexia and muscle regeneration. MyD88 a TLR adaptor molecule expressed inmuscle has been implicated in cancer cachexia yet it is also required for myofiber regeneration. We willemploy a skeletal muscle MyD88 knockout transgenic animal to determine whether MyD88 exerts a pro-restorative or pro-wasting effect following burn injury. These projects collectively support our overarching aim:to enhance our understanding of burn-induced cellular and molecular dysfunction which will identify noveltherapeutic targets for improving muscle function in patients after severe burn injury.

project_terms:
Agonist;Architecture;Atrophic;Attention;Burn Trauma;Burn injury;Cachexia;Cancer Cachexia;Cell Physiology;Cells;Collagen;Deposition;Epigenetic Process;Extracellular Matrix;Fibroblasts;Fibrosis;Functional disorder;Goals;Hospitals;Immune;Immunologics;Impairment;Injury;Intervention;Knock-out;Knowledge;Macrophage;Mechanics;Mediator;Metabolic;Molecular;Morbidity - disease rate;Mus;Muscle;Muscle Cells;Muscle Weakness;Muscle function;Muscular Atrophy;Myopathy;Natural regeneration;Pathologic;Patients;Phenotype;Positioning Attribute;Process;Proteomics;Quality of life;Recovery of Function;Research;Role;Signal Pathway;Signal Transduction;Skeletal Muscle;Survivors;Techniques;Tissues;Toll-like receptors;Transgenic Animals;Transgenic Organisms;cell type;crosslink;immunoregulation;improved;innovation;mortality;multiple omics;muscle physiology;muscle regeneration;new therapeutic target;pharmacologic;preservation;programs;severe burns;therapeutic target;transcriptomics;wasting

public_health_relevance:
PROJECT NARRATIVESevere burn injury triggers profound muscle wasting and weakness which continues long after hospitaldischarge and results in functional limitations that impair quality of life and contribute to increased morbidityand mortality among burn survivors. The information gained in this program will advance our currentunderstanding of the mechanisms by which burn injury triggers skeletal muscle dysfunction with a uniquefocus on fibrogenic and immunologic mechanisms. Elucidating non-canonical cellular and molecularmechanisms of burn-induced muscle dysfunction will unveil therapies to mitigate atrophy and weakness afterburn injury thus improving physical functional recovery in survivors.


application_id: 10939099
project_number: 1R16AI177410-01A1
project_title: Role of epigenetic changes in intracellular survival and replication of Legionell pneumophila
administering_ic: NIAID
award_notice_date: 2024-08-30
opportunity_number: PAR-21-173
application_type: 1
activity_code: R16
ic: AI
serial_number: 177410
suffix: A1
program_official: ERNST, NANCY L
project_start_date: 2024-09-01
project_end_date: 2028-08-31
study_section: Special Emphasis Panel[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
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;Up-Regulation;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: 10938495
project_number: 7R01AG068330-05
project_title: The metabolic interplay of sleep and Alzheimer's disease
administering_ic: NIA
award_notice_date: 2024-02-13
opportunity_number: PA-21-268
application_type: 7
activity_code: R01
ic: AG
serial_number: 068330
program_official: MACKIEWICZ, MIROSLAW
project_start_date: 2020-08-01
project_end_date: 2025-04-30
study_section: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]
contact_pi_person_id: 8504528
contact_pi: MACAULEY-RAMBACH, SHANNON L
other_pis: Not Applicable
congressional_district: 06
department: PHYSIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACTA bidirectional relationship exists between Alzheimers disease and sleep where disrupted sleep increasesamyloid-beta (A) and tau pathology and conversely A and tau aggregation disrupt sleep. The sleep/wakecycle is a master regulator of metabolic and neuronal activity where daily oscillations in activity are coupled tothe production and clearance of A and tau. Although modulating neuronal activity alters both sleep/wake cyclesand A/tau release less is known about how fluctuations in glucose metabolism drive changes in sleep andAlzheimers disease related pathology. Therefore the goal of this proposal is to determine whether changes inmetabolic activity lead to changes in neuronal activity to disrupt sleep in Alzheimers disease and whethermetabolic dysfunction can serve as a novel therapeutic target to rescue sleep and Alzheimers pathology. Usinghippocampal biosensors coupled with EEG/EMG recordings this proposal will investigate how glycemicvariability and peripheral glucose intolerance affect sleep and Alzheimers disease in rodent models ofAlzheimers related pathology. Moreover we will establish whether normalizing peripheral glucose homeostasisthrough treatment with the diabetic medication metformin is sufficient to preserve and restore sleep architecturein the setting of Alzheimers disease.

public_health_relevance:
PROJECT NARRATIVEAlzheimers disease is the 6th leading cause of death in the United States and is expect to triple by 2050.Individuals with Alzheimers disease suffer from sleep disturbances and sleep disorders are associated with anincreased risk for Alzheimers disease. Since sleep/wake cycles are a dynamic interplay between metabolismand neuronal activity the goal of this project is to understand how changes in metabolism impact the relationshipbetween sleep and Alzheimers disease and whether metabolic dysfunction is a novel therapeutic target fortreating Alzheimers disease and sleep.


application_id: 10938328
project_number: 1R01HD115554-01
project_title: The Impact of Leukocyte-derived Cytokines on Ovulation in Humans
administering_ic: NICHD
award_notice_date: 2024-08-22
opportunity_number: PA-20-185
application_type: 1
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)]
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;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: 10934544
project_number: 5U54DA058256-02
project_title: AppalTRuST Biostatistics and Informatics Core
administering_ic: NIDA
award_notice_date: 2024-08-07
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 COREThe 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 willinclude biostatistics and informatics experts and staff with extensive experience developing surveys managingand analyzing data and ensuring ongoing data security. Leveraging technology resources available throughUK Markey Cancer Center BIC will house all the biostatistical and informatics resources and expertise neededto 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 needsof the AppalTRuST projects and cores; (2) collaborate with the Community Outreach & ParticipantEngagement (COPE) Core to develop data collection instruments harmonized across projects and datacollection 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 Centerinformation.BIC will oversee and coordinate all aspects of research design as well as data collection harmonization andanalyses for all projects and pilots. Data files including structured semi-structured and unstructured dataalong with data dictionaries and other documentation will be managed centrally for projects pilots and coresin BIC. To facilitate the generalizability of inferential statistical analyses BIC will also develop survey weightsfor all participants recruited to the AppalTRuST cohort. In collaboration with COPE BIC will assist each projectand pilot with coordinated development of data collection instruments to support seamless data sharinglimiting response burden for participants enrolled in more than one project and promoting synergy throughoutthe Center.BIC will also deploy informatics portals and reporting mechanisms to make data widely accessible tostakeholders with users able to access only the data they have been authorized for commensurate with theirneeds. The informatics portal will include dashboards and analytical and query tools which can be customizedto coincide with the level of stakeholder data access needed. State-of-the-art analytical methods andinformation science will support and permeate all projects pilots and cores within AppalTRuST to ensure thatthe TCORS successfully meets its goal of investigating FDA CTP regulatory priorities in Appalachian Kentuckythrough 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;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;participant enrollment;patient engagement;peri-urban;query tools;recruit;response;rural counties;socioeconomic disadvantage;structured data;synergism;timeline;tobacco products;tobacco regulatory science;tool;unstructured data;web site


application_id: 10934540
project_number: 5U54DA058256-02
project_title: AppalTRuST Community Outreach and Participant Engagement Core
administering_ic: NIDA
award_notice_date: 2024-08-07
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) COREThe Community Outreach and Participant Engagement (COPE) Core will recruit and retain the AppalTRuSTCohort of 2000 adults (ages 18+) in Appalachian Kentucky (KY) including a) an address-based probabilitysample (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 thefull AppalTRuST Cohort (N=2000) providing an adequate sample to capture estimates of tobacco usebehaviors (e.g. initiation switching transitions) over time among subpopulations of interest (e.g. youngadults tobacco users). Project 2 (n=308 ages 18-24) and Project 3 (n=473 tobacco users ages 21+) will drawfrom the Cohort. All projects pilots and TCORS partners will have access to the Cohort data through ourAppalTRuST Data Warehouse.Using established rural/urban taxonomies we selected heterogeneous counties that make up a ruralcatchment of 5 counties and a peri-urban (i.e. intermediate and smaller cities and towns) catchment of 3counties enabling projects to assess contextual- and individual-level effects of rurality on outcomes enhancinginnovation and our ability to inform more equitable FDA regulations. COPE Aims are to: (1) develop andimplement a culturally tailored community-engaged outreach campaign to promote participation in theAppalTRuST Cohort; (2) implement strategic recruitment and baseline data collection for the AppalTRuSTCohort (Project 1) and recruitment into the other projects and pilot studies; (3) implement strategic retentionstrategies and administer 6-month follow-up surveys; and (4) disseminate AppalTRuST research findings tothe community to sustain support and retention.COPE will co-design a community outreach campaign with two community advisory boards (one percatchment) with promotional materials tailored for Appalachian KY that are strategically disseminated to reachsubpopulations of interest (e.g. tobacco users). COPE will hire train and monitor local field staff to recruit andenroll participants into the AppalTRuST Cohort and manage completion of 6-month follow-up surveys. Cohortparticipants will complete 3 to 8 surveys depending on time of enrollment in Project 1. Multiple strategies willmaximize retention including our community outreach campaign and monthly contact between participantsand field staff. Our community dissemination plan will report back AppalTRuST study findings to sustaincommunity support and Cohort retention. The innovative approaches implemented by COPE will supportAppalTRuST in closing a critical knowledge gap in rural tobacco use behaviors marketing and impact analysisto help shape more equitable FDA regulations.

project_terms:
Address;Adult;Age;Appalachian Region;Back;Behavior;Biometry;Calibration;Cities;Communities;Community Outreach;County;Data;Data Collection;Devices;Electronic Mail;Electronics;Enrollment;Ensure;Equity;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: 10934537
project_number: 5U54DA058256-02
project_title: AppalTRuST Career Enhancement Core
administering_ic: NIDA
award_notice_date: 2024-08-07
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 COREThe need for researchers who understand Tobacco Regulatory Science (TRS) and can translate science tosupport effective regulatory policies is vital for rural communities which have some of the highest tobacco useand associated morbidity rates in the nation. The goal of the AppalTRuST Career Enhancement Core (CEC) isto create a transformative environment that provides mentored multidisciplinary and immersive careerenhancement experiences to expand and support TRS scholars with a critical emphasis on the impact ofregulatory policies in rural communities. The CEC will target inquisitive and dedicated scholars with diverseprofessional and demographic backgrounds and high potential to become independent TRS researchers.Building on Center expertise we will recruit two cohorts of AppalTRuST Scholars each consisting of twoFaculty Scholars and two Postdoctoral Scholars. These AppalTRuST Scholars will be recruited for a two-yearnon-overlapping experience. Each scholar will work with a mentoring team and participate in multidisciplinaryTRS enrichment activities enjoying close monitoring of progress toward scientific career independence.Specifically AppalTRuST Scholars will receive personalized mentoring and career enhancement experiencesthrough cohort-building multidisciplinary TRS enrichment activities including weekly meetings seminarsjournal clubs and a NIH-modeled grant writing series of workshops. AppalTRuST Scholars will also receivehands-on experience in TRS research working as part of the research team of one of three AppalTRuSTprojects and then developing their own (Scholar-led) TRS pilot project. AppalTRuST Scholars will benefit fromthe Cross-TCORS Visiting Scholars Program that will introduce them to scientific domains outside ofAppalTRuST and promote collaborative networks among other TCORS investigators.CEC will work closely with Project Leads the Administrative Core the Community Outreach and ParticipantEngagement Core (COPE) and the Biostatistics and Informatics Core (BIC) to ensure AppalTRuST Scholarshave ample resources and opportunities to learn innovative methodologies applied to the rural context. FinallyCEC will collaborate with the Administrative Core to sponsor an AppalTRuST TRS Seminar Series. Four timesa year CEC will host these seminars to create collegial and collaborative networks. We will specifically inviteFDA scientists and TCORS faculty and scholars from other TCORS to present and inform AppalTRuSTresearchers and the broader TRS community about synergistic opportunities methodologic advances andnew research findings across the TCORS community. The seminars will be open to all as they will bestreamed recorded and archived on the AppalTRuST website. Impact. The AppalTRuST CareerEnhancement Core will develop independent scholars who can design and lead rigorous studies that informFDAs tobacco regulatory decision-making in underserved and understudied rural communities ultimatelyreducing tobacco-related morbidity and mortality.

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;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: 10934533
project_number: 5U54DA058256-02
project_title: AppalTRuST Administrative Core
administering_ic: NIDA
award_notice_date: 2024-08-07
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 COREThe Administrative Core (Admin Core) will provide leadership and communications infrastructure strategicplanning and financial management to facilitate the work of all AppalTRuST components as well as advancecollaboration with the wider TCORS community. AppalTRuSTs overarching goal is to investigate the impact ofFederal Drug Administration Center for Tobacco Products regulatory policies in rural communities throughcollaboration education and pioneering tobacco regulatory science (TRS). Specifically the Admin Core willprovide scientific oversight by fostering shared knowledge and maximizing interactions to ensure scientific rigorand transparency. The Admin Core will lead an Executive Committee meeting twice per month with all ProjectPIs and Core Leaders. To ensure representation engagement and input from the study communities inAppalachian 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. Toadvance educational collaboration and maximize interactions with the wider TCORS community and Federalpartners the Admin Core will work with the Career Enhancement Core (CEC) to sponsor a quarterlyAppalTRuST TRS Seminar Series to engage the TCORS community and share synergistic opportunitiesmethodologic advances and new research findings. The Admin Core will also collaborate with the CEC tosponsor an AppalTRuST Visiting Scholar Program to allow faculty and/or trainees from other TCORS toparticipate in a one-week in-depth learning experience in rural TRS. To provide quality control and evaluationacross projects and cores the Admin Core alongside the Biostatistics and Informatics Core (BIC) and COPEwill oversee a monthly quality control and evaluation meeting to foster seamless tracking and coordinating ofall activities recruitment participant flow data collection and data management. To provide administrativeoversight the Admin Core will guide and coordinate internal and external communications and coordinationfinancial planning and management as well as the research and grants administrative processes. An ExternalAdvisory Board made up of leading scientific experts will meet annually to provide critical counsel and ensurethe Center is meeting its stated goals. An Internal Advisory Board of key University scientific and administrativestakeholders will meet annually to provide counsel and advice and ensure AppalTRuST is able to effectivelyleverage UK and community resources to meet its goals. Impact: The Admin Core will provide the necessaryorganization and leadership to ensure an efficient collaborative infrastructure that will enhance synergiesacross AppalTRuST as well as advance collaboration with the wider TCORS community. Given thatAppalachia is a vulnerable rural region disproportionately impacted by socioeconomic disadvantage andtobacco use the Admin Core will lead AppalTRuST in closing a critical knowledge gap in rural tobacco usebehaviors marketing and impact analysis to help shape more equitable FDA regulations.

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;Equity;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;Pharmaceutical Preparations;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 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: 10934529
project_number: 5U54DA058256-02
administering_ic: NIDA
award_notice_date: 2024-08-07
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: 2024-09-01
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 3Our overall goal reflecting AppalTRuSTs Integrative Theme of investigating the effects of regulatory changeson tobacco product use in Appalachian KY is to assess the impact of proposed tobacco product regulationsusing behavioral economic methods that we have developed and refined in past years to characterize theconsumption of tobacco products within the complex nicotine marketplace of Appalachian KY a diverse andunderserved rural region that would greatly benefit from focused tobacco regulatory science research. Thisproject primarily falls under the Regulatory Scientific Domain of Impact Analysis. In 2009 the Food and DrugAdministration (FDA) was granted authority to regulate tobacco products to benefit public health. In the yearssince the FDA has proposed potential regulatory actions that may benefit public health including regulatingthe maximum nicotine content in combustible cigarettes and restricting flavors of combusted and non-combusted tobacco products. Estimating the impact of any proposed regulatory action is complicated by theexistence of a complex tobacco marketplace containing multiple products that are economic substitutes for oneanother and the frequent introduction of new tobacco products by manufacturers. Furthermore whencompared to more urban non-Appalachian communities rural Appalachian communities often have 1) higherrates of tobacco product use overall 2) different use patterns that include more combusted tobacco productsand 3) different product availability in tobacco stores. It is therefore important to estimate any differential impactof 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 ismeasured across tobacco products we will estimate the impact of regulating 1) nicotine content of combustedcigarettes 2) menthol flavor restrictions in combustible cigarettes and 3) flavor additive restrictions in non-combusted nicotine/tobacco products including ENDS. Across two aims we will assess the impact of thesethree regulations within Appalachia (Aim 1) and the effect of rurality on impact of these proposed regulations inAppalachia (Aim 2).

project_terms:
Appalachian Region;Behavior;Biometry;Catchment Area;Cigarette;Cities;Communities;Community Outreach;Complex;Consumption;Data;Economics;Elasticity;Environment;Goals;Grant;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;rural underserved;rurality;tobacco products;tobacco regulation;tobacco regulatory science;urban area


application_id: 10934522
project_number: 5U54DA058256-02
administering_ic: NIDA
award_notice_date: 2024-08-07
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: 2024-09-01
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 2Federal tobacco regulatory policies enacted by the US Food and Drug Administration (FDA) are critical to curbthe tobacco epidemic in rural Appalachia and reduce cancer burden. Kentucky (KY) is 50th in the nation foradult smoking rates with 21.4% of KY adults smoking cigarettes a rate not seen nationally in 20 years.Kentucky also has wide geographic disparities between rural and urban residents particularly in AppalachianKY an economically disadvantaged part of the state. In this context Federal policies can be particularlyinfluential in areas with weak tobacco control policies and high rates of tobacco use. In particular (1) theintroduction of novel non-combustible products (2) product standards on flavored cigars/menthol cigarettesand (3) lowering nicotine in cigarettes have great potential to shift the tobacco marketplace moving ruralAppalachian residents to quit smoking switch to potentially less harmful products or never initiate tobacco useat all. Project 2 seeks to expand the evidence base about the extent to which marketing exposure tobacco usebehaviors and attitude towards tobacco products differ across rural communities and the extent to whichregulatory 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 couldinteract to reduce tobacco-related health disparities among young adult populations by rurality. Tobaccoretailer density is higher in rural areas by population but little is known about how retailers market in stores inthis region. The purpose of the study is to examine how marketing and product availability of such noveltobacco products may change over time and how these patterns may influence tobacco use attitudes andpatterns in rural communities providing guidance on future policy targets. To accomplish the study purposewe 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 comparemarketing exposure to and appeal and harm perceptions of novel products in young adults through ecologicalmomentary 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 marketingexposure on use of tobacco at 6-month and 12-month follow-up and evaluate whether these outcomes areassociated with rurality. For all of these activities we will partner closely with the AppalTRUST team coresand local community advisory boards to disseminate lessons learned to communities about industry actionsand potential regulatory policies. Achieving the aims of this Project will expand the evidence base of thepotential impacts of FDA policies on reducing tobacco use and potential geographic equity impact of thesepolicies to reduce tobacco and ultimately cancer disparities.

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;Disparity;Ecological momentary assessment;Electronic cigarette;Environment;Epidemic;Equity;Exposure to;Frequencies;Future;Geography;Goals;Individual;Industry;Influentials;Kentucky;Link;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;cancer health disparity;community advisory board;density;digital;economic disparity;electronic liquid;evidence base;experience;federal policy;follow-up;geographic disparity;health disparity;innovation;low nicotine content cigarette;novel;peri-urban;public policy on tobacco;reduce tobacco use;response;rural area;rural counties;rural disparities;rurality;smoking cessation;social media;socioeconomic disadvantage;theories;tobacco advertising;tobacco exposure;tobacco flavor;tobacco products;tobacco regulation;tobacco regulatory science;tobacco user;urban area;web site;young adult


application_id: 10934519
project_number: 5U54DA058256-02
project_title: AppalTRuST Project 1: Population based Cohort study of tobacco use prevalence in Appalachian KY
administering_ic: NIDA
award_notice_date: 2024-08-07
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 1Rural populations who use tobacco at almost double national rates have largely been omitted from studies ofthe potential impact of tobacco regulations. AppalTRuSTs overarching goal is to investigate the impact ofFederal Drug Administration Center for Tobacco Products (FDA CTP) regulatory changes on tobacco productuse in rural communities and examine variation based on relative rurality. The FDA regulatory policies have anoutsized potential to reduce tobacco-related disparities in rural Appalachia and the rest of rural America giventhe relatively limited disincentives for use in these areas (i.e. few smoke-free laws and low tobacco taxes). Thegoal of Project 1 (P1) is to close the rural tobacco disparities knowledge gap by documenting tobacco usebehaviors and related factors over time among Appalachian KY adults (18+ years) to inform current and futureFDA 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 andexternal cues with tobacco use behaviors. P1 will use the AppalTRuST Cohort to enroll 2000 participantsusing a longitudinal cohort design that will collect participant data every 6 months for four years. We will recruitadults 18+ years from two catchment areas comprising 8 Appalachian KY counties; these two areas representa 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 useindicators and relative rurality within each catchment area. In addition 40 participants from the Cohort per yearwill complete key informant interviews to assess opinions about tobacco products and regulations and allow usto make annual updates to the survey. We will address the following aims: (1) evaluate baseline prevalenceand longitudinal trends in the use of conventional (cigarettes smokeless tobacco hookah cigars/cigarillosand 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 amongAppalachian adults testing for the effect of rurality and controlling for individual- and county-leveldemographics; (2) assess changes over time in knowledge attitudes and perceptions relative to tobaccoproduct characteristics (including flavors/menthol and VLN) among Appalachian KY adults while evaluatingthe effect of rurality and controlling for demographics; and (3) explore perceived benefits risks and intentionsto use novel tobacco products among current tobacco product users and individuals susceptible to initiatingnovel product use with annual key informant interviews to capture reaction to changes in the product andregulatory landscape. We will evaluate the effects of the introduction of novel products and potentialrestrictions on flavored and high-nicotine products in rural communities so that regulatory decisions will bemade using a health equity lens and be guided by a definition of rurality that is diverse and heterogeneous.

project_terms:
Address;Adult;Appalachian Region;Area;Attitude;Behavior;Catchment Area;Censuses;Characteristics;Cigar;Cigarette;Cities;Cohort Studies;County;Cues;Data;Disincentive;Disparity;Electronic cigarette;Enrollment;Equity;Funding;Future;Geographic Locations;Goals;Health;Heterogeneity;Income;Individual;Inequity;Interview;Kentucky;Knowledge;Longitudinal Studies;Longitudinal cohort;Longitudinal trends;Marketing;Masks;Measures;Menthol;Methods;Modeling;Nicotine;Participant;Pattern;Perception;Pharmaceutical Preparations;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 National Institutes of Health;Update;Urbanization;Variant;Visit;cigarette smoking;cigarillos;cohort;demographics;density;design;electronic cigarette use;health belief;health equity;heated tobacco products;hookah;informant;innovation;insight;low nicotine content cigarette;multidisciplinary;novel;peri-urban;policy implication;population based;recruit;residence;rural America;rural area;rurality;smoke-free policy;tobacco products;tobacco regulation;tobacco regulatory science;urban area


application_id: 10934518
project_number: 5U54DA058256-02
project_title: Appalachian Tobacco Regulatory Science Team (AppalTRuST)
administering_ic: NIDA
award_notice_date: 2024-08-07
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:
ABSTRACTThe overall goal of the Appalachian Tobacco Regulatory Research Team (AppalTRuST) is to investigate theimpact of Federal Drug Administration Center for Tobacco Products (FDA CTP) regulatory policies in ruralcommunities a vulnerable and understudied population through collaboration education and pioneeringregulatory scientific research. Our multidisciplinary team will investigate this question with two aims.Aim 1. Facilitate and pioneer regulatory science research in rural communities. Our multidisciplinaryteam of researchers will evaluate current and potential regulatory policies across Projects 1-3 that aremethodologically coherent and interrelated with a focus on the regulatory scientific domains of BehaviorMarketing and Impact Analysis. P1-P3 will leverage the AppalTRuST Cohort to address the critical regulatoryquestion of whether FDA CTP policy actions will be beneficial shifting individuals to lower harm products orquitting tobacco in rural communities or not in a way that assesses the association between outcomes andlevel of rurality. P1 will measure the factors associated with tobacco use behaviors of conventional and novelproducts including initiation progression dual/poly tobacco use product switching and cessation-relatedbehaviors across levels of rurality over time. P2 will evaluate how FDA regulations may affect patterns of usefor conventional and novel products among young adults across levels of rurality. P3 will use a randomizedparallel groups trial to assess the impact of three proposed tobacco regulations using an ExperimentalTobacco Marketplace to estimate effects of regulatory policies on use behavior across levels of rurality.Aim 2. Support and create new opportunities for innovative tobacco regulatory science and contributeto the national efforts to advance TCORS research through education and collaboration. The followingfour cores will support the projects to ensure Center coordination integration and collaboration: (1) anAdministrative Core to provide efficient collaborative infrastructure to enhance synergies across the threeprogram projects and four cores as well as collaboration with the wider TCORS community; (2) a CommunityOutreach and Participant Engagement Core to engage rural and peri-urban Appalachian communities tosupport our AppalTRuST Cohort; (3) a Biostatistics and Informatics Core to build a centralized integrated datawarehouse supported by statistical and informatics expertise to collect harmonize and analyze data andprovide statistical support for projects and cores; and (4) a Career Enhancement Core to create atransformative environment offering mentored multidisciplinary and immersive experiences to expand andsupport TRS scholars with emphasis on the impact of regulatory policies in rural areas. Impact: AppalTRuSTwill provide the scientific resources needed to evaluate the effects of the introduction of novel products andpotential restrictions on flavored and high-nicotine products in rural communities so that regulatory decisionswill be made using a health equity lens and guided by a definition of rurality that is diverse and heterogeneous.

project_terms:
Address;Adult;Affect;Age;Appalachian Region;Area;Behavior;Biometry;Calibration;Cancer Center;Collaborations;Communities;Community Outreach;County;Data;Data Science;Discipline of Nursing;Disparity;Ecological momentary assessment;Education;Ensure;Environment;Epidemiology;Evaluation;Future;Goals;Heterogeneity;Individual;Informatics;Infrastructure;Kentucky;Knowledge;Link;Marketing;Measures;Medicine;Menthol;Mentors;Methodology;Nicotine;Outcome;Participant;Patient Recruitments;Pattern;Pharmaceutical Preparations;Policies;Population;Probability Samples;Public Health;Randomized;Regulation;Research;Research Institute;Research Personnel;Resources;Rural;Rural Community;Sampling;Science;Shapes;Subgroup;Time;Tobacco;Tobacco use;Traumeel S;Universities;Variant;career;cohort;college;community engaged research;cost efficient;data integration;data warehouse;design;experience;health economics;health equity;innovation;low nicotine content cigarette;multidisciplinary;novel;patient engagement;peri-urban;polytobacco use;programs;prospective;public policy on tobacco;recruit;rural area;rurality;synergism;tobacco advertising;tobacco products;tobacco regulation;tobacco regulatory science;tobacco user;young adult

public_health_relevance:
Project NarrativeThe Appalachian Tobacco Regulatory Research Team (AppalTRuST) will investigate the impact of FederalDrug Administration Center for Tobacco Products (FDA CTP) regulatory policies in rural communities avulnerable and understudied population through collaboration education and pioneering regulatory scientificresearch. Our three projects and four cores are designed to bridge the knowledge gap in rural tobacco usebehaviors guided by a definition of rurality that accounts for heterogeneity. Our approach is designed to informthe use of a health equity lens in shaping current proposed and future FDA regulatory actions to reduce ruraltobacco use disparities.


