# projects

application_id: 10164176
project_number: 1R21AI157903-01
project_title: RNA-dependent RNA Polymerase Assays for Biochemical Characterization and Antiviral Drug Discovery
administering_ic: NIAID
award_notice_date: 2021-07-19
opportunity_number: PAR-20-177
application_type: 1
activity_code: R21
ic: AI
serial_number: 157903
program_official: PLIMACK, MARY KATHERINE BRADFORD
project_start_date: 2021-07-20
project_end_date: 2024-06-30
study_section: Special Emphasis Panel[ZAI1 JP-W (S1)]
contact_pi_person_id: 9509796
contact_pi: VAN LANEN, STEVEN GARY
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
SARS-CoV-2 is a positive-sense single-stranded RNA [(+)ssRNA] virus that relies on its RNA-dependent RNApolymerase (RdRp) for survival. Within the months of April and May five groups have independently reportedthe production of recombinant SAR-CoV-2 RdRp and a preliminary activity assessment of this essential enzyme.Included in these studies was direct evidence that the triphosphate version of the nucleoside analogueremdesivir which has received Emergency Use Authorization from the Food and Drug Administration to treatSARS-CoV-2 is incorporated in place of ATP into the growing RNA oligonucleotide ultimately leading to chaintermination. Other nucleobase and nucleoside analogues including EIDD-1931 and favipiravir the latter of whichhas been approved in Japan to treat the (-)ssRNA influenza virus have demonstrated promise as therapeuticagents against SARS-CoV-2 by likely interfering with RNA metabolism via inhibition or processing as alternativesubstrates for RdRp. This and other data suggest that RdRp is an excellent target for the discovery anddevelopment of novel SARS-CoV-2 therapeutics. However one of the major bottlenecks in exploiting RdRp asa drug target is the relatively low throughput activity-based assays that are costly prone to interference and/orlack flexibility in the experimental design. The primary objective of this proposal is to develop a broadly applicableRdRp activity-based assay that will be used for antiviral drug discovery efforts. Our specific aim is to establish anovel real-time assay using a five-enzyme coupled system with a colorimetric readout. The new assay will bedirectly compared to the traditional polyacrylamide gel electrophoresis and a liquid scintillation proximity end-point assay and further validated with high resolution mass spectrometry. It is expected that by accomplishingthis aim the assay will enable a thorough biochemical characterization of SARS-CoV-2 RdRp and for the firsttime enable the testing of synthetic compound and natural product libraries to identify inhibitors alternativesubstrates modulators or effectors of SARS-CoV-2 RdRp activity in a high throughput screening format. Notablythe strategy implemented herein is expected to complement on-going structural-based anti-SARS-CoV-2discovery efforts. Finally the activity-based assay can be readily adapted for RdRp from other (+)ssRNA and (-)ssRNA viruses in an effort to identify therapeutics against a broad spectrum of pandemic-causing viruses.

project_terms:
2019-nCoV;Address;American;Antiviral Agents;Biochemical;Biochemistry;Biological Assay;COVID-19 assay;COVID-19 outbreak;COVID-19 pandemic;COVID-19 therapeutics;COVID-19 treatment;Cessation of life;Chemicals;Clinical;Clinical Trials;Communicable Diseases;Communities;Complement;Complex;Coronavirus;Coupled;Data;Detection;Development;Diphosphates;Drug Design;Drug Targeting;Ebola virus;Emergency Situation;End Point Assay;Enterovirus;Enzymes;Evaluation;Event;Experimental Designs;FDA Emergency Use Authorization;FDA approved;Flavivirus;Foundations;Future;Genetic Materials;Genetic Transcription;Goals;In Vitro;Influenza A Virus H1N1 Subtype;Influenza A virus;Infrastructure;Japan;Libraries;Life;Liquid substance;Mass Spectrum Analysis;Mediating;Methods;Molecular;Mutate;Names;National Institute of Allergy and Infectious Disease;Natural Products;Nucleotides;Oligonucleotides;Patients;Poliomyelitis;Polyacrylamide Gel Electrophoresis;Polymerase;Price;Production;Proteins;RNA;RNA Polymerase I;RNA metabolism;RNA-Directed RNA Polymerase;Recombinants;Recovery;Reporting;Research;Resolution;Resources;Rhinovirus;Structure;System;Testing;Therapeutic;Therapeutic Agents;Time;Vaccines;Virus;Virus Diseases;West Nile virus;Yellow Fever;base;catalyst;combat;cost;drug discovery;expectation;flexibility;high throughput screening;in vivo;influenzavirus;inhibitor/antagonist;interest;intravenous injection;novel;nucleobase analog;nucleoside analog;pandemic disease;pandemic influenza;polymerization;reconstitution;remdesivir;scaffold;screening;side effect;tool;tripolyphosphate

public_health_relevance:
The current COVID-19 pandemic has highlighted the importance of establishing continued and sustained effortstoward finding new broad-spectrum antiviral therapeutics that can be used in these emergencies. We will developa universal RNA-dependent RNA polymerase assay to enable high-throughput screens for inhibitors and tothoroughly characterize the biochemistry and mechanism of SARS-CoV-2 RNA-dependent RNA polymerase.


application_id: 10163832
project_number: 5R01DA048876-03
administering_ic: NIDA
award_notice_date: 2021-05-14
opportunity_number: PA-18-484
application_type: 5
activity_code: R01
ic: DA
serial_number: 048876
program_official: MULFORD, CARRIE FRIED
project_start_date: 2019-08-01
project_end_date: 2024-05-31
study_section: Community Influences on Health Behavior Study Section[CIHB]
contact_pi_person_id: 6264981
contact_pi: OSER, CARRIE BETH
other_pis: Not Applicable
congressional_district: 06
department: SOCIAL SCIENCES
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2021-06-01
project_title:
DAT18-08 Geographic variation in Opioid Addiction Treatment (GATE) study: Multi-Level Factors Influencing MAT Use Other Treatment & Adverse Outcomes among Re-entering Rural and Urban Prisoners

project_abstract:
ABSTRACT: As outlined in DAT18-08 NIDA has a strong interest in understanding treatment utilization amongpersons with opioid use disorders (POUDs) as they transition from prison to the community because treatingindividuals with opioid use disorder (OUD) simultaneously improves public health and public safety. Kentuckyis in the midst of an opioid crisis with many POUDs cycling through the criminal justice system each year. Whileevidenced-based medications for addiction treatment (MAT) exist for treating OUD MAT is underutilized withinprisons which elevates the risk of relapse and overdose when POUDs are released and re-enter theircommunities. Research is scant regarding the multi-level factors associated with offenders willingness to initiateMAT while in prison and their continued engagement in treatment after release. Furthermore rural and urbanpopulations have not been compared. In response to NIDA DAT18-08 we propose to conduct the high-impactGeographic variation in Addiction Treatment (GATE) study which will address the knowledge gap on multi-levelfactors influencing prison-based extended-release injectable naltrexone (XR-NTX) initiation as well as examinepredictors of post-release MAT use and adverse outcomes (i.e. relapse overdose recidivism) among both ruraland urban POUDs. This mixed methods study employs a social ecological framework to understand individualcharacteristics that influence MAT initiation and adverse outcomes as well as contexts more distal to theindividual including social networks and structural factors. The specific aims of the GATE study are: 1) toidentify the individual personal network and structural factors associated with XR-NTX initiation inprison among rural as compared to urban POUDs and 2) to examine the individual personal networkand structural factors predicting MAT use treatment use and adverse outcomes in the communityamong re-entering rural as compared to urban POUDs over time. A prospective observational longitudinalcohort study will be conducted with 500 POUDs using survey and social network data collected in prison andat 6- and 12-months post-release to explore multi-level rural-urban variation in key outcomes. In-depth guidedqualitative interviews will be conducted with POUDs prison-based treatment staff and social service clinicians.To maximize rigor and reproducibility we will employ a concurrent triangulation strategy whereby qualitativeand quantitative data contribute equally to the analysis and are used for cross-validation. This study is led by aqualified interdisciplinary team and is the first mixed methods study examining the processes of social influencesthat occur in rural and urban social networks as POUDs transition from prison back to geographically diversecounties. The GATE study will enhance our ability to address the opioid epidemic within the correctional contextsof prisons and community supervision by informing process improvement efforts for prison-based MAT initiationand post-release retention in care applying network science findings to improve the re-entry planning processand establishing the foundation for future R-level intervention applications.

project_terms:
Address;Aftercare;Back;Caring;Characteristics;Communities;Continuity of Patient Care;County;Crime;Criminal Justice;Data;Distal;Drug Screening;Drug usage;Economically Deprived Population;Education;Elements;Enrollment;Equipment and supply inventories;Foundations;Future;Geographic Locations;Geography;Goals;Health;Health Services Accessibility;Healthcare;Imprisonment;Individual;Injectable;Intervention;Interview;Kentucky;Knowledge;Literature;Longitudinal cohort study;Measures;Mediating;Medicaid;Mentors;Methods;Naltrexone;National Institute of Drug Abuse;Opiate Addiction;Outcome;Outpatients;Overdose;Persons;Pharmaceutical Preparations;Pilot Projects;Predictive Factor;Prisoner;Prisons;Process;Public Health;Recovery;Relapse;Reproducibility;Research;Resources;Rural;Rural Appalachia;Rural Population;Safety;Sampling;Science;Social Network;Social Work;Structure;Substance abuse problem;Supervision;Support Groups;Surveys;System;Time;Treatment outcome;United States National Institutes of Health;Urban Population;Validation;Variant;Woman;addiction;adverse outcome;base;effective therapy;evidence base;experience;follow-up;geographic difference;improved;interest;offender;opioid epidemic;opioid misuse;opioid use disorder;primary outcome;programs;prospective;recidivism;recruit;relapse risk;response;social;social structure;uptake;willingness

public_health_relevance:
PROJECT NARRATIVE To improve future treatment interventions for persons with opioid use disorders (POUDs) who areincarcerated this study compares the multi-level factors influencing prison- and community-based initiation ofmedications for addiction treatment (MAT) and associated post-release outcomes under real-world conditionsin rural Appalachian Kentucky an economically-deprived region with limited service availability and moreresource-rich urban counties. This study will make significant contributions to public health and public safetyby examining how rural-urban variation in personal social network characteristics support or impede the effortsof POUDs to access continuing treatment post-release achieve stable recovery and desist from crime duringthe vulnerable re-entry period.