application_id: 10933760
project_number: 3UL1TR001998-08S1
project_title: Kentucky Center for Clinical and Translational Science
administering_ic: NCATS
award_notice_date: 2024-07-17
opportunity_number: PA-21-071
application_type: 3
activity_code: UL1
ic: TR
serial_number: 001998
suffix: S1
program_official: DOYLE, JAMIE MIHOKO
project_start_date: 2016-08-15
project_end_date: 2026-06-30
study_section: ZTR1-SRC(99)
contact_pi_person_id: 6773599
contact_pi: KERN, PHILIP A
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
project_abstract:
Contact PD/PI: Kern Philip A.PROJECT SUMMARY  OVERALL The University of Kentucky (UK) Center for Clinical and Translational Science (CCTS) has created anintegrated home for clinical and translational research which promotes scientific progress and discoveries atevery phase of the translational continuum. The CCTS has partnered with communities in Central Appalachiato address multiple generations of recalcitrant health inequities related in part to the economic distress of ruralcommunities. The CCTS has fundamentally transformed UK and Central Appalachia through the developmentof strong academic-community research networks and collaborations within the CTSA consortium.Appalachian health disparities are further magnified by the opioid and substance abuse epidemic which hasgreatly impacted eastern Kentucky and West Virginia. The strong UK research portfolio puts the UK CCTS inan optimal position to lead local regional and national research efforts focused on rural health inequities. The aligned missions of UK UK HealthCare and the CCTS focus on achieving health equity by engaging inhighly innovative collaborative and dynamic translational research to address rural health needs. The CCTSwill continue to educate the translational workforce of the future engage rural communities in translational andbi-directional team science and work with the national network to advance transdisciplinary research andclinical trials through the following Specific Aims: 1) develop innovate and transform our research environmentto promote impactful science and discovery within our integrated health care system to meet the unique healthneeds of Central Appalachian residents; 2) lead institutional innovation in the delivery of impactful clinical andtranslational research that covers the lifespan fully engages the community and embraces team science; 3)catalyze an efficient university-wide clinical trials organization which adds value to the CTSA consortium byengaging participants from rural Central Appalachia; and 4) foster and enhance a workforce characterized bydiversity and inclusivity across all translational science disciplines and populations. The UK CTSA hub isuniquely positioned in the National CTSA Consortium to foster novel technologies team science clinical trialstart-up and cutting-edge translational research across the lifespan with a focus on rural communities. Wehave a particular focus on the Central Appalachian community a rural area with many of the highest levels ofhealth disparities in the nation. This focus will ultimately elevate the health and quality of life of ruralcommunities throughout the United States.Project Summary/Abstract Page 276Contact PD/PI: Kern Philip A.

project_terms:
Academic Medical Centers;Acceleration;Address;Agriculture;Appalachian Region;Award;COVID-19 pandemic;Cardiovascular system;Clinical;Clinical Research;Clinical Sciences;Clinical Trials;Clinical and Translational Science Awards;Collaborations;Communities;Complement;Computer software;Dedications;Development;Diabetes Mellitus;Discipline;Distress;Economics;Engineering;Environment;Epidemic;Fostering;Funding;Future;Generations;Grant;Growth;Health;Health Sciences;Health Status;Healthcare;Home;Institution;Integrated Health Care Systems;Intervention;Investments;Kentucky;Lead;Malignant Neoplasms;Medical;Medical center;Mission;Modeling;National Center for Advancing Translational Sciences;Neurosciences;Obesity;Participant;Patients;Persons;Phase;Policies;Population;Positioning Attribute;Quality of life;Reporting;Research;Resources;Rural;Rural Community;Rural Health;Science;Sports;Substance Use Disorder;Substance abuse problem;Translational Research;Translations;Underserved Population;United States;Universities;West Virginia;Work;clinical center;clinical research site;collaborative environment;college;community engagement;community research;diversity and inclusion;health disparity;health equity;health inequalities;improved;innovation;inter-institutional;life span;new technology;opioid abuse;patient engagement;programs;recruit;response;rural area

public_health_relevance:
PROJECT NARRATIVE  OVERALLThe UK CTSA program hub is uniquely positioned in the National CTSA Consortium to foster noveltechnologies team science clinical trial start-up and cutting-edge translational research across the lifespan.Our UK CTSA hub has a significant presence on the national stage and our focus on the Central Appalachiancommunity a rural region with many of the highest priorities (i.e. cardiovascular neuroscience cancerobesity/diabetes) of health disparities in the nation and an epicenter for the opioid and substance abuseepidemic distinguishes our mission and activities. The programs in this proposal will ultimately elevate thehealth and quality of life for people of this region and provide a national model for rural underservedpopulations.Project Narrative Page 277


application_id: 10933403
project_number: 5R42CA243600-03
administering_ic: NCI
award_notice_date: 2025-08-27
opportunity_number: PA-22-178
application_type: 5
activity_code: R42
ic: CA
serial_number: 243600
program_official: EVANS, GREGORY
project_start_date: 2023-09-25
project_end_date: 2026-08-31
study_section: Special Emphasis Panel[ZRG1-ISB-Z(10)B]
contact_pi_person_id: 8252681
contact_pi: YU, GUOQIANG
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 078515036
primary_uei: HSZNRZ4JS954
duns_number: 078515036
uei: HSZNRZ4JS954
fips: US
organization_id: 10032228
organization_name: BIOPTICSTECHNOLOGY, LLC
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 405131245
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2025-09-01
project_title:
Development of a Wearable Fluorescence Imaging Device for IntraoperativeIdentification of Brain Tumors

project_abstract:
ABSTRACTApproximately 700000 people in the United States are diagnosed with a primary brain tumor. Of these malignantgliomas (MGs) account for approximately 40% of all intracranial tumors with an overall survival rate of only~34%. Surgical resection remains the cornerstone of therapy and the extent of resection correlates with survival.Fluorescence imaging has emerged as an adjunctive technique allowing for real-time cancer-specific detection.Surgeries guided by fluorescence imaging achieve gross-total-resection (GTR) rates of 75-100% which aresignificantly higher than conventional surgeries with GTR rates of 30-55%. However most clinical-grade imagingsystems are hampered by high costs limited portability and lack of operation flexibility. Some neurosurgicalfluorescence microscopes cost upwards of ~$500K and weigh ~800 pounds (PENTERO 900 with fluorescencekits Carl Zeiss). Many surgeons prefer and continue to use wearable surgical eye loupes which allow forconvenient and fast operation but are not capable of fluorescence visualization. Supported by the STTR Phase1 Award (R41CA243600) and Kentucky State Matching Fund Bioptics Technology (BOT) has developed a low-cost wearable FLoupe device (US Patent Application #62/530613 2017) attached to surgical eye loupes forintraoperative identification of fluorescent MGs. We have tested FLoupe prototypes to image fluorescent MGsduring surgery in a small group of patients. Comparable results are observed against the PENTERO 900system. Based on neurosurgeons feedback in Phase 1 this Phase 2 project will further optimize the headlights(LEDs) video camera emission filters electrical control system and mechanical design of the FLoupe devicein terms of weight size imaging quality and ease to wear/operate (Aim 1). The optimized FLoupe device willbe calibrated and validated against the PENTERO 900 system for equivalence to image fluorescent MGs in alarge group of patients (Aim 2). We expect that fluorescence images taken at the surgical site and from biopsiedsamples by both devices will be equivalent and agree with the blinded histopathological analyses (the goldstandard). Resulting data will be used for FDA clearance via the pre-market notification 510(k) submission withthe PENTERO 900 system as the primary predicate. Compared to the PENTERO 900 system the FLoupedevice is significantly less expensive (<$10K unit sale price) more compact (wearable) and easier to operate(hand free with wireless control). This affordable and wearable device will significantly increase the ability ofneurosurgeons to conduct fast and thorough operations thus improving patient safety and outcomes. At the endof this Phase 2 a clinical-grade FLoupe device will be generated as a pre-manufactured product forintraoperative identification of MGs. Moreover the FLoupe device with a modular design is easily modifiedwith optimized excitation lights and emission filters to image a variety of visible dyes (e.g. fluorescein 5-ALAmethylene blue). Thus our product has the potential to be incorporated in other surgical settings beyond braintumor resection based on the fluorescence characteristics of cancers thereby expanding its market share.

project_terms:
Agreement;Amino-Levulinic Acid;Award;Biopsy Specimen;Blinded;Bluetooth;Brain Neoplasms;Calibration;Characteristics;Clinical;Clinical assessments;Color;Conventional Surgery;Data;Detection;Development;Devices;Diagnosis;Diffuse;Dyes;Ensure;Equilibrium;Equipment;Excision;Eye;Feedback;Fluorescein;Fluorescence;Fluorescent Dyes;Funding;Hand;Hospitals;Image;Imaging Device;Intracranial Neoplasms;Kentucky;Legal patent;Malignant Glioma;Malignant Neoplasms;Marketing;Mechanics;Methylene blue;Microscope;Movement;Neurosurgeon;Normal tissue morphology;Notification;Obstruction;Operative Surgical Procedures;Outcome;Patient-Focused Outcomes;Patients;Performance;Persons;Phase;Price;Primary Brain Neoplasms;Raspberry Pi;Resected;Sales;Side;Site;Small Business Technology Transfer Research;Surgeon;Survival Rate;System;Techniques;Technology;Testing;Time;Tissues;Touch sensation;Tracer;United States;Visualization;Weight;brain tumor resection;cancer imaging;commercialization;cost;design;flexibility;fluorescence imaging;fluorescence microscope;fluorescence-guided surgery;imaging system;improved;innovation;manufacture;miniaturize;neoplastic cell;neurosurgery;operation;patient safety;portability;prototype;tumor;wearable device;wireless;wireless fidelity

public_health_relevance:
PROJECT NARRATIVEFluorescent imaging of cancers during surgery allows real-time cancer-specific detection for guiding tumorremoval often resulting in significant improvements in patient survival; however it is hampered by largeexpensive equipment. Bioptics Technology (BOT) is developing an innovative low-cost wearable fluorescenceimaging device (FLoupe BOT brand) that attaches to standard surgical eye loupes to help neurosurgeonseasily and accurately identify brain tumors for safe and maximal removal. This affordable and wearable devicewill significantly increase the ability of more surgeons to conduct fast and thorough operations and thusimproving patient safety and outcomes.


application_id: 10933393
project_number: 5R01GM149620-02
administering_ic: NIGMS
award_notice_date: 2024-08-23
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: GM
serial_number: 149620
program_official: WANG, PEGGY
project_start_date: 2023-09-25
project_end_date: 2026-08-31
study_section: Clinical Data Management and Analysis Study Section[CDMA]
contact_pi_person_id: 10376668
contact_pi: CLARKSON, MELISSA
other_pis: Not Applicable
congressional_district: 06
department: 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
budget_start_date: 2024-09-01
project_title:
Representing Human Anatomy for Computation and Communication: Synergistic Development of an Anatomical Ontology and Semantically-Augmented Anatomical Graphics

project_abstract:
Project summaryOntologies represent a domain of knowledge in a form that can be used by both computers andpeople. Biomedical ontologies provide standardized representations of knowledge that underlie modernbiomedical research and serve as knowledge bases for enabling intelligent software applications. TheFoundational Model of Anatomy (FMA) is an ontology of human anatomy and has a rich history as one ofthe first biomedical ontologies. After 20 years of development two issues that affect the ability of theFMA to continue to serve as a source for standardized computable knowledge of human anatomy havebecome apparent: First variation in modeling schemes and inter-author variation have introducedinconsistencies such that similar structures within the body are represented in slightly different ways.Second ontologies rely on textual and logical representations yet visual representations are often moreeffective for communicating about anatomy. These issues highlight the need for a next-generationresource for human anatomy that is optimized for use by both computers and people. In this project we will undertake synergistic development of an ontology of human anatomy andstandardized visual representations of human anatomy. Aim 1: To develop an ontology of humananatomy suitable for computational reasoning that will serve as a knowledgebase for the next generationof medical information systems we will create the Foundational Model of Human Anatomy (FMHA) as aderivative of the FMA. Aim 2: To provide standardized visual representations of human anatomy for usein information systems we will develop libraries of composable graphics depicting canonical anatomythat will be augmented with computer-readable semantics. Aim 3: To demonstrate use of the FMHA andstandardized graphics to address real-world needs in research education and clinical contexts we willexpand our graphic libraries beyond depictions of canonical anatomy and develop two web applications.Aim 4: To demonstrate how developers can leverage the FMHA and graphics in their own webapplications we will develop a web application for graphically-driven exploration of the DiseaseOntology. By developing the FMHA and anatomical graphics libraries as highly-curated resources they willserve as trustworthy knowledge sources for biomedical applications in data science. By integrating text-based and visual representations of anatomy we will help to ensure that researchers accuratelyannotate the anatomical content of datasets and models using FMHA classes thereby helping topreserve the integrity of integrated datasets and models.1

project_terms:
Address;Affect;Anatomic Models;Anatomy;Biomedical Research;Body System;Clinical;Clinical Medicine;Communication;Communities;Computer software;Computers;Data Science;Data Set;Development;Disease;Education;Human;Human Resources;Informatics;Information Resources;Information Systems;Knowledge;Libraries;Medical Illustration;Medicine;Modeling;Modernization;Names;Ontology;Patient Care;Patients;Pattern;Persons;Positioning Attribute;Production;Readability;Recording of previous events;Research;Research Personnel;Resources;Scheme;Semantics;Source;Standardization;Structure;Text;Time;Variant;Visual;Work;base;biomedical ontology;clinical application;computable knowledge;computational anatomy;computational reasoning;data integration;data modeling;design;human model;knowledgebase;medical information system;multidisciplinary;next generation;ontology development;preservation;skills;trustworthiness;web app

public_health_relevance:
Project narrativeThis project will create knowledge resources about human anatomy that will combine textual logical andvisual representations. These are designed to be understood by both computers and people. This workwill enable clinical research and educational software applications to use information about humananatomy.1


application_id: 10932537
project_number: 3R01DK121797-06S1
project_title: Novel Liver Signaling Pathways Controlling Adiposity
administering_ic: NIDDK
award_notice_date: 2024-05-08
opportunity_number: PA-19-056
application_type: 3
activity_code: R01
ic: DK
serial_number: 121797
suffix: S1
program_official: BURGESS-BEUSSE, BONNIE L
project_start_date: 2020-07-03
project_end_date: 2024-12-31
study_section: Molecular and Cellular Endocrinology Study Section[MCE]
contact_pi_person_id: 9293438
contact_pi: HINDS, TERRY 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
project_abstract:
There is little doubt that we are in the midst of a worldwide epidemic of obesity. Almost two-thirds of adults in theUnited States are obese or overweight. Whether if obesity arises from genetic factors or high caloric intake itstill may lead to insulin resistance and type II diabetes. Our recent data show that bilirubin (BR) which has beentypically considered as an antioxidant may function as a metabolic ligand that signals to the nuclear receptortranscription factor PPAR to reduce lipid accumulation. We also found that BR induces the hepatic fibroblastgrowth factor 21 (FGF21) hormone via PPAR which is known to have systemic effects on insulin sensitivity.Hepatic lipid accumulation and insulin resistance are interlocking pathophysiologic events but the mechanismsof these abnormalities and how these distinct processes interact are inadequately understood. For unknownreasons BR plasma levels are lower in the obese and several obese patients progress to nonalcoholic fattyliver disease (NAFLD) which is likely due to obesity-induced insulin resistance. However in patients withpathological liver disease such as Crigler-Najjar syndrome the BR plasma levels are very high. This paradoxmay be explained by the hepatic UDP-glucuronosyltransferase 1-1 (UGT1A1) enzyme that conjugates BR tomake it soluble and for deposition into bile and eventually into the intestine which lowers unconjugated BR fromthe blood. In humans a polymorphism in the UGT1A1 gene (UGT1A1*28) known as Gilberts syndrome (GS)reduces expression resulting in increased plasma BR levels but not in liver disease. We have shown thathumanized mice with the Gilberts polymorphism (UGT1A1*28) on a high-fat diet have significantly higher plasmaBR levels reduced adiposity and insulin intolerance and are resistant to fatty liver disease. Agents that regulateUgt1a1 during weight gain or loss are unknown. In the preliminary data we show exciting data that microRNA-365 (miR365) suppresses Ugt1a1 expression and increases plasma BR levels. We also found that Ugt1a1expression is higher in the livers of obese mice while miR365 and plasma BR levels are lower which indicatesthat miR365 targeting Ugt1a1 may be beneficial in increasing plasma BR to regulate adiposity. Our centralhypothesis is that BR functions as a metabolic ligand that activates the liver PPAR-FGF21 pathway to reduceadiposity and insulin resistance. We will pursue this plan with three primary scientific aims: 1) Determine theselectivity of BR on PPAR isoforms; 2) Determine the systemic effects of BR mediated by hepatic FGF21; and3) Determine if miR365 elevation of BR reduces adiposity and insulin resistance via PPAR. Collectively thisproject is the first systematic investigation of the BR-PPAR-FGF21 module and its control of insulin resistanceassociated with obesity. The proposal provides advances to new strategies (miR365) of targeting this module tocontrol adiposity which offers therapeutic benefits.

project_terms:
Adenovirus Vector;Adipocytes;Adipose tissue;Adult;Affect;Antioxidants;Attenuated;Bile fluid;Bilirubin;Biliverdin reductase;Biliverdine;Binding;Blood;Blood Glucose;Body Weight;Body Weight decreased;Cardiovascular Diseases;Cardiovascular system;Cell Size;Crigler-Najjar Syndrome;Data;Deposition;Diabetes Mellitus;Energy Intake;Energy Metabolism;Enzymes;Event;Excretory function;Fatty Liver;Fatty acid glycerol esters;Fenofibrate;Genes;Genetic;Genetic Polymorphism;Gilbert Disease;Glucose;Glucose Intolerance;Health;Health Expenditures;Hepatic;Hepatocyte;Hepatotoxicity;High Fat Diet;Hormones;Human;Hyperbilirubinemia;Icterus;Inflammatory;Inherited;Insulin;Insulin Resistance;Intestines;Investigation;Knock-out;Knockout Mice;Knowledge;Ligands;Lipids;Liver;Liver diseases;LoxP-flanked allele;Measures;Mediating;Metabolic;Metabolic hormone;Metabolism;MicroRNAs;Molecular;Mus;Non-Insulin-Dependent Diabetes Mellitus;Nuclear Receptors;Obese Mice;Obesity;Obesity Epidemic;Obesity associated disease;Outcome;Overweight;Oxidative Stress;PPAR alpha;Pathologic;Pathway interactions;Patients;Peripheral;Peroxisome Proliferator-Activated Receptors;Physiological;Plasma;Population Study;Process;Protein Isoforms;Publications;Resistance;Risk;Rodent;Serum;Shapes;Signal Pathway;Signal Transduction;Signaling Molecule;Testing;Therapeutic;Tissue Expansion;Tissues;Transactivation;UDP-Glucuronosyltransferase 1A1;Uncertainty;United States;Visceral fat;Weight Gain;carbohydrate metabolism;clinically relevant;comparison control;cost;cytokine;fatty liver disease;fibroblast growth factor 21;hormonal signals;humanized mouse;improved;insulin sensitivity;lipid metabolism;microRNA delivery;mouse model;non-alcoholic fatty liver disease;novel;novel therapeutics;obese patients;oxidation;preference;promoter;recruit;transcription factor

public_health_relevance:
During obesity visceral fat tissue expands causing oxidative stress and the release of pro-inflammatorycytokines that can cause insulin resistance and cardiovascular complications. This project explores theantioxidant bilirubin in molecular detail as a signaling molecule to reduce adiposity and insulin resistance andimprove metabolic health. A comprehensive investigation of the signaling preferences for bilirubin may open newavenues for potential new therapeutics for obesity and insulin resistant diabetes and for cardiovascular diseasesin humans.


application_id: 10932407
project_number: 5R01CA279455-02
project_title: Pdcd4-Rictor Interaction in Suppression of Lung Tumorigenesis
administering_ic: NCI
award_notice_date: 2024-08-06
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: CA
serial_number: 279455
program_official: FORRY, SUZANNE L
project_start_date: 2023-09-20
project_end_date: 2028-08-31
study_section: Mechanisms of Cancer Therapeutics B Study Section[MCTB]
contact_pi_person_id: 8737920
contact_pi: YANG, HSIN-SHENG
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/AbstractLung cancer is the leading cause of cancer-related deaths in the United States. The high mortality rate is notonly due to the lack of effective early detection but also due to poor tumor response to currently availabletherapies. These underscore the urgent need to better understand the biological events and mechanism of lungcancer suppression as is the need for important new therapeutic approaches that specifically target theseprocesses to improve survival rates. Lung cancer is mainly divided into two types: small cell lung cancer (SCLC)and non-small cell lung cancer (NSCLC) the latter of which accounts for 80-85% of all cases. A new subset oflung cancer in both SCLC and NSCLC was recently identified in which Rapamycin-insensitive companion ofmTOR (Rictor) gene is amplified. Rictor is an essential component of the mammalian target of rapamycincomplex 2 (mTORC2) and is required for mTORC2 complex activity and integrity. Activation of mTORC2 resultsin promotion of cancer cell proliferation and survival. This application builds on exciting preliminary data thatProgrammed cell death 4 (Pdcd4) bound with Rictor through a Rictor binding domain (RBD) to inhibit mTORC2activity 6-phosphofructo-2-kinase/fructose-26-biphosphatase 3 (PFKFB3) level cell proliferation and colonyformation. In addition a peptide containing the RBD specifically inhibits mTORC2 but not mTORC1. Our datafurther demonstrated that the RBD peptide suppressed NSCLC proliferation in cultured cells and nude mice. Thecentral hypothesis is that Pdcd4-Rictor binding specifically inhibits mTORC2 to preferentially suppressproliferation in Rictor-elevated NSCLC via induction of proteasomal degradation of PFKFB3. To test thishypothesis three specific aims are proposed: i) Delineate the mechanism of how Pdcd4-Rictor binding interfereswith mTORC2 activity to suppress tumor growth in NSCLC; ii) Dissect how Pdcd4-Rictor-mTORC2 axis impactsPFKFB3 stability and metabolic pathways; iii) Demonstrate that mTORC2-specific inhibition by RBD peptidepreferentially suppresses the growth of Rictor-elevated NSCLC to improve survival rate. The accomplishment ofthe proposed study will not only uncover novel regulatory mechanisms of mTORC2 activity and PFKFB3expression by Pdcd4 but also reveal the importance of mTORC2-specific inhibition by RBD peptide on NSCLCtumorigenesis. The expected findings will guide us to develop new strategies that are particularly relevant toprecision medicine approaches for NSCLC patients with elevated Rictor.

project_terms:
6-Phosphofructo-2-kinase;Acetylation;Apoptosis;Binding;Biological;Biological Assay;Cancer Etiology;Cancer Patient;Cause of Death;Cell Proliferation;Cell Survival;Cells;Cessation of life;Companions;Complex;Cultured Cells;Data;Death Rate;Drug Kinetics;Early Diagnosis;Event;Exhibits;FRAP1 gene;Feedback;Fructose;Gene Amplification;Genes;Genetic;Genetic Transcription;Glycolysis;Growth;In Vitro;Inhibition of Cell Proliferation;Invaded;Investigation;Knock-out;Laboratories;Malignant neoplasm of lung;Maps;Mediating;Metabolic Pathway;Mutation;Mutation Analysis;Neoplasm Metastasis;New Agents;Non-Small-Cell Lung Carcinoma;Nude Mice;Outcome Study;Patients;Penetration;Peptides;Phosphorylation;Phosphorylation Site;Phosphotransferases;Process;Prognosis;Proliferating;Proteasome Inhibitor;Proteins;Regulation;Reporting;Resistance;Role;Signal Transduction;Sirolimus;Site;Subgroup;Survival Rate;Tertiary Protein Structure;Testing;Therapeutic;Tumor Suppressor Proteins;Ubiquitination;United States;Up-Regulation;Woman;Work;Xenograft procedure;cancer cell;cancer diagnosis;cancer type;improved;in vivo;inhibitor;knock-down;lung cancer cell;lung tumorigenesis;men;metabolomics;migration;multicatalytic endopeptidase complex;mutant;novel;novel therapeutic intervention;novel therapeutics;patient derived xenograft model;precision medicine;prevent;research clinical testing;response;small cell lung carcinoma;therapy resistant;tumor;tumor growth;tumorigenesis;ubiquitin-protein ligase

public_health_relevance:
Project NarrativeLung cancer is the most commonly diagnosed cancer and the first leading cause of death in both men andwomen in the United Sates. In this proposal we intend to understand of how Pdcd4 a tumor suppressor bindswith Rictor an important protein in suppression of the lung cancer cells. This work will provide new strategiesfor lung cancer with Rictor elevation therapeutics and potentially develop new agents for treatment of this typeof lung cancer.


application_id: 10932126
project_number: 5R25CA221765-07
project_title: Appalachian Career Training in Oncology (ACTION) Program
administering_ic: NCI
award_notice_date: 2024-08-28
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:
PROJECT SUMMARY/ABSTRACT The rural Appalachian Kentucky region has the highest cancer incidence and mortality rates in the UnitedStates and it is also one of the most economically disadvantaged medically underserved and poorly educatedregions of the country. These disparities reveal a critical need for educational and scientific workforcepreparedness intervention strategies targeted to this population. Through a Continuing Umbrella of ResearchExperiences (CURE) supplement in 2016 the research clinical care educational and outreach strengths of theUniversity of Kentuckys Markey Cancer Center were leveraged to create the Appalachian Career Training InONcology (ACTION) Program which has been funded as a Youth Enjoy Science education intervention since2018. In this renewal each year the ACTION Program will immerse 20 underrepresented high school and 20undergraduate students from Appalachian Kentucky in mentored cancer research cancer care observationexperiences cancer education and career development activities as well as hands-on community outreachactivities. The goal of the program is to enhance the diversity of the biomedical workforce by preparingunderrepresented Appalachian Kentucky high school and undergraduate students for biomedical careers whilealso increasing the communitys understanding of cancer thereby addressing the cancer and educationdisparities in Appalachian Kentucky and beyond. Impacts of the program will include: 1) supporting studentsmatriculation into post-secondary professional and/or graduate biomedical degree programs; 2) instilling instudents a lifelong commitment to research education/outreach and/or health care careers focused on thecancer burden and unique challenges in Appalachian Kentucky and beyond; and 3) enhancing the AppalachianKentucky communitys understanding of cancer cancer research and clinical care and linking these facets tothe benefits of science education. The overarching goal and the program impacts will be accomplished throughthree Specific Aims: 1) to develop students cancer research knowledge and skills through cross-disciplinaryfaculty- and peer-mentored research training experiences; 2) to enhance students career preparation byproviding cancer education and career development curriculum through faculty- and peer-led coursesworkshops seminars and career coaching and mentoring; and 3) to increase the understanding of the researchand clinical aspects of cancer and the importance of science education among students and teachersparents/caregivers and families of ACTION students and general community members through impactfuloutreach activities in students communities. New features of the program will include virtual research educationexperiences that complement hands-on research and education activities a multi-institutional virtual outreachprogram and a cancer curriculum outreach program for middle and high school students and teachers. Withsignificant momentum achieved since its creation the ACTION Program will continue having a transformationalimpact on Appalachian Kentucky students their families and their communities.