application_id: 10162656
project_number: 5R01HL147856-03
project_title: Mechanisms underlying metal nanoparticle-induced lung injury and fibrosis
administering_ic: NHLBI
award_notice_date: 2021-05-04
opportunity_number: PA-18-484
application_type: 5
activity_code: R01
ic: HL
serial_number: 147856
program_official: VUGA, LOUIS J
project_start_date: 2019-06-01
project_end_date: 2023-05-31
study_section: Nanotechnology Study Section[NANO]
contact_pi_person_id: 8567542
contact_pi: ZHANG, QUNWEI
other_pis: Not Applicable
congressional_district: 03
department: PUBLIC HEALTH & PREV 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 PUBLIC HEALTH
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Metal nanoparticles have been widely used in cosmetics medicine electronics and industry and occupationalor non-occupational exposure to metal nanoparticles is growing. In this proposal we have selected severaltransition metal nanoparticles (Nano-Co Nano-Ni and Nano-TiO2) as `model' metal nanoparticles to examinetheir ability to induce pulmonary injury and fibrosis and the potential underlying mechanisms involved. Aninflammasome is a multiprotein complex that serves as a platform for caspase-1-dependent proteolyticmaturation and secretion of interleukin-1 (IL-1). The central component of an inflammasome is a member ofthe NLRP family and this protein associates with the adaptor protein ASC which in turn recruits pro-inflammatorycaspase precursors (such as procaspase-1). Among a number of inflammasomes the NLRP3 inflammasome isthe most extensively studied. Our working hypothesis is that exposure to metal nanoparticles will causeactivation and/or dysregulation of the inflammasome and IL-1 secretion in alveolar macrophages (AMs)lung epithelial cells and lung fibroblasts which will cause dysregulation of matrix metalloproteinases(MMPs) and tissue inhibitors of metalloproteinases (TIMPs) initiating and promoting metal nanoparticle-induced pulmonary injury and fibrosis. This project will use both in vitro and in vivo systems to address thefollowing specific aims: (1) Determine the role of inflammasome activation in IL-1 secretion induced bymetal nanoparticles in vitro and in vivo. We will identify whether activation of the inflammasome is involvedin metal nanoparticle-induced IL-1 secretion in alveolar macrophages (AMs) lung epithelial cells and lungfibroblasts by: (1) using ac-YVAD-cmk a particular inhibitor of caspase-1; (2) knocking-down one of theinflammasome components such as NLRP3 ASC or caspase-1 by using CRISPR/Cas9 technology; and (3)using NLRP3 or ASC knock-out mice. We will then determine whether NADPH oxidase- and/or mitochondria-dependent ROS generation and potassium efflux are involved in metal nanoparticle-induced inflammasomeactivation and IL-1 secretion. We will also measure IL-1 secretion in mice exposed to metal nanoparticles. (2)Examine the role of IL-1 in the alteration of MMPs and TIMPs expression and activity in lung cellsexposed to metal nanoparticles. While IL-1 is an inducer for MMP-2 and MMP-9 activity it is unclear how itregulates MMPs and TIMPs with exposure to metal nanoparticles. To test the role of the inflammasome and IL-1 in the regulation of MMPs and TIMPs the strategies in Aim 1 will be used to inhibit inflammasome functionand strategies to inhibit IL-1 function will be applied by using: (1) the pharmacologic IL-1 inhibitor; (2) anti-IL-1 antibody; and (3) IL-1RI-/- mice that will not respond to IL-1. After exposure to metal nanoparticles MMP-2MMP-9 and TIMPs expression and activity will be determined. (3) Investigate the role of inflammasomeactivation in metal nanoparticle-induced lung injury and fibrosis in vivo. We will first investigate whetherexposure to metal nanoparticles will cause lung fibroblasts to produce more collagen. Then the role of theinflammasome in metal nanoparticle-induced lung fibrosis will be explored by short- and long-term exposure ofmice to metal nanoparticles. We will use the strategies in Aim 1 and 2 to inhibit inflammasome and IL-1 functionto investigate the role of the inflammasome and IL-1 in metal nanoparticle-induced lung fibrosis.

project_terms:
Adaptor Signaling Protein;Address;Alveolar Macrophages;Antibodies;Apoptosis;Asbestos;Asthma;Attenuated;Biological;Bronchoalveolar Lavage Fluid;CASP1 gene;CRISPR/Cas technology;Caspase;Cells;Collagen;Cosmetics;Development;Electronics;Epithelial Cells;Exposure to;Family;Fibroblasts;Fibrosis;Gelatinase A;Gelatinase B;Generations;Health;In Vitro;Industrialization;Industry;Inflammasome;Inflammatory;Injury;Interleukin-1;Interleukin-1 Receptors;Interleukin-1 beta;Knockout Mice;Lead;Lesion;Lung;Lung Inflammation;Lung diseases;Malignant neoplasm of lung;Matrix Metalloproteinases;Measures;Medical;Medicine;Metal exposure;Metal fever;Metals;Mitochondria;Modeling;Multiprotein Complexes;Mus;NADPH Oxidase;Normal Range;Occupational;Pharmacology;Play;Potassium;Proteins;Pulmonary Fibrosis;Regulation;Role;Silicon Dioxide;System;Testing;Tissue Inhibitor of Metalloproteinases;Toxic effect;Transition Elements;Wild Type Mouse;anakinra;base;exposed human population;in vivo;inhibitor/antagonist;interest;interleukin-1beta-converting enzyme inhibitor;knock-down;lung injury;macrophage;member;monocyte;nano;nanomaterials;nanoparticle;particle;recruit;response;titanium dioxide;tool

public_health_relevance:
This project aims to explore how exposure to metal nanoparticles may cause lung diseases. We expect thatour results will provide tools for evaluating other nanomaterials. Successful completion of this project will notonly lead to a better understanding of the mechanisms by which metal nanoparticles induce lung injury butalso provide scientific evidence to reduce their toxicity.


application_id: 10160948
project_number: 5R01HL147343-03
project_title: The Role of E-cigarette Characteristics and Constituents in Cardiac Dysfunction
administering_ic: NHLBI
award_notice_date: 2021-05-07
opportunity_number: RFA-OD-18-002
application_type: 5
activity_code: R01
ic: HL
serial_number: 147343
program_official: POSTOW, LISA
project_start_date: 2019-05-20
project_end_date: 2023-04-30
study_section: Special Emphasis Panel[ZRG1-BST-T(55)R]
contact_pi_person_id: 11702638
contact_pi: CARLL, ALEX PERROW
other_pis: Not Applicable
congressional_district: 03
department: PHYSIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
ABSTRACTE-cigarettes (e-cigs) have become increasingly popular but their acute and chronic health effects aremostly unknown. Conventional cigarette smoking increases the risk of cardiac arrhythmia by slowingventricular repolarization and inducing QT interval prolongation on the electrocardiogram (ECG). E-cigsproduce several of the harmful and potentially harmful constituents (HPHCs) found in cigarette smoke.When aerosolized the e-cig solvents propylene glycol (PG) and vegetable glycerin (VG) may similarlyaffect repolarization. Our preliminary data indicate exposure to e-cig solvent aerosols of equal-ratio PGand VG (PG:VG) prolongs QT and alters gene expression of ion channels key for repolarization in themouse heart suggesting inhalation of e-cig solvent aerosols may convert the heart into an arrhythmogenicsubstrate. However e-cigs produce HPHCs at levels that vary markedly according to devicecharacteristics operating conditions and use patterns. Thus the full spectrum of their health impactsremains unclear. This project is designed to identify specific device characteristics and e-cig constituentsassociated with cardiac toxicity. It will apply both ECG and programmed stimulus electrophysiology (EP)studies to test the hypothesis that e-cigs induce electrical disturbances in the heart and that these effectsdepend upon e-cig characteristics and constituents. The studies will 1: Determine how devicecharacteristics influence the acute electrophysiologic effects of e-cigs in mice and 2: Assess theimpacts of chronic e-cig exposure on cardiac electrophysiology and hemodynamics. Real-timecardiac physiology will be monitored through ECG telemetry during and after acute exposures to PG:VGaerosols from e-cigs of various characteristics (device type user settings nicotine levels) to delineate howthey affect both HPHC production and ECG measures of cardiac dysfunction. The device characteristicswith the greatest and slightest acute cardiac effects will then be selected for chronic exposure studies inwhich cardiac EP and hemodynamics will be comprehensively assessed through telemetryechocardiography programmed electrical stimulation of the heart molecular and histologic assaysaerosol assessments of HPHCs and analyses of biomarkers of HPHC exposures. All exposure groupswill be simultaneously compared to cigarette smoke and filtered-air exposure groups. Our research plan isresponsive to the research priorities of the FDA/CTP especially the interest area of toxicity. We expectthat our results will elucidate the relative toxicity of different e-cig devices constituents and settings andprovide novel and significant insights into how each influences the arrhythmogenic potential of e-cigaerosols. We believe the outcome of our project would provide comprehensive and rigorous data to guidepolicies on e-cig product standards and to inform regulatory authorities of the cardiac risks associated withspecific e-cig constituents and characteristics.

project_terms:
Acute;Adverse effects;Aerosols;Affect;Aldehydes;Animals;Area;Arrhythmia;Biochemical;Biochemistry;Biological Assay;Biological Markers;Blood Pressure;Cardiac;Cardiac Electrophysiologic Techniques;Cardiac health;Cardiotoxicity;Characteristics;Chronic;Data;Devices;Echocardiography;Electric Stimulation;Electrocardiogram;Electrodes;Electronic cigarette;Electrophysiology (science);Exposure to;Failure;Female;Functional disorder;Gap Junctions;Gene Expression;Generations;Goals;Harm Reduction;Health;Health Policy;Heart;Heart Atrium;Histologic;Histopathology;Human;Inhalation;Ion Channel;Mainstreaming;Measures;Mission;Molecular;Monitor;Mus;Myocardial dysfunction;Nicotine;Outcome;Particulate Matter;Pattern;Periodicity;Physiology;Policies;Predisposition;Production;Propylene Glycols;Public Health;Refractory;Regimen;Research;Research Personnel;Research Priority;Risk;Role;Safety;Smoking;Solvents;Stimulus;Structure;Telemetry;Testing;Time;Tissues;Toxic effect;United States National Institutes of Health;Ventricular;Western Blotting;Work;aerosolized;air filter;atrioventricular node;authority;cardiovascular effects;cardiovascular health;cigarette smoke;cigarette smoking;combustible cigarette;design;disability;e-cigarette aerosols;electronic cigarette use;heart function;heart rate variability;hemodynamics;insight;interest;male;novel;sex;urinary;vegetable glycerin

public_health_relevance:
Project NarrativeThe proposed project is relevant to public health because it will provide new insight on the cardiac risks ofelectronic cigarette use and identify the characteristics of e-cigarette devices that pose the greatest harm toheart health. Upon this project identifying the device characteristics with the greatest cardiac effects in animalsthese observations may guide human studies and be used to set product standards to protect the public fromthe most harmful e-cigarette features. Thus the proposed research is relevant to the FDA mission to assurethe safety of FDA-regulated products and also relevant to the NIH mission to reduce illness and disability.


application_id: 10160868
project_number: 5R01DA045700-04
administering_ic: NIDA
award_notice_date: 2021-05-13
opportunity_number: PA-16-160
application_type: 5
activity_code: R01
ic: DA
serial_number: 045700
program_official: RAMEY, TANYA S
project_start_date: 2018-08-01
project_end_date: 2025-05-31
study_section: Addiction Risks and Mechanisms Study Section[ARM]
contact_pi_person_id: 8906159
contact_pi: BABALONIS, SHANNA
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2021-06-01
project_title:
Evaluation of Marijuana and Opioid Drug Interactions: Assessment of the Safety Profile Abuse-Related Pharmacodynamic Effects and Models of Drug Intake

project_abstract:
Abstract Misuse of prescription opioids and heroin is a global epidemic with an estimated 33 million peoplemisusing opioids worldwide and 2.6 million individuals in the U.S. meeting criteria for an opioid use disorder.This public health crisis is occurring on the background of a precipitous increase in the availability of marijuanaboth in the U.S. and worldwide. Marijuana use is at peak levels in the U.S.  in 2014 22.2 million individuals 12years and older reported past month marijuana use and 8.4 million individuals reported daily/near-dailymarijuana use. Marijuana and opioids are the two most commonly misused illicit drug classes (with manymore taking these drugs therapeutically); however despite these high rates of use there are no carefullycontrolled human data available on their co-use specifically in regard to drug response abuse-relatedmeasures and safety outcomes. Thus the current project aims to explore the 1) safety/physiological effects ofmarijuana and opioid combinations 2) impact of marijuana use on opioid response and opioid drug-taking 3)effects of opioid use on marijuana drug-taking and 4) behavioral and cognitive effects of combined opioid-cannabinoid use. Two independent inpatient studies will be conducted during this 4-year project and each willutilize a randomized within-subject double-blind double-dummy placebo-controlled design and will enrollsamples of non-physically dependent recreational opioid users with histories of marijuana use. Study 1 willexamine the effects of smoked marijuana pre-treatment over a range of THC concentrations (0 5 &15% THC)on intranasal oxycodone (0 15 & 30 mg) response using a full battery of pharmacodynamic outcomesincluding safety/physiological response and abuse-related subjective and observer-rated effects. Secondaryaims will examine the psychomotor/cognitive effects across the dose conditions. Study 2 will explore 1) theeffects of smoked marijuana pre-treatment (0 15% THC) on intranasal oxycodone (0 15 & 30 mg) self-administration and 2) intranasal oxycodone pre-treatment (0 30 mg) on smoked marijuana (0 5 & 15% THC)self-administration. Overall these studies will provide some of the first empirical data on the interaction effectsof the two most commonly misused drug classes providing information on the safety impact physiologicaleffects and abuse-related effects of their co-use. These findings will be highly relevant to public healthconsiderations will help determine the risk profile of marijuana and opioid interactions and will provide newcontrolled information relevant to clinical practice prescribing and public safety.