project_terms:
Academic achievement;Achievement;Address;Appalachian Region;Area;Bachelor's Degree;COVID-19 pandemic;Cancer Burden;Cancer Center;Cancer Research Project;Caregivers;Clinical;Communities;Community Outreach;Complement;Country;County;Death Rate;Degree Completion;Degree program;Disparity;Doctor's Degree;Early Intervention;Education;Education and Outreach;Educational Activities;Educational Curriculum;Educational Intervention;Educational workshop;Faculty;Family;Female;Funding;Goals;Health;Health behavior;Healthcare;High School Student;Home;Incidence;Income;Individual;Institution;Intervention;Kentucky;Knowledge;Link;Malignant Neoplasms;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;Underrepresented Populations;Underrepresented Students;United States;Universities;Youth;anti-cancer research;burden of illness;cancer care;cancer education;cancer health disparity;career;career development;career preparation;clinical care;curriculum development;economic disparity;economic indicator;education research;experience;faculty mentor;hands on research;health inequalities;high school;high school degree;higher education;matriculation;medically underserved;member;oncology program;outreach;outreach program;peer;peer coaching;peer networks;programs;science education;skills;social;social health determinants;socioeconomics;teacher;training opportunity;undergraduate student;virtual

public_health_relevance:
PROJECT NARRATIVEThe renewal of the University of Kentucky Markey Cancer Centers Appalachian Career Training In ONcology(ACTION) Program will continue a culturally centered cancer education and training opportunity for studentsfrom rural disease-burdened low socioeconomic and low education-attainment Appalachian Kentuckycommunities. The program will enhance the diversity of the biomedical workforce by preparing underrepresentedAppalachian Kentucky high school and undergraduate students for biomedical careers. ACTION will alsoincrease the communitys understanding of cancer thereby addressing the cancer and education disparities inAppalachian Kentucky and beyond.


application_id: 10930804
project_number: 5R01AR081002-02
project_title: Muscle and physical function recovery after acute critical illness
administering_ic: NIAMS
award_notice_date: 2024-08-19
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;Observational Study;Outcome;Patients;Pattern;Pharmacological Treatment;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;nutrition;participant enrollment;patient subsets;pharmacologic;physical impairment;physically handicapped;predictive modeling;protein biomarkers;protein degradation;proteostasis;response;sepsis induced ARDS;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: 10928962
project_number: 75N91023P00127-0-0-1
project_title: NCI PATTERNS OF CARE STUDIES FOR DIAGNOSIS YEAR 2020 BREAST CANCER AND COLORECTAL CANCER CASES
administering_ic: NCI
project_start_date: 2022-12-23
project_end_date: 2023-12-22
contact_pi_person_id: 79045977
contact_pi: DURBIN, ERIC
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
funding_mechanism: R and D Contracts
project_abstract:
NCI Patterns of Care Studies (POC) describe characterize and compare practice patterns and treatments provided for cancer in different geographic areas of the United States. POC are conducted to satisfy a Congressional directive (under Public Law 100-607 Sec. 413 (a) (2) (C) adopted November 4 1988) to the National Cancer Institute (NCI) to assess the incorporation of state-of-the-art cancer treatments into clinical practice and the extent to which cancer patients receive such treatments and include the results of such assessment in the biennial reports. To satisfy the directive and to update and enhance the utility of the POC Studies a working group including representatives from the NCIs Divisions of Cancer Control and Population Sciences and Cancer Treatment and Diagnosis and a representative from the American Cancer Society was developed to review knowledge gaps cancer therapy dissemination and to develop priority areas for study. This years Patterns of Care Study shall investigate state-of-the-art therapies for patients diagnosed with breast or colorectal cancer.

project_terms:
Adjuvant Therapy;Adopted;Affect;Age;American Cancer Society;Area;Beds;Biological Markers;COVID-19 pandemic;Cancer Patient;Characteristics;Colorectal Cancer;Communities;Diagnosis;Diagnostic tests;Division of Cancer Control and Population Sciences;Documentation;Educational process of instructing;Ethnic Origin;Geographic Locations;Hospitals;Immunotherapy;Incidence;Individual;Inpatients;Insurance Coverage;Knowledge;Laws;Malignant Neoplasms;Medical Records;National Cancer Institute;Neoplasm Metastasis;Operative Surgical Procedures;Outpatients;Palliative Care;Patients;Pattern;Patterns of Care;Physicians;Physicians' Offices;Race;Radiation therapy;Recommendation;Records;Recurrent Malignant Neoplasm;Reporting;Systemic Therapy;Testing;Time;United States;Update;cancer care;cancer diagnosis;cancer recurrence;cancer therapy;chemotherapy;clinical practice;comorbidity;hormone therapy;malignant breast neoplasm;pandemic potential;sex;targeted treatment;treatment pattern;working group


application_id: 10928218
project_number: 5R01ES035133-02
project_title: Pre- and postnatal chemical mixture exposure adolescent sleep health and allostatic load
administering_ic: NIEHS
award_notice_date: 2024-07-30
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: ES
serial_number: 035133
program_official: GRAY, KIMBERLY A
project_start_date: 2023-09-12
project_end_date: 2028-06-30
study_section: Reproductive, Perinatal and Pediatric Health Study Section[RPPH]
contact_pi_person_id: 14131718
contact_pi: SEARS, CLARA G
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 / ABSTRACTA majority of U.S. adolescents are not getting sufficient sleep for optimal health. Sleep health is critical duringadolescence because of rapid neurodevelopment growth and body composition changes. Moreoverinadequate and poor-quality sleep can increase allostatic load or cumulative physiological wear and tear fromdisruptions across multiple regulatory systems that coordinate immune cardiovascular and metabolic function.Evidence indicates that developmental exposures to ubiquitous environmental toxicants may disruptneurobiological mechanisms that regulate sleep and allostasis. However whether these exposures aremodifiable risk factors for poor sleep during adolescence has not been rigorously examined. Our multidisciplinaryproject brings together experts in pediatric environmental health sleep and cardiometabolic health to identifywhether early life exposure to environmental toxicant mixtures disrupts adolescent sleep health and increasesallostatic load. This project focuses on mixtures of phthalates per-/polyfluoroalkyl substances (PFAS) andmetals. Most pregnant people infants and children are exposed to mixtures of these toxicants through diet andconsumer goods. The project leverages existing and new data from two well-characterized prospectivepregnancy and birth cohorts the Health Outcomes and Measures of the Environment (HOME) Study and theMaternal-Infant Research on Environmental Chemicals (MIREC) Study. Both cohorts previously enrolledpregnant women and followed children until ages 7-9 (MIREC n=300) or 10-12 (HOME n=256) years withadditional visits underway at ages 10-12 (MIREC) and 16-18 (HOME) years. Sleep characteristics will beexamined at two timepoints in both cohorts using actigraphy. We will quantify relations between environmentaltoxicant biomarkers during gestation early childhood school age and adolescence with sleep characteristics(Aim 1) and allostatic load (Aim 2) during adolescence. We will also examine whether exposure to environmentaltoxicant mixtures is associated with hypothalamus-pituitary-adrenal (HPA) activity catecholamines andsystemic inflammation biological intermediates of sleep-wake regulation and allostasis (Aim 3). Our analyseswill identify individual and joint effects of environmental toxicant mixtures and examine periods of heightenedsusceptibility during critical developmental periods. Identifying modifiable environmental factors that contributeto poor sleep health and allostatic load may inform novel interventions to reduce the risk of cardiovasculardisease the leading cause of morbidity and mortality in adulthood worldwide.

project_terms:
Adolescence;Adolescent;Adolescent Development;Adrenal Glands;Adult;Age;Biological;Biological Markers;Biometry;Birth;Body Composition;Cardiovascular system;Catecholamines;Characteristics;Chemicals;Child;Childhood;Cortisone;Data;Development;Diet;Disease;Enrollment;Environment;Environmental Exposure;Environmental Health;Environmental Risk Factor;Epidemiology;Exposure to;Foundations;Glycoproteins;Goals;Growth;Hair;Health;Homeostasis;Hydrocortisone;Hypertension;Hypothalamic structure;Immune;Individual;Infant;Inflammation;Intervention;Joints;Knowledge;Life;Link;Longitudinal Studies;Longitudinal cohort;Measures;Metabolic;Metals;Middle School Student;Morbidity - disease rate;Neurobiology;Neurosecretory Systems;Obesity;Outcome;Outcome Measure;Pathway interactions;Persons;Physiological;Pituitary Gland;Pituitary-Adrenal System;Poly-fluoroalkyl substances;Predisposition;Pregnancy;Pregnant Women;Process;Prospective cohort;Questionnaires;Regulation;Research;Risk;Risk Factors;Risk Reduction;School-Age Population;Serum;Shapes;Sleep;System;Testing;Toxic Environmental Substances;Toxicant exposure;Visit;actigraphy;adequate sleep;allostasis;allostatic load;blood pressure elevation;cardiometabolism;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;cohort;consumer product;critical developmental period;design;early childhood;early life exposure;environmental chemical;high school;improved;improvement on sleep;indexing;infancy;modifiable risk;mortality;multidisciplinary;neurobiological mechanism;neurodevelopment;neurotoxic;novel;phthalates;pollutant;poor sleep;postnatal;pregnant;prenatal;prospective;public health intervention;sleep health;sleep quality;systemic inflammatory response;toxic metal;toxicant;urinary

public_health_relevance:
PROJECT NARRATIVEExposure to environmental toxicants during early life development may negatively impact sleep health duringadolescence. This project will examine whether mixtures of phthalates per-/polyfluoroalkyl substances (PFAS)and metals during gestation infancy childhood and adolescent development are related to poorer sleep andhigher allostatic load cumulative wear and tear from physiological disruptions. Understanding whetherenvironmental toxicants that are commonly found in consumer products and residential environments impactsleep characteristics may lay the foundation for novel interventions to improve health.


application_id: 10925222
project_number: 5R01HL158779-03
project_title: Low Density Neutrophils Link Inflammation and Coagulopathy in COVID-19
administering_ic: NHLBI
award_notice_date: 2024-09-12
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;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;pathogen;pathogenic virus;peripheral blood;prevent;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: 10925159
project_number: 5T32CA261786-04
project_title: Addressing Rural cancer Inequities through Scientific Excellence (ARISE)
project_terms: Address;Inequity;Malignant Neoplasms;Rural
administering_ic: NCI
award_notice_date: 2024-07-29
opportunity_number: PA-20-142
application_type: 5
activity_code: T32
ic: CA
serial_number: 261786
program_official: LIM, SUSAN E
project_start_date: 2021-08-01
project_end_date: 2026-07-31
study_section: Institutional Training and Education Study Section (F)[NCI-F]
contact_pi_person_id: 1871398
contact_pi: DIGNAN, MARK B
other_pis: SCHOENBERG, NANCY E.
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
ABSTRACTThe Addressing Rural cancer Inequities through Scientific Excellence (ARISE) program aims to providetransdisciplinary and translational postdoctoral research training in rural cancer prevention control andsurvivorship. To achieve health equity and reduce the highest cancer morbidity and mortality rates in thenation University of Kentuckys (UK) behavioral cancer training efforts must develop a new generation ofcollaborative and rigorous scientists. Led by two well-established cancer and health equity researchers withextensive track records of training ARISE will meet this critical need by providing multifaceted trainingopportunities to well-qualified postdoctoral scholars in applied behavioral science including intervention anddissemination and implementation science. Training will emphasize translating knowledge of risk factors intoevidence-based behavioral interventions across the cancer spectrum (prevention to survivorship) forvulnerable rural residents. ARISE postdoctoral trainees will select one of three thematic behavioral cancertracks: environment risk behavior and health care delivery. We will recruit two trainees each year for a two-year fellowship. The training program based in the Center for Health Equity Transformation will operate inclose collaboration with UKs National Cancer Institute-designated Markey Cancer Center; Center for Clinicaland Translational Science; Center for Appalachian Research in Environmental Sciences; Office of PostdoctoralAffairs; Office of the Vice President for Research and departments across UKs 16 colleges. The 25preceptors co-mentors and methodology mentors include well-funded investigators in transdisciplinaryresearch with established collaborative relationships representing diverse yet complementary areas ofexpertise including behavioral science; environmental carcinogenesis; clinical and translational research; andintervention and implementation science. Additional mentoring includes geospatial analysis mHealth andcluster randomized designs. Each trainee will have a mentoring committee with one primary mentor in her/hisspecified track and two secondary mentors with one from another track and a methodology mentor. Traineeswill participate in a rigorous structured program that includes formal coursework training in the responsibleconduct of research and workshops and seminars. Trainees will gain career development experiences andbuild a professorial network through scientific writing; presentations; grant preparation and review; andleadership opportunities. Special programming designed to improve expertise in rural cancer disparitiesincludes research shadowing experience a personalized rural cancer patient experience and attendance atrural health disparities conferences. We will track trainee progress and mentor support through detailedannual evaluation. ARISE will build a next generation of cancer behavioral researchers aiming to achieve ruralhealth equity.

public_health_relevance:
PROJECT NARRATIVEAmong current T32 training programs for cancer prevention control and survivorship few focus on healthequity among rural populations and none focus on cancer in the rural Appalachian population. AddressingRural cancer Inequities through Scientific Excellence (ARISE) is a postdoctoral training program at theUniversity of Kentucky that will be a collaboration among the Center for Health Equity Transformation (CHET)the NCI-designated Markey Cancer Center (MCC) Center for Clinical and Translational Science (CCTS) UKCenter for Appalachian Research in Environmental Sciences (UK-CARES) six colleges and 10 departments toprovide interdisciplinary training in behavioral cancer research focused on rural disparities. The trainingprogram will have three tracks environment risk behavior and health care delivery and will provide didacticresearch experience and mentoring.


application_id: 10924070
project_number: 5K26DK138370-02
project_title: Initiate Research Opportunities and Networks for Underrepresented Early Career Investigators (IRON)
administering_ic: NIDDK
award_notice_date: 2024-07-26
opportunity_number: RFA-DK-22-012
application_type: 5
activity_code: K26
ic: DK
serial_number: 138370
program_official: SPAIN, LISA M
project_start_date: 2023-09-15
project_end_date: 2028-08-31
study_section: ZDK1-GRB-1(O3)
contact_pi_person_id: 11808527
contact_pi: SMALLS, BRITTANY L.
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
project_abstract:
PROJECT SUMMARYThis current proposal is in response to NIDDKs awareness and need for a more diverse workforce to achieveits mission. Hence early career investigators need the opportunity to gain research knowledge coupled withquality mentorship to assist with the proper application of those skills resulting in innovative and meaningfulresearch. In addition to providing mentorship on research skills it is also important to understand thecircumstances as mentioned in the second quote in which early career investigators have found themselvesand work to develop needed soft (non-research) skills. In some cases mentees may need to unlearn learn andrelearn certain behaviors and habits to be successful. Taken together my philosophy as a mentor is toprovide experiences for early career investigators especially from underrepresented groups that willhelp them develop into well-rounded individuals who contribute to advancing science as well as bedemonstrative of reputable citizens in academe. To achieve this goal I am committed to the following specificaims:Aim 1: Continue to develop and hone mentoring skills that will equip me to meaningfully contribute tothe career development and advancement of underrepresented early-stage investigators. I will participatein mentor focused trainings and workshops offered nationally as well as locally through the University ofKentuckys Center for Clinical and Translational Science (UK CCTS).Aim 2: Use funded research to provide opportunities for mentees to gain hands-on experience incommunity-based research health inequities and research addressing social determinants of healththat are aligned with NIDDKs mission as well as develop soft skills necessary to navigate a researchcareer in academe. Funded research aligned with NIDDKs mission will be utilized to provide teachablemoments in research design responsible conduct of research data management team science anddissemination of research findings. During these interactions I will work with mentees to identify and cultivatesoft skills that need development for future success.Aim 3: Provide training and networking opportunities for mentees. I will utilize resources provided by thisgrant to identify trainings and workshops that will assist mentees with developing research and leadership skillsattend scientific meetings and participate in networking events.

project_terms:
Academia;Address;Awareness;Back;Behavior;Career Mobility;Clinical Sciences;Coupled;Dedications;Descriptor;Development;Diverse Workforce;Educational workshop;Event;Faculty;Funding;Future;Goals;Grant;Growth;Habits;Individual;Internships;Kentucky;Knowledge;Leadership;Learning;Mentors;Mentorship;Minority Women;Mission;National Institute of Diabetes and Digestive and Kidney Diseases;Phase;Philosophy;Research;Research Design;Research Personnel;Resource Sharing;Resources;Rewards;Role;Science;Scientist;Training;Translational Research;Underrepresented Populations;Universities;Work;career;career development;clinical center;community based research;data management;early experience;experience;foot;gratitude;health inequalities;innovation;knock-down;man;meetings;member;mid-career faculty;next generation;response;responsible research conduct;skills;social health determinants;success;undergraduate research

public_health_relevance:
PROJECT NARRATIVEUnderrepresented early career investigators need the opportunity to gain research knowledge coupled withquality mentorship to assist with the proper application of those skills resulting in innovative and meaningfulresearch. In addition to providing mentorship on research skills it is also important to understand thecircumstances in which early career investigators have found themselves and work to develop needed soft (non-research) skills. Taken together my philosophy as a mentor is to provide experiences for early careerinvestigators especially from underrepresented groups that will help them develop into well-roundedindividuals who contribute to advancing science as well as be demonstrative of reputable citizens inacademe.


application_id: 10922122
project_number: 2R44HL158430-02
administering_ic: NHLBI
award_notice_date: 2024-09-17
opportunity_number: PA-23-230
application_type: 2
activity_code: R44
ic: HL
serial_number: 158430
program_official: FENTON, KATHLEEN NELLE
project_start_date: 2021-04-01
project_end_date: 2026-06-30
study_section: Special Emphasis Panel[ZRG1 IVBH-V (11)]
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: 2024-09-19
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;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: 10922026
project_number: 1R43AG082596-01A1
administering_ic: NIA
award_notice_date: 2024-09-24
opportunity_number: PAS-22-196
application_type: 1
activity_code: R43
ic: AG
serial_number: 082596
suffix: A1
program_official: BHATTACHARYYA, PARTHA
project_start_date: 2024-09-25
project_end_date: 2026-08-31
study_section: Special Emphasis Panel[ZRG1 SCIL-D (10)]
contact_pi_person_id: 78588939
contact_pi: MAZUR, ROBERT
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 149325255
primary_uei: FJ4SVZZPD654
duns_number: 149325255
uei: FJ4SVZZPD654
fips: US
organization_id: 10028837
organization_name: B A MAZE, INC.
organization_city: Louisville
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 402131086
organization_country: UNITED STATES
arra_indicator: N
project_title:
Connection Independence and Circular Support: Prompted Health Awareness Enabled by the At-Home Health Station

project_abstract:
ABSTRACTIn 2020 the financial burden associated with the care and treatment of individuals afflicted by Alzheimer'sdisease (AD) and AD-Related Dementias (ADRD) amounted to $305 billion for a population of 6 million(including young onset disease) and 2050 projections indicate that the costs will quadruple while the numberaffected will exceed 13 million people. ADRD and cognitive impairment (CI) disability is characterized by adiminishing ability to learn recall information and make decisions and judgments changes that threaten theCI/ADRD individuals autonomy and ability to live independently. Access to the internet smart devices andtelehealth have the potential to help people with CI/ADRD maintain independence but current technologiescan be difficult for these adults to use. B.A. Maze Inc. has designed a technology platform the At-home HealthStation (AHS) that is a plug-and-play modular system designed to use the circular economy to simplify thedigital experience for the CI/ADRD-user and provide caregivers/administrator (AC) the ability to set uniqueprompted health reminders via a secure multi-device management AHS-Webapp. The AHS system will ensureconsistent access to basic health measurements through remote patient monitoring (RPM) to promote healthfunction and independence. Our goal is to develop appropriate RPM and care systems to enable long-termindependence and health in people living with CI/ADRD and give caregivers a care and communicationplatform for proactive health decision-making. Our objective in this Phase I project is to advance the design ofthe AHS through usability testing and feedback from CI/ADRD individuals. The outcome of this developmentstudy will be an AHS design that achieves a System Usability Scale (SUS) of 70 and a cognitive baseline ofusability for cognitively impaired adults aged 40+. The product of Phase I will be an AHS minimum viableproduct that will be further validated and prepared for commercialization in Phase II.

project_terms:
Activities of Daily Living;Administrator;Adult;Affect;Age;Age of Onset;Alzheimer's Disease;Alzheimer's disease related dementia;Awareness;Black race;COVID-19 pandemic;Caregivers;Caring;Cognitive;Communication;Communication Tools;Computerized Medical Record;Data;Decision Making;Dementia;Development;Devices;Diagnosis;Disparity population;Ensure;Evaluation;Face;Feedback;Financial Hardship;Frontotemporal Dementia;Goals;Health;Health Promotion;Home;Home Care Services;Home visitation;Impaired cognition;Incentives;Incidence;Independent Living;Individual;Internet;Interview;Judgment;Learning;Machine Learning;Measurement;Measures;Medicare;Methods;Monitor;Onset of illness;Outcome;Participant;Patient Care;Patients;Persons;Phase;Play;Population;Prevalence;Process;Psychological Stress;Publishing;Quality of life;Research;Secure;Security;Software Design;Software Engineering;Structure;System;Technology;Testing;Time;United States National Aeronautics and Space Administration;Universities;Vascular Dementia;Woman;Workload;acute care;aged;aging population;aging process;care systems;cognitive ability;cognitive testing;commercial application;commercialization;cost;design;digital;disability;empowerment;end of life;experience;health care service;health organization;human centered design;human old age (65+);improved;improved outcome;innovation;instrumental activity of daily living;lifetime risk;men;multiple chronic conditions;older adult;operation;population health;programs;remote patient monitoring;smart device;social;technology platform;telecare;telehealth;tool;usability;young adult

public_health_relevance:
PROJECT NARRATIVEIndividuals living with cognitive impairment (CI) and/or Alzheimer's Disease (AD) and AD-Related Dementias(ADRD) often struggle to maintain independence and existing technologies that aim to support in-home livingcan be difficult for this population to use. At-Home Health Station (AHS) systems by B A Maze Inc. provide atechnology platform that organizes health monitoring tools enables prompted health information and hassecure data for streamlined patient-caregiver care and communication. The AHS will be developed viaimplementation feedback from individuals living with CI/ADRD ensuring the design is appropriate to thespecific needs of this population.


application_id: 10920454
project_number: 5R01DK133195-02
project_title: Targeting urinary tract dysfunctions after spinal cord injury with epidural stimulation
administering_ic: NIDDK
award_notice_date: 2024-08-02
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: DK
serial_number: 133195
program_official: MULLINS, CHRISTOPHER V
project_start_date: 2023-09-15
project_end_date: 2026-06-30
study_section: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]
contact_pi_person_id: 6490947
contact_pi: HUBSCHER, CHARLES H.
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
(PLEASE KEEP IN WORD DO NOT PDF)AbstractSpinal cord epidural stimulation (scES) which creates an electrical field directly over the spinal cord has shown early promise for the restoration of voluntary and reflex control of the lower urinary tract (LUT) among individuals with spinal cord injuries (SCI). A major advantage of the proposed multi-electrode array over the Interstim system and transcutaneous approach is the versatility of the multi-electrode and the ability to activate multiple structures and functions simultaneously with a single electrode placement and device. The goal of this pre-clinical research is to optimize scES for functional benefits and identify mechanism(s) to better facilitate daily management and improve quality of life. It is hypothesized that effective scES for both bladder storage and emptying occurs when initiated chronically post-SCI through activation of spinal bladder circuits including neurons within the dorsal commissure superficial dorsal horn sacral parasympathetic nucleus and Onufs nucleus with the requirement of intact hypogastric/pelvic/pudendal nerves and with greater effectiveness when given in combination with locomotor training. For Aim 1 previously identified optimal parameters will be used to identify neural components of the spinal networks contributing to scES-induced LUT effects with different chronicitys post-SCI in urethane-anesthetized rats using two approaches: a) Fos protein induction (a marker for postsynaptic activation of spinal neurons) and b) select peripheral nerve transections. Examining the contributing spinal central regions activated with scES and key peripheral components for different aspects of LUT function will provide novel targets for further development and refinement of epidural arrays and controllers. For Aim 2 the impact of scES on LUT functions in SCI rats after treatment with differing periodicities of locomotor training will be examined to address the potential added benefit of a combinatory approach (neuromodulation with rehabilitation). A sub-aim examines the underlying Fos induced central neural components as plasticity is likely induced with training. Both aims will also include bladder histology/molecular biology assessments re the effects of chronicity/training. These studies will significantly move the SCI field forward by providing optimal parameters and locations for targeting LUT function that will be key for advancing the existing technology.

project_terms:
Acute;Address;Aftercare;Anesthesia procedures;Ataxia;Bilateral;Biological Markers;Bladder;Bladder Tissue;Cell Nucleus;Cells;Chronic;Clinical Trials;Clinical effectiveness;Commissure;Contusions;Development;Devices;Dorsal;Effectiveness;Electrodes;FOS Protein;Functional disorder;Goals;Health;Health Care Costs;Histology;Hour;Human;Immune;Individual;Induced Neurons;Location;Locomotor training;Lower urinary tract;Maintenance;Maps;Mediating;Modeling;Molecular Biology;Motor;Nerve;Neurons;Outcome;Pattern;Pelvis;Peripheral;Quality of life;Rattus;Recommendation;Reflex action;Reflex control;Rehabilitation therapy;Source;Sphincter;Spinal;Spinal Cord;Spinal Cord Tract;Spinal cord injury;Structure;Synapses;System;Technology;Training;Urethane;Urinary tract;chemokine;cholinergic;clinically relevant;design;dorsal horn;electric field;experimental study;functional outcomes;gray matter;improved;multi-electrode arrays;nerve transection;neural;neurological rehabilitation;neuroregulation;novel;peripheral nerve transection;postsynaptic;pre-clinical research;preclinical study;pressure;response;response to injury;restoration;timeline;treadmill;urologic

public_health_relevance:
Spinal cord epidural stimulation which creates an electrical field directly over the spinal cord has shown early promise with clinical effectiveness for restoration of voluntary and reflex control of the lower urinary tract. The goal of this pre-clinical research is to optimize epidural stimulation alone and in combination with neurorehabilitation for functional urological benefits and identify mechanism(s) to better facilitate daily management and improve quality of life for those with spinal cord injuries.


application_id: 10920438
project_number: 5P30CA177558-12
project_title: Shared Resource Management
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5472
contact_pi_person_id: 7719959
contact_pi: WEISS, HEIDI L
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT Management of Shared Resource Facilities (SRF) fosters the execution of strategic science goals of theMarkey Cancer Center (MCC). Since their inception MCC SRFs have benefitted from strong and experiencedleadership significant investment and support from MCC and the University of Kentucky utilization of uniqueprocesses to facilitate effective delivery and coordination of services and governance by evaluation andoversight from advisory committees and the MCC Directors Council. The aims of SRF Management are to: 1)Promote state-of-the-art technology methodologic and content expertise to foster MCC scientific strategiesacross three Research Programs; 2) Conduct rigorous monitoring and evaluation processes and supportfinancial health for stability of SRF infrastructure and 3) Facilitate robust and stable access to MCC sharedresources through innovative initiatives. The SRFs received improved ratings from NCIs 2018 site visit andhave exhibited continued growth in breadth of services depth of skills and service provision aligned with theresearch direction of MCCs programs. In addition SRF management was guided by a culture of integratedand collaborative relationships with MCC researchers with formalized processes for hand-offs among SRFsfacilitating enhanced support and the bi-directional continuum of MCC research from basic science to clinicand into the community. MCC is supported by seven established SRFs: Biospecimen Procurement andTranslational Pathology (BPTP) Biostatistics and Bioinformatics (BB) Cancer Research Informatics (CRI)Flow Cytometry and Immune Monitoring (FCIM) Redox Metabolism (RM) with Oncogenomics (OG) andPatient-Oriented and Population Sciences (POP) as new fully operational facilities in this application resultingfrom rigorous SRF management evaluation processes and advisory committee recommendations andapproval. SRFs are led by Dr. Heidi Weiss (TO) Associate Director for Shared Resources; she is assisted byDr. Thrse Bocklage (MCO) Assistant Director for Shared Resources the SRF Management Office and MCCAdministration. MCC has invested $8.3M in SRF enhancements since 2018. SRF usage is robust evident byhigh numbers of users; SRFs also appropriately prioritize their services evident by the percent of users from2018-2022 who are MCC members: BB (156 users 79%) BPTP (150 users 61%) CRI (161 users 65%)FCIM (87 users 61%) OG (61 users 69%) POP (34 users 71%) and RM (72 users 68%). MCC ResearchProgram members heavily utilize SRFs as follows: 84% of Molecular and Cellular Oncology 85% ofTranslational Oncology and 82% of Cancer Prevention and Control. The total number of MCC members usingall SRFs remains consistently high (151 and 171 over MCCs first two CCSG cycles respectively). Fiscalmanagement and business planning from MCC Administration ensure SRF income mechanisms and financialprocesses are robust and appropriate. These management strategies and consequent value-added metricsdemonstrate the critical role of SRFs and their direct contributions to MCCs mission.

project_terms:
Advisory Committees;Affect;Applications Grants;Assessment tool;Basic Science;Bioinformatics;Biometry;Budgets;Businesses;Cancer Center;Cancer Center Support Grant;Cancer Control;Cancer Prevention Intervention;Cancer Therapy Evaluation Program;Clinic;Clinical Research;Clinical Trials;Communication;Communities;Comprehensive Cancer Center;Decision Making;Dedications;Dissemination and Implementation;Documentation;Electronics;Ensure;Evaluation;Evidence based intervention;Exhibits;Financial Support;Flow Cytometry;Fostering;Funding;Genomics;Goals;Growth;Health;Health Insurance Portability and Accountability Act;Human Resources;Immunologic Monitoring;Improve Access;Income;Informatics;Infrastructure;Institution;Investigation;Investments;Kentucky;Laboratories;Lead;Leadership;Marketing;Measurement;Metabolism;Methodology;Mission;Modeling;Modification;Molecular;Monitor;NCI Center for Cancer Research;Office Management;Oncology;Outcome;Oxidation-Reduction;Pathology;Peer Review Grants;Performance;Population Intervention;Population Sciences;Population Study;Process;Productivity;Recommendation;Reporting;Research;Research Personnel;Resource Sharing;Resources;Role;Science;Screening for cancer;Secure;Service provision;Services;Site Visit;Strategic Planning;System;Technical Expertise;Technology;Therapeutic Trials;Tobacco;Training;Training and Education;Universities;Work;anti-cancer research;biomarker driven;cancer genomics;cancer prevention;cancer research center director;cellular oncology;community based research;cost;cost effective;cost effectiveness;data sharing;epidemiology study;experience;implementation facilitation;improved;innovation;instrumentation;member;molecular oncology;oncology program;operation;patient oriented;programs;service coordination;skills;survivorship;targeted treatment;tool;translational oncology;translational study;treatment program

public_health_relevance:
Project NarrativeNot applicable. This document is attached to satisfy electronic submission requirements.


application_id: 10920436
project_number: 5P30CA177558-12
project_title: Protocol Review and Monitoring System
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5471
contact_pi_person_id: 1926108
contact_pi: ANTHONY, LOWELL B.
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT In accordance with CCSG guidelines the Markey Cancer Center (MCC) has established appropriate mechanisms for ensuring rigorous scientific oversight of cancer clinical trials through the Protocol Review and Monitoring System (PRMS). Protocols undergo initial scientific review by Clinical Care and Research Teams (CCARTs) including assessment of relevance to the patient population fit within the portfolio and interest of investigators. In 2019 the MCC formalized first-stage review by CCARTs expanding structure and function and enhancing communication with the Protocol Review and Monitoring Committee (PRMC). Following CCART approval review for operational feasibility is completed by the Feasibility Review Committee. The goal of these reviews is to ensure that only the highest quality trials are submitted to the PRMC. The MCC PRMC is responsible for independent peer-review of scientific merit feasibility and prioritization of new protocols. Following activation PRMC monitors protocols for ongoing scientific progress and has ultimate authority to suspend or close protocols that do not meet MCC scientific standards. The Specific Aims of the PRMS are: 1) Optimize the PRMS structure and process for sufficient size and breadth of expertise to conduct a critical rigorous and fair scientific review of all institutional cancer-related research protocols involving human subjects; 2) Ensure that clinical trials conducted at MCC support and enable the scientific mission of the center are relevant to patients in the catchment area including those from understudied populations; 3) Safeguard the scientific integrity feasibility and prioritization of all cancer-related interventional clinical research of the MCC and apply rigorous scientific review criteria in a consistent and objective manner; 4) Oversee the progress and performance of all interventional cancer clinical trials to ensure their continued scientific merit and accomplishment of the scientific goals of the protocol and the MCC. Highlights during the funding period include incorporation of first-stage reviews into PRMS framework enhanced member education expanded representation in key scientific areas and strengthened quorum expectations. From 2019 to 2021 the CCARTs reviewed 409 clinical trials for potential opening approved 294 (72%) and declined 115 (28%); the Feasibility Review Committee declined 20 (4%) due to lack of feasibility. From 2019 to 2021 the PRMC reviewed and/or prioritized 239 new protocols of which 230 were approved and 9 were disapproved. In the past three years the PRMC reviewed 552 active protocols for scientific progress closing 29 protocols due to low accrual or a change in scientific merit. The PRMC continuously assesses its own performance. In 2021 median time from PRMC submission to approval was 8 days overall (7 national 8 industry 24 institutional). As the MCC has matured the PRMS has continued to optimize the first- and second-stage review and to increase scientific rigor objectivity and scrutiny of each trials relevance to our population in order to ensure MCC brings the highest quality clinical research to Kentuckians.

project_terms:
Area;Basic Science;Biometry;Cancer Burden;Cancer Center;Cancer Center Support Grant;Cancer Control;Cancer Intervention;Catchment Area;Charge;Clinical Cancer Center;Clinical Oncology;Clinical Protocols;Clinical Research;Clinical Trials;Committee Members;Communication;Conduct Clinical Trials;Data;Discipline;Disease;Education;Electronics;Ensure;Evaluation;Faculty;Funding;Goals;Guidelines;Individual;Industry;Institution;Institutional Review Boards;Intervention;Intervention Studies;Kentucky;Laboratory Research;Malignant Neoplasms;Mission;Modification;Monitor;Observational Study;Outcome;Pathology;Patients;Peer Review;Performance;Pharmacology;Policies;Population Heterogeneity;Prevention;Process;Protocols documentation;Radiology Specialty;Recommendation;Reporting;Research;Research Personnel;Resources;Review Committee;Safety;Scientific Advances and Accomplishments;Structure;System;Time;Underserved Population;Universities;Vulnerable Populations;authority;cancer clinical trial;cancer prevention;cancer research center director;clinical care;clinical translation;clinically relevant;community engagement;expectation;human subject;innovation;interest;member;mid-career faculty;patient population;professor;success;trial enrollment


application_id: 10920430
project_number: 5P30CA177558-12
project_title: Community Outreach and Engagement
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5470
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:
PROJECT SUMMARY/ABSTRACT The University of Kentucky (UK) Markey Cancer Center (MCC) embraces the entire Commonwealth of Kentucky as its catchment area. Despite notable recent advances Kentucky has the highest all-site cancer incidence and mortality in the U.S. driven largely by socioeconomic geographic and racial/ethnic inequities. With a 47-year history the goal of MCC Community Outreach and Engagement (COE) is to engage communities practitioners and researchers in mutually beneficial collaborations to reduce cancer incidence and mortality. MCCs long-standing COE programs include regionally-based community outreach management of the states cancer coalition and policy efforts and the MCC Affiliate Network (MCCAN) MCCs innovative clinical outreach program with 19 community-based (non-UK) hospitals across the state. Since 2018 MCC made strategic investments to enhance COE strengths and further integrate research and cancer control. COEs previous needs assessment shaped the FY19-23 MCC Research Priorities. Key accomplishments include conducting the 2021 Kentucky Cancer Needs Assessment (KY CNA) launching new research engagement initiatives (e.g. Community Impact Ambassadors as Research Program liaisons Research Advocacy Program Clinical Trial Referral Ambassadors internal COE funding) and cancer control activities with extensive reach (e.g. training/technical assistance policy changes individual education facilitating access to services). Building on existing efforts and FY24-28 MCC Research Priorities COE Specific Aims are to: 1) Monitor cancer rates in Kentucky and identify community-driven priorities. In addition to monitoring cancer rates and conducting the next KY CNA in 2026 each year COE will carry out a focused needs assessment to address data gaps and underserved populations identified in the 2021 KY CNA. 2) Foster impactful research that responds to community needs. COE will expand the Research Advocacy Program with a training module for basic and clinical researchers and Rapid Feedback Sessions. COE will add two new strategies to facilitate clinical trial participation: providing appropriate patient and community education including testimonial videos and assisting studies accrue patients from all backgrounds through consultations and research advocate feedback. 3) Disseminate and implement sustainable guidelines practices and policies. COE is currently using the 2021 KY CNA to guide development of the states new five-year Cancer Action Plan. Next COE will assess its portfolio of community cancer control programs to strategically realign them with the new state plan to address gaps leverage partnership opportunities and maximize impact. IMPACT: COE has made important advances in synergizing MCC research and cancer control efforts with statewide partners and significant contributions to population-level improvements in colon and lung cancer screening and outcomes and smoking. COE is poised to further accelerate MCC impact.

project_terms:
Acceleration;Address;Advocacy;Advocate;Appalachian Region;Award;Back;Black Populations;Cancer Burden;Cancer Center;Cancer Center Support Grant;Cancer Control;Catchment Area;Cervical;Clinical;Clinical Trials;Collaborations;Colon Carcinoma;Colorectal;Communities;Community Health Education;Community Outreach;Consultations;Data;Data Sources;Development;Disparity;Dissemination and Implementation;Education;Education and Outreach;Electronics;Environmental Exposure;Equity;Evidence based practice;Feedback;Fostering;Funding;Geography;Goals;Grant;Head and neck structure;Health Services Accessibility;Hepatitis C virus;Hispanic Populations;Hospitals;Human Papilloma Virus Vaccination;Human Papillomavirus;Incidence;Individual;Investments;Kentucky;Leadership;Lung;Malignant Neoplasms;Melanoma;Monitor;NCI Center for Cancer Research;Needs Assessment;Obesity;Outcome;Patient Education;Patients;Persons;Policies;Population;Poverty;Preventive service;Printing;Process;Professional Practice;Quality Indicator;Race;Recording of previous events;Reporting;Research;Research Personnel;Research Priority;Risk Factors;Rural;Screening for cancer;Shapes;Smoking;Therapeutic Trials;Tobacco;Training;Training Activity;Underrepresented Minority;Universities;Virus;Visit;cancer care;cancer health disparity;cancer site;colon cancer screening;community engagement;ethnic disparity;evidence based guidelines;geographic disparity;health equity;improved;innovation;lung cancer screening;meetings;member;mortality;outreach program;programs;racial disparity;screening program;social media;socioeconomics;volunteer


application_id: 10920427
project_number: 5P30CA177558-12
project_title: Clinical Protocol and Data Management
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5469
contact_pi_person_id: 6772940
contact_pi: ARNOLD, SUSANNE M
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT The Markey Cancer Center (MCC) Clinical Protocol and Data Management (CPDM) facilitates all clinical cancer research at the University of Kentucky. CPDMs Specific Aims are: 1) To provide comprehensive centralized support for MCC clinical research activities; 2) To ensure the safety compliance and quality of all clinical cancer research performed at the center and MCCs Research Network (MCCRN) in accordance with the Data Safety and Monitoring Plan and NCI requirements; 3) To integrate all efforts of the Cancer Center to provide clinical trial access to all MCC patients including women racial/ethnic minorities understudied populations and individuals across the lifespan; and 4) To provide ongoing education and training services for CPDM and MCCRN staff and faculty that enhance teams and lead to increased engagement with MCCs catchment population. The CPDM facilitates clinical research through the Clinical Research Offices four units (72 FTEs) Protocol Development Teams (10 FTE) a Quality Assurance Program (5 FTE) and MCCRN (11 FTE) which provide centralized expertise for development coordination and execution of trials. In 2022 the Clinical Research Office managed 369 active trials211 cooperative group 113 industry sponsored and 45 investigator-initiated (12 investigational new drug-enabling). MCCs statewide infrastructure supports research referral and accrual within the catchment area. As the CPDM has matured the center increased clinical research engagement to 98 of Kentuckys 120 counties with 18753 total accruals (8857 interventional; 9896 non-interventional 2018-2022). The Quality Assurance Program and Audit Committee function independently from other CPDM components to support education safety and quality of trial conduct. All cancer trials are guided by MCCs Data and Safety Monitoring Plan which provides oversight in accordance with NCI CCSG requirements. The Data and Safety Monitoring Committee ensures patient safety and protocol compliance by staff and investigators. MCC leaders investigators and staff promote the inclusion of women racial/ethnic minorities and Appalachian Kentucky residents in clinical cancer research in alignment with CCSG guidelines. Enhanced efforts have increased trial participation to reflect this patient population focusing on important cancers such as lung and prostate. In alignment with NIH policies MCC strives for inclusion of individuals across the lifespan in clinical research. In 2021 40% of therapeutic trial accruals were adults 65 or older surpassing national averages. Cancer care for children is provided by one of two comprehensive pediatric oncology programs in the state. MCC is the first center in the region to offer germline testing to all pediatric oncology patients supported by the Molecular Tumor Board interpretation of results.

project_terms:
Adherence;Adult;Age;Appalachian Region;Awareness;Biometry;COVID-19 pandemic;Cancer Center;Cancer Center Support Grant;Catchment Area;Child Care;Clinical;Clinical Cancer Center;Clinical Data;Clinical Management;Clinical Protocols;Clinical Research;Clinical Research Associate;Clinical Trials;Clinical Trials Network;Collaborations;Community Outreach;County;Data;Data Collection;Data Management Resources;Dedications;Development;Devices;Disease;Education;Electronics;Ensure;Ethnic Origin;Faculty;Female;Gender;Germ Lines;Goals;Improve Access;Individual;Industry;Infrastructure;Institution;Institutional Review Boards;Intervention;Investigational Drugs;Investigational Therapies;Kentucky;Leadership;Malignant Neoplasms;Malignant neoplasm of lung;Malignant neoplasm of prostate;Minority;Mission;Molecular;Monitor;NCI Center for Cancer Research;National Cancer Institute;National Clinical Trials Network;Needs Assessment;Nurses;Office Management;Patients;Pediatric Oncology;Performance;Policies;Population;Procedures;Process;Protocol Compliance;Protocols documentation;Race;Reporting;Research;Research Activity;Research Design;Research Personnel;Research Priority;Research Support;Resource Allocation;Resource Sharing;Risk;Safety;Services;Site;Special Population;Specialist;System;Testing;Therapeutic Trials;Time;Toxic effect;Training;Training and Education;Translational Research;Underserved Population;United States National Institutes of Health;Universities;Vision;Woman;anti-cancer research;cancer care;cancer health disparity;clinical care;community engagement;community partners;data management;design;experience;human old age (65+);improved;industry partner;investigator-initiated trial;life span;oncology program;operation;patient engagement;patient oriented;patient population;patient safety;programs;protocol development;quality assurance;response;success;tool;tumor


application_id: 10920424
project_number: 5P30CA177558-12
project_title: Developmental Funds
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5468
contact_pi_person_id: 1901765
contact_pi: EVERS, BERNARD MARK
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT CCSG Developmental Funds are a vital mechanism for furthering the strategic mission and vision of the Markey Cancer Center (MCC) through pilot funding to MCC members and support of emerging Shared Resource Facilities. During the current funding period Developmental Funds helped support 17 basic clinical population and translational cancer research pilot projects from MCCs Molecular and Cellular Oncology Cancer Prevention and Control and Translational Oncology Research Programs stimulating a high return on investment of $15.16 per CCSG dollar. These projects have fostered five new extramurally funded grants and have opened clinical trials that accrued 241 new participants. In close alignment with MCCs scientific direction 14 of the 17 projects are on topics that correspond to the centers FY19-23 Research Priorities for the current funding period. Outside of the routine CCSG pilot award process MCC also elected to use Developmental Funds to support two interdisciplinary teams of researchers who ultimately successfully applied for a CCSG Supplement designed to foster the development of multiproject research programs. Developmental Funds were also invested in two developing Shared Resource Facilities (Oncogenomics and Patient-Oriented and Population Sciences) which have supported research projects from all three MCC programs and after careful annual evaluation have been approved by the MCC Directors Council as fully functioning resources presented as such in this CCSG application. Leveraged with philanthropic investment and institutional support Developmental Funds will also be strategically allocated during the upcoming funding period to address two Specific Aims: 1) Cultivate innovative and collaborative science through the use of pilot grants in areas that align with MCCs FY24-28 Strategic Plan and Research Priorities and reflect the scientific aims of MCCs three Research Programs; and 2) Foster deeper collaboration across the UK campus through strategic partnerships to fund innovative pilot awards and ensuring the continuation of community input through the CCSG pilot review process. To achieve these aims MCC requests $150000 per year in Developmental Funds allowing the center to achieve several key objectives outlined in the Strategic Plan including fostering research that aligns with its research priorities expanding transdisciplinary opportunities for research teams and increasing clinical studies that are informed by MCC basic research. MCC will also continue partnerships with other major research centers across campus allowing cancer research to have an impact far beyond what MCC alone can achieve and will foster the maturity of a new process by which Community Advisory Board members directly contribute to the CCSG pilot reviews allowing community input to inform and influence funding decisions.

project_terms:
Address;Area;Award;Basic Science;Cancer Burden;Cancer Center;Cancer Center Support Grant;Cancer Control;Cancer Research Project;Catchment Area;Clinical;Clinical Cancer Center;Clinical Research;Clinical Sciences;Clinical Trials;Collaborations;Colorectal Cancer;Communities;Community Participation;Comprehensive Cancer Center;Data;Dedications;Development;Ecosystem;Education;Electronics;Ensure;Evaluation;Extramural Activities;Fostering;Funding;Funding Agency;Future;Goals;Grant;Guidelines;Institution;Investments;Kentucky;Leadership;Link;Mission;Molecular;NCI Center for Cancer Research;National Cancer Institute;Obesity;Participant;Philanthropic Fund;Pilot Projects;Population;Population Sciences;Prevention;Process;Program Description;Program Research Project Grants;Racial Equity;Recurrence;Research;Research Personnel;Research Priority;Research Project Grants;Research Support;Resource Allocation;Resource Sharing;Resources;Science;Secure;Strategic Planning;Translational Research;Universities;Vision;Vulnerable Populations;Work;anti-cancer research;cancer genomics;cancer prevention;cancer research center director;cellular oncology;clinical center;clinically relevant;community advisory board;community engagement;design;evidence base;flexibility;health disparity;innovation;interest;member;molecular oncology;novel;patient oriented;programs;recruit;screening;translational cancer research;translational oncology


application_id: 10920418
project_number: 5P30CA177558-12
project_title: Leadership Planning and Evaluation
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5467
contact_pi_person_id: 1901765
contact_pi: EVERS, BERNARD MARK
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT B. Mark Evers MD (TO) Director of the Markey Cancer Center (MCC) is assisted by eight Senior Leaders who support activities in cancer research outreach education and training clinical care and administration. With the exception of some notable additions during this reporting period that have expanded the effectiveness and expertise of the Senior Leadership team this highly experienced group of leaders has worked together since 2009 overseeing MCCs initial NCI designation in 2013 a successful renewal application in 2018 the preparations for this renewal and quest for Comprehensive Cancer Center status as well as a future five-year outlook in the form of MCCs FY24-28 Strategic Plan. MCCs Senior Leaders leverage all available resources at the University of Kentucky state and national levels to further their cohesive plan to fulfill MCCs mission to reduce cancer incidence and mortality with a focus on Kentucky through research prevention treatment education and community engagement. To that end MCCs Leadership Planning and Evaluation efforts are centered around the following Specific Aims: 1) Implement and execute MCCs FY24-28 Strategic Plan and lead MCC based on the opportunities and needs of the statewide catchment area and in tandem with institutional and NCI priorities; 2) Lead the ongoing planning and evaluation of the center coordinating and responding to internal and external reviews; and 3) Ensure the appropriate resources and infrastructure to foster success across all areas of MCCs Strategic Plan including the success of MCCs Research Programs Shared Resources clinical and translational scientific endeavors and outreach and mentoring initiatives. MCCs planning and evaluation efforts sustaining its substantial growth since 2018 are accomplished through External and Internal Advisory Boards that meet regularly the Directors Council and committees that provide both the Director and Senior Leadership ongoing guidance and support. Future directions for the center are guided by plans outlined in MCCs FY24-28 Strategic Plan which was constructed through an extensive review and vetting process with input from key internal and external stakeholders. The plan is a living document and roadmap to guide the next five years of excellence in key pillars of activity across the center: 1) basic research 2) clinical translation 3) cancer prevention and control 4) cancer education and mentoring 5) community outreach and engagement and 6) clinical care. These pillars are reinforced by strong institutional support philanthropy Shared Resource Facilities and administration all of which work in tandem to support a cancer center poised to continue its trajectory of increasing contributions to cancer research training education and outreach.

project_terms:
Address;Area;Basic Science;Cancer Burden;Cancer Center;Cancer Center Support Grant;Cancer Control;Catchment Area;Clinical;Clinical Research;Communities;Community Outreach;Comprehensive Cancer Center;Consultations;Development;Education;Effectiveness;Electronics;Ensure;Epidemiologist;Equity;Evaluation;Fostering;Funding;Future;Goals;Growth;Healthcare;Infrastructure;Institution;Intervention Trial;Investments;Kentucky;Lead;Leadership;Legal patent;Malignant Neoplasms;Mentors;Mission;Molecular;NCI Center for Cancer Research;Names;Needs Assessment;Patients;Population Sciences;Positioning Attribute;Preparation;Prevention;Process;Recording of previous events;Reporting;Research;Research Personnel;Resource Sharing;Resources;Scientist;Secure;Source;Strategic Planning;Time;Training;Training and Education;Universities;University resources;Vision;Vulnerable Populations;Work;anti-cancer research;cancer education;cancer genomics;cancer prevention;cancer research center director;clinical care;clinical translation;community engagement;community organizations;diversity and inclusion;equity diversity and inclusion;experience;functional status;improved;meetings;novel therapeutics;outreach;patient oriented;programs;recruit;success;translational pipeline;translational scientist;tumor metabolism


application_id: 10920414
project_number: 5P30CA177558-12
project_title: Translational Oncology Research Program
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5466
contact_pi_person_id: 2020455
contact_pi: KOLESAR, JILL MARIE
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT The Markey Cancer Centers (MCC) Translational Oncology (TO) Research Program is scientifically focused on identifying novel targets discovering new anticancer agents and devices and leading catchment-relevant clinical trials to decrease cancer incidence and mortality in Kentucky and the nation. The overarching theme of the TO Program is to use precision medicine to enhance patient outcomes through three Specific Aims: 1) Identify and validate mechanistic targets of cancer 2) Discover re-design and develop new anticancer agents and devices and 3) Develop and lead biomarker directed catchment-relevant clinical trials. Currently 33 ongoing translational studies are evaluating molecular targets and mediators of cancer. Since 2018 38 new drugs novel combinations and repurposed anticancer agents and devices have been developed with a focus on identified mutations and phenotypes as informed by COE catchment area data. TO is a cross-disciplinary program with 67 investigators from four colleges and 16 departments producing research awards of approximately $10M in annual direct costs a 68% increase from 2017 including $1.8M from the NCI and $3.4M from other NIH agencies. Members have published 613 manuscripts (2018 to 2022) of which 148 (24%) are inter-programmatic 169 (28%) are intra-programmatic 344 (56%) are inter-institutional and 13% of which have an impact factor >10. TO members lead 26 new therapeutic interventional investigator-initiated trials (IITs) a 53% increase since the previous funding period (17 IITs 2013-2017). These IITs have enrolled 870 patients (2018-2022) a 111% increase in IIT accruals (413 patients 2013-2017) with 52% of participants from Appalachia. In addition TO investigators enrolled 12689 individuals to the programs interventional and non-interventional trials compared to 8571 from 2013-2017 a 48% increase. TO Program members are international leaders in target discovery and validation have national and international collaborations and hold leadership roles in the National Cancer Institutes Experimental Therapeutics Clinical Trials Network the Oncology Research Information Exchange Network and Onco-Array Networks and the MCC-led Global Cancer Consortium. The TO Program fosters continuous collaboration among MCC program members to inform and advance MCC basic science into the clinic. A notable example is translating early identification of the biomarker FASN to an ongoing colorectal cancer trial. The TO Program has a cohesive and collaborative team focused on translating MCC scientific discoveries into safe and effective anticancer treatments with a demonstrated depth and breadth of impact in MCCs catchment area nationally and internationally.

project_terms:
Address;Antineoplastic Agents;Appalachian Region;Area;Award;Basic Science;Biological Markers;Biological Models;Breast;Cancer Burden;Cancer Center;Cancer Center Support Grant;Cancer Control;Cancer Patient;Catchment Area;Clinic;Clinical;Clinical Oncology;Clinical Trials;Clinical Trials Network;Collaborations;Colorectal Cancer;Communities;Community Outreach;Data;Development;Devices;Diet;Direct Costs;Disparity;EIF4EBP1 gene;Early Therapeutic-Clinical Trials Network;Early identification;Electronics;Enrollment;FASN gene;Fostering;Funding;Future;Genomics;Goals;Gold Compounds;Hydroxychloroquine;Incidence;Individual;Infrastructure;Institution;Interdisciplinary Study;International;Intestinal Hormones;Investigational Drugs;Investigational Therapies;Kentucky;Lead;Leadership;Malignant Neoplasms;Manuscripts;Mediator;Mission;Molecular;Molecular Target;Multi-Institutional Clinical Trial;Mutation;NCI Center for Cancer Research;National Cancer Institute;Natural Products;Nursing Faculty;Obesity;Oncology;Participant;Patient-Focused Outcomes;Patients;Peer Review;Pharmaceutical Preparations;Phase;Phenotype;Population;Prostate;Public Policy;Publications;Publishing;Radiopharmaceuticals;Research;Research Personnel;Research Priority;Resources;Role;Ruthenium Compounds;Science;Strategic Planning;Structure;Therapeutic;Therapeutic Agents;Therapeutic Intervention;Translating;Translations;Tumor Suppressor Proteins;United States National Institutes of Health;Universities;Up-Regulation;Validation;anti-cancer treatment;cancer care;cancer prevention;cancer therapy;cellular oncology;clinical development;clinical translation;clinical trial enrollment;clinically relevant;college;community engagement;cross disciplinary program;design;drug repurposing;early phase clinical trial;ethnic disparity;genome resource;inhibitor;insight;inter-institutional;intervention program;investigator-initiated trial;member;molecular oncology;mortality;next generation sequencing;novel;novel anticancer drug;novel therapeutic intervention;novel therapeutics;oncology program;phase 1 study;pre-clinical;precision medicine;preclinical development;programs;racial disparity;recruit;repository;translational goal;translational oncology;translational pipeline;translational study;treatment trial;tumor;working group


application_id: 10920411
project_number: 5P30CA177558-12
project_title: Molecular and Cellular Oncology Research Program
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5465
contact_pi_person_id: 1918859
contact_pi: PLATTNER, RINA
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT The goal of the Molecular and Cellular Oncology (MCO) Research Program is to gain a comprehensive understanding of basic mechanisms driving cancer initiation progression metastasis and therapeutic resistance to facilitate development of novel and rational approaches for cancer prevention and therapy. MCO research efforts are central to the overall Markey Cancer Center (MCC) mission to reduce cancer rates in Kentucky through research prevention treatment education and community engagement. MCO investigators determine signaling genetic epigenetic and metabolic mechanisms that promote cancer development fuel tumor progression and contribute to therapeutic resistance. To achieve its goal MCO proposes three inter-related aims: 1) Identify aberrant signaling networks and critical interactions of tumor cells with their microenvironment to delineate molecular mechanisms that drive tumor initiation progression and metastasis and resistance; 2) Determine the contribution of metabolic reprogramming and epigenetic dysregulation to define novel pathways promoting cancer cell survival and adaptation; 3) Delineate the mechanisms by which dysregulation of redox signaling promotes genomic instability therapeutic resistance and normal tissue toxicity. The 54 members of the MCO Program are experts in cancer cell signaling tumor microenvironment cancer metabolism epigenetic regulation and redox biology who hail from 16 departments in the Colleges of Medicine; Engineering; Arts and Sciences; and Agriculture Food and Environment reflecting diverse disciplinary perspectives. Cancer-related MCO funding is nearly $10.3M in annual direct costs and 53% of MCO peer-reviewed funding is from the NCI. Members have published 320 manuscripts (July 2018June 2022) of which 106 (33%) are inter-programmatic 81 (25%) are intra-programmatic and 195 (61%) are inter-institutional. The program is co-led by three researchers with expertise in each of the three programmatic areas. Dr. Rina Plattner (an expert in oncogenic kinase signaling and tumor metastasis) Dr. Binhua Peter Zhou (a specialist in epigenetic and metabolic reprogramming of epithelial-mesenchymal transition) and Dr. Tianyan Gao (an expert in protein phosphatases and mitochondrial regulation of cancer stem cells) bring together expertise in cancer signaling (Plattner Aim 1) epigenetics and metabolism (Zhou Aim 2) and redox biology and mitochondrial bioenergetics (Gao Aim 3). In addition to their scientific leadership each offers significant strengths in clinical translation junior faculty mentoring communications among MCC Research Programs and expertise on the MCC catchment area. By leveraging comprehensive program strengths the MCO Program collectively provides a rich environment to facilitate multidisciplinary collaboration and builds a productive pipeline for translation of MCO science into the clinic.