project_terms:
Absence of pain sensation;Accidents;Acute;Address;Age;Agonist;Analgesics;Animals;Attenuated;Automobile Driving;Autopsy;Behavior;Behavioral;Biochemical;CNR1 gene;Cannabinoids;Chemosensitization;Cognitive;Data;Dose;Double-Blind Method;Dronabinol;Drug Interactions;Drug Modelings;Enrollment;Epidemic;Evaluation;Funding;Heroin;Human;Illicit Drugs;Individual;Inpatients;Intake;Laws;Legal;Marijuana;Measures;Medical Marijuana;Mus;Opioid;Opioid Receptor;Outcome;Oxycodone;Oxymorphone;Pharmaceutical Preparations;Pharmacodynamics;Physiological;Placebos;Population;Public Health;Randomized;Recording of previous events;Reporting;Research;Risk;Safety;Sampling;Self Administration;Series;Smoke;Specimen;Statutes and Laws;System;THC concentration;Taxes;Therapeutic;Time;Ventilatory Depression;cannabinoid receptor;clinical practice;design;drug discrimination;drug misuse;endogenous cannabinoid system;endogenous opioids;epidemiologic data;functional outcomes;human data;innovation;marijuana use;meetings;mortality;mu opioid receptors;neurochemistry;neurophysiology;nonhuman primate;opioid misuse;opioid mortality;opioid overdose;opioid use;opioid use disorder;opioid user;pain outcome;pain relief;prescription opioid;prescription opioid misuse;receptor;response;safety assessment;safety outcomes;substance use prevention;young adult

public_health_relevance:
PROJECT NARRATIVEThis research will provide important public health and safety information regarding the interaction effects ofopioids and smoked marijuana on a full range of pharmacodynamic safety and abuse-related outcomes.


application_id: 10159289
project_number: 5R01ES031846-02
administering_ic: NIEHS
award_notice_date: 2021-02-23
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: ES
serial_number: 031846
program_official: TYSON, FREDERICK L
project_start_date: 2020-05-06
project_end_date: 2022-02-28
study_section: Xenobiotic and Nutrient Disposition and Action Study Section[XNDA]
contact_pi_person_id: 10313148
contact_pi: FONDUFE-MITTENDORF, YVONNE NSOKIKA
other_pis: Not Applicable
congressional_district: 06
department: BIOCHEMISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2021-03-01
project_title:
Molecular Underpinnings in the Establishment of an Oncogenic 3D Genome in Response to Environmental Arsenic Exposure

project_abstract:
AbstractEstablishing the influence of pollutants on genome function is essential in defining their impact on humanhealth. Environmental pollutants such as inorganic arsenic (iAs) are responsible for over thirteen million deathsyearly. Importantly 24% of the diseases caused by environmental exposures might have been avoided bydisease prevention diagnosis and the development of safer metal-based therapeutic agents. In order tounderstand how these pollutants cause disease we need to understand how pollutants change geneexpression. Proper gene regulation is essential for normal growth development and etiology of diseases suchas cancer. Eukaryotic DNA stored as chromatin plays an integral role in gene regulation. At the one-dimensional (1D) level chromatin is found as nucleosomes and at the three dimensional level (3D) chromatinis found in loops and topological domains both of which regulate gene expression by allowing accessibility tothe DNA wrapped up as chromatin. Inorganic arsenic is a ubiquitous metal that impacts gene regulationthrough modulating the epigenome. We recently provided the epigenetic landscape (DNA methylation histonePTMs and histone variants) mediated by iAs. This landscape though important makes it difficult to decipherwhether the observed effects on gene activity are due to local changes in epigenetic environments or effectscaused by remote changes several kilobases away such as the activity of enhancer(s). Additionally the effectof the 3D chromatin structure supersedes that at the 1D chromatin level. This 3D information is mediated byCTCF known as a master weaver of the genome and any dysregulation of the CTCF binding alters this 3Dstructure resulting in gene dysregulation. We recently showed that iAs selectively inhibits CTCF from bindingto some of its target sites and instigating oncogenic expression patterns. Interestingly carcinogenesis is not alinear process but involves a several hybrid in-between stages till final cancer state. We therefore hypothesizethat by inhibiting CTCF binding iAs reorganizes the genome to maintain specific topologically-activateddomains at the 3D chromatin structure to drive specific oncogenic potentials. To test this hypothesis we willmap CTCF binding (Aim 1) chromatin 3D (Aim 2) and ChIP-seq of histone marks (Aim 3) as cells undergo iAs-mediated carcinogenesis. The knowledge derived from the proposed studies will allow us to characterize theresulting gene regulatory network mediated by iAs exposure and allow us to unambiguously anchor iAsexposure to changes in the CTCF interactome in the process of iAs-mediated cancer. Additionally thesestudies will allow us to decipher how iAs initiates establishes and maintains particular chromatin signaturesthat ultimately drive gene expression in iAs pathogenesis. Such studies are critically needed for theidentification of translational targets and the development of therapeutic drugs needed in iAs-diseasepathology.

project_terms:
3-Dimensional;ATAC-seq;Affect;Alternative Splicing;Animal Model;Arsenic;Automobile Driving;Binding;Binding Sites;Biochemical;Biology;CCCTC-binding factor;Cancer Biology;Carcinogens;Cell model;Cells;Cessation of life;ChIP-seq;Chromatin;Chromatin Loop;Chromatin Structure;DNA;DNA Binding;DNA Damage;DNA Methylation;DNA Modification Methylases;Development;Diagnosis;Diagnostic;Dimensions;Disease;Enhancers;Environment;Environmental Exposure;Environmental Pollutants;Epigenetic Process;Etiology;Exposure to;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Genes;Genome;Genomic Segment;Genomics;Goals;Growth and Development function;Health;Histones;Human;Hybrids;Knowledge;Light;Malignant Neoplasms;Maps;Mediating;Metals;Modeling;Molecular;Mutation;Neoplasm Metastasis;Nucleosomes;Oncogenic;Organism;Pathogenesis;Pathogenicity;Pathology;Pattern;Pharmaceutical Preparations;Play;Process;Proteins;Reactive Oxygen Species;Regulator Genes;Risk;Role;Site;Spliced Genes;Techniques;Testing;Therapeutic;Therapeutic Agents;Transcription Initiation;Variant;Work;Writing;arsenic carcinogenesis;base;carcinogenesis;carcinogenicity;chromatin remodeling;disorder prevention;epigenome;epigenomics;epithelial to mesenchymal transition;genome-wide;in vivo;metaplastic cell transformation;pollutant;prevent;promoter;response;targeted treatment;therapeutic development;three dimensional structure;tool

public_health_relevance:
The proper regulation of gene expression is essential for the development and health of all organisms. Ourwork advances the study of how DNA found as chromatin plays an integral part in gene regulation(transcription initiation and gene splicing. This knowledge will help guide the development of diagnostic andtherapeutic tools e.g. built upon knowledge of alternative splicing.


application_id: 10158506
project_number: 5T32HL134644-05
project_title: Current Trends in Stem Cell Therapies
project_terms: stem cell therapy;trend
administering_ic: NHLBI
award_notice_date: 2021-04-26
opportunity_number: PA-16-152
application_type: 5
activity_code: T32
ic: HL
serial_number: 134644
program_official: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN
project_start_date: 2017-05-01
project_end_date: 2023-04-30
study_section: NHLBI Institutional Training Mechanism Study Section[NITM(JA)]
contact_pi_person_id: 2265592
contact_pi: RATAJCZAK, MARIUSZ Z
other_pis: KAKAR, SHAM S.
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
project_abstract:
PROJECT SUMMARY/ABSTRACTStem cell biology has become one of the most exciting scientific areas of investigation. Stem cells are a key tounderstanding: i) the physiology of tissue rejuvenation ii) organ regeneration after injury and iii) the regulationof the lifespan. A looming educational challenge is the preparation of young investigators to engage inresearch on these very important cells in the body. The focus of this training program Current Trends in StemCell Therapies (CTSCT) Training Program is to understand the role of stem cells in hematology and tissueinjury. The training program is derived from the experience of mentoring faculty and the strength of clinicalutilization of adult stem cells isolated from postnatal tissues in stem cell processing laboratories employed inthe Bone Marrow Transplant Unit Department of Cardiology and the Department of Pediatrics at theUniversity of Louisville (UofL). This grant will involve the post-doctoral fellows by engaging them in conceptuallaboratory work aimed at the optimization of the: i) isolation of versatile populations of stem cells from adultissues ii) their ex vivo expansion alone or in combination with synthetic scaffolds iii) studies on the role ofparacrine-related effects of stem cells in regeneration with special emphasis on extracellular microvesicles(ExMV) and iv) strategies of stem cell delivery to damaged organs including mechanism orchestrating theirhoming and engraftment. The goals of our training program (CTSCT) will be achieved with a multidisciplinaryapproach that includes the dedicated faculty from various departments centers institutes and schools. Thehighly experienced and multidisciplinary faculty at the UofL will provide critical resources and expertise inperforming cutting-edge basic and clinical research in this field. This proposal is an innovative postdoctoraltraining program that will serve as a platform for developing interdisciplinary and integrated approaches thatwill shed more light on the stem cell compartment under steady-state and pathological conditions. Theproposed training program will support five postdoctoral trainees. Two of them will be recruited in year one andthen three more in year two to maintain a total of 5 trainees. These may be existing postdoctoral fellows whohave matriculated at UofL or candidates selected by an open recruitment from highly reputed researchinstitutions. This training program will also serve as an important vehicle to integrate the stem cell researchperformed at UofL. This will be achieved by organizing integrated stem cell-related special courses seminarslectures journal clubs and open discussions to exchange new ideas among postdoctoral fellows participatingin this program and with other students and faculty members at UofL. In addition the teams of mentors(including both basic and clinical scientists) will promote the importance of multidisciplinary training and thetranslation of basic science research findings to the community of Kentucky. In summary our CTSCT trainingprogram will effectively facilitate multidisciplinary approaches to studying stem cell biology and is consistentwith the NIH Roadmap and the strategic plans of the NHLBI and the overall developmental goals of the UofL.

public_health_relevance:
PROJECT NARRATIVEStem cells play a multifaceted role in many normal biological functions including organ development tissuerejuvenation regeneration and aging. The focus of this Current Trends in Stem Cell Therapies trainingprogram is based on the experience of the mentoring faculty and the strength of clinical utilization of adult stemcells isolated from postnatal tissues in stem cell processing laboratories employed in clinic in the Bone MarrowTransplant Unit Institute of Molecular Cardiology and Department of Pediatrics at the University of Louisville(UofL). This proposed program is consistent with the NIH Roadmap and the NHLBI and the UofL strategicplans emphasizing the importance of multidisciplinary training and the translation of basic science findings tobenefit the patient and community.


application_id: 10158383
project_number: 5R37AI052218-20
project_title: In Vitro Glycorandomization of Natural Products
administering_ic: NIAID
award_notice_date: 2021-06-02
opportunity_number: PA-11-260
application_type: 5
activity_code: R37
ic: AI
serial_number: 052218
program_official: DAVIS, MINDY I
project_start_date: 2002-06-03
project_end_date: 2024-05-31
study_section: NSS
contact_pi_person_id: 2212695
contact_pi: THORSON, JON SCOTT
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
ABSTRACT OF THE RESEARCH PLAN The studies to be pursued under the proposed extension fall within three general areas: i) enzyme catalystengineering and modulation (theme 1); ii) selected platform applications (theme 2); and iii) a systematic studyof the impact of glycosylation on fundamental drug properties (theme 3). The key tenets of each are brieflydescribed below and parallel the consistently high level of significance and innovation reflected in past periodsof support. The overarching significance stems from the anticipated advancements of universal principles forenzyme catalyst engineering/modulation novel enabling strategies for synthesis and biosynthetic study uniqueprobes or leads of significance to diverse therapeutic areas and a potential new conceptual framework for thegeneral use of glycosylation in drug development. Anticipated drivers of innovation are both by design(particularly novel synthetic and assay strategies) and directed discovery (unprecedented glycosyltransferasemodulators and probes/leads with high potential to lead to new understanding in the fundamentals ofimmunomodulation and/or inflammation). Studies directed toward enzyme catalyst engineering and modulation (theme 1) will focus on comparing thedirected evolutionary paths among the structurally similar glycosyltransferases (GTs) OleD and OleI assessingthe transferability of beneficial mutations across OleD and OleI and identifying mutational hot spots within theatypical GTB-fold GT AmphD1. The comparative OleD/OleI studies will consist of: i) the evaluation of an OleILoki which contains the 5 key mutations of structurally conserved residues that led to OleD Loki; and ii) aparallel epPCR-directed evolution approach for increasing OleI proficiency/permissivity using the same screensand mutational strategy that led to the discovery of enhanced OleD progeny. Key outcomes of this comparativestudy will be a potential universal blueprint for improving the proficiency/promiscuity of most GTB-fold GTs andimproved GTs for select sugar-conjugation (D-Gal analogs) to support theme 3. The directed evolution ofAmphD1 (and parallel proposed structure elucidation and structure-based engineering) will also follow our OleDprecedent and offers both the potential to expand the universal GT engineering blueprint toward atypical GTsand to identify GT variants to dramatically simplify the targeted synthesis of the unique preclinical antifungal lead2-epi-amphotericin (theme 2). In addition we will pursue the mechanistic study of small molecule inhibitors andactivators identified via the ClNP-Glc-based HT screen - studies that hold high potential in the discovery of newparadigms for GT catalytic modulation that may extend to other enzyme families and/or have pharmacologicapplications. Finally while we remain enthusiastic about the uncharted frontier of enzyme modulation viacontrolled electrical fields such technically challenging experiments require the physical presence of both thematerials scientists and enzymologists and unfortunately our local collaborator (Prof. Hinds) recently relocatedto the University of Washington. Thus this has become a lower priority in the near term. Among the various selected platform applications (theme 2) we will direct the real-time NMR-based assaytoward key and novel late-stage biosynthetic transformations - specifically to understand the stepwiseaminopentose N-alkylation reactions en route to enediynes and indolocarbazoles and the key steps of enediyne-associated thiosugar biosynthesis. The main outcome of these studies will be the elucidation of what isanticipated to be (based on bioinformatics) novel enzyme-catalyzed chemistries. In addition we will continue theongoing studies discussed within the progress report (immunomodulatory studies with macrolide neoglycosidesanti-Mtb studies with spectinomycin neoglycosides and further advancing protein glycosylation studies) andinitiate new combined (neo)glycorandomization diversification efforts toward a prioritized list of additional targets.Specifically we seek to generate and evaluate (neo)glycorandomized libraries of a third or fourth generation -lactam antibiotic (primary objective to broaden antibacterial scope) rapamycin (primary objectives to assessmechanistic modulation and potency) and daptomycin (primary objectives to improve formulation potencyand/or antibacterial scope). For all targets selected we have access to the necessary fundamental evaluativeactivity assays within my lab or via the Center of Pharmaceutical Research and Innovation (under mydirectorship) and these new initiatives hold promise for the discovery of new potential anti-infective anticancerand/or immunomodulatory probes/leads and for advancing new tools for biopharmaceutical development. As highlighted in the progress report we have also initiated arguably one of the first broad systematic studiesof the impact of glycosylation on fundamental drug properties (theme 3) the strategic design of which will probeboth the impact of the sugar and corresponding drug leaving group on key drug property principles. Thecorresponding in vitro and in vivo drug properties of the -glucosides will be evaluated by Vertex. In parallelProf. Leggas (co-I) will evaluate the in vitro and in vivo drug properties of a SN-38 10-O--glycoside sugar variantseries from which the top 2-3 analogs will be selected for subsequent in vivo anticancer efficacy studies. Thesestudies are anticipated to reveal fundamental insights regarding the impact of the sugar drug and correspondingglycosidic bond as the basis of a potentially new conceptual framework for the general use of glycosylation as atransformative drug development tool.

project_terms:
Alkylation;Amphotericin;Anabolism;Anti-Bacterial Agents;Anti-Infective Agents;Antifungal Agents;Area;Bioinformatics;Biological Assay;Biological Products;Chemistry;Comparative Study;Daptomycin;Development;Directed Molecular Evolution;Engineering;Enzymes;Evaluation;Family;Formulation;Generations;Glucosides;Glycosides;Hot Spot;In Vitro;Inflammation;Lead;Libraries;Macrolides;Monobactams;Mutation;Mycobacterium tuberculosis;Natural Products;Outcome;Outcome Study;Pharmaceutical Preparations;Pharmacologic Substance;Pharmacology;Progress Reports;Property;Protein Glycosylation;Reaction;Research;Route;SN-38;Scientist;Series;Sirolimus;Spectinomycin;Structure;Therapeutic;Time;Universities;Variant;Washington;analog;anti-cancer;base;beta-Lactams;catalyst;comparative;design;drug development;efficacy study;electric field;experimental study;falls;frontier;glycosylation;glycosyltransferase;immunoregulation;improved;in vivo;innovation;insight;novel;pre-clinical;small molecule inhibitor;stem;sugar;thiosugar;tool;tool development


application_id: 10156987
project_number: 3R01ES019217-08S1
project_title: Administrative supplement to Endothelial Progenitor Cells and Particulate Air Pollution
administering_ic: NIEHS
award_notice_date: 2020-09-11
opportunity_number: PA-18-817
application_type: 3
activity_code: R01
ic: ES
serial_number: 019217
suffix: S1
program_official: NADADUR, SRIKANTH
project_start_date: 2011-09-23
project_end_date: 2023-03-31
study_section: Special Emphasis Panel[ZRG1(02)]
contact_pi_person_id: 8911484
contact_pi: O'TOOLE, TIMOTHY E
other_pis: BHATNAGAR, ARUNI ;POPE, ARDEN
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
project_abstract:
ABSTRACTImprovements in clinical care and the promotion of health life styles have contributed to an aging populationbut one that also increasingly presents with neurological disorders such as Alzheimer's Parkinson's dementiaand cognitive decline in general. While the basis of these outcomes is complex they likely result from aninterplay of genetic and environmental factors and are biochemically associated with inflammation andoxidative stress. One environmental factor linked to neurological dysfunction across all age groups is exposureto fine air borne particulate matter (PM2.5). PM2.5 exposures have been associated with autism spectrumdisorders and learning disabilities in the young and with dementia in older populations. Carnosine is anaturally-occurring -alanine-L-histidine dipeptide found in abundance in skeletal muscle and the brain. It isthought to promote physiological homeostasis through its ability to sequester hydroxyl radicals and oxidizedlipids chelate metals buffer pH and limit glycation. Given these chemical properties and abundance in thebrain carnosine has been proposed to limit neurological dysfunction and promote cognition. In this regardprior supplementation studies generated inconsistent results or reported limited efficacy but most of thesestudies have used vulnerable populations or had an abbreviated interventional time frame. It remains uncleartherefore if carnosine supplementation can promote cognition in a generally healthy cohort devoid ofcomorbidities. Thus to test the efficacy of carnosine in promoting cognition and in limiting PM2.5-inducedneurological dysfunction in humans we will measure cognitive function in participants in the NucleophilicDefense Against PM Toxicity (NEAT) trial. In this study we will enroll participants in the Louisville KY areawith endogenous carnosine levels that are in the lower third of the normal distribution. Once we have obtainedbaseline measures of biomarkers and indices of pre-clinical cardiovascular disease these participants will beinstructed to take carnosine or placebo supplements for the following 12 weeks during the summer monthswhen local PM2.5 levels are at their highest. At two intervals during this time the participants will return and wewill collect blood and urine samples to assess cardiovascular function immune responses and oxidative stresslevels. As outlined in this supplement application we will also assess cognitive function at baseline and followup clinical visits using the validated and highly sensitive Cognition software platform. By enrolling participantswith the lowest endogenous carnosine levels we will enhance our ability to observe carnosine-mediatedprotective effects. Thus by leveraging the ongoing NEAT study we will be able to test the additionalhypothesis that dietary carnosine supplementation improves cognitive function in a generally healthy cohortand mitigates the adverse influences of PM2.5 exposure.

project_terms:
Address;Administrative Supplement;Affect;Age-Years;Aging;Air;Air Pollution;Airborne Particulate Matter;Alzheimer's Disease;Antioxidants;Area;Atherosclerosis;Biochemical;Biological Markers;Blood;Brain;Buffers;Cardiovascular Diseases;Cardiovascular Physiology;Cardiovascular system;Carnosine;Clinical;Cognition;Cognitive;Cohort Studies;Complex;Computer software;Decision Making;Dementia;Development;Diagnosis;Diet;Dietary Supplementation;Dipeptides;Disease;Enrollment;Environmental Exposure;Environmental Impact;Environmental Risk Factor;Etiology;Exposure to;Functional disorder;Genetic;Health;Health Promotion;Health Promotion and Care;Hematology;Histidine;Homeostasis;Human;Hydroxyl Radical;Immune response;Impaired cognition;Inflammation;Infrastructure;Inhalation;Intervention;Learning Disabilities;Life Style;Link;Measures;Mediating;Modification;Mus;Nervous System Physiology;Neurodegenerative Disorders;Neurologic Dysfunctions;Normal Statistical Distribution;Older Population;Outcome;Oxidative Stress;Parkinson Disease;Participant;Particulate;Particulate Matter;Peptides;Physiological;Placebos;Population;Property;Reporting;Research Design;Role;Sampling;Series;Skeletal Muscle;Structural defect;Supplementation;Support Groups;Technology;Testing;Time;Toxic effect;Urine;Visit;Vulnerable Populations;Water;Work;age group;aged;aging population;autism spectrum disorder;beta-Alanine;chemical property;clinical care;cognitive function;cohort;comorbidity;dementia risk;diagnostic biomarker;dietary supplements;early life exposure;efficacy testing;endothelial stem cell;epidemiology study;follow-up;glycation;improved;indexing;insight;metal chelator;nervous system disorder;neurotoxicity;oxidized lipid;parent grant;pre-clinical;prevent;protective effect;trend

public_health_relevance:
NARRATIVEEnvironmental exposure to fine airborne particulate matter (PM2.5) is one factor that can adversely affectcognitive function through mechanisms involving oxidative stress and inflammation. Carnosine is a naturallyoccurring peptide and dietary supplement with anti-oxidant properties. In this study we will determine howdietary supplementation with carnosine impacts cognition in a cohort with limited co-morbidities and determineif this is influenced by exposure to high levels of ambient PM2.5.