project_terms:
Address;Adhesions;Agriculture;Area;Arts;Automobile Driving;Bioenergetics;Biogenesis;Biology;Cancer Burden;Cancer Center;Cancer Center Support Grant;Cancer Control;Caregivers;Catchment Area;Cell Proliferation;Cell Survival;Chromatin;Clinic;Clinical Trials;Collaborations;Colorectal Cancer;Communication;Community Outreach;DNA Repair;Development;Direct Costs;Disparity;Education;Electronics;Engineering;Ensure;Environment;Enzymes;Epigenetic Process;Epithelium;Extracellular Matrix Proteins;FASN gene;FDA approved;Food;Funding;Future;Genetic;Genomic Instability;Goals;Heart Injuries;Incidence;Interdisciplinary Study;Intervention;Invaded;Joints;Kentucky;Leadership;Maintenance;Malignant - descriptor;Malignant Neoplasms;Manuscripts;Medicine;Mesenchymal;Metabolic;Metabolism;Metastatic Melanoma;Mission;Mitochondria;Modeling;Molecular;NCI Center for Cancer Research;Neoplasm Metastasis;Normal tissue morphology;Oncogenic;Oxidation-Reduction;Pathway interactions;Patients;Peer Review;Phosphoric Monoester Hydrolases;Phosphotransferases;Population;Prevention;Production;Productivity;Protein Kinase;Protein phosphatase;Publications;Publishing;Reactive Oxygen Species;Recurrence;Regulation;Research;Research Personnel;Research Priority;Resistance;Science;Signal Transduction;Signaling Molecule;Specialist;Stress;Survivors;Tissues;Toxic effect;Translating;Treatment Efficacy;Universities;Vulnerable Populations;base;cancer cell;cancer health disparity;cancer initiation;cancer prevention;cancer stem cell;cancer therapy;cellular oncology;clinical translation;college;community engagement;diagnostic biomarker;epigenetic regulation;extracellular vesicles;faculty mentor;immune checkpoint blockade;inter-institutional;member;microbiome;molecular oncology;mortality;multidisciplinary;neoplastic cell;novel;novel therapeutic intervention;oncology program;programs;recruit;stem cell biology;therapeutic target;therapy resistant;tissue injury;translational oncology;translational pipeline;tumor;tumor immunology;tumor initiation;tumor metabolism;tumor microenvironment;tumor progression


application_id: 10920407
project_number: 5P30CA177558-12
project_title: Cancer Prevention and Control Research Program
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5464
contact_pi_person_id: 14510566
contact_pi: KUHS, KRYSTLE 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
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT Markey Cancer Centers (MCC) Cancer Prevention and Control (CP) Research Program fosters high-impact population-based and community-engaged research with the overarching goal of reducing cancer incidence and mortality in Kentucky. CP research spans the population science translation pipeline from advancing understanding of risk factors and intervention targets to developing and testing new interventions to studying the process of dissemination and implementation of interventions into practice. Impactful scientific contributions include research into patient survival in oropharyngeal cancer timely regulatory and policy research on novel smokeless tobacco products trials of innovative interventions to reduce carcinogenic environmental exposures trials of interventions to promote quality of life outcomes among rural cancer survivors and community implementation trials to prevent hepatitis C transmission and implement cancer prevention and screening guidelines in communities throughout Kentucky and Appalachia. CP impact also extends to public health policy within Kentucky and nationally and in advancing standards of care related to tobacco cessation and lung cancer screening. The CP Program combines these strengths to address three Aims: Advance the understanding of risk factors and intervention targets for cancer prevention and control (Aim 1); Develop and test the efficacy of interventions across the cancer control continuum (Aim 2); Study the dissemination and implementation of interventions (Aim 3). The CP Program has been transformed by substantial strategic investments that have led to new leadership and by the infusion of multiple recruitments that have expanded the breadth and depth of program research combined with the continued success of long-standing program members. The programs peer-reviewed funding has increased by 50% and NCI funding has grown dramatically by 567% to now comprise 33% of peer-reviewed funding compared to 7% in 2017. The maturation of the program is evident in a 24% increase in clinical trial accrual and by the awarding of NCI P01 and UH3 multi-investigator inter-institutional grants and an NCI T32 focused on rural cancer. CP investigators are highly engaged with and responsive to the needs of MCCs catchment area residents and are engaged in inter-programmatic research that addresses MCCs catchment research priorities in collaboration with Community Outreach and Engagement. Thus the CP Program is integral to achieving the overall MCC mission to reduce cancer in Kentucky through research prevention treatment education and community engagement.

project_terms:
Address;Adoption;Affect;Appalachian Region;Area;Award;Behavioral;Cancer Burden;Cancer Center;Cancer Center Support Grant;Cancer Control;Cancer Control Research Program;Cancer Survivor;Cancer Survivorship;Caring;Catchment Area;Clinic;Clinical Trials;Collaborations;Communities;Community Outreach;County;Disclosure;Dissemination and Implementation;Early Diagnosis;Education;Electronics;Ensure;Environmental Exposure;Evidence based intervention;Financial Hardship;Fostering;Funding;Future;Genetic Markers;Goals;Grant;Growth;Health Policy;Healthcare;Hepatitis C Transmission;Hospitals;Human Genetics;Human Papillomavirus;Infusion procedures;Intervention;Intervention Studies;Intervention Trial;Investments;Kentucky;Knowledge;Leadership;Malignant Neoplasms;Mission;Modeling;Molecular;NCI Center for Cancer Research;Obesity;Oncology;Outcome;Patient-Focused Outcomes;Patients;Peer Review;Pilot Projects;Policies;Policy Research;Population Sciences;Population Study;Prevention;Prevention Guidelines;Prevention program;Process;Public Health;Quality of life;Radon;Regulation;Research;Research Personnel;Research Priority;Resources;Risk;Risk Factors;Rural;Science;Science Policy;Screening for cancer;Smokeless Tobacco;Survivors;Technology;Testing;Tobacco;Tobacco Use Cessation;Translating;Treatment Efficacy;Universities;Vulnerable Populations;Work;Youth;cancer care;cancer health disparity;cancer prevention;cancer risk;carcinogenicity;cellular oncology;college;community collaboration;community engaged research;community engagement;design;efficacy testing;ethnic minority population;genetic association;genetic epidemiology;implementation intervention;implementation research;implementation science;implementation trial;improved;innovation;inter-institutional;lung cancer screening;malignant oropharynx neoplasm;member;molecular marker;molecular oncology;novel;oncology program;population based;prevent;programs;racial minority population;recruit;risk stratification;routine care;screening guidelines;screening program;smoke-free policy;success;survivorship;tobacco flavor;tobacco products;tobacco regulation;translational oncology;translational pipeline;treatment risk


application_id: 10920404
project_number: 5P30CA177558-12
project_title: Plan to Enhance Diversity
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5463
contact_pi_person_id: 10552456
contact_pi: WILLIAMS, LOVORIA B
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT The proposed Plan to Enhance Diversity (PED) at the University of Kentucky (UK) Markey Cancer Center(MCC) under the leadership of Dr. Lovoria Williams (CP) applies an equity lens to MCCs comprehensivemission to reduce the cancer burden with a focus on Kentucky and its most vulnerable populations throughresearch prevention treatment education and community engagement. As the MCC inaugural AssociateDirector (AD) for Equity Diversity and Inclusion Dr. Williams (CP) has a prominent role with direct reporting toMCC Director Dr. B. Mark Evers (TO) as part of MCCs priority on diversity equity and inclusion (DEI) within ahighly collaborative senior leadership team. DEI efforts are fully integrated into MCCs FY24-28 Strategic Planwith a dedicated pillar of activity. PED is supported by DEI Coordinator Ms. Tianna Acree and operatescollaboratively with Cancer Research Training and Education Coordination (CRTEC) and MCC Administration.PED builds on early DEI successes that established a DEI Committee leveraged campus-wide trainee andfaculty career-enhancing programs (such as NIH-funded T32s) and applied a highly successful model of rural-focused cancer research education to the development of new dynamic DEI-focused pathway programs led byCRTEC. Moreover MCCs Leadership and members are participating in training in foundational DEI and healthequity education that will prepare them to cultivate diverse inclusive environments. The overall objectives ofPED are to integrate DEI throughout the fabric of the MCC and to promote a climate that advances inclusiveexcellence in cancer research education and community outreach. Three Specific Aims of the proposed PEDare to: 1) Enhance participation of underrepresented minority (URM) and women trainees staff and faculty inthe cancer center. To achieve this Aim we plan on developing equitable processes to bolster implement andsustain efforts to recruit retain and develop diverse talent; 2) Accelerate the career and leadershipdevelopment of women and URM early career faculty. This Aim will be accomplished by leveraging internaland national research and leadership development programs to support career and research agendasincreasing engagement in MCC decision-making processes and developing a new leadership academy; 3)Establish a sustainable infrastructure to advance DEI throughout the MCC and criteria for monitoring progresstoward achievement of diversity goals. This Aim will be achieved by maintaining the MCC DEI Committeecoalescing DEI resources providing DEI training and developing appropriate methods and timepoints toevaluate fidelity to the methods proposed under each Specific Aim and track DEI progress. Baselinedemographic data of MCC members trainees and staff will allow the examination of data gaps. With continuedCCSG support MCC will build on early successes and MCCs strong infrastructure and will leverageinstitutional commitment to advance workforce diversity of trainees research staff faculty and leadersreflective of the statewide Kentucky catchment area and eventually the nation.

project_terms:
Academy;Acceleration;Achievement;Address;Appalachian Region;Appointment;Area;Black race;Cancer Burden;Cancer Center;Cancer Center Support Grant;Career Choice;Career Mobility;Catchment Area;Climate;Clinical Sciences;Community Outreach;Comprehensive Cancer Center;Data;Decision Making;Dedications;Development;Disparity;Education;Education and Outreach;Electronics;Environment;Equity;Faculty;Funding;Goals;Growth;Hispanic Populations;Infrastructure;Institution;Kentucky;Leadership;Malignant Neoplasms;Methods;Minority;Minority Access;Mission;Modeling;Monitor;NCI-Designated Cancer Center;Not Hispanic or Latino;Oncology;Pathway interactions;Population;Prevention;Process;Program Development;Racial Equity;Recommendation;Reporting;Research;Research Personnel;Research Priority;Resources;Role;Rural;Rural Appalachia;Scholars Program;Science;Strategic Planning;Talents;Textiles;Training;Training and Education;Translational Research;Underrepresented Minority;United States National Institutes of Health;Universities;Vulnerable Populations;Woman;Workforce Development;anti-cancer research;cancer health disparity;cancer research center director;career;career development;clinical center;clinical encounter;community engagement;demographics;early-career faculty;education research;equity diversity and inclusion;experience;health equity;high school;improved;leadership development;lens;male;member;minority trainee;multidisciplinary;oncology program;programs;recruit;research and development;success;undergraduate student

public_health_relevance:
Project NarrativeNot applicable. This document is attached to satisfy electronic submission requirements.


application_id: 10920400
project_number: 5P30CA177558-12
project_title: Cancer Research Training and Education Coordination
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5462
contact_pi_person_id: 1947523
contact_pi: O'CONNOR, KATHLEEN L.
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT The Markey Cancer Center (MCC) at the University of Kentucky collectively delivers highly successful training programs spanning from K-12 to faculty level through the Cancer Research Training and Education Coordination (CRTEC) component. MCCs CRTEC programs and activities are structured around specific aims to: 1) Generate early interest in cancer-related careers; 2) Promote education and career development of graduate and postdoctoral cancer researchers; and 3) Foster research faculty career development in basic population and clinical/translational sciences. Key education activities address the academic challenges across rural Appalachian Kentucky through support from five grants that include an NCI Youth Enjoy Science R25 program. These efforts complement impactful structured academic and research training at the graduate postdoctoral and medical residency levels including three NCI-funded T32 training grants. Through new initiatives such as the recently funded NCI T32 and undergraduate research programs MCCs CRTEC component expands its comprehensive training reach to implement bold initiatives that complement well-established and emerging state-of-the-art cancer curricula and enrich MCC Research Programs. The establishment of sustainable NIH-funded Centers of Biomedical Research Excellence awards with dedicated cancer themes and associated junior faculty mentorship augment MCCs long-standing American Cancer Society Institutional Research Grant support for early-stage faculty and effective team-based faculty mentorship mechanisms across basic population and clinical research levels that are significantly expanding MCCs extramural funding base. Further targeted mentorship of early career clinical investigators through mechanisms such as the Clinical Trials Boot Camp fosters the development of investigator-initiated trials that translate MCC science to the clinic. The MCC Affiliate Network provides an effective conduit for multi-faceted statewide training of health care professionals in state-of-the-art cancer care which is needed to address cancer rates within Kentucky and the region. A rich cadre of seminars symposia meetings and career enrichment activities facilitate successful career development for all individuals engaged in cancer research and clinical practice. The MCCs collective efforts draw on vital institutional training resources to achieve the overarching goals of this program which are to guide cohesive growth and coordinate transdisciplinary education and mentoring endeavors across the MCC and integrate them with efforts campus-wide and nationally. Through coordination supported by MCCs Cancer Center Support Grant this comprehensive program will continue to evolve innovative curricula and strategically linked initiatives to prepare trainees and faculty for evolving cancer career opportunities.

project_terms:
Academic Training;Address;American Cancer Society;Award;Basic Science;Cancer Burden;Cancer Center;Cancer Center Support Grant;Cancer Control;Career Choice;Catchment Area;Centers of Research Excellence;Clinic;Clinical;Clinical Investigator;Clinical Research;Clinical Trials;Community Outreach;Complement;Dedications;Development;Education;Education Projects;Educational Activities;Educational Curriculum;Educational Status;Electronics;Evolution;Extramural Activities;Faculty;Fostering;Foundations;Funding;Goals;Grant;Growth;Health Professional;High School Student;Individual;Institution;Investments;Kentucky;Link;Malignant Neoplasms;Medical;Medical Residency;Mentors;Mentorship;Middle School Student;Mission;Modernization;NCI Center for Cancer Research;Oncology;Physicians;Population;Population Research;Postdoctoral Fellow;Prevention;Research;Research Personnel;Research Project Grants;Research Training;Resources;Rural Appalachia;Rural Population;Science;Scientist;Structure;Time;Training;Training Programs;Training and Education;Translating;Translational Research;Underrepresented Minority;Underrepresented Populations;Underserved Population;United States National Institutes of Health;Universities;Urban Population;Vulnerable Populations;Youth;anti-cancer research;base;cancer care;cancer education;cancer prevention;career;career development;cellular oncology;clinical practice;community engagement;design;diversity and inclusion;education research;educational atmosphere;health equity;health training;high school;improved;innovation;interest;investigator-initiated trial;meetings;molecular oncology;next generation;programs;research faculty;rural underserved;symposium;training data;training opportunity;translational oncology;undergraduate research experience;undergraduate student


application_id: 10920394
project_number: 5P30CA177558-12
project_title: Cancer Center Administration
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PAR-21-321
application_type: 5
activity_code: P30
ic: CA
serial_number: 177558
project_start_date: 2013-07-08
project_end_date: 2028-06-30
study_section: ZCA1-RTRB-F
subproject_number: 5461
contact_pi_person_id: 78871078
contact_pi: ROGERS, JENNIFER F
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACT Markey Cancer Center (MCC) Administration provides efficient administrative support to MCCs Director Senior Leadership Research Program leaders Shared Resource Facility (SRF) directors and MCC members. Administration fosters exceptional science and impact through the following Specific Aims: 1) Lead MCCs planning and evaluation efforts; 2) Foster collaboration through inter- and intra-programmatic activities and investing in and leveraging resources and infrastructure; 3) Support MCCs comprehensive research education and community outreach activities; and 4) Support sustainability and business planning. During the current reporting period Administration has facilitated member science through: 1) creating a new FY24-28 MCC Strategic Plan which is coupled with a $64.4M financial commitment and investment from UK Leadership in the cancer center; 2) assisting in the restructuring of MCCs Research Programs; 3) expanding MCCs Research Communications Office in key areas to continue robust support of CCSG-related activity; 4) driving a 128% expansion of MCCs Clinical Protocol and Data Management teams which paved the way for a 56% increase in accruals to interventional treatment trials; 5) overseeing a 78% expansion of MCCs physical space which has grown from 128587 sq. ft. to 228237 sq. ft. since 2009; 6) facilitating all MCCs pilot and seed award programs which have awarded $2.2M to investigators since 2018; 7) streamlining the membership application and review process; and 8) improving MCCs internal and external communication channels ranging from upgrades to MCCs public-facing website to establishing new channels for internal communication among staff leaders. To enhance cancer focus Administration created and implemented a center-wide policy on determining cancer-relatedness of all grants and contracts listed on Data Table 2. Together these efforts supported an increase in peer-reviewed funding of $11.1M since 2017 and the addition of 66 new cancer center members. Over the coming five years Administration will work closely with the MCC Director and Senior Leaders to: 1) implement and evaluate the centers FY24-28 Strategic Plan; 2) implement the planned expansion of MCCs capabilities to lead multi-site clinical trials which represents a $2.2M commitment from the center to build out this new competency; 3) expand MCCs faculty and staff recruitment and retention practices; 4) expand reporting and analysis capabilities and achieve greater efficiency through the implementation of CCSG data and electronic regulatory systems; and 5) facilitate planning efforts for an advanced ambulatory building site work for which is slated to begin in late fall 2022. Through robust planning and evaluation efforts Administration will lead the alignment of MCC functions in support of the centers Comprehensive Cancer Center status.

project_terms:
Administrative Efficiency;Area;Automobile Driving;Award;Businesses;Cancer Center;Cancer Center Support Grant;Characteristics;Clinical Cancer Center;Clinical Data;Clinical Protocols;Clinical Research;Clinical Treatment;Clinical Trials;Collaborations;Communication;Community Health Education;Community Outreach;Competence;Comprehensive Cancer Center;Contracts;Coupled;Data;Decision Making;Education;Electronics;Ensure;Evaluation;Faculty;Fostering;Funding;Future;Goals;Grant;Growth;Healthcare;Infrastructure;Intervention;Investments;Kentucky;Lead;Leadership;Malignant Neoplasms;Mentors;Mission;Monitor;Multi-Institutional Clinical Trial;NCI Center for Cancer Research;Organization and Administration;Output;Patients;Peer Review;Play;Policies;Process;Reporting;Research;Research Activity;Research Personnel;Resource Sharing;Resources;Role;Science;Site;Strategic Planning;Structure;System;Technology;Training and Education;Universities;Vision;Work;anti-cancer research;cancer research center director;data management;diversity and inclusion;equity diversity and inclusion;experience;falls;improved;innovation;meetings;member;outreach;programs;recruit;square foot;success;treatment trial;web site


application_id: 10920314
project_number: 1R41HL170893-01A1
project_title: Novel Urine Collection Kit for Obstructive Sleep Apnea
administering_ic: NHLBI
award_notice_date: 2024-07-11
opportunity_number: PA-23-232
application_type: 1
activity_code: R41
ic: HL
serial_number: 170893
suffix: A1
program_official: ALFINI, ALFONSO JOSEPH
project_start_date: 2024-07-15
project_end_date: 2025-06-30
study_section: Special Emphasis Panel[ZRG1 RCCS-B (11)]
contact_pi_person_id: 14097488
contact_pi: BURNS, CHRISTOPHER THOMAS
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 012986391
primary_uei: ZFN5J433DCT1
duns_number: 012986391
uei: ZFN5J433DCT1
fips: US
organization_id: 10019586
organization_name: PGXL TECHNOLOGIES, LLC
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 40206
organization_country: UNITED STATES
project_abstract:
PROJECT SUMMARY This Phase I STTR project is a collaboration between PGXL Technologies LLC(Company) and the University of Louisville Research Foundation (University) to develop aninnovative urine collection kit used to detect obstructive sleep apnea (OSA) in patients. PGXL Technologies is developing a US-Patented non-invasive urine-based assay forobstructive sleep apnea (OSA) in children. The test is comprised of a panel of four proteinbiomarkers detected in urine. OSA occurs in up to 3% of children and as much as 10% of thepediatric orthodontic population including 7% in adults. OSA can lead to disturbed sleepneurobehavioral problems neurocognitive impairments and hypertension in children andadults. Diagnosis is primarily limited to in-clinic sleep studies because patient history andphysical examinations are not adequately able to differentiate OSA from primary snoring (PS).Polysomnography (PSG) tests are administered in sleep studies and are the gold standard fordiagnosis but they are highly expensive require an overnight stay in a supervised sleep clinicare difficult for children as well as adults and do not meet the need for efficient screening forOSA. There is only one at-home sleep diagnostic that has been cleared by the FDA for use inchildren and it requires attachment of wires and sensors overnight which is challenging toimplement with children. There is an unmet need for a rapid and sensitive test for OSA that canbe used for potential diagnosis patient monitoring as they undergo treatment and screening ofbroader populations. The Company is developing an immunoassay-based multiplex panel comprised of fourproteins (uromodulin urocortin-3 orosomucoid-1 and kallikrein) associated with stress andhypoxia detected in the urine of children with OSA. Preliminary published data indicates that thisset of markers provides a diagnostic sensitivity of 100% and specificity of 96.5% for OSA inchildren. To confirm the efficacy of this test-panel with controlled studies we will require shippingof urine samples to our testing facility after collection. Securing the integrity of the proteinsduring shipping and storage is essential to our success. To address this challenge there is animminent need to develop a simple yet rigorous process for stabilizing the proteins duringspecimen transport. In this Phase I STTR project we will use an innovative silica-based reagent(BioCaRGOS) developed by our team and demonstrate that the reagent is compatible with ourimmunoassay system and stabilizes the target proteins in urine under shipping conditions. Thisproof-of-concept will enable the design of a rigorous urine collection kit required for our Phase IIclinical studies. Completion of these goals will enable advancement toward a laboratory developed testusing a novel method for stabilizing and processing of urine samples needed for routinecollection and provide an approach towards FDA clearance of a multiplexed high throughputassay for OSA. Commercialization of these products will enable delivery of a critically neededrapid test that can be administered by PGXL Technologies or licensed to CLIA-certified clinicallabs. This will fill a need for rapid sensitive and cost-effective identification of OSA in childrenand adults.

project_terms:
Address;Adenoidectomy;Adult;Advanced Development;Biological Assay;Biological Markers;CLIA certified;Calibration;Child;Childhood;Clinic;Clinical;Clinical Research;Collaborations;Collection;Controlled Study;Data;Detection;Development;Diagnosis;Diagnostic;Diagnostic Equipment;Diagnostic Sensitivity;Diagnostic tests;Exposure to;Foundations;Funding;Gel;Goals;Home;Hypertension;Hypoxia;Immunoassay;Kininogenase;Laboratories;Legal patent;Licensing;Measurement;Methods;Monitor;Myocardial dysfunction;Neurocognitive Deficit;Obstructive Sleep Apnea;Orosomucoid;Orthodontic;Patient Monitoring;Patients;Phase;Physical Examination;Physicians;Polysomnography;Population;Predictive Value;Process;Proteins;Publishing;Reagent;Recording of previous events;Recovery;Recurrence;Reproducibility;Research;Sampling;Secure;Sensitivity and Specificity;Shipping;Silicon Dioxide;Sleep;Sleep disturbances;Small Business Technology Transfer Research;Snoring;Specificity;Specimen;Stress;System;Technology;Testing;Time;Tonsillectomy;Treatment Efficacy;UMOD gene;Universities;Urine;Work;commercialization;cost;cost effective;design;diagnosis standard;efficacy evaluation;efficacy testing;high throughput screening;improved;in-vitro diagnostics;innovation;interest;neurobehavioral;novel;novel strategies;point of care;protein biomarkers;rapid test;reduce symptoms;sample collection;screening;sensor;standard of care;success;systemic inflammatory response;urocortin

public_health_relevance:
PROJECT NARRATIVEPGXL Technologies LLC and ULRF are developing a rapid simple-to-use and cost-effective urine collectionkit for detection of obstructive sleep apnea (OSA) in children which will support diagnosis patient monitoringand screening. Approximately 3% of children have OSA and many are not diagnosed. Polysomnography(PSG) tests are reliable but limited by their high cost and requirement for an overnight sleep study at a clinicmaking a simple non-invasive urine test beneficial and commercially attractive.


application_id: 10919604
project_number: 1R43HD115442-01
administering_ic: NICHD
award_notice_date: 2024-05-30
opportunity_number: PA-23-231
application_type: 1
activity_code: R43
ic: HD
serial_number: 115442
program_official: LONGO, MONICA
project_start_date: 2024-06-01
project_end_date: 2026-05-31
study_section: Special Emphasis Panel[ZRG1 CCHI-J (10)]
contact_pi_person_id: 14342405
contact_pi: TINIUS, RACHEL ANN
other_pis: Not Applicable
congressional_district: 02
department: Unavailable
primary_uei: VDCAHL6PVLV7
uei: VDCAHL6PVLV7
fips: US
organization_id: 10076801
organization_name: BUMPTUP LABS, INC.
organization_city: BOWLING GREEN
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 421043860
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2024-06-01
budget_end_date: 2026-05-31
assistance_listing_number: 93.865
project_title:
Clinical Testing and Refinement of BumptUp: A mobile health app to increase physical activity and improve obstetric outcomes among pregnant and postpartum women

project_abstract:
PROJECT SUMMARYU.S. maternal mortality rates have risen by 63.7% since 2019 making the U.S. the most dangerous developednation to give birth in. A major contributor is that many women are becoming pregnant with chronic healthconditions like obesity hypertension and diabetes. Underserved and minority women are particularlyvulnerable to chronic health conditions (e.g. black women are 2.3 times more likely to be overweight comparedto white women) and poor pregnancy outcomes (e.g. black women are 2.6 times more likely to suffer apregnancy-related death than white women). These populations also have limited access to prenatal care (6.9million women of childbearing age have little or no access to maternal health care). Fortunately physicalactivity during and after pregnancy improves maternal and infant outcomes. Professionals recommend allpregnant women exercise for 150 minutes per week. However less than 15% of pregnant women meet theseguidelines because they lack time and resources fear they will harm the unborn baby or have pregnancy-related symptoms (e.g. fatigue nausea discomfort). There remains a significant unmet need to developeffective intervention strategies to reduce obesity rates and increase physical activity in pregnant andpostpartum women. To address this need BumptUp Labs Inc. created BumptUp the first mobile health appto provide pregnant and postpartum women with careful screening and evidence-based safe exerciseprogramming. Strong preliminary data support the apps potential for impact but more work is needed to testthe apps efficacy for improving key health outcomes. The objective of this project is to conduct a clinical trial todemonstrate BumptUps efficacy while also utilizing real-time customer feedback to enhance the appsexperience and features. BumptUp seeks to enter the market of mHealth apps through business-to-consumer and business-to-business sales. During Phase I the following aims will be completed: Aim 1Conduct a randomized controlled clinical trial to assess the efficacy of BumtpUp for increasing physicalactivity levels during pregnancy (13-15 23-25 and 35-37 weeks gestation) and postpartum (6 and 12 weeks).Aim 2Perform design changes to BumptUp in response to results from the completed clinical trial toimprove usability and algorithm performance. These goals support the National Institute of Child Health andHuman Developments mission to improve reproductive health. At the end of Phase I BumptUp Labs will haveclinical trial data to demonstrate its efficacy and a refined app that is prepped for success in commercial marketspaces. During Phase II a new app featurea mobile maternal and fetal heart rate monitorwill beengineered and synced with the app to provide additional reassurance to mothers during exercise. We will alsomake additional app adaptations to meet the specific needs of underserved subgroups (black lowsocioeconomic status rural). Overall the development of BumptUp is expected to improve maternal healthoutcomes while lowering healthcare costs for consumers and insurance companies.