application_id: 10154450
project_number: 1F31AA028423-01A1
project_title: sEH Inhibition in Alcoholic Liver Disease: A Novel Therapeutic Strategy
administering_ic: NIAAA
award_notice_date: 2020-08-13
opportunity_number: PA-19-195
application_type: 1
activity_code: F31
ic: AA
serial_number: 028423
suffix: A1
program_official: RADAEVA, SVETLANA
project_start_date: 2020-09-01
project_end_date: 2023-08-31
study_section: Special Emphasis Panel[ZAA1 GG (32)]
contact_pi_person_id: 15958059
contact_pi: WARNER, JEFFREY B
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
project_abstract:
Project SummaryAlcoholic liver disease (ALD) is the most common liver disease and is responsible for nearly half of all deathsfrom diseases affecting this organ. Despite this there remain no FDA-approved treatments for any stage of thedisease highlighting the need for the discovery of new therapies. As an aspiring scientist whose goal is to pursuea career in alcohol-related multi-organ pathology investigating new therapies for ALD treatment would not onlyhelp fill this medical need but also serve as an excellent platform from which to learn how to become a successfulscientist. With the help and supervision of my co-mentors Dr. Kirpich (an expert in basic research on ALD) andDr. McClain (an expert on clinical aspects of the disease) as well as several knowledgeable collaborators I willinvestigate soluble epoxide hydrolase (sEH) inhibition as a novel therapeutic strategy for the treatment of ALDusing pre-clinical mouse models. This approach has been applied to other inflammatory diseases but not toALD a disease shown by previous work in our group to be characterized by a loss of anti-inflammatoryepoxygenated lipids (epoxides) in part due to their rapid degradation by sEH. I have generated substantialpreliminary data with an orally-administered sEH inhibitor in a chronic-binge mouse model of ALD thatrecapitulates human ALD. Through two related but independent specific aims proposed in this application I willfurther assess the efficacy of sEH inhibition and explore its mechanisms of action. Aim 1 will use pharmacologicaland genetic ablation of sEH to further characterize the effects of sEH inhibition in mouse models of ALD. Aim 2will describe the mechanistic effects of individual anti-inflammatory epoxides on changes in hepatocyte andimmune cell health and function to explain changes seen in vivo. To complete this research I will follow a detailedtraining plan laid out for me by my co-mentors and pursue the career goals that I have set for myself. Theseinclude among others continuing my didactic training in areas relevant to my research gaining experience innew laboratory techniques developing effective written and oral communication skills and building aprofessional network of scientists. For example to assess liver injury and changes in cellular function I will learnto read histological liver slides use enzymatic assays set up ELISAs isolate and culture primary hepatocytesand macrophages and learn flow cytometry. The research environment at the University of Louisvilles state-of-the-art Clinical and Translational Research Building is highly productive and staffed with expert faculty andresearch personnel willing to help me learn these techniques and advise me as I pursue my training and careergoals. My academic department the Department of Pharmacology & Toxicology is equally positioned to supportmy training in the classroom and provide many resources (e.g. travel funds career development seminars andnew courses) to ensure my success. Collectively the training and research proposed here will not only fill asignificant need for the development of ALD treatments but will also foster my development from a youngscientist to a successful independent investigator in the field of alcohol-induced organ disease.

project_terms:
ANXA5 gene;Ablation;Affect;Alcoholic Hepatitis;Alcoholic Liver Diseases;Alcohols;Animals;Anti-Inflammatory Agents;Area;Attenuated;Basic Science;Biological;Biological Assay;CXCL1 gene;Cell Death;Cell Line;Cell physiology;Cells;Cellular biology;Cessation of life;Chronic;Clinical;Clinical Research;Data;Development;Disease;Ensure;Environment;Enzyme-Linked Immunosorbent Assay;Epoxide hydrolase;Epoxy Compounds;Ethanol;FDA approved;Fatty Acids;Flow Cytometry;Fostering;Funding;Genetic;Goals;Health;HepG2;Hepatic;Hepatocyte;Histologic;Human;IL6 gene;Immune;Individual;Inflammation;Inflammatory;Interleukin-1 beta;Knock-out;Knockout Mice;Kupffer Cells;Laboratories;Learning;Lipids;Liver;Liver diseases;Medical;Mentors;Modeling;Mus;Neutrophil Infiltration;Oral;Organ;Palmitic Acids;Pathogenesis;Pathology;Patients;Pharmaceutical Preparations;Pharmacology;Pharmacology and Toxicology;Phenotype;Physiological;Polyunsaturated Fatty Acids;Positioning Attribute;Predisposition;Prevention;Production;Propidium Diiodide;Research;Research Personnel;Resolution;Resources;Role;Scientist;Slide;Stains;Supervision;TNF gene;Techniques;Testing;Therapeutic;Training;Translational Research;Translations;Travel;Universities;Work;alcohol exposure;bench to bedside;career;career development;career networking;chronic liver disease;cytokine;experience;experimental study;faculty research;feeding;improved;in vivo;inhibitor/antagonist;lipid mediator;liver inflammation;liver injury;macrophage;mouse model;novel therapeutics;oral communication;pre-clinical;prevent;recruit;skills;success;treatment strategy

public_health_relevance:
Project NarrativeAlcoholic liver disease (ALD) is responsible for nearly half of liver disease deaths yet there are no FDA-approvedtherapies available for the treatment of any stage of its progression. Discovery of unique changes in the hepaticlipidome reveal soluble epoxide hydrolase (sEH) inhibition as a therapeutic strategy with high potential to lessenliver damage associated with ALD. Full assessment of the efficacy of sEH inhibition through this proposedresearch will allow us to better understand its uses and mechanisms of action and contribute to the translationof this approach from bench to bedside.


application_id: 10154082
project_number: 1R01DA053070-01
project_title: Functional and Genomic Signatures of Escalated Fentanyl Use
administering_ic: NIDA
award_notice_date: 2021-03-04
opportunity_number: PA-19-056
application_type: 1
activity_code: R01
ic: DA
serial_number: 053070
program_official: POLLOCK, JONATHAN D
project_start_date: 2021-03-15
project_end_date: 2025-12-31
study_section: Molecular Neuropharmacology and Signaling Study Section[MNPS]
contact_pi_person_id: 10484112
contact_pi: TURNER, JILL R.
other_pis: BARDO, MICHAEL T;ORTINSKI, PAVEL IVANOVICH
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_terms:
Agonist;Animal Behavior;Animal Model;Animals;Astrocytes;Awareness;Behavior;Behavior Therapy;Behavioral;Behavioral Model;Biological;Biology;Biometry;Brain;Calcium;Calcium Signaling;Cells;Centers for Disease Control and Prevention (U.S.);Cessation of life;Chronic;Clinical;Clinical Research;Consumption;Coupled;Data;Databases;Dependence;Development;Diagnosis;Drug Targeting;Drug usage;Economic Burden;Electrophysiology (science);Evaluation;Family;Fentanyl;Genetic Databases;Genetic Markers;Genomics;Goals;Heroin;Human;Individual;Individual Differences;Intake;Joints;Laboratory Animals;Life;Link;Literature;Maintenance;Microglia;Modeling;Modernization;Molecular;Molecular Profiling;Monitor;Morphine;Motivation;Neurobiology;Neurons;Nucleus Accumbens;Opiate Addiction;Opioid;Outcome;Output;Patch-Clamp Techniques;Pathway interactions;Pattern;Permeability;Pharmaceutical Preparations;Pharmacogenomics;Pharmacology;Phenotype;Play;Policies;Population;Potassium;Potassium Channel;Prefrontal Cortex;Prevention;Probability;Protein Family;Publishing;Rattus;Regulation;Relapse;Rewards;Role;Sampling;Self Administration;Shapes;Source;Statistical Models;Structure;Substance Use Disorder;Sucrose;System;Testing;Therapeutic;Training;United States National Center for Health Statistics;base;behavioral pharmacology;behavioral phenotyping;big-data science;cancer therapy;cell type;drug abstinence;fentanyl abuse;functional genomics;gene product;genomic biomarker;genomic profiles;genomic signature;imaging approach;individual variation;interdisciplinary approach;medication-assisted treatment;mu opioid receptors;neural circuit;non-drug;novel;novel therapeutics;opioid misuse;opioid mortality;opioid overdose;opioid use;opioid use disorder;opioid user;personalized approach;personalized cancer therapy;pre-clinical;reinforcer;success;synthetic opioid;targeted treatment;transcriptome sequencing;transcriptomics;whole genome


application_id: 10153866
project_number: 5R01HL137910-04
project_title: HDAC6 regulation of ICAM-1 expression and endothelial inflammatory signaling in sepsis
administering_ic: NHLBI
award_notice_date: 2021-04-09
opportunity_number: PA-16-160
application_type: 5
activity_code: R01
ic: HL
serial_number: 137910
program_official: AGRAWAL, NITIN
project_start_date: 2018-06-15
project_end_date: 2024-04-30
study_section: Innate Immunity and Inflammation Study Section[III]
contact_pi_person_id: 8693493
contact_pi: FU, JIAN
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project SummarySepsis is a life-threatening disease with high morbidity and mortality. New therapeutic strategiesare urgently needed to treat this devastating disease. Uncontrolled endothelial inflammatoryresponses which often leads to inflammatory vascular injury contribute to the pathogenesis ofmultiple organ failure in sepsis. HDAC6 a histone deacetylase has been reported to modulatenuclear and non-nuclear protein function through deacetylation. In this project we willinvestigate HDAC6 regulation of endothelial inflammatory injury during sepsis. In our preliminarystudies we demonstrated that HDAC6 knockdown or selective HDAC6 inhibition preventedTNF- induced endothelial ICAM-1 expression which was associated with increased -tubulinacetylation and reduced STAT1 activation. Furthermore in mouse models of sepsis HDAC6inhibition blocked sepsis-induced lung ICAM-1 expression induced -tubulin acetylation andsuppressed STAT1 activation in lung tissues which was associated with reduced lunginflammatory injury and increased survival rate. In the proposed studies we will conduct a serialof experiments to assess the role of HDAC6 in sepsis-induced endothelial inflammatoryresponses and to investigate therapeutic mechanisms of HDAC6 inhibition against endothelialinflammatory signaling in sepsis.

project_terms:
Acetylation;Binding;Cell Adhesion Molecules;Cell Communication;Cell physiology;Cessation of life;Clinical Trials;Cytoplasm;Cytoskeleton;Data;Deacetylase;Deacetylation;Development;Disease;Endothelial Cells;Endothelium;Future;Gene Expression;HDAC4 gene;HDAC6 gene;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;Injury;Intercellular adhesion molecule 1;JAK2 gene;Knockout Mice;Leukocytes;Life;Lung;Mediating;Mediator of activation protein;Microtubule Stabilization;Microtubules;Morbidity - disease rate;Multiple Organ Failure;Nuclear;Pathogenesis;Play;Regulation;Reporting;Role;STAT1 gene;STAT1 protein;Sepsis;Signal Pathway;Signal Transduction;Structure of parenchyma of lung;Survival Rate;TNF gene;Testing;Therapeutic;Therapeutic Effect;Tubulin Interaction;alpha Tubulin;experimental study;inhibitor/antagonist;knock-down;mortality;mouse model;novel;novel therapeutic intervention;novel therapeutics;prevent;protective effect;protein function;transcription factor;tumor;vascular injury

public_health_relevance:
Project NarrativeSuccessful completion of the proposed studies will reveal a novel role of HDAC6 in sepsis-inducedendothelial inflammatory signaling. The studies will validate the therapeutic potential of HDAC6 inhibitionagainst inflammatory vascular injury in sepsis. The proposed studies will provide important information forfuture clinical trials.


application_id: 10153811
project_number: 5P20GM103436-21
project_title: Electron Microscopy Core
administering_ic: NIGMS
award_notice_date: 2021-04-29
opportunity_number: PAR-18-262
application_type: 5
activity_code: P20
ic: GM
serial_number: 103436
project_start_date: 2001-09-30
project_end_date: 2024-04-30
study_section: ZGM1-RCB-9
subproject_number: 7346
contact_pi_person_id: 1871981
contact_pi: BICKFORD, MARTHA E
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Electron Microscopy Core Summary While methods to image fluorescent molecules have advanced dramatically in recentyears the resolution of electron microscopy remains unsurpassed. In the state of Kentucky thereare numerous research programs that require the resolution that can only be achieved by theinteraction of a beam of electrons with a specimen to distinguish ultrastructural features of tissuescell components viruses or bacteria. However due to declining institutional support for electronmicroscopy facilities many established Kentucky investigators have utilized facilities andexpertise outside the state for their electron microscopic analyses. Furthermore new Kentuckyinvestigators are hesitant to add electron microscopy to their research programs withoutaccessible training and technical support. We propose to address these gaps in infrastructure andeducation by establishing a statewide electron microscopy core to facilitate equipment sharingprovide technical support and offer training.