project_terms:
37 weeks gestation;Accelerometer;Address;Adoption;Age;Algorithms;American;American College of Obstetricians and Gynecologists;Birth;Black race;Blood Pressure;Businesses;Cellular Phone;Cessation of life;Chronic;Clinical Trials;Control Groups;Dangerousness;Data;Death Rate;Developed Countries;Development;Diabetes Mellitus;Discipline of obstetrics;Engineering;Exercise;Fatigue;Feedback;Female of child bearing age;Fetal Heart Rate;Fetal health;Focus Groups;Fright;Goals;Growth;Guidelines;Health;Health Care Costs;Health Personnel;High-Risk Pregnancy;Hypertension;Income;Insurance;Internet;Intervention;Interview;Life Style;Life Style Modification;Link;Marketing;Maternal Health;Maternal Health Services;Maternal Mortality;Measures;Mental Health;Minority Women;Mission;Mobile Health Application;Mothers;National Institute of Child Health and Human Development;Nausea;Obesity;Outcome;Overweight;Participant;Performance;Phase;Physical activity;Population;Postpartum Period;Postpartum Women;Pregnancy;Pregnancy Complications;Pregnancy Outcome;Pregnant Women;Prenatal care;Randomized Controlled Clinical Trials;Recommendation;Reporting;Reproductive Health;Resources;Rural;Sales;Social support;Socioeconomic Status;Subgroup;Symptoms;Target Populations;Testing;Time;Translating;Weight Gain;White Women;Woman;Work;black women;blood glucose regulation;blood pressure reduction;child bearing;clinical care;college;commercial application;commercialization;design;dietary;effective intervention;efficacy evaluation;evidence base;experience;gestational weight gain;healthy lifestyle;heart rate monitor;improved;improved outcome;infant outcome;low socioeconomic status;maternal morbidity;maternal outcome;maternal weight;medical attention;mobile application;mobile phone based intervention;mortality;novel;obstetric outcomes;post pregnancy;postpartum care;pregnancy related death;pregnant;prenatal;research clinical testing;response;screening;secondary outcome;success;usability

public_health_relevance:
PROJECT NARRATIVEWomen are dying from pregnancy-related issues at higher rates in the U.S. than in any otherdeveloped nation in the world and more than 50% of these deaths are linked to issues related tomaternal weight (i.e. overweight/obesity). BumptUp is the only mobile health app that providespregnant and postpartum women with evidence-based exercise programming along with progressand symptom tracking dietary recommendations and social support. It is well-established that mobilehealth apps positively impact user lifestyle changes; thus development of BumptUp has greatpotential to reduce the large number of preventable maternal deaths in the U.S. while also reducinghealthcare costs.


application_id: 10919156
project_number: 1R44HL174221-01
project_title: UroMarker Test Panel for Obstructive Sleep Apnea
administering_ic: NHLBI
award_notice_date: 2024-09-17
opportunity_number: PA-23-230
application_type: 1
activity_code: R44
ic: HL
serial_number: 174221
program_official: DIXIT, SHILPY
project_start_date: 2024-09-20
project_end_date: 2025-06-30
study_section: Special Emphasis Panel[ZRG1 RCCS-B (11)]
contact_pi_person_id: 14097488
contact_pi: BURNS, CHRISTOPHER THOMAS
other_pis: VALDES, ROLAND
congressional_district: 03
department: Unavailable
primary_duns: 012986391
primary_uei: ZFN5J433DCT1
duns_number: 012986391
uei: ZFN5J433DCT1
fips: US
organization_id: 10019586
organization_name: PGXL TECHNOLOGIES, LLC
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 40206
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY PGXL Technologies is developing a patented non-invasive urine-based assay for obstructive sleepapnea (OSA) in children. OSA occurs in up to 3% of children and as much as 10% of the pediatric orthodonticpopulation. OSA can lead to disturbed sleep neurobehavioral problems neurocognitive impairments andhypertension in children. Diagnosis is primarily limited to in-clinic sleep studies because patient history andphysical examinations are not adequately able to differentiate OSA from primary snoring (PS) i.e. snoringwithout associated sleep apnea or underlying sleep disorder. Polysomnography (PSG) tests are the goldstandard for diagnosis but they are highly expensive require an overnight stay in a supervised sleep clinic aredifficult for children and do not meet the need for screening OSA. There are several home sleep tests (HSTs)that have been cleared for use in children that use similar sensors and methods as PSG studies in the homebut the Academy of Sleep Medicine currently does not recommend the use of HSTs for diagnosis of OSA inchildren due to the lack of physician supervision and a lack of sufficient evidence of efficacy. There is an unmetneed for a rapid and sensitive test for OSA that can be used for potential diagnosis patient monitoring as theyundergo treatment and screening of broader populations. PGXL Technologies is advancing development of aurine-based multiplexed immunoassay for screening children for OSA. The four biomarkers urocortin-3(UCN3) kallikrein-1 orosomucoid-1 and uromodulin are present in urine and have previously shown highsensitivity and specificity for detection of OSA in children using ELISA assays. Prior to this project PGXL hasadapted two of the four biomarkers to the Meso Scale Discovery (MSD) platform a clinical diagnostic platformbased on a highly sensitive electrochemiluminescent detection approach. PGXL has demonstrated initialclinically relevant detection for two biomarkers and acquired a retrospective set of pediatric urine samples thatcan be used to determine reference ranges. The goal of this Fast-Track proposal will be to advancedevelopment through initial clinical validation. In Phase I of this Fast-Track project PGXL will integrateimmunoassays for the remaining biomarkers and optimize the analytical range for each of the assays in theUroMarker panel using pediatric urine specimens. In Phase II PGXL will complete analytical validationrequired to meet CLIA requirements and conduct a prospective study to establish clinical cutoffs for analgorithm that includes all four biomarkers. PGXL will also develop a prototype urine collection kit that can beused for urine collection at home and mailed to a CLIA lab for analysis. Success with these goals will alsoinform a larger multi-site clinical study that is expected in Phase IIb and will support FDA clearance of the test.These milestones provide a path toward the commercial deployment of a high-throughput multiplex test forrapid OSA screening through simple home-based sample collection to improve patient outcomes.

project_terms:
Academy;Adenoidectomy;Advanced Development;Affect;Algorithms;Antibodies;Apnea;Biological Assay;Biological Markers;CLIA certified;Child;Childhood;Clinic;Clinical;Clinical Research;Clinical Trials;Collection;Detection;Diagnosis;Diagnostic Equipment;Diagnostic Procedure;Enzyme-Linked Immunosorbent Assay;Frequencies;Future;Goals;Health;Home;Hypertension;Hypoxia;Immunoassay;Impaired cognition;Institutional Review Boards;Investments;Laboratories;Legal patent;Literature;Measures;Medicine;Methods;Multi-site clinical study;Myocardial dysfunction;Neurocognitive Deficit;Obstructive Sleep Apnea;Orosomucoid;Orthodontic;Patient Monitoring;Patient-Focused Outcomes;Patients;Phase;Physical Examination;Physicians;Polysomnography;Population;Prevalence;Prospective Studies;Proteins;Recording of previous events;Reference Values;Sampling;Sensitivity and Specificity;Severities;Shipping;Site;Sleep;Sleep Apnea Syndromes;Sleep Disorders;Sleep disturbances;Snoring;Specific qualifier value;Specificity;Specimen;Stress;Supervision;System;Technology;Testing;Time;Tonsillectomy;UMOD gene;Urinary Kallikrein;Urine;Validation;biomarker panel;clinical diagnostics;clinically relevant;commercialization;cost;cost effective;design;detection test;diagnosis standard;diagnostic algorithm;diagnostic development;diagnostic platform;experience;improved;improved outcome;in-vitro diagnostics;indexing;multiplex assay;neurobehavioral;novel;prospective;prototype;rapid test;sample collection;screening;sensor;standard care;success;systemic inflammatory response;urocortin

public_health_relevance:
PROJECT NARRATIVE Approximately 3% of children have obstructive sleep apnea (OSA) but many remain undiagnosed dueto limited testing capabilities. Polysomnography tests (overnight sleep studies) are the primary method fordiagnosis of OSA in children but these tests are highly expensive have limited throughput and can be difficultto administer in children. PGXL Technologies is developing a rapid sensitive and cost-effective urine-basedtest for detection of OSA in children which will support rapid cost-effective screening.


application_id: 10918321
project_number: 5R01DK135267-02
project_title: Signaling and metabolic functions of nSMase-2 in hepatic steatosis and onset of insulin resistance
administering_ic: NIDDK
award_notice_date: 2024-07-29
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: DK
serial_number: 135267
program_official: LIANG, HANYU
project_start_date: 2023-09-01
project_end_date: 2026-08-31
study_section: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]
contact_pi_person_id: 6730250
contact_pi: NIKOLOVA-KARAKASHIAN, MARIANA N
other_pis: Not Applicable
congressional_district: 06
department: PHYSIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Revised ABSTRACT:The onset of insulin resistance is a hallmark of metabolic syndrome and its complications. Together with other tissues (the adipose and the muscle) liver also becomes insulin resistant thus contributing to the onset of hyperglycemia and type II diabetes. The mechanisms of hepatic insulin resistance are not well understood; but ceramide a bioactive lipid metabolite is considered one of the main culprits. Drugs targeting pathways for ceramide de novo synthesis have shown effectiveness in ameliorating aspects of metabolic syndrome in the mouse. These approaches however typically exert a very broad effect on all sphingolipids both structural and bioactive instead on ceramide alone.  Due to the diverse roles that ceramide play in metabolic health of hepatocytes the range of subcellular locations where it resides and the variety of metabolic pathways for its generation specific approaches to target distinct ceramide effects are needed for successful translation to the clinic but are not available at the moment. The hypothesis to be tested in this proposal is that an enzyme called Neutral Sphingomyelinase-2 (nSMase-2 gene name smpd3) one of four distinct enzymes that can generates ceramide by the turnover of sphingomyelin plays an unique role in the regulation of the insulin response of hepatocytes. This hypothesis is supported by strong preliminary data documenting its key aspects. The proposed plan will identify the underlying mechanisms of this novel signaling axis in cellular response to insulin. Aim 1 will decipher the impact of nSMase-2 at the plasma membrane on ceramide homeostasis and insulin signaling in vitro. Aim 2 is to test the cause-effect relationship between nSMase-2 and insulin resistance in vivo and examine the impact of ceramide generated at the plasma membrane on de novo lipogenesis lipid secretion lipotoxicity and gluconeogenesis in vivo. A recently developed liver specific knockout mouse will be used in these studies.

project_terms:
Address;Adipose tissue;Adverse effects;Affect;Animal Disease Models;Animal Model;Antibodies;Autophagocytosis;Biochemical Pathway;Biological;Cell membrane;Ceramides;Clinic;Data;Development;Diabetes Mellitus;Diet;Drug Targeting;Effectiveness;Enzymes;FOXO1A gene;Fatty Liver;Fatty acid glycerol esters;Gene Expression;Generations;Genes;Genetic;Gluconeogenesis;Health;Hepatic;Hepatocyte;Homeostasis;Human;Hydrophobicity;Hyperglycemia;Hyperinsulinism;In Vitro;Inflammation;Inflammatory;Insulin;Insulin Resistance;Knockout Mice;Link;Lipids;Liver;Location;Mediating;Metabolic;Metabolic Pathway;Metabolic syndrome;Metabolism;Molecular;Mus;Muscle;Names;Non-Insulin-Dependent Diabetes Mellitus;Obesity;Organelles;Palmitic Acids;Pathway interactions;Peripheral;Persons;Physiological;Play;Production;Protein phosphatase;Regulation;Research;Role;Signal Transduction;Site;Solid;Sphingolipids;Sphingomyelinase;Sphingomyelins;Testing;Tissues;Translations;clinically relevant;endoplasmic reticulum stress;experimental study;gain of function;in vivo;inhibitor;insulin regulation;insulin signaling;lipid biosynthesis;lipidomics;loss of function;mitochondrial dysfunction;mutant;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;obese patients;pharmacologic;preclinical study;prevent;protein kinase C zeta;public health relevance;response;saturated fat;sphingosine 1-phosphate

public_health_relevance:
Public Health relevance: This proposal will discover novel targets to treat insulin resistance in obese patients.


application_id: 10917679
project_number: 1R41AG084384-01A1
project_title: Targeted Exosomal Delivery of siRNA Therapeutics for Neuroinflammatory Diseases
administering_ic: NIA
award_notice_date: 2024-09-18
opportunity_number: PAS-22-197
application_type: 1
activity_code: R41
ic: AG
serial_number: 084384
suffix: A1
program_official: MARTIN, ZANE
project_start_date: 2024-09-20
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: WALLEN, RENA MARGARET
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 if not all are mediated byinflammation. Even though several drugs have recently been approved by the FDA for treating neurologicaldisorders including Alzheimer's disease (AD) their efficacy as AD therapeutics has not been realized as extremelylow levels of the drug reach the brain. The goal of this Phase I project is to develop an effective targeted deliverysystem for siRNA against NFB expression (siNFB) to mitigate neuroinflammatory diseases. We have recentlyshown that siRNA entrapped in bovine colostrum-derived exosomes and polyethyleneimine matrix (EPM) caneffectively deliver siRNA to reduce target gene expression. We will apply our extensive experience in exosomessiRNA therapeutics and inflammatory responses for efficient targeted delivery of siNFB to the microenvironmentof the brain where progressive increase in inflammation ultimately leads to manifestation of neuroinflammatorydiseases including AD. We hypothesize that EPM-siNFB formulations administered via a novel trans-spinal (t.s.)route can effectively deliver siNFB to the brain and knockdown the inflammatory regulator NFB and attenuatecorresponding disease markers. We also hypothesize that use of smaller exosomes (smExo) (average size 45nm) coupled with folic acid (FA)-functionalization can enhance the brain delivery presumably due to more efficientcrossing of the blood brain barrier and high expression of folate receptor- (FR) in the brain respectively. Ourhypotheses are supported by high siRNA entrapment (>90%) in the EPM protection of EPM-siRNA fromenzymatic degradation higher knockdown of NFB in murine cells than conventional reagents higher brainaccumulation of smEPM-siRNA in mice treated via t.s. route compared with the traditional routes intravenouslyand intranasally and FA-functionalization of exosomes for brain targeting. Innovation in this project lies in the useof bovine colostrum powder - an abundant and cost-effective source of native exosomes use of smaller exosomesand FA-functionalization coupled with t.s. administration. Investigators experienced in exosomes drug deliverysiRNA therapeutics and animal models leveraging extensive experience of Dr. Robert Friedland in AD researchwill pursue the following specific aims: Aim 1. Optimize delivery of siNFB using FA-functionalized exosomalvector in vitro and in vivo. Murine cell lines bearing WT sequences of NFB will be used to identify effective siNFBsequences based on NFB knockdown. Aim 2. In vivo efficacy of brain-targeted FA-smEPM-siNFB. The leadformulation from Aim 1 will be tested for efficacy in murine models of AD. Therapeutic benefit will be based onknockdown of NFB in the target (cortex and hippocampus) and non-target tissues related histopathological andAD biomarker changes and assessment of behavioral endpoints. This project will provide proof-of-principle forinhibition of neuroinflammation by targeted t.s. delivery of siNFB. In Phase II we will compare inhibition of othertargets such as BACE1 a key target for AD alone and in combination with NFB using multiple rodent AD modelsto identify the optimal gene target(s) for this disease.

project_terms:
Affect;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease therapeutic;Alzheimers disease biomarker;Animal Model;Animals;Area;Attenuated;Base Sequence;Behavior assessment;Behavioral;Biodistribution;Biological Markers;Brain;Brain region;Cattle;Cell Line;Cells;Colostrum;Coupled;Data;Disease;Disease Marker;Dose;Drug Delivery Systems;Drug Targeting;Dryness;Dyes;Encephalitis;Euthanasia;FDA approved;FOLR1 gene;Female;Fibroblasts;Fluorescence;Folic Acid;Formulation;Gene Expression;Gene Targeting;Genes;Goals;Hippocampus;In Vitro;Inflammation;Inflammatory;Inflammatory Response;Intravenous;Label;Lead;Liver;Mediating;Mouse Cell Line;Mus;Nervous System Disorder;Neurodegenerative Disorders;Persons;Pharmaceutical Preparations;Phase;Polyethyleneimine;Powder dose form;Radiolabeled;Reagent;Regimen;Research;Research Personnel;Rodent;Route;Signal Transduction;Small Interfering RNA;Source;Spinal;Standardization;Sum;System;Testing;Therapeutic;Tissue imaging;Tissues;Topical application;Toxic effect;Treatment Efficacy;beta-site APP cleaving enzyme 1;blood-brain barrier crossing;candidate identification;cost effective;efficacy study;efficacy testing;ex vivo imaging;exosome;experience;folate-binding protein;imager;immunogenicity;immunotoxicity;in vivo;inflammatory marker;inflammatory modulation;innovation;knock-down;mouse model;nanoformulation;nanoparticle;neuroinflammation;novel;public health relevance;safety assessment;siRNA delivery;targeted delivery;therapeutic siRNA;treatment response;vector

public_health_relevance:
Narrative (Public Health Relevance Statement) In the proposed project we will use a novel nano formulation of small interfering siRNA to mitigateneuroinflammation and attenuate neurological diseases including Alzheimer's disease (AD). In our approachsiRNA of the key inflammation regulator NFB (siNFB) is sequestered in exosomes (native nanoparticles)isolated from standardized bovine colostrum powder the exosomes are attached to folic acid to target thebrain sub tissues such as cortex and hippocampus and the formulation is delivered trans-spinally by topicalapplication for efficient brain targeting. The novel formulation will be optimized using mouse cell lines and thetrans-spinal delivery system tested using mouse models for inflammation and AD.


application_id: 10917396
project_number: 5R01AA028435-05
administering_ic: NIAAA
award_notice_date: 2024-07-19
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: AA
serial_number: 028435
program_official: MURRAY, GARY
project_start_date: 2020-08-01
project_end_date: 2026-07-31
study_section: Special Emphasis Panel[ZRG1-IFCN-C(02)M]
contact_pi_person_id: 7035096
contact_pi: CHEN, SHAO-YU
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
budget_start_date: 2024-08-01
project_title:
Role of exosomes in the coordinated migration of neural crest cells and placodes and ethanol-induced teratogenesis

project_abstract:
Fetal Alcohol Spectrum Disorders (FASD) is the leading known cause of mental retardation. Growing evidencesuggests a major contribution of the disruption of neural crest cell (NCC) and placode (PC) migration to ethanol-induced craniofacial and cranial nerve defects. However there is a fundamental gap in understanding howethanol disrupts the coordinated migration of NCCs and PCs in embryos. Exosomes have recently emerged asan important mode of intercellular communication. Exosomes carry and transfer a variety of active moleculesincluding microRNAs to and act on local and distant recipient cells and affect their functions. We have recentlydemonstrated that exosomes derived from human NCCs mediated ethanol-induced repression of SDF1/CXCR4signaling and subsequently disrupted the coordinated migration of NCCs and PCs and that disruption of NCCand PC migration contributes to ethanol-induced craniofacial and cranial nerve defects in zebrafish embryos.The overall objective of this proposal is to elucidate the mechanisms by which exosomes mediate ethanol-induced repression of SDF1/CXCR4 signaling disruption of the coordinated migration of NCCs and PCs andcraniofacial and cranial nerve defects and to establish plant-derived exosome-like nanoparticles as a feasiblestrategy for the prevention of FASD. The central hypothesis of this project is that ethanol disrupts the coordinatedmigration of NCCs and PCs through NCC-derived exosome-mediated repression of SDF1/CXCR4 signalingsubsequently leading to craniofacial and cranial nerve defects and that modulation of SDF1/CXCR4 signalingby grape exosome-like nanoparticles (GELNs) or GELNs loaded with miRNA modulators can prevent ethanol-induced teratogenesis. To test our hypothesis the following specific aims will be addressed: Aim 1: Tocharacterize the role of exosomes in ethanol-induced disruption of the coordinated migration of NCCs and PCsin vitro and in zebrafish embryos. Aim 2: To elucidate the mechanisms by which NCC-derived exosomes mediateethanol-induced repression of SDF1/CXCR4 signaling and disruption of the coordinated migration of NCCs andPCs. Aim 3: To test the hypothesis that exosomes derived from NCCs mediate ethanol-induced craniofacial andcranial nerve defects and that modulation of SDF1/CXCR4 signaling by GELNs or GELNs loaded with miRNAmodulators represents a novel therapeutic strategy for preventing FASD. The proposed work is innovativebecause this is the first study attempting to prevent FASD through the newly recognized role of exosomes inintercellular communication and the actions of SDF1/CXCR4 signaling in modulating the coordinated migrationof NCCs and PCs. It also represents the first attempt to prevent FASD using edible plant-derived exosome-likenanoparticles. The proposed research is expected to characterize a novel exosome-mediated intercellularinteraction between NCCs and PCs during ethanol-induced teratogenesis. Such results will be significantbecause the insights gained from this study will help in elucidating the mechanisms underlying FASD and yieldexosome-based strategies for the prevention of FASD.

project_terms:
Address;Affect;Alcohols;CRISPR/Cas technology;CXCR4 gene;Cells;Cephalic;Congenital Abnormality;Cranial Nerves;Craniofacial Abnormalities;Data;Defect;Distant;Edible Plants;Embryo;Ethanol;Fetal Alcohol Spectrum Disorder;Grapes;Human;In Vitro;Knowledge;Laboratories;Life;Mediating;Mental Retardation;MicroRNAs;Mission;Modeling;Molecular;National Institute on Alcohol Abuse and Alcoholism;Neural Crest Cell;Pathogenesis;Plants;Prevention;Prevention strategy;Public Health;Regulation;Repression;Research;Role;Signal Transduction;Site;Skeleton;Stromal Cell-Derived Factor 1;Testing;Therapeutic;Therapeutic Intervention;Work;Zebrafish;alcohol effect;alcohol exposure;craniofacial;exosome;fetal;in vivo;innovation;insight;intercellular communication;microRNA delivery;migration;nanoparticle;novel;novel strategies;novel therapeutic intervention;prevent;preventive intervention;public health relevance;sensory system;teratogenesis;transcriptome sequencing;translational potential

public_health_relevance:
PUBLIC HEALTH RELEVANCE The proposed research is relevant to public health because the insights gainedby the accomplishments of the proposed studies will help in elucidating the molecular mechanisms underlyingethanol-induced birth defects and characterizing a novel exosome-mediated intercellular interaction betweenneural crest cells and placodes during ethanol-induced teratogenesis. These studies are expected to establishthe administration of edible plant-derived exosome-like nanoparticles as a novel strategy for the prevention ofhuman FASD. Thus the proposed research is relevant to the NIAAA's mission that pertains to using theknowledge gained in uncovering target sites for alcohol's action on the embryonic and fetal stages of life to begindeveloping potential therapeutic or preventative interventions.


application_id: 10917316
project_number: 5R01AA027990-05
project_title: Estradiol Effects on Behavioral and Reward Sensitivity to Alcohol across the Menstrual Cycle
administering_ic: NIAAA
award_notice_date: 2024-08-08
opportunity_number: PA-19-055
application_type: 5
activity_code: R01
ic: AA
serial_number: 027990
program_official: AKBAR, MOHAMMED
project_start_date: 2020-09-25
project_end_date: 2026-08-31
study_section: Addiction Risks and Mechanisms Study Section[ARM]
contact_pi_person_id: 6368360
contact_pi: FILLMORE, MARK T
other_pis: MARTEL, MICHELLE M
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:
PROJECT SUMMARY/ABSTRACTAlcohol use poses significant health problems particularly when characterized by bouts of heavy consumption(i.e. binges). It is now recognized that women demonstrate greater vulnerability to the adverse effects ofalcohol including greater physiological risk of organ damage (e.g. liver cirrhosis) than do men withcomparable histories of alcohol use. Research suggests that ovarian hormones play a role in substance abuse.With regard to alcohol use there is evidence to suggest that women may exhibit distinct patterns of heavydrinking across the menstrual cycle. Indeed our preliminary research shows that surges in follicular estradiol[E2] at ovulation predict increased alcohol use in young women. Yet to date no research has aimed todetermine the specific behavioral mechanisms by which rapid surges in E2 confer increased abuse potential ofalcohol. The proposed study directly examines ovarian hormone flux and acute sensitivity to alcohol to providethe first rigorous and integrative test of the hypothesis that rapid rises in estradiol increase the acute rewardingand disinhibiting effects of alcohol and that this heightened sensitivity increases alcohol use outside thelaboratory. A sample of 100 naturally-cycling women will be examined daily over their menstrual cycle using anintegrative combination of daily ecological assessments of hormone fluctuations and alcohol use along withstrategically-timed laboratory tests of their acute sensitivity to the rewarding and disinhibiting effects of acontrolled dose of alcohol. The findings will advance understanding of the neurobehavioral mechanismslinking E2 to alcohol abuse and inform clinical assessment practice by highlighting the importance of menstrualcycle phase and hormonal profiles when assessing alcohol abuse risk in young women.

project_terms:
Acute;Adult women;Adverse effects;Affect;Alcohol abuse;Alcohol consumption;Alcohols;Animal Experimentation;Area;Behavior;Behavioral;Behavioral Mechanisms;Clinical assessments;Consumption;Data;Data Reporting;Disinhibition;Dose;Estradiol;Estrogens;Exhibits;Female;Grain;Health;Heavy Drinking;High Risk Woman;Hormonal;Hormones;Impulsivity;Intervention;Investigation;Laboratories;Link;Liver Cirrhosis;Longitudinal Studies;Maintenance;Measures;Menstrual cycle;Neurobiology;Oral Contraceptives;Organ;Ovarian hormone;Ovulation;Ovulation Prediction;Patient Self-Report;Pattern;Periodicity;Phase;Physiological;Placebos;Progesterone;Puberty;Public Health;Recording of previous events;Relapse;Research;Rewards;Risk;Risk Taking;Saliva;Sampling;Sex Behavior;Sex Differences;Substance abuse problem;Testing;Theoretical model;Visit;Woman;Work;abuse liability;alcohol abuse therapy;alcohol craving;alcohol effect;alcohol sensitivity;alcohol use disorder;binge drinking;craving;drinking behavior;men;neurobehavioral;personalized intervention;proliferative phase Menstrual cycle;relapse prevention;reproductive;sexual assault;theories;university student;women's treatment;young adult;young woman

public_health_relevance:
The proposed research aims to determine the behavioral mechanisms by which ovulatory surges in estradiolincrease alcohol use in young women by increasing their sensitivity to the rewarding and disinhibiting effects ofalcohol that promote patterns of binge drinking. The research will provide important new information on howcertain hormonal phases such as those linked with estradiol surges can challenge relapse prevention andother alcohol treatment efforts in young women with alcohol use disorders.