project_terms:
Address;Adopted;Applications Grants;Bacteria;Biomedical Research;Businesses;Cellular Structures;Collaborations;Cost Sharing;Cost efficiency;Education;Education and Outreach;Educational workshop;Electron Beam;Electron Microscope;Electron Microscopy;Electron Microscopy Facility;Electrons;Ensure;Equipment;Faculty;Fee-for-Service Plans;Fostering;Funding;Health;Infrastructure;Kentucky;Methods;Microscopic;Pilot Projects;Postdoctoral Fellow;Research;Research Personnel;Research Project Grants;Research Training;Resolution;Resources;Site;Specimen;Students;Techniques;Tissues;Training;Universities;Virus;fluorescence imaging;graduate student;outreach;programs;undergraduate student


application_id: 10151958
project_number: 7R15MH106885-03
project_title: Preschool Internalizing Psychopathology: Behavioral Phenotypes and Stress Physiology
administering_ic: NIMH
award_notice_date: 2020-06-09
opportunity_number: PA-18-590
application_type: 7
activity_code: R15
ic: MH
serial_number: 106885
program_official: MURPHY, ERIC ROUSSEAU
project_start_date: 2019-08-01
project_end_date: 2022-07-31
study_section: Child Psychopathology and Developmental Disabilities Study Section[CPDD]
contact_pi_person_id: 9225777
contact_pi: BUFFERD, SARA J
other_pis: DELUCA BISHOP, HAYLEE
congressional_district: 03
department: PSYCHOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/AbstractAnxiety and mood dysregulation are impairing often persistent emotional difficulties in preschool-aged childrenthat cause substantial personal familial and economic burden over time. However these behaviors aredevelopmentally normative in young children and the level at which such behaviors may be clinicallysignificant is largely unknown. Without established norms identified with developmentally sensitive methodsover time it is difficult to distinguish mild transient behaviors from risk for persistent impairingpsychopathology. The proposed renewal project will follow-up with a sample of 3-5-year-old children when theyare 6-8-years-old using multi-method assessment to generate norms of early anxiety and mood dysregulationand map individual differences and patterns of behavior family environment and stress physiology. A noveldaily diary method will assess the daily frequencies of internalizing behaviors a diagnostic interview willassess childrens symptomatology and functioning and teacher report will provide information about childrensbehavior at school. In a subsample correlates of psychopathology will be assessed to validate the internalizingphenotypes and further clarify normative and problematic behavior including child observed and self-reportbehavior parental psychopathology and parenting behavior and family stressors along with acute and chronicstress physiology specifically salivary inflammatory markers (C-reactive protein and cytokines) as well ascumulative hypothalamic pituitary axis cortisol activity measured via hair samples respectively. Follow-upinformation about childrens functioning in early school age is vital for characterizing the spectrum of behaviorand clarifying variation in behavior that increases clinical risk for psychopathology in preschool age. Theseefforts will advance the NIMH mission to better understand mental illness trajectories and know whether andwhen to intervene as early as possible. In particular the work is aligned with NIMH Strategic Objective 2 thatcalls for clarification of the spectrum of typical to atypical development to characterize mental illness risk earlyin life. Knowledge gained from this proposal will significantly advance the field by 1) providing developmentallysensitive information on the phenomenology of early-emerging psychopathology over time 2) advancing thetransdiagnostic dimensional approach by assessing the full variation of anxiety and mood dysregulation and3) identifying biomarkers that reflect early deviation in emotional development over time 4) utilizing datacollected in early school-age for informing which preschool-aged children would benefit from prevention andintervention efforts for emerging internalizing psychopathology. Importantly consistent with the R15mechanism this study will continue to strengthen the PIs institutions research environment by providingstudents in-depth experience with multi-method longitudinal research in developmental psychopathology.

public_health_relevance:
Project NarrativeAnxiety and mood dysregulation are common emotional difficulties in young children and when persistent cancause substantial personal familial and economic burden; however these behaviors are developmentallynormative and the level at which such behaviors may be clinically significant is largely unknown. Using a multi-level approach the present study will follow-up with a sample of 3-5-year-old children in early school age toassess psychopathology impairment and psychophysiology. These data will generate developmentallymeaningful distinctions between normative individual differences and clinically-significant persistent patterns ofbehavior to discover when to intervene as early as possible to reduce psychopathology promote healthyemotional development and improve outcomes for children families and society.


application_id: 10150733
project_number: 5R01AG057290-05
project_title: Programming amylin secretion to slow brain aging - an animal model
administering_ic: NIA
award_notice_date: 2021-05-05
opportunity_number: RFA-AG-17-050
application_type: 5
activity_code: R01
ic: AG
serial_number: 057290
program_official: OROSZ, ANDRAS
project_start_date: 2017-09-15
project_end_date: 2024-04-30
study_section: ZAG1-ZIJ-6(A1)
contact_pi_person_id: 9696701
contact_pi: DESPA, FLORIN
other_pis: THINAKARAN, GOPAL
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 SUMMARYProteostasis dysfunction of pancreatic -cells results in accumulation of oligomerized amylin within pancreaticislets which is a hallmark of type-2 diabetes. We recently showed that oligomerized amylin also incorporatesinto the brain blood vessel walls forms neuritic deposits and co-localizes with Alzheimer's disease (AD) -amyloid peptides (A) as mixed A-amylin plaques in brains of individuals with late-onset AD as well as familialearly-onset AD. It is unknown whether cerebral amylin deposits are a consequence of AD or type-2 diabetesor a hidden trigger of AD. Moreover we found that overexpressing human amylin within pancreatic islets inrats induces systemic amylin dyshomeostasis brain amylin accumulation microglia activation and behaviorchanges. Furthermore elevated human amylin in the periphery greatly accelerates behavior changes in a ratmodel of AD pathogenesis. These findings suggest the hypothesis that amylin dyshomeostasis in pancreaticislets and subsequent secretion of oligomerized amylin in the blood can affect the progression of AD bycompromising the ability of microglia to efficiently clear A and by inducing mixed A-amylin pathology. Thusameliorating amylin dyshomeostasis in the periphery can limit the progression of AD. The overarching goal ofthis proposal is to test our hypothesis and investigate molecular mechanisms underlying the interaction ofamylin with A pathology. We will accomplish this goal by characterizing novel transgenic mice with inducibleand reversible expression of human amylin in the pancreas (HuAmy line). We will carefully dissect proteostasisdysfunction of pancreatic -cells in the periphery and the consequent liability it imposes on the central nervoussystem. We will also cross HuAmy line and 85Dbo line to generate APP/PS1 transgenic mice with regulatedexpression of human amylin in the periphery. We predict that turning off the human amylin transgeneexpression at early time points during aging mitigates the disease progression in HuAmy:APP/PS1 mice bylimiting the blood-brain barrier injury and rescuing the ability of microglia to clear A. This investigation usingnovel regulated amylin expression represents the most direct in vivo approach to rigorously test theinvolvement of peripheral amylin in the biological pathways of AD pathogenesis. The completion of these aimswill elucidate the interplay of amylin dyshomeostasis with the progression of A pathology and whetherameliorating amylin dyshomeostasis in the periphery can reduce or reverse AD in a preclinical model. Webelieve that the proposed investigation fills significant gaps in our understanding of the molecular link betweentype-2 diabetes and AD.

project_terms:
APP-PS1;Affect;Age;Aging;Alzheimer's Disease;Alzheimer's Disease Pathway;Alzheimer's disease brain;Alzheimer's disease model;Amyloid;Amyloid beta-Protein;Amyloidosis;Animal Model;Behavior;Biological;Blood;Blood - brain barrier anatomy;Blood Vessels;Brain;Cerebrovascular system;Cerebrum;Data;Deposition;Development;Diabetes Mellitus;Disease Progression;Early Onset Familial Alzheimer's Disease;Feasibility Studies;Functional disorder;Genes;Goals;Heart;Heart failure;Hormones;Human;Impaired cognition;Individual;Injury;Insulin;Intravenous;Intravenous infusion procedures;Investigation;Islets of Langerhans;Kidney;Late Onset Alzheimer Disease;Link;Longevity;Mediating;Microglia;Molecular;Mus;Neuraxis;Neuronal Dysfunction;Neurons;Non-Insulin-Dependent Diabetes Mellitus;Pancreas;Pathogenesis;Pathology;Pericytes;Peripheral;Pre-Clinical Model;Protein Isoforms;Rattus;Structure of beta Cell of islet;Synapses;Testing;Time;Transgenes;Transgenic Mice;aging brain;amyloid formation;apolipoprotein E-4;behavior change;beta amyloid pathology;cognitive performance;design;diabetic patient;early onset;in vivo;islet amyloid polypeptide;mouse model;neural network;non-diabetic;novel;overexpression;proteostasis;transgene expression;transgenic model of alzheimer disease;uptake

public_health_relevance:
NarrativeRecent studies suggest that proteostasis dysfunction of pancreatic -cells is linked with Alzheimer's disease bythe brain accumulation of oligomerized amylin. Our proposed studies will elucidate the interplay of amylindyshomeostasis in the periphery with the progression of  amyloid pathology and whether ameliorating amylindyshomeostasis in the periphery can reduce or reverse Alzheimer's disease in a preclinical model.


application_id: 10150171
project_number: 3U01CE002711-05S1
administering_ic: NCIPC
award_notice_date: 2020-08-13
opportunity_number: RFA-CE-15-002
application_type: 3
activity_code: U01
ic: CE
serial_number: 002711
suffix: S1
program_official: PANERO, MARIA SUSANA
project_start_date: 2015-09-30
project_end_date: 2021-09-29
study_section: Special Emphasis Panel[ZCE1 MLW (06)]
contact_pi_person_id: 9182607
contact_pi: WENDEL, MONICA L.
other_pis: BROWN, AISHIA A
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_title:
Changing the Narrative:  Using Media to Shift Social Norms of Violence Among Youth in West Louisville

project_abstract:
PROJECT ABSTRACTYouth violence is a serious public health issue particularly in the disproportionate burden upon economicallydisadvantaged inner city and minority populations. Intentional injury is the leading cause of death amongpersons 10 to 24 years of age in Kentucky and the second leading cause of death for this age group nationally.Alarmingly Kentuckys homicide rate for this same age group is 10 times higher for Black males(38.7/100000) than for White males (3.9/100000). In Louisville KY substantial social and healthdisparitiesincluding violence and related risk factorsare concentrated in West Louisville (WL) aneconomically disadvantaged urban primarily Black community. Led by the School of Public Health &Information Sciences (SPHIS) researchers at the University of Louisville (UofL) propose to establish the UofLYouth Violence Prevention Center partnering with researchers from Vanderbilt University. The specific aimsof the proposed center include: 1. Strengthen the infrastructure to support youth violence prevention research and practice at the University of Louisville. 2. Develop implement and evaluate a community-level social norming campaign to change the norms of violence among youth in West Louisville using mass and social media. 3. Document the development and implementation of the social norming campaign to improve replication and scalability in other settings or communities. 4. Evaluate the relationship between community readiness community capacity and the implementation of the community-level social norming campaign. 5. Disseminate study findings in meaningful and actionable format to a variety of relevant audiences (i.e. community local organizations and leaders youth violence prevention researchers and practitioners academic peers and policy-makers).The interdisciplinary research team proposes a quasi-experimental design to examine the effectiveness of usinga community-level 3-year social norming campaign utilizing new media to change norms of violence amongyouth 10-24 and introduce prosocial norms driven by cultural identity with WL as the intervention communityand East Nashville TN as the control community. The researchers and a team of community collaborators willwith a professional advertising agency to plan and design the campaign which will be deployed in Year 2.Surveys and interviews will capture data measuring our dependent variables of social norms and violentbehavior (independent variables: campaign exposure by media type demographics) and population-levelyouth violence data from schools emergency departments and local police departments will offer measures ofchange in serious youth violence at the population level.

public_health_relevance:
RELEVANCEIntentional injury is the leading cause of death among youth ages 10 to 24 in Kentucky and the homicide ratein the state for the same age group is 10 times higher for Black males (38.7/100000) than for White males(3.9/100000). Youth in West Louisville a predominantly Black economically disadvantaged urbancommunity are subjected to social norms of violence. A targeted community-level social norming campaignholds potential to shift existing norms and reduce serious violence among young people in this community.


application_id: 10150112
project_number: 5R01NS108529-04
project_title: The integrated stress response and oligodendrocyte survival after spinal cord injury
administering_ic: NINDS
award_notice_date: 2021-04-02
opportunity_number: PA-16-160
application_type: 5
activity_code: R01
ic: NS
serial_number: 108529
program_official: BAMBRICK, LINDA LOUISE
project_start_date: 2018-06-15
project_end_date: 2023-03-31
study_section: Acute Neural Injury and Epilepsy Study Section[ANIE]
contact_pi_person_id: 1895692
contact_pi: WHITTEMORE, SCOTT R
other_pis: HETMAN, MICHAL
congressional_district: 03
department: NEUROLOGY
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:
Abstract. We identified the ER stress response (ERSR) as a potential target for therapeutic interventionsagainst white matter loss and locomotor impairment after spinal cord injury (SCI). Specifically the signalingpathway that involves the ERSR kinase PERK the PERK target elongation initiation factor 2 (eIF2) andPERK-activated transcription factor CHOP may be manipulated in a time-dependent manner to promote SCIrecovery. PERK signaling has a partial overlap with the integrated stress response (ISR) that via severalstress-activated kinases leads to increased levels of phospho-eIF2 (peIF2) transient inhibition of proteinsynthesis and activation of the transcription factor ATF4. ATF4 regulates CHOP as well as genes involved inROS metabolism translational regulation and amino acid synthesis. In this way the ISR attempts to restorehomeostasis. Excessive and prolonged activation of the ISR results in anabolism-associated oxidative stressmitochondrial damage cell death and inflammation. Pro-ISR stimuli such as hypoxia lack of nutrientsoxidative stress and ER stress are present after SCI. However the role of the principal ISR components eIF2 kinases other than PERK and their common downstream target ATF4  has not been addressed in thecontext of white matter loss after contusive SCI. Our overarching hypothesis is that the ISR plays a critical rolein pathogenesis of contusive SCI by promoting OL/OPC death and white matter loss. Aim 1 will examine therole of the 4 upstream ISR kinases (PERK PKR GCN2 HRI which are activated by different stressors) thatphosphorylate eIF2 which in turn inhibits global translation and enhances stress-induced gene expression.We will use a combination of previously optimized gain and loss of function in vitro OPC/OL and in vivo SCIassays that utilize pharmacological inhibitors as well as Hri-/- Pkr-/- and Gcn2-/-mice. Preliminary data from ERstressed OPCs or SCI tissue show activation of these kinases as well as compensatory activation of the ISRpathway when PERK is inhibited. Aim 2 will examine the role of the central ISR effector ATF4 in SCI-associated white matter loss. Our preliminary data show activation of ATF4 after SCI or in ER-stressed OPCs.We will determine whether ATF4 is a mediator of OL/OPC death white matter damage and functional declineafter contusive SCI. In summary current experimental design is based on data from our previouscharacterization of the ERSR after SCI. Here we propose to delineate novel mechanisms of ISR-mediated celldeath after SCI as well as define which of ISR mediators may best be suited for therapeutic translation toacutely treat SCI patients. Such treatments are likely to be applicable to other types of CNS trauma such asTBI and stroke.

project_terms:
Acute;Address;Affinity Chromatography;Amino Acids;Anabolism;Attenuated;Biological Assay;Brain Injuries;Cell Death;Cessation of life;Chronic;Data;Disease;Double-Stranded RNA;Enzymes;Experimental Designs;Functional disorder;Gene Expression;Genes;Glucose;Grant;Homeostasis;Hypoxia;Hypoxia Inducible Factor;Impairment;In Vitro;Inflammation;Intracranial Hemorrhages;Iron;Mediating;Mediator of activation protein;Metabolism;Mitochondria;Mus;Nutrient;Oligodendroglia;Outcome;Oxidative Stress;PERK kinase;Pathogenesis;Pathway interactions;Peptide Initiation Factors;Pharmacological Treatment;Pharmacology;Phosphotransferases;Play;Procollagen-Proline Dioxygenase;Proteasome Inhibition;Protein Synthesis Inhibition;Recovery of Function;Response to stimulus physiology;Ribosomes;Role;Signal Pathway;Signal Transduction;Spinal Cord Contusions;Spinal cord injury;Spinal cord injury patients;Starvation;Stress;Stroke;Testing;Therapeutic;Therapeutic Agents;Therapeutic Intervention;Time;Tissue Sample;Tissues;Transcriptional Activation;Translating;Translational Regulation;Translations;Traumatic CNS injury;Up-Regulation;Work;base;biological adaptation to stress;central nervous system injury;cytotoxic;deprivation;endoplasmic reticulum stress;functional decline;functional outcomes;genetic approach;improved;in vivo;inhibitor/antagonist;injury recovery;loss of function;new therapeutic target;novel;novel therapeutics;response;stressor;targeted treatment;transcription factor;transcription factor CHOP;transcriptome sequencing;white matter;white matter damage

public_health_relevance:
Project Narrative This grant examines the role of the integrated stress response in functional recovery afterSCI. It follows logically from previous work and looks both to find novel therapeutic agents to abrogate thecytotoxic actions of the integrated stress response. It is hoped that these data will provide new therapeutictargets for pharmacological treatment of the devastating acute and chronic dysfunction that occurs after SCI.


application_id: 10150075
project_number: 5R01HL142640-03
project_title: Inflammasome Activation Triggers Systemic Coagulation in Sepsis
administering_ic: NHLBI
award_notice_date: 2021-05-11
opportunity_number: PA-18-484
application_type: 5
activity_code: R01
ic: HL
serial_number: 142640
program_official: AGRAWAL, NITIN
project_start_date: 2019-05-15
project_end_date: 2021-11-30
study_section: Hemostasis and Thrombosis Study Section. Committee was terminated on 11/30/2020. [HT]
contact_pi_person_id: 8558885
contact_pi: LI, ZHENYU
other_pis: WEI, YINAN
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:
AbstractSeptic shock is invariably associated with systemic coagulation leading to thrombus formation. Sepsis-relatedorgan dysfunction has been attributed to microvascular thrombosis. Mortality rate doubles in septic patientswith disseminated intravascular coagulation (DIC). DIC is even considered as a sign that death is coming.Previous studies have demonstrated the important roles of tissue factor (TF) in sepsis-associated DIC.However the mechanism leading to TF release which triggers systemic coagulation in sepsis is unknown.Recent in vitro studies revealed that bacterial components (flagellin the rod protein of the type III secretionsystem (T3SS) or LPS) induce programmed cell death (called pyroptosis) of macrophages through activationof inflammasome pathways. We show that intravenous injection of a T3SS rod protein E. coli EprJ induceddepletion of peripheral monocytes and macrophages in tissues. Importantly injection of EprJ or LPS whichelicit canonical and noncanonical inflammasome activation respectively induced systemic coagulationactivation as evident by prolonged prothrombin time (PT) due to increased consumption of coagulation factorsthrombocytopenia increased plasma levels of thrombin-antithrombin complex (TAT) and reduced plasmafibrinogen levels. Thus our findings made connections between the in vitro and in vivo observations andsuggested monocyte/macrophage pyroptosis as a trigger of DIC in sepsis. The goal of this application is todelineate the underlying mechanisms by which inflammasome activation and pyroptosis trigger DIC in sepsis.Specific Aim 1 will establish inflammasome activation and pyroptosis as a common mechanism for DICinduced by bacterial infection. The working hypothesis is that bacteria and bacterial components from differentstrains elicit DIC through Inflammasome activation and pyroptosis. We will use a combination of variousdeficient mice to elucidate the role of inflammasome activation and pyroptosis in DIC elicited by Gram-negativebacteria. Specific Aim 2 is to identify the molecular mechanism of TF release from macrophages followinginflammasome activation. We will also use the myeloid-specific TF knockout mice and a low TF mouse modelto elucidate whether DIC elicited by the bacterial components depends on release of TF from macrophages.Specific Aim 3 will demonstrate the role of inflammasome activation in sepsis-associated coagulopathy. We willuse the cecal ligation and puncture (CLP) sepsis model and bacterial infusion sepsis model to investigate therole of inflammasome activation and pyroptosis in coagulation. Completion of the proposed studies willdemonstrate the molecular mechanism of systemic coagulation is sepsis. Such findings would have profoundramifications for the identification of new drug targets for DIC the deadly complication of sepsis.

project_terms:
Apoptosis;Bacteria;Bacterial Infections;Blood Coagulation Disorders;Blood Coagulation Factor;Bone Marrow;Burkholderia;CASP1 gene;Cells;Cessation of life;Clinical;Coagulation Process;Complication;Consumption;Data;Development;Disease;Disseminated Intravascular Coagulation;Escherichia coli;Family;Fibrinogen;Flagellin;Functional disorder;Goals;Gram-Negative Bacteria;In Vitro;Infection;Inflammasome;Infusion procedures;Injections;Intervention;Knockout Mice;Lead;Link;Modeling;Molecular;Morbidity - disease rate;Mus;Myelogenous;Needles;Organ;Outcome;Pathway interactions;Patients;Peripheral;Phagocytosis;Physiological;Plasma;Play;Proteins;Prothrombin time assay;Pseudomonas aeruginosa;Reagent;Research Project Grants;Rod;Role;Salmonella;Sepsis;Septic Shock;Testing;Thrombocytopenia;Thromboplastin;Thrombosis;Thrombus;Tissues;Type III Secretion System Pathway;Work;antithrombin III-protease complex;base;cecal ligation puncture;driving force;in vivo;insight;intravenous injection;macrophage;monocyte;mortality;mouse model;multidisciplinary;new therapeutic target;protein E;release factor;septic patients;targeted treatment

public_health_relevance:
Project NarrativeSystemic coagulation is a major driving force for morbidity and mortality in sepsis. This research projectseeks to understand the mechanism of coagulation in sepsis. Completion of this work will provide newinsights into the molecular mechanisms eliciting coagulation during sepsis that could lead to targetedtherapies to treat this deadly disease.


application_id: 10148807
project_number: 5R01HL147921-02
administering_ic: NHLBI
award_notice_date: 2021-03-05
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: HL
serial_number: 147921
program_official: TJURMINA, OLGA A
project_start_date: 2020-04-22
project_end_date: 2025-03-31
study_section: Cardiac Contractility, Hypertrophy, and Failure Study Section[CCHF]
contact_pi_person_id: 15587997
contact_pi: MOHAMED, TAMER M A
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: 2021-04-01
project_title:
Induction of Cardiomyocyte Proliferation via Transient Expression of Cell Cycle Factors as a Promising Therapy for Heart Failure

project_abstract:
Heart failure kills 1 in 10 people over the age of 65 in the USA. We recently identified a combination of four cell-cycle regulators that induces stable cytokinesis in adult cardiomyocytes to replace their loss following myocardialinfarction. Specifically adenoviral overexpression of cyclin-dependent kinase 1 (CDK1) CDK4 cyclin B1 andcyclin D1 (collectively known as 4F i.e. four factors) efficiently induced cell division in post-mitotic mouse ratand human cardiomyocytes. Overexpression of the cell-cycle regulators was self-limiting through proteasome-mediated degradation of the protein products in cardiomyocytes. In vivo lineage tracing using the MosaicAnalysis of Double Marker (MADM) mouse model revealed that 1520% of adult cardiomyocytes expressing the4F underwent stable cell division with significant improvement in cardiac function after acute or subacutemyocardial infarction. Currently our approach is the most robust method to induce cardiomyocyte proliferation;however clinical applicability in humans is limited by concerns for tumorigenic potential in other organs. Ourpreliminary data in vitro shows that in other cell types (e.g. neurons) 4F induce cell proliferation continuously for5-6 successive rounds over 7 days. Therefore in this proposal we will focus on approaches to make cell cycleinduction in cardiomyocytes more clinically applicable and avoid any oncogenic potential.We hypothesize that a transient and cardiomyocyte-specific expression is needed to induce one cycle ofcardiomyocyte proliferation to avoid any potential adverse effects on other tissues. Our preliminary data showsthat TNNT2 derived 4F expression in NIL is robustly inducing proliferation in vitro and in vivo and improvedcardiac function after myocardial infarction. Here we will rigorously demonstrate the efficacy and safety of thispolycistronic NIL encoding 4F expression driven by the cardiac specific promoter of TNNT2 (TNNT-4F-NIL) ininducing cardiomyocyte division and improving cardiac function after myocardial infarction in vivo in rat and pigmodels as well as in situ in human heart slices from healthy and infarcted hearts. Here we aim first to fullydemonstrate the efficacy and specificity of TNNT-4F-NIL to induce proliferation only in cardiomyocytes in vivo.Secondly we will test the functional efficacy and perform initial safety studies for TNNT-4F-NIL in rat and pigmodels of heart failure. Lastly we will demonstrate the efficacy of TNNT-4F-NIL in inducing adult humancardiomyocyte proliferation in situ in human heart slices and improving contractile function of failing human heartslices. This study will address all preclinical efficacy testing and perform initial safety studies for one of the mostpromising approaches to regenerate the heart. The successful completion of this study will allow the start of firstin human clinical trial.