application_id: 10916561
project_number: 5U01DE031223-03
project_title: Susceptibility Patterns for Grade C Periodontitis in Young Individuals
administering_ic: NIDCR
award_notice_date: 2024-08-12
opportunity_number: PAR-20-060
application_type: 5
activity_code: U01
ic: DE
serial_number: 031223
program_official: CHOU, ALICIA YESIU
project_start_date: 2022-09-22
project_end_date: 2027-08-31
study_section: ZDE1-YM(12)
contact_pi_person_id: 8964577
contact_pi: SHADDOX, LUCIANA MACCHION
other_pis: Not Applicable
congressional_district: 06
department: DENTISTRY
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 DENTISTRY/ORAL HYGN
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
The American Academy of Periodontology and European Federation of Periodontology have recently adoptedthe new terminology Grade C Periodontitis to identify individuals with a high risk for disease progression. Thelocalized form of this disease now termed Stage 3-4 Grade C molar-incisor pattern periodontitis (C/MIP)exhibits a very well-defined clinical presentation. Although less common than other periodontitis C/MIP has asignificant public health impact as it affects systemically healthy young individuals of low social economicstatus who usually cannot afford its expensive and complex treatment as their affected teeth are often lost dueto its rapid progression and delayed diagnosis. This leads to early function and aesthetics issues and life-longdifficulties for functional and aesthetic rehabilitation. Due its common aggregation in families several studieshave searched for genetic associations with grade C disease but not in large cohorts of C/MIP. Thus geneticcontributions for C/MIP are not yet identified. The team put together for this proposal have conducted ground-breaking work in this field over the last 3 decades including the identification of candidate genetic susceptibilityvariants hyper-inflammatory response and strong association with Aa and Aa JP2 clone. However differentpopulations have different genetic predispositions environmental exposures and microbial colonization whichfurther complicates unveiling the true etiology and pathogenesis of this disease. Thus there is a critical need toexamine a large well-defined cohort of C/MIP families from different world regions to systematically andcomprehensively determine the genetic host response and microbial determinants of this disease. The goal ofthis proposal is to characterize the genetic host and microbial factors of the early onset well-defined localizedform of periodontitis in populations worldwide. We propose to do this by gathering large cohort of C/MIP familiesin 4 different continents to 1)identify genetic susceptibility variants within C/MIP families via WES; 2)Identify theinflammatory networks associated with C/MIP 2 via transcriptome and network analysis and inflammatorymediator profile in the oral environment of these affected families; and 3) Determine common microbiome profilesvia metagenomic analysis and unique Aa strains in C/MIP families from different regions of the world associatedwith this disease. Our hypotheses are that 1-C/MIP will be associated with identifiable genetic variants whichmay vary in different regions of the globe 2-a specific transcriptome is linked to pro-inflammatory pathways inC/MIP and 3-genotypically and phenotypically different strains of Aa will differ among regions of the globe andwill correlate with microbiome communities of distinct functionality and virulence potential. The impact of the proposed work is the development of an integrative series of interaction network andfunctional analyses which will lead to the characterization of susceptibility molecular and microbial phenotypesof C/MIP in different populations around the world which will provide criteria for early disease diagnosis anddevelopment of targeted and individualized therapies for these highly susceptible families.

project_terms:
Academy;Actinobacillus actinomycetemcomitans;Adopted;Affect;African ancestry;Age;American;Bacteria;Characteristics;Clinical;Communities;Complex;DNA;DNA sequencing;Development;Diagnosis;Dideoxy Chain Termination DNA Sequencing;Disease;Disease Progression;Economics;Environment;Environmental Exposure;Epithelial Cells;Esthetics;Etiology;European;Exhibits;Family;Genes;Genetic;Genetic Predisposition to Disease;Genotype;Geographic Locations;Gingival Crevicular Fluid;Goals;Immune response;Incisor;Individual;Inflammation Mediators;Inflammatory;Inflammatory Response;Link;Metagenomics;Molecular;Multicenter Studies;Names;Oral;Pathogenesis;Pathway Analysis;Pathway interactions;Pattern;Periodontitis;Phenotype;Population;Predisposition;Property;Public Health;Rehabilitation therapy;Saliva;Sampling;Series;Shotguns;Siblings;Site;Susceptibility Gene;Taxonomy;Terminology;Testing;Tooth structure;Variant;Virulence;Virulent;Work;candidate identification;case control;cohort;data integration;disease diagnosis;early onset;exome sequencing;gene interaction;genetic association;genetic variant;genome-wide analysis;high risk;individualized medicine;metagenome;microbial;microbial colonization;microbial community;microbiome;neutrophil;older adult;oral cavity epithelium;oral microbiome;peripheral blood;social;targeted treatment;transcriptome;transcriptome sequencing

public_health_relevance:
NarrativeAggressive periodontitis now named Grade C periodontitis (C/MIP) is a group of less frequently often severeand rapidly progressive form of periodontitis affecting young individuals at an early age usually aggregating infamilies of lower social economic background. The factors that render affected individuals to C/MIP diseaseare yet to be clearly identified which affects the proper control of this aggressive disease. This multi-centerstudy will gather clearly-defined cases of C/MIP from different regions of the globe and within families toevaluate genetic susceptibility variants using whole exome sequencing host response via epithelial celltranscriptome to pinpoint mechanistic pathways associated with C/MIP and with genetic variants and microbialcommunity profile via metagenomics as well as specific species strains associated with this disease.


application_id: 10916543
project_number: 5UG1HD107649-03
project_title: Neonatal Opioid Withdrawal Syndrome (NOWS) in Kentucky: Improving Outcomes for Infants
administering_ic: NICHD
award_notice_date: 2024-08-13
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 Personnel;Healthcare Systems;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;Pharmacological Treatment;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: 10916451
project_number: 5K23ES034462-02
project_title: Household Air Pollution Adiposity and Cardiorenal Disease Risk in Children
administering_ic: NIEHS
award_notice_date: 2024-08-15
opportunity_number: PA-20-206
application_type: 5
activity_code: K23
ic: ES
serial_number: 034462
program_official: JOUBERT, BONNIE
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;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: 10916406
project_number: 5UG1OD024954-07
project_title: The Kentucky ECHO Pediatric IDeA Research Center (KE-PIRC)
administering_ic: OD
award_notice_date: 2024-08-27
opportunity_number: RFA-OD-19-026
application_type: 5
activity_code: UG1
ic: OD
serial_number: 024954
program_official: RAJU, TONSE N
project_start_date: 2016-09-23
project_end_date: 2025-08-31
study_section: Special Emphasis Panel[ZRG1-BBBP-J(51)R]
contact_pi_person_id: 14437890
contact_pi: WATSON, SARA E
other_pis: DEVLIN-PHINNEY, LORI ANN
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 As a predominantly rural state Kentucky leads the nation in many pediatric and adult chronic andenvironmentally-related diseases and ranks nationally in low educational achievement. These adverse factorscombine to make Kentuckians especially unhealthy residents with a high prevalence of obesity diabetessmoking alcohol use heart disease stroke lung cancer etc. Many of these diseases are environmentallyrelated to poor nutrition obesity smoking drug abuse and work-place exposures. Kentucky also leads thenation in the percentage of pediatric populations with special health care needs. Prior work has shown thatmost adult diseases have their origin in childhood and some begin during fetal development making childhoodthe ideal time for intervention with the goal of improving health outcomes into adulthood. Improving healthcare outcomes and wellness in children is contingent on expanding and sustaining highquality clinical research that includes diverse populations. Pediatricians at the University of Louisville (UofL)with our Healthcare Partners serve a highly diverse patient population that includes the rural and urban poor aunique Appalachian community refugees and numerous ethnic minorities. To better serve this population wepropose to build upon our current programs expand our bidirectional community engagement effortscollaborate with other institutions on pediatric clinical trials through the ECHO IDeA Pediatric Clinical TrialsNetwork and collaborate with ECHO cohort INBRE and CTSA sites to advance healthcare for children.Education and training of local and regional faculty and staff is critical to sustain this initiative. The Kentucky ECHO-Pediatric IDeA Research Center (KE-PIRC) as part of the IDeA States Pediatric ClinicalTrials Network will make it possible for 1) rural and underserved infants children and adolescents toparticipate in clinical research; 2) junior investigators to be trained in clinical research and communityengagement improve the health of both children and adults in Kentucky through this research and developtheir academic career; and 3) the development of a regional network of partners to sustain this clinicalresearch initiative. The five primary focus areas are 1) pre- peri- and postnatal outcomes; 2)neurodevelopmental; 3) upper and lower airway disease; 4) obesity; and 5) positive health. These primaryfocus areas are highly prevalent in Kentucky; therefore KE-PIRC will enable strengthening currentcollaborations and accelerate the development of new networks within the state through bidirectionalcommunity engagement and feedback to support pediatric clinical research. Through these efforts we aim toimprove the health outcomes of Kentucky children and adults and establish a local and national sustainablepediatric clinical research workforce.

project_terms:
Academic Medical Centers;Acceleration;Address;Adolescent;Adult;Airway Disease;Alcohol consumption;Appalachian Region;Area;Child;Child Health;Child health care;Childhood;Chronic;Clinical;Clinical Research;Clinical Trials;Clinical Trials Network;Collaborations;Communication;Communities;Development;Diabetes Mellitus;Disease;Drug abuse;Education;Educational Status;Environment;Environmental Health;Etiology;Faculty;Family;Feedback;Fetal Development;Funding;Generations;Goals;Health;Health Benefit;Healthcare;Heart Diseases;High Prevalence;Individual;Infant;Institution;Intervention;Kentucky;Leadership;Malignant neoplasm of lung;Mentors;Mentorship;Multi-Institutional Clinical Trial;Neonatal;Neurologist;Obesity;Occupational Exposure;Outcome;Participant;Patients;Pediatric Hospitals;Perinatal;Physicians;Population;Population Heterogeneity;Preventive;Primary Care;Process;Provider;Refugees;Research;Research Infrastructure;Research Personnel;Resources;Rural;Rural Community;Rural Population;Site;Smoking;Stroke;System;Talents;Teacher Professional Development;Time;Training;Training and Education;Underrepresented Minority;Underserved Population;United States National Institutes of Health;Universities;Urban Community;Vulnerable Populations;Work;autism spectrum disorder;biomedical referral center;care outcomes;career;cohort;community engagement;community partners;community partnership;ethnic minority;fetal;improved;innovation;member;next generation;novel strategies;nutrition;outreach program;patient population;pediatrician;pediatrician scientist;postnatal;programs;racial minority;recruit;rural area;rural underserved;senior faculty;skills;success;underserved area;urban underserved

public_health_relevance:
PROJECT NARRATIVEThe Kentucky ECHO-Pediatric IDeA Research Center (KE-PIRC) as part of the ECHO IDeA States PediatricClinical Trials Network will continue to make it possible for 1) rural and underserved infants children andadolescents to participate in clinical research; 2) junior investigators to be trained in clinical research andcommunity engagement improve the health of both children and adults in Kentucky through this research anddevelop their academic career; and 3) the development of a regional network of partners to sustain this clinicalresearch initiative. The five primary focus areas are 1) pre- peri- and postnatal outcomes; 2)neurodevelopmental; 3) upper and lower airway disease; 4) obesity; and 5) positive health. These primaryfocus areas are highly prevalent in Kentucky therefore the efforts of the KE-PIRC in collaboration with ourcommunity partners will improve the health outcomes of Kentucky children and adults.


application_id: 10916193
project_number: 5R01CA274981-02
project_title: The PLOD2/succinate axis in cancer cell plasticity and stemness
administering_ic: NCI
award_notice_date: 2024-07-30
opportunity_number: PA-20-185
application_type: 5
activity_code: R01
ic: CA
serial_number: 274981
program_official: AULT, GRACE S
project_start_date: 2023-09-01
project_end_date: 2028-08-31
study_section: Biochemical and Cellular Oncogenesis Study Section[BCO]
contact_pi_person_id: 10533977
contact_pi: XU, REN
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
AbstractTumor cells in TNBC tissue exhibit enhanced cell plasticity and stemness which is crucial for cancer metastasis.Metabolic and epigenetic reprogramming plays crucial roles in the regulation of cell plasticity. Succinate is anintermediate metabolite of the tricarboxylic acid (TCA) cycle. Aberrant accumulation of succinate has beendetected in many cancers. However the cellular function and regulation of succinate in breast cancerdevelopment and progression have not been well investigated. We showed that the epithelial-to-mesenchymaltransition (EMT) was associated with profound changes in metabolites including elevation of cytoplasmicsuccinate. Importantly treatment with the membrane permeable succinate was sufficient to induce mesenchymalphenotypes enhance cancer cell stemness and colonization and reduce DNA hydroxymethylation and genetranscription in mammary epithelial cells. Procollagen-Lysine 2-Oxoglutarate 5-Dioxygenase 2 (PLOD2)catalyzes lysine hydroxylation in endoplasmic reticulum and generates succinate as another product. We foundthat PLOD2 expression was induced in cancer cells in TNBC tissue and increased PLOD2 expression correlateswith poor prognosis and high chances of cancer metastasis. Silence of PLOD2 in cancer cells significant reducedcancer cell colonization and metastasis. PLOD2 expression was induced during EMT and associated withelevation of cytoplasmic succinate levels. Using gain- and loss-of function approaches we showed thatincreased PLOD2 expression is necessary and sufficient to enhance the accumulation of cytoplasmic succinate.Importantly silencing PLOD2 in breast cancer cells inhibited cancer cell stemness. The overall objective of thisproject is to define roles of the PLOD2/succinate axis in regulating cancer cell plasticity and stemness and toevaluate biological activity of the new PLOD2 inhibitor in suppressing TNBC progression and metastasis. Thecentral hypothesis of this proposal is that PLOD2-induced succinate accumulation enhances cancer cellplasticity and metastasis by reducing DNA hydroxymethylation; therefore targeting the PLOD2/succinate axis isa potential strategy to halt TNBC progression and metastasis. To test this hypothesis we propose the followingaims: Aim 1. Elucidate the molecular and cellular mechanisms by which succinate enhances cancer cell plasticityand stemness. Aim 2. Define roles of the PLOD2/succinate axis in regulating breast cancer progression. Aim 3.Evaluate the potential of targeting PLOD2 to suppress breast cancer metastasis. Successfully completion of theproject will reveal novel function of collagen hydroxylation enzymes in regulating succinate-associated epigeneticreprogramming and identify PLOD2 as a potential therapeutic target to suppress breast cancer metastasis.

project_terms:
Aftercare;Biochemistry;Biological;Biometry;Breast;Breast Cancer Cell;Breast Epithelial Cells;Cell Membrane Permeability;Cell Physiology;Cells;ChIP-seq;Chromatin;Citric Acid Cycle;Clinical;Collagen;CpG Islands;Cytoplasm;DDR1 gene;DNA;Development;Dioxygenases;Endoplasmic Reticulum;Enzymes;Epigenetic Process;Exhibits;FDA approved;Fibroblasts;Fibrosis;Gene Expression Profiling;Genetic Transcription;Human;Hydroxylation;In Vitro;Incidence;Knockout Mice;Knowledge;Loperamide;Lysine;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Mesenchymal;Metabolic;Modeling;Modification;Molecular;Mouse Mammary Tumor Virus;Mus;Neoplasm Metastasis;Pathologist;Pathway interactions;Pharmaceutical Preparations;Phenotype;Play;Positioning Attribute;Procollagen;Prognosis;Regulation;Relapse;Repression;Research;Role;Scheme;Succinates;TP53 gene;Testing;Tissue Sample;Tissues;Weight;Xenograft Model;alpha ketoglutarate;breast cancer metastasis;breast cancer progression;cancer cell;cancer subtypes;cell growth regulation;conditional knockout;crosslink;epigenetic regulation;epithelial to mesenchymal transition;experimental study;gain of function;inhibitor;loss of function;metabolomics;mid-career faculty;mouse model;multidisciplinary;neoplastic cell;novel;patient derived xenograft model;screening;small hairpin RNA;stable isotope;stemness;therapeutic target;transcription factor;transcriptome sequencing;triple-negative invasive breast carcinoma

public_health_relevance:
Defining roles of succinate in regulating cancer cell plasticity and stemness will fill critical gaps in our knowledgeabout function of metabolites in breast cancer progression. The study of PLOD2 in regulating cytoplasmicsuccinate will reveal a novel pathway in succinate regulation; and further evaluating the PLOD2 inhibitor in TNBCxenograft model and PDX models will identify a potential target to halt TNBC progression and metastasis.


application_id: 10916179
project_number: 5F31DA055445-02
project_title: Claustrum serotonin and spike-timing plasticity associated with cognitive deficits after cocaine
administering_ic: NIDA
award_notice_date: 2024-10-16
opportunity_number: PA-21-051
application_type: 5
activity_code: F31
ic: DA
serial_number: 055445
program_official: FALCON-MORALES, EDGARDO
project_start_date: 2023-11-01
project_end_date: 2025-03-31
study_section: Special Emphasis Panel[ZRG1-F02A-K(20)L]
contact_pi_person_id: 78025221
contact_pi: ANDERSON, TANNER
other_pis: Not Applicable
congressional_district: 06
department: NEUROSCIENCES
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/AbstractOver 40 million individuals in the US have a substance use disorder (SUD) and therapies for treating SUD haveremained largely inadequate for decades. One of the key challenges in SUD treatment is that many drugs ofabuse including cocaine negatively impact cognitive flexibility leaving patients less likely to abstain from druguse. An emerging body of literature shows that agonists of the serotonin 2A receptor (5HT2AR) psychedelichallucinogens have remarkable potential for improving long-term cognitive flexibility with implications for treatingvarious psychiatric disorders including substance use. The highest density of the 5HT2AR expression in thebrain is in the claustrum (CLA) an understudied subcortical brain structure with extensive innervation of fronto-cortical areas. The main projection target of the CLA is the anterior cingulate cortex (ACC) and both the CLAand the ACC have been implicated in regulation of drug-seeking behavior and cognitive flexibility. My preliminarybehavioral data in rats show that extended access to self-administered cocaine induces cognitive flexibilitydeficits in a strategy set-shift task and that 5HT2ARs in the CLA likewise robustly modulate set-shift taskperformance. Preliminary electrophysiology data show that 5HT induces inhibition of glutamatergicneurotransmission in CLA neurons projecting to the ACC (CLA-ACC neurons) by activating CLA 5HT2ARs.Furthermore serotonergic signaling via the 5HT2ARs has a profound impact on long-term plasticity of CLAsynapses. My preliminary data indicate that application of 5HT2AR agonist DOI reverses spike timing-dependent long-term depression (t-LTD) in CLA-ACC neurons and promotes instead spike timing-dependentlong-term potentiation (t-LTP) of glutamatergic signaling in these cells. The current proposal will test thehypothesis that cocaine changes the timing window for induction of long-term synaptic plasticity in CLA-ACCneurons resulting in cognitive flexibility deficits and increased drug seeking behavior. I speculate that a singleactivation of 5HT2ARs in the CLA reverses cocaine-induced LTD with a long-term improvement of cognitiveflexibility leading to attenuated reinstatement of cocaine-seeking behavior. I will test this hypothesis by targetedmicroinjections of DOI into the CLA of rats trained to self-administer cocaine. I will use patch-clampelectrophysiology to establish the timing rules for serotonergic modulation of spike-timing dependent plasticity ofexcitatory synapses onto CLA-ACC neurons of cocaine exposed rats. Finally I will combine chemogenetics withCa2+ imaging in ACC-containing brain slices to establish the extent to which CLA neurons control ACC excitabilityin control and cocaine experienced rats. The findings of this proposal will reveal the role of CLA serotonin as anovel regional target for substance use research and specifically explore the impact of 5HT2ARs in the CLA oncortically-mediated cognitive flexibility deficits linked to cocaine use.

project_terms:
Agonist;Animals;Anterior;Area;Attenuated;Behavior;Behavioral;Bilateral;Brain;Cells;Cerebral Dominance;Claustral structure;Cocaine;Cognitive;Cognitive deficits;Data;Drug Regulations;Drug usage;Electrophysiology (science);Excitatory Synapse;Functional Magnetic Resonance Imaging;Genetic;Glutamates;Goals;Habits;Hallucinogens;Human;Image;Individual;Insula of Reil;Investigation;Link;Literature;Long-Term Depression;Long-Term Potentiation;Major Depressive Disorder;Mediating;Mediator;Mental disorders;Microinjections;Modeling;Modification;Neurons;Output;Patients;Pattern;Pharmaceutical Preparations;Picrotoxin;Protocols documentation;Rattus;Recording of previous events;Regulation;Relapse;Research;Role;Saline;Scientist;Serotonin;Serotonin Agonists;Serotonin Receptor 5-HT2A;Signal Transduction;Slice;Structure;Substance Use Disorder;Substance abuse problem;Symptoms;Synapses;Synaptic plasticity;Task Performances;Testing;Therapeutic;Training;Withdrawal;antagonist;behavioral phenotyping;career development;cingulate cortex;cocaine exposure;cocaine seeking;cocaine self-administration;cocaine use;density;drug development;drug of abuse;drug relapse;drug seeking behavior;experience;experimental study;flexibility;glutamatergic signaling;improved;in vivo;in vivo Model;nerve supply;neurotransmission;novel;patch clamp;putamen;receptor;substance use;substance user;synaptic inhibition

public_health_relevance:
Project NarrativeDrug-seeking and drug relapse behaviors are linked to deficits in cognitive flexibility that are induced by historyof substance use. We hypothesize that the anterior cingulate cortex a key brain structure that regulates cognitiveflexibility is under potent inhibitory control by the serotonin 2A receptors within the claustrum a little-studiedsubcortical brain area. Psychedelic serotonin 2A receptor agonists are under active investigation of therapeuticpotential for substance use disorder symptoms in humans and our research proposes a central role forserotonin-dependent plasticity at claustro-cortical synapses in development of drug-induced cognitive deficits ina rat model of cocaine self-administration.


application_id: 10915702
project_number: 5U01DK074007-18
administering_ic: NIDDK
award_notice_date: 2024-07-31
opportunity_number: RFA-DK-20-504
application_type: 5
activity_code: U01
ic: DK
serial_number: 074007
program_official: SHEA-DONOHUE, TEREZ
project_start_date: 2006-04-15
project_end_date: 2027-07-31
study_section: ZDK1-GRB-9(M2)S
contact_pi_person_id: 8264660
contact_pi: ABELL, THOMAS LYMAN
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: 2024-08-01
project_title:
U of L Clinical Center to Investigate the Pathogenesis Etiology and Treatment of Gastroparesis through the NIDDK Gastroparesis Consortium

project_abstract:
Gastroparesis is a disorder of gastric function characterized by delay in gastric emptying frequently associatedwith chronic nausea and vomiting early satiety postprandial fullness abdominal pain and malnutrition thatmay require nutritional support. Gastroparesis has a devastating impact on quality of life and predominantlyaffects younger women. In the past 5 years the Gastroparesis Clinical Research Consortium (GpCRC) hasmade a series of important contributions (see below) to improve our understanding of this disorder andadvancing the goals of patients physicians and the NIH for management of gastroparesis. Yet much remainsto be learned about its etiology natural history treatment strategies and clinical course whichis the rationale behind our response to the Continuation of the Gastroparesis Consortium. The biggest barrierto effective therapeutic approaches to gastroparesis is our lack of knowledge about either its pathogenesis orits pathophysiology. Further the correlation between the major symptoms such as nausea vomiting pain andcurrent methods to measure change in gastric function (electrical motor activity meal emptying times) is poorat best. Finally we do not understand the long-term outcomes of these patients and whether outcomes differon the basis of etiology symptom severity and degree of emptying abnormalities. Consequently our approachto these patients is erratic and treatment has been empirical and only partially effective if at all in relieving themajor symptoms. The mission of the GpCRC is completely aligned with the recommendations of the NationalCommission on Digestive Diseases: specifically Research Goal 2.6 relates to gastroparesis and states:"Understand the noxious visceral signaling causing nausea and vomiting related to gastric neuro-electricaland/or motor dysfunction and the bi-directional brain-gut interactions. Gastroparesis provides an archetypaldisease for investigative inquiry. Chronic vomiting a debilitating and socially isolating digestive symptomcreates potentially life-threatening disruptions in fluid and electrolyte homeostasis and compromises nutritionalstatus. Chronic nausea remains a significant hidden disability. Nausea and vomiting usually occur in tandemand overlay with other Gl symptoms as well as presenting in numerous digestive diseases. More effectivetreatments for nausea and vomiting would improve quality of life and physical functioning in a vast array ofillnesses. A paucity of research exists for defining peripheral noxious signaling of nausea and vomiting relatedto primary Gl motor/sensory disturbances." The Specific Aims of this proposal are to: 1. Complete the currentGpCRC registry (Registry Three); 2. Extend the GpCRC core lab responsible for anatomic and related studieson tissue samples of patients with Gp syndromes; 3. Perform pharmacologic studies on patients with Gpsyndromes.; 4. Perform a new device/pyloric intervention study protocol for patients with the Gp syndromes;and 5. Utilize several novel approaches to some of the unmet needs in patients with gastroparesis symptomswhich could be incorporated in new studies of the Consortium.

project_terms:
Abdominal Pain;Affect;Age;Anatomy;Autoimmune;Botulinum Toxins;Caring;Characteristics;Chronic;Clinical;Clinical Research;Databases;Devices;Digestive System Disorders;Disease;Electric Stimulation;Electrolytes;Enrollment;Esophagus;Ethnic Origin;Etiology;Feces;Functional disorder;Gastric Emptying;Gastrointestinal Diseases;Gastroparesis;Gender;Genomics;Goals;Health;Health Services Accessibility;Homeostasis;Hormonal;Inflammatory;Intervention Studies;Invisible disability;Knowledge;Learning;Life;Liquid substance;Malnutrition;Maps;Measures;Methods;Microanatomy;Mission;Motor;Motor Activity;National Institute of Diabetes and Digestive and Kidney Diseases;Natural History;Nausea;Nausea and Vomiting;Nortriptyline;Nutritional Requirements;Nutritional Support;Nutritional status;Outcome;Pain;Pathogenesis;Patient-Focused Outcomes;Patients;Peripheral;Pharmacology Study;Physical Function;Physicians;Physiological;Physiology;Protocols documentation;Psychological Impact;Publishing;Quality of life;Questionnaires;Race;Randomized;Recommendation;Registries;Research;Resolution;Sensory;Series;Severities;Signal Transduction;Social isolation;Stomach;Symptoms;Syndrome;Therapeutic;Tissue Sample;United States National Institutes of Health;Visceral;Vomiting;Weight;Work;clinical center;early satiety;effective therapy;evidence base;frailty;gastrointestinal function;gut-brain axis;improved;metabolomics;motor disorder;neuromuscular;novel;novel strategies;nutrition;persistent symptom;psychologic;recruit;response;therapeutically effective;treatment strategy;young woman

public_health_relevance:
This proposal aims to gather a better understanding of gastroparesis which is a devastating disorder inpredominantaly younger women. This is a continuation of the Gastroparesis Clinical Research Consortium(GpCRC). The GpCRC has made a series of important contributions to improve our understanding of thisdisorder and advancing the goals of patients physicians and the NIH for management of gastroparesis.


application_id: 10915626
project_number: 5R01EY035523-02
project_title: The Influence of the Pretectum on the Visual Thalamus
administering_ic: NEI
award_notice_date: 2024-08-26
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;MCGEE, AARON W
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;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: 10914902
project_number: 5R01AA030308-02
project_title: Sex and Sex Hormone Factors Influencing Acute Alcohol Effects on Sleep Physiology
administering_ic: NIAAA
award_notice_date: 2024-07-29
opportunity_number: PA-20-184
application_type: 5
activity_code: R01
ic: AA
serial_number: 030308
program_official: KUMAR, SHAILESH
project_start_date: 2023-09-01
project_end_date: 2028-08-31
study_section: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]
contact_pi_person_id: 12510124
contact_pi: WHITEHURST, LAUREN
other_pis: WEAFER, JESSICA J
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:
Rates of heavy drinking and Alcohol Use Disorder (AUD) are increasing in women at an alarming pace. Suchdrastic increases in drinking will have a significant negative impact on womens health. Unfortunately untilrecently heavy drinking has been considered a male-oriented problem and consequently research on alcohol-related harms in women has been minimal. One specific aspect of womens health that may be negativelyaffected by alcohol is sleep. Numerous studies in men show that although alcohol has an initial sedative effectit leads to frequent awakenings and impaired rapid eye movement sleep in the second half of the night.Preliminary evidence suggests that women experience similar impairment and that they may be even moresensitive to alcohol-disrupted sleep than men. Further in the general population women are at greater risk forinsomnia and sleep disturbances than men in part because womens sleep is sensitive to fluctuations inovarian hormones. Hormonal influences on sleep are especially pronounced in older women of latereproductive age. However the influence of sex and sex hormones on alcohol-disrupted sleep across thereproductive lifespan in women is unknown. Here we will determine the influence of sex menstrual cyclephase and sex hormones on alcohol-disrupted sleep in adults across the reproductive age range for women.Healthy women and men (age 21-45) will complete two pairs of experimental sessions in which they receive adose of alcohol (target BrAC = 100mg% intravenous) or placebo (saline) one hour prior to eight hours ofpolysomnographically-monitored sleep in the lab. Women will complete one alcohol-placebo session pairduring the mid-follicular phase of the menstrual cycle and one pair during the late luteal phase. Men willcomplete two session pairs at matched intervals. Participants will also complete two 5-day at-home monitoringperiods of naturalistic sleep and alcohol consumption patterns during the mid-follicular and late luteal phases.Sleep and alcohol use will be assessed with actigraphy daily sleep and wake diaries and alcohol wristsensors. We hypothesize that women will show greater disruption of sleep following alcohol than men and thatalcohol-disrupted sleep measured in lab with polysomnography and at-home with actigraphy will be morepronounced in the late luteal phase compared to the mid-follicular phase. We also expect that estradiol will benegatively associated with alcohol-disrupted sleep whereas progesterone will be positively associated withalcohol-disrupted sleep. This study will provide essential information regarding alcohol effects on sleep acrossthe reproductive age span in women and critically how these effects are moderated by sex menstrual cycleand fluctuations in sex hormones. Findings will directly inform future interventions aimed at reducing alcoholconsumption and the negative impacts of alcohol on sleep in women. Given the wide-ranging impact of sleepon other areas of function including cognition stress and well-being such interventions will have a substantialpositive impact on womens health.

project_terms:
21 year old;Acute;Adult;Affect;Age;Alcohol consumption;Alcohols;Area;Biosensor;Blood specimen;Cognition;Data;Dose;Estradiol;Future;General Population;Goals;Gonadal Steroid Hormones;Heavy Drinking;Home;Hormonal;Hormones;Hour;Impairment;Infusion procedures;Intervention;Intravenous;Laboratories;Luteal Phase;Measures;Mediating;Menstrual cycle;Menstruation;Monitor;Older Population;Ovarian hormone;Ovulation;Participant;Patient Self-Report;Pattern;Personal Satisfaction;Pharmaceutical Preparations;Phase;Placebos;Polysomnography;Prevention;Progesterone;REM Sleep;Reporting;Research;Research Personnel;Risk;Saline;Sex Differences;Sleep;Sleep disturbances;Sleeplessness;Stress;Wakefulness;Woman;Women's Health;Wrist;actigraphy;age effect;alcohol consequences;alcohol effect;alcohol monitoring;alcohol use disorder;behavioral pharmacology;breath alcohol measurement;design;diaries;drinking;experience;innovation;life span;male;men;older women;poor sleep;proliferative phase Menstrual cycle;rapid eye movement;reproductive;sedative;sensor;sex;sex cycle;sleep behavior;sleep physiology;sleep quality;sobriety

public_health_relevance:
The findings from this project will determine the degree to which sex and sex hormones influence alcoholeffects on sleep physiology. The results will inform future interventions aimed at reducing alcohol consumptionand the negative impacts of alcohol on sleep in women. Given the wide-ranging impact of sleep on other areasof function including cognition stress and well-being such an intervention will have a substantial positiveimpact on womens health.


application_id: 10914097
project_number: 5P42ES023716-08
project_title: Community Engagement Core
administering_ic: NIEHS
award_notice_date: 2024-06-11
opportunity_number: RFA-ES-20-014
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2025-06-30
study_section: ZES1-LAT-S
subproject_number: 7386
contact_pi_person_id: 11775218
contact_pi: HEBERLE, LAUREN
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_terms:
Address;Affect;Air;Area;Awareness;Cardiometabolic Disease;Chronic;Chronic Disease;Communication;Communities;Development;Diabetes Mellitus;Elements;Ensure;Environmental Engineering technology;Environmental Exposure;Environmental Health;Environmental Science;Equipment and supply inventories;Ethnic Origin;Exposure to;Face;Farm;Geographic Locations;Goals;Green space;Hazardous Substances;Hazardous Waste;Health;Health Food;Health Sciences;Heart Diseases;Home;Housing;Hypertension;Industry;Institution;Intervention;Kentucky;Knowledge;Natural Sciences;Neighborhoods;Obesity;Outcome;Patient Recruitments;Persons;Play;Policy Maker;Population;Populations at Risk;Poverty;Prevention;Productivity;Race;Research;Research Personnel;Research Project Grants;Resources;Risk;Role;Science;Site;Social Sciences;Source;Structural Racism;Superfund;Syndrome;Toxic effect;Toxin;Training;Transcend;Transportation;biological systems;cardiometabolic risk;cardiometabolism;community advisory board;community center;community empowerment;community engaged approach;community engagement;community involvement;community partners;fatty liver disease;health disparity;interest;landfill;meetings;member;pollutant;risk mitigation;social;superfund site;therapy design

public_health_relevance:
Relevance:We are beginning to understand that toxin exposure can initiate/exacerbate multiple adverse health outcomesespecially cardiometabolic diseases. Kentuckians are disproportionately affected by many chronic diseasesincluding obesity hypertension heart disease diabetes fatty liver disease etc. which are all aspects ofcardiometabolic syndrome. Certain communities are more highly impacted than others and it is critical tounderstand why. We hypothesize that exposure to toxics specifically VOCs initiates/exacerbates theseconditions. It is fundamental to our understanding of the effects of these toxics to engage the communities mostdeeply affected by exposure to these pollutants and to try to mitigate the effects of these exposures. Thusdetermining the influence of pollutant exposures on the development/progression of these chronic conditions isvital. Also vital is examining this influence within the proposed areas within West and Southwest LouisvilleKentucky that face added social environmental health burdens including an uneven distribution of race andethnicity a traumatic introduction into the racial reckoning historic redlining and poverty. Bidirectional researchin this community will support understanding of the impacts of VOCs on cardiometabolic disease and communityempowerment.


application_id: 10914095
project_number: 5P42ES023716-08
project_title: Metabolism and Toxicity Core
administering_ic: NIEHS
award_notice_date: 2024-06-11
opportunity_number: RFA-ES-20-014
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2025-06-30
study_section: ZES1-LAT-S
subproject_number: 7385
contact_pi_person_id: 8911484
contact_pi: O'TOOLE, TIMOTHY E
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY (METABOLISM AND TOXICITY CORE)The overall purpose and the function of the Metabolism and Toxicity Core is to provide high quality analyticalservices and validated data in support of all projects at the University of Louisville Superfund Research Center.The Core personnel will conduct measurements and assays of biomarkers and indices of cardiovascularmetabolism and hepatic function used for assessing the risk and progression of cardiometabolic disease uponexposure to volatile organic compounds (VOCs). The Core personnel will also provide intellectual input andadvice in selection of specific methodological approaches and provide training to students fellows techniciansand junior faculty. The Core will employ strict quality control procedures to validate data and generateharmonized data reports and data dictionaries to be stored in the Data Management and Analysis Core. Thecore will support all Superfund Center research projects through its state-of-the-art equipment and assay. Thesupport offered by the core encompasses three main components  a flow cytometry component for the detectionand characterization of circulating cells and microparticles; a metabolism component for measuring biochemicaland metabolic endpoints such as urinary metabolites of VOCs bile acids and catecholamines by LC/MS/MS andGC/MS; and a pathology component to assay systemic toxicity using a battery of tests relating to glucose controlliver function and hepatic toxicity. However the scope of the core exceeds that of the projects to encompassthe development of cutting-edge techniques and analytical platforms to expand its repertoire of services. TheCore will continually upgrade its infrastructure as well as its technical capabilities to remain at the leading edgeof assays relating to biomarkers of exposure and harm. The core is also committed to the continued educationof its users as well as the research community at the university. The Core will also disseminate educationalinformation regarding the potential utility and accessibility of its services to enhance environmental healthresearch. By ensuring central deposition of harmonized and validated data the core will provide a firm foundationfor research not only by the University of Louisville Superfund investigators but investigators at other SuperfundCenters as well. Because of its state-of-the-art equipment highly sophisticated technologies and skilledtechnical personnel the Core will provide premier toxicological and clinical pathology services. By meeting thesegoals the core will continue to be an essential vehicle for growth and innovation within the Center as well as aneducational hub for the training the next generation of scientists in the field of environmental health research.

project_terms:
Address;Analytical Chemistry;Animals;Bile Acids;Biochemical;Biological Assay;Biological Markers;Biology;Blood;Bone Marrow;Cardiometabolic Disease;Cardiovascular system;Catecholamines;Cells;Chemical Exposure;Clinical;Clinical Pathology;Communities;Complex;Continuing Education;Data;Data Analyses;Data Reporting;Deposition;Detection;Development;Dimensions;Education;Ensure;Environmental Exposure;Environmental Health;Equipment;Exposure to;Extramural Activities;Faculty;Flow Cytometry;Foundations;Functional disorder;Future;Goals;Growth;Health;Hepatic;Hepatotoxicity;Histologic;Human;Human Resources;Individual;Infrastructure;Injury;Laboratories;Measurement;Measures;Metabolic;Metabolism;Methodology;Methods;Mus;Pathologic;Pathology;Physiological;Population;Postdoctoral Fellow;Procedures;Property;Protocols documentation;Quality Control;Research;Research Personnel;Research Project Grants;Resolution;Resources;Risk Assessment;Sampling;Scientist;Services;Signal Transduction;Students;Superfund;Technical Expertise;Techniques;Technology;Testing;Toxic effect;Toxicology;Training;Training and Education;Universities;Urine;blood glucose regulation;cardiometabolism;career development;data dictionary;data harmonization;data management;flexibility;graduate student;indexing;innovation;interest;investigator training;liquid chromatography mass spectrometry;liver function;meetings;member;next generation;novel;operation;particle;response;superfund chemical;systemic toxicity;urinary;volatile organic compound

public_health_relevance:
RELEVANCEThe primary function of the research within the Metabolism and Toxicity Core is to measure environmentalexposures and their resulting effects on health. Using state-of-the-art analytical approaches to measure urineand blood components the core will provide quantitative data on the extent of chemical exposures and theextent to which these exposures cause injury and dysfunction.


application_id: 10914094
project_number: 5P42ES023716-08
project_title: Research Experience and Training Coordination Core
administering_ic: NIEHS
award_notice_date: 2024-06-11
opportunity_number: RFA-ES-20-014
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2025-06-30
study_section: ZES1-LAT-S
subproject_number: 7384
contact_pi_person_id: 1924912
contact_pi: HEIN, DAVID W
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary. The RETCC has played a coordinating role in the success of ULSRC since its inception inSeptember 2017. By working closely with other NIEHS-supported training programs at the UofL (T32ES011564;T35ES014559) the RETCC has developed a rich diverse and comprehensive training program that is bothmultidisciplinary and inclusive. In addition to the course work and on the bench training activities RETCCroutinely organizes participatory field trips to the Lees Lane Superfund site to better understand and appreciatehealth concerns of residents in the adjacent community of Riverside Gardens; facilitates the meeting of traineeswith regional Superfund site coordinators and officials and the Metro Louisville Public Health and WellnessDepartment. Our training core in collaboration with Superfund Research Centers at Duke University Universityof Kentucky and University of Pennsylvania organized a trip to Washington D.C. so trainees could attend aScience and Policy Institute meeting that included interactions with congressional leaders and their staff. Suchactivities have been instrumental in the well-rounded growth of our trainees. Moreover these trainees not onlyprovide the force that turns the wheel but also are the focus and hub of intellectual crosstalk and fertilizationacross projects cores other SRCs and the National SRP. To date ULSRC success is the product of our traineessuccesses through their many accomplishments including publications presentations awards degreesfellowships interactions with community partners and environmental health sciences-related careeropportunities. Thus although we are proud of our current success via integration of trainee activities across theULSRC we continue to strive to build on these successes by implementing innovative and unifying features intoRETCC-directed activities that focus on fulfilling the goals and furthering the success of our trainees.

project_terms:
Advisory Committees;Age;Arts;Award;Awareness;Cardiometabolic Disease;Chemistry;Collaborations;Communication;Communities;Community Health Education;Congresses;County;Data;Data Analyses;Dentistry;Development;Discipline of Nursing;Disparate;Engineering;Environmental Exposure;Environmental Health;Exposure to;Fellowship;Fertilization;Fostering;Goals;Government;Growth;Hazardous Substances;Health;Health Professional;Human;Institution;Kentucky;Laboratories;Medicine;Metals;Mission;National Institute of Environmental Health Sciences;Pennsylvania;Phase;Play;Policies;Postdoctoral Fellow;Public Health;Publications;Research;Research Project Grants;Role;Schools;Science;Scientist;Signal Recognition Particle;Statistical Data Interpretation;Students;Superfund;Training;Training Activity;Training Programs;Training Support;Translational Research;Universities;Washington;Work;cardiometabolism;career;career development;cohort;college;community engagement;community partners;community research;data management;experience;field trip;graduate student;health science research;innovation;interdisciplinary approach;knowledge base;meetings;multidisciplinary;next generation;pre-doctoral;programs;skills;success;superfund site;training opportunity

public_health_relevance:
Relevance: The overall goal of the Research Experience and Training Coordination Core(RETCC) is to direct successful training of graduate students and post-doctoral fellows(designated trainees) in the University of Louisville Superfund Research Center (ULSRC). Thisincludes scientific interdisciplinary training within defined ULSRC projects and cores as well aspromoting development of a broad knowledge base and the skills needed to communicate andengage with relevant community partners government liaisons and health-care professionalsregarding the importance of environmental health sciences research in the Superfund Program.


application_id: 10914091
project_number: 5P42ES023716-08
project_title: Data Management and Analysis Core
administering_ic: NIEHS
award_notice_date: 2024-06-11
opportunity_number: RFA-ES-20-014
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2025-06-30
study_section: ZES1-LAT-S
subproject_number: 7383
contact_pi_person_id: 9753394
contact_pi: RAI, SHESH N.
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARYThe primary objective of the Sample and Data Management Core (DMAC) is to provide statistical support anddata management and storage capabilities to all components of the University of Louisville Superfund ResearchCenter (ULSRC). The functions of the Core are matched to the needs of each project and cover a full range ofservices from collaboration and routine service to protocol preparation to procedural review and oversight. TheCore will provide two main services: it will establish a repository for the long-term storage and archiving of data;and it will assist Center investigators in the statistical analysis of their results. The core will assure the authenticityand quality of these specimens and it will prepare these samples for long-term storage or dispense samples asneeded. The Core will also provide scientifically valid and rigorous statistical analysis of data and support thedevelopment of innovative methods to enhance the basic and translational research efforts of Centerinvestigators. It will provide state-of-the-art biostatistics and bioinformatics expertise and analytical support. Corebiostatisticians will also develop new statistical methods such as quantitative risk assessment modelsmultipollutant exposure analysis and land-use regression models for estimating cardiometabolic disease risk inexposed populations and for the analysis and evaluation of exposures and health effects. In collaboration withother projects and cores DMAC statisticians will harmonize the data by defining standards (e.g. creatingsearchable data dictionaries and defining variables relevant for each project. In the next funding cycle we willcontinue to use these procedures. The core will serve as a unique educational resource for training graduatestudents post-doctoral fellows residents and junior faculty and in collaboration with the Training andAdministration Cores. This Core will allow Center investigators easy access to high quality centralized datamanagement and statistical services and thereby will strengthen the organizational cohesion of the Center. Thiscomprehensive and integrated service permits one or more biostatisticians to be involved from the initial planningstage of a project (when statistical consultation is most beneficial) throughout its implementation analysis andcompletion. The Core will provide a stable and collegial environment that fosters long-term working relationshipsbetween biostatisticians and investigators and continues to promote sophisticated approaches to experimentaldesign and analysis. The biostatisticians of this Core are knowledgeable about clinical research and have broadexpertise in statistical applications for epidemiological investigations clinical trials pre-clinical studies andprevention and control research. Their interdisciplinary interactions with basic scientists and clinical investigatorswill add a new dimension to the interpretation of experimental results one that is only possible when collaboratorsshare a mutual appreciation of problems and issues.

project_terms:
Anacondas;Animal Experiments;Animals;Artificial Intelligence;Atmosphere;Basic Science;Bioinformatics;Biological Assay;Biometry;Cardiometabolic Disease;Characteristics;Clinical Investigator;Clinical Research;Clinical Trials;Code;Collaborations;Consultations;Data;Data Analyses;Data Collection;Data Files;Data Set;Data Storage and Retrieval;Databases;Development;Dimensions;Disease;Educational workshop;Ensure;Environment;Environmental Exposure;Evaluation;Experimental Designs;Exposure to;FAIR principles;Faculty;Fostering;Funding;Future;Gases;Geography;Hazardous Chemicals;Health;Health protection;Human;Human Resources;Individual;Institution;Linux;Machine Learning;Manuscripts;Maps;Mass Spectrum Analysis;Measurement;Methods;Modeling;Molecular;Operating System;Output;Participant;Population;Postdoctoral Fellow;Preparation;Prevention;Procedures;Process;Protocols documentation;Pythons;Quality Control;Research;Research Design;Research Personnel;Resources;Risk;Risk Assessment;Risk Estimate;Sampling;Scientist;Secure;Series;Services;Site;Source;Spatial Distribution;Specimen;Statistical Data Interpretation;Statistical Methods;Study Subject;Superfund;Testing;Toxic effect;Training;Translational Research;Universities;Validation;Variant;Visual;Work;archive data;cardiometabolism;central database;cohesion;computing resources;data curation;data dictionary;data exchange;data harmonization;data hub;data interoperability;data management;data quality;data sharing;data streams;data structure;data submission;design;detection limit;disorder risk;education resources;efficacy testing;epidemiology study;experience;experimental analysis;graduate student;improved;innovation;land use;large datasets;lipidomics;meetings;metabolomics;novel;novel strategies;operation;platform-independent;pollutant;portability;preclinical study;privacy protection;quality assurance;remediation;repository;statistical service;tool;transcriptomics;usability;volatile organic compound

public_health_relevance:
RELEVANCEBy ensuring proper study designs and supporting appropriate data analysis and by providing efficient andorganized data management and storage capabilities the core will further our understanding of risk sources andcardiometabolic disease risk estimation due to exposure to hazardous chemicals. Well annotated data basescreated and supported by the core will facilitate data sharing and collaborative projects within the Center andwith other Superfund Centers and academic institutions.


application_id: 10914090
project_number: 5P42ES023716-08
project_title: Administrative Core
administering_ic: NIEHS
award_notice_date: 2024-06-11
opportunity_number: RFA-ES-20-014
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2025-06-30
study_section: ZES1-LAT-S
subproject_number: 7382
contact_pi_person_id: 6871611
contact_pi: SRIVASTAVA, SANJAY
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARYThe Administrative Core of the Louisville Superfund Center (LSC) will provide administrative and fiscal supportto all Projects and Cores supported by the Center. The Core will be directed by the Center Director who withassistance from the Program Administrator will facilitate communication and collaboration between individualCores and Projects and provide scientific and logistic oversight to Center activities. The Core will act as a liaisonfor individual Center members in order to best promote collaboration to ensure all Center work effectivelycontributes issues relevant to the SRP. The Core will also disseminate scientific knowledge acquired from theUniversity of Louisville Superfund Research Center (ULSRP) in a timely manner to key constituencies in formsthat are targeted and useful to our audience. These include scientists and public health professionals; localstate and federal policy makers; and the media and press. To assist in the planning and coordination of researchand core activities the Core personnel will organize scientific work-in-progress sessions monthly meetingsrelevant focus groups and frequent formal and informal interactions. To integrate cross-disciplinary researchthe Core will provide leadership and administrative support needed for integration and coordination of research.The Core will leverage existing resources on campus to optimize the productivity of the Center and will seekinput from both an Internal Advisory Committee and an External Advisory Committee in evaluating progress andin maintaining the relevance of Center activities to the Superfund Research Program mandate. Core leaderswill maintain close contact with NIEHS program officials and with UofL administration. Core administrators willalso manage the finances and resources of the Center to optimize usage and appropriate allocation. They willalso coordinate the timely development of progress reports and financial statements. To ensure qualitymanagement the Core will monitor and facilitate attainment of Center objectives in research training educationand community engagement and ensure compliance with state and federal regulations. The Administrative Corewill be the go-to place for students and trainees community members public media and press so that all suchactivities can be appropriately facilitated and coordinated.

project_terms:
Achievement;Administrator;Advisory Committees;Cardiometabolic Disease;Collaborations;Communication;Communities;Consultations;Core Facility;Counseling;Data;Development;Diabetes Mellitus;Discipline;Education;Emergency response;Ensure;Environment;Environmental Exposure;Evaluation;Focus Groups;Funding;Future;Goals;Hazardous Chemicals;Health;Health Professional;Heart Diseases;Human Resources;IACUC;Individual;Institution;Institutional Review Boards;Knowledge acquisition;Leadership;Link;Liver diseases;Logistics;Medical;Mentors;Monitor;National Institute of Environmental Health Sciences;Nongovernmental Organizations;Policies;Policy Maker;Productivity;Progress Reports;Protocols documentation;Public Health;Quality Control;Reagent;Regulation;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;Scientific Evaluation;Scientist;Selection Criteria;Signal Recognition Particle;Specimen;Students;Superfund;Training;Training Activity;Training and Education;Translational Research;Universities;Work;community engagement;effectiveness research;experimental study;federal policy;meetings;member;operation;participant enrollment;programs;scientific organization;tool;training opportunity;web site

public_health_relevance:
RELEVANCEThe Administrative Core is essential for the efficient functioning of the Center. It is required for the Centersfiscal management and resource sharing and will ensure quality control and compliance with regulations andevaluation of Center activities. It will facilitate and optimize research training community engagement andresearch translational activities of the Center and assist in developing a new understanding of the effects ofhazardous chemicals on liver disease diabetes and heart disease.


application_id: 10914083
project_number: 5P42ES023716-08
project_title: Project 2 - Molecular and Cellular Mechanisms of Cardiometabolic Toxicity of VOCs
administering_ic: NIEHS
award_notice_date: 2024-06-11
opportunity_number: RFA-ES-20-014
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2025-06-30
study_section: ZES1-LAT-S
subproject_number: 7379
contact_pi_person_id: 6871611
contact_pi: SRIVASTAVA, SANJAY
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
SUMMARYExposure to toxicants has been linked to the development or exacerbation of chronic disease. However little isknown about how volatile organic chemicals (VOC)a class of toxicants associated with higher prevalence oftype 2 diabetes (T2D) and strokepromote the development of cardiometabolic disease (CMD). Accordinglythe overarching goals of this Superfund project are to determine the mechanisms by which VOCs negativelyimpact cardiovascular health and metabolism identify biomarkers for VOC exposure and vascular injury andtest therapeutic strategies to minimize VOC-induced CMD. Our studies in the current funding cycle andpreliminary data suggest that VOC such as benzene vinyl chloride and crotonaldehyde promote endoplasmicreticulum (ER) stress and trigger the unfolded protein response (UPR) in endothelial cells. Specifically wehypothesize that aldehyde metabolites of VOC which are generally more toxic than their parent compounddiminish endothelial toxicity by inducing ER stress which triggers metabolic changes that accelerate ectopic lipiddeposition and promote cardiometabolic dysfunction. To test this hypothesis we will: (1) examine the effects ofVOC exposure on endothelial function and insulin resistance; (2) delineate the contribution of protein misfoldingto the cardiometabolic toxicity of VOC. The design of these studies includes molecular and pharmacologicalinterventions designed to detoxify or quench the reactive intermediates evoked by VOC exposure as well asstudies that could lead to the identification of novel sensitive and robust biomarkers of both VOC exposure andvascular injury. These studies were designed to synergize with and provide biological plausibility for theassociations identified in Project 1. Successful completion of this project will lead to identification of theunderlying cellular and molecular mechanisms by which VOC affect cardiometabolic function and provideinsights into how VOC toxicity could be prevented or therapeutically minimized by targeting aldehydes or protein-folding pathways.

project_terms:
13-Butadiene;2-butenal;ATF6 gene;Acceleration;Acrolein;Adipose tissue;Adult;Affect;Aldehydes;Animal Model;Apoptosis;Apoptotic;Atherosclerosis;Benzene;Biological;Biological Markers;Blood Vessels;Body Burden;Butadiene;Cardiometabolic Disease;Cardiovascular Physiology;Cardiovascular system;Carnosine;Cell Physiology;Chemical Exposure;Chemical-Induced Change;Chemicals;Chronic Disease;Data;Deposition;Development;Diabetes Mellitus;Disease Resistance;Dose;Drug Metabolic Detoxication;Endoplasmic Reticulum;Endothelial Cells;Endothelium;Environmental Exposure;Environmental Impact;Exposure to;Fatty acid glycerol esters;Formaldehyde;Functional disorder;Funding;Glutathione;Goals;Hazardous Chemicals;Hazardous Substances;Health;Heart Diseases;Heart failure;Heat shock proteins;Hepatic;High Prevalence;Human;Hypertension;Individual;Inflammatory;Inhalation;Injury;Insulin Resistance;Investigation;Link;Lipid Peroxidation;Lipids;Measures;Mediating;Mediator;Metabolic;Metabolism;Molecular;Molecular Chaperones;Mus;Non-Insulin-Dependent Diabetes Mellitus;Nutritional;Nutritional status;Obesity;Oxidative Stress;Oxidative Stress Induction;Parents;Pathway interactions;Plasma;Platelet Activation;Poison;Process;Production;Property;Proteins;Protocols documentation;Reporting;Risk;Role;Signal Recognition Particle;Signal Transduction;Source;Stroke;Structure;Superfund;Surveys;Testing;Therapeutic;Tobacco smoke;Toxic effect;Trichloroethylene;Vinyl Chloride;Work;ambient air pollution;biomarker identification;cardiometabolic risk;cardiometabolism;cardiovascular health;cardiovascular injury;design;diet-induced obesity;disorder risk;endoplasmic reticulum stress;endothelial dysfunction;fatty liver disease;heart function;indexing;insight;insulin sensitivity;metabolomics;mouse model;novel;overexpression;pharmacologic;preclinical study;prevent;protein folding;protein misfolding;response;superfund site;synergism;systemic inflammatory response;therapeutic evaluation;therapy design;toxicant;urinary;vascular inflammation;vascular injury;volatile organic compound;western diet

public_health_relevance:
PROJECT NARRATIVEExposure to hazardous substances has been linked to the development or worsening of chronic disease. Thepurposes of this Superfund project are to understand how a particular class of compounds i.e. volatile organiccompounds affect cardiovascular health and the onset or progression of diabetes heart disease and fatty liverdisease as well as to develop therapeutic strategies to minimize these affect after exposure to toxic compounds.