project_terms:
Acute;Address;Adenoviruses;Adult;Adverse effects;Area;Blood;CDC2 gene;CDK4 gene;Calcium;Cardiac;Cardiac Myocytes;Cell Cycle;Cell Proliferation;Cell division;Cells;Clinical Trials;Contracts;Cyclin D1;Cytokinesis;Data;Daughter;Disease;Electrophysiology (science);Event;Family suidae;Gene Expression Profile;Generations;Heart;Heart failure;Hip region structure;Human;In Situ;In Vitro;Infarction;Ischemia;Kidney;Lentivirus;Liver;Mediating;Methods;Mitotic;Modeling;Mosaicism;Mus;Muscle Cells;Myocardial Infarction;Natural regeneration;Neurons;Oncogenic;Organ;Pancreas;Parents;Proliferation Marker;Property;Rattus;Recording of previous events;Reperfusion Therapy;Reporter;Rest;Rodent;Safety;Slice;Specificity;System;Technology;Testing;Therapeutic;Time;Tissues;Transgenic Organisms;Treatment Failure;Troponin T;cell type;clinical application;cyclin B1;dosage;efficacy evaluation;efficacy testing;first-in-human;gene therapy;healing;heart function;human old age (65+);improved;in vivo;mouse model;multicatalytic endopeptidase complex;novel;novel strategies;overexpression;porcine model;preclinical efficacy;promoter;protein degradation;safety study;tool;transcriptome sequencing;tumorigenic

public_health_relevance:
After heart attack the heart loses many muscle cells which leads to the loss of ability to bump blood tothe rest of the body. The muscle cells in the heart are not able to regenerate themselves which madeit difficult to treat such disease. Here we are developing new transient gene therapy approach toregenerate these muscle cells in the heart and make them able to heal the heart.


application_id: 10147156
project_number: 5R01HL152081-02
administering_ic: NHLBI
award_notice_date: 2021-06-16
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: HL
serial_number: 152081
program_official: HASAN, AHMED A K
project_start_date: 2020-07-01
project_end_date: 2024-06-30
study_section: Atherosclerosis and Inflammation of the Cardiovascular System Study Section[AICS]
contact_pi_person_id: 10451500
contact_pi: VENDITTO, VINCENT JOSEPH
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2021-07-01
project_title:
Understanding the role of immune complexes between apolipoprotein A-I and IgG in atherosclerotic cardiovascular disease

project_abstract:
The identification of autoantigens in atherosclerotic plaques has prompted investigation of the antibody-mediatedpathogenesis of atherosclerotic cardiovascular disease (ASCVD). One target of IgG antibody induction inASCVD patients is apolipoprotein A-I (ApoA-I) the major protein of high density lipoprotein (HDL). Although anti-ApoA-I antibodies have been identified in mice and human subjects their role has not been elucidated. The PIhas identified immune complexes formed between ApoA-I and IgG (ApoA-I/IgG IC) that exhibit anti-inflammatorycharacteristics and associate with decreased CVD risk. Continued evaluation of ApoA-I/IgG ICs will improve ourunderstanding of this component of the immune responses associated with ASCVD. The overall goal of thisproject is to determine the role of ApoA-I/IgG ICs and elucidate their functional impact in ASCVD. To achievethis goal we will characterize the molecular components of ApoA-I/IgG ICs in mouse and patient sera samplesand correlate these factors with cellular interactions functional outcomes and disease progression. Thehypothesis is that ApoA-I/IgG ICs exhibit anti-inflammatory effects mediated through the inhibitory Fc-receptordepending on antibody characteristics (i.e. epitope specificity subclass) and these effects are capable ofsuppressing inflammation and disease. The rationale for this proposed research is that understanding onecomponent of the humoral immune response associated with ASCVD will lead to a better understanding of theunderlying mechanisms and improve patient outcomes. Encouraged by strong preliminary data this hypothesiswill be tested through two specific aims: 1) Elucidate the molecular components and functional implications ofApoA-I/IgG ICs using cultured cells and mouse models of atherosclerosis; and 2) Determine the characteristicsand anti-inflammatory activity of ApoA-I/IgG ICs from human plasma and delineate the association among ApoA-I/IgG ICs and ASCVD in a large community-based cohort. Aim 1 will employ novel immunomodulation strategiesdeveloped in Dr. Venditto's laboratory to achieve epitope-specific immune modulation of antibody responses inmice to elucidate antibody/epitope function and the role in atherosclerosis progression. Aim 2 will employ serafrom human subjects to characterize antibody/epitope function and evaluate the association between ApoA-I/IgGICs and disease progression in the Multi-Ethnic Study of Atherosclerosis (MESA). The approach is innovativedue to the utilization of in vivo immunomodulation approaches to alter ApoA-I/IgG IC profiles and our approachfocused on obtaining detailed ApoA-I/IgG IC profiles in patients for association studies with disease. Theproposed research is significant as the outcomes of this research will improve our understanding of antibody-mediated immune responses to ApoA-I to elucidate the role of antibodies on ASCVD progression. Detailedcharacterizations of the prefinalantigen epitope specificity antibody subclass and receptor engagement willenhance our understanding of ASCVD to guide therapeutic development and future efforts to improve riskstratification procedures to decrease the burden of ASCVD in patients.

project_terms:
Anti-Inflammatory Agents;Antibodies;Antibody Response;Antigen-Antibody Complex;Antiinflammatory Effect;Apolipoprotein A-I;Arterial Fatty Streak;Atherosclerosis;Autoantibodies;Autoantigens;Autoimmunity;Blood Circulation;Cardiovascular Diseases;Cell model;Cells;Characteristics;Communities;Complex;Cultured Cells;Data;Death Rate;Development;Disease;Disease Progression;Epitopes;Evaluation;Event;Exhibits;Fc Receptor;Foundations;Future;Goals;High Density Lipoproteins;Homeostasis;Human;IgG4;Immune Complex Diseases;Immune response;Immunization;Immunoglobulin G;Incidence;Inflammation;Investigation;Laboratories;Measures;Mediating;Molecular;Multi-Ethnic Study of Atherosclerosis;Multivariate Analysis;Mus;Myocardial Infarction;Outcome;Outcomes Research;Participant;Pathogenesis;Patient-Focused Outcomes;Patients;Phenotype;Plant Roots;Plasma;Procedures;Prospective cohort;Proteins;Protocols documentation;Receptor Signaling;Research;Risk;Risk Factors;Role;Sampling;Specificity;Stroke;Testing;adjudicate;base;burden of illness;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;clinical risk;cohort;drug development;follow-up;functional outcomes;human subject;immunoregulation;improved;in vitro activity;in vivo;innovation;male;mouse model;new therapeutic target;novel;novel strategies;novel therapeutics;obese patients;profiles in patients;programs;protocol development;receptor;response;risk stratification;therapeutic development;treatment strategy;western diet

public_health_relevance:
PROJECT NARRATIVEThis proposal seeks to investigate the antibody response targeting apolipoprotein A-I by implementing novelstrategies to modulate epitope-specific immune responses in mice and characterize the antibody profiles inhumans. These objectives will improve our understanding of the immune response associated withatherosclerosis and promote the identification of novel therapeutic targets. These data will also guide futureclinical risk stratification protocols and drug development studies to reduce the cardiovascular disease burdenin patients.


application_id: 10147017
project_number: 5UG1DA050069-03
project_title: Kentucky Women's Justice Community Opioid Innovation Network (WJCOIN)
administering_ic: NIDA
award_notice_date: 2021-04-07
opportunity_number: RFA-DA-19-025
application_type: 5
activity_code: UG1
ic: DA
serial_number: 050069
program_official: MULFORD, CARRIE FRIED
project_start_date: 2019-07-15
project_end_date: 2024-04-30
study_section: ZDA1-HXO-H(05)R
contact_pi_person_id: 14909213
contact_pi: STATON, MICHELE
other_pis: Not Applicable
congressional_district: 06
department: PSYCHIATRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
ABSTRACTThe opioid crisis continues to ravage US communities with overdose deaths at an all-time high. Women aredisproportionately affected by the opioid crisis due to increased pain sensitivity physician prescribing practicesand self-medication as well as a faster trajectory from opioid exposure to the development of opioid use disorder(OUD). The opioid overdose death rate among women has risen 492% since 1999 a higher rate than men(404%). However research on approaches to increase initiation of life-saving medications for opioid use disorder(MOUD) among women is limited. The University of Kentucky proposes to establish the Womens ClinicalResearch Center as part of the NIDA Justice Community Opioid Innovation Network (W-JCOIN). The overallgoal of the W-JCOIN is to increase initiation and maintenance of MOUD among high-risk justice-involved womenin the transition from jail to the community to reduce opioid relapse and overdose. As part of this NIH collaborativenetwork the W-JCOIN will lead a type 1 hybrid effectiveness and implementation trial to examine an innovativeMOUD pre-treatment model using telehealth (alone and in combination with peer navigators) for justice-involvedwomen in transition from jail to the community in 6 experimental and 3 comparison (Services as Usual-SAU)sites. The following aims guide the study: (1) Compare the effectiveness of MOUD Pre-Treatment Telehealth(alone versus in combination with Peer Navigators) to increase MOUD initiation and maintenance among high-risk justice-involved women in the community after release relative to services as usual (SAU). (2) Estimate theincremental cost and cost effectiveness of MOUD Pre-Treatment Telehealth (alone and in combination with PeerNavigators) relative to SAU for high-risk justice involved women with OUD in achieving desired changes inclinical public health and public safety outcomes over one-year post-release. (3) Examine temporal changes inkey implementation constructs hypothesized by the EPIS framework to influence successful innovationimplementation. This application is supported by an experienced team of NIH funded investigators with a trackrecord of engaging in NIH justice research cooperative. The research team is well-positioned to be active membersof the JCOIN network to rapidly conduct studies on quality care for OUD with special focus on underserved andunderstudied justice-involved women. The KY W-JCOIN has the potential for significant impact on the OUDtreatment field by contributing empirical evidence on the effectiveness and implementation of innovativetechnologies to increase initiation and maintenance of life-saving medications during a critical high-risk time ofcommunity re-entry among vulnerable justice-involved women in both urban and non-urban communities. Thelong-term goal of this research is to increase the capacity for the justice system to respond to the opioid crisisthrough increased access to treatment to reduce opioid relapse and overdose.

project_terms:
Affect;Benefits and Risks;Caring;Climate;Clinical;Clinical Research;Communities;Cost Analysis;Criminal Justice;Death Rate;Development;Drug abuse;Drug usage;Effectiveness;Exposure to;Funding;Goals;Health Services Accessibility;High Risk Woman;Hybrids;Imprisonment;Intervention;Jail;Justice;Kentucky;Lead;Leadership;Life;Link;Maintenance;Methods;Modeling;National Institute of Drug Abuse;Opioid;Outcome;Overdose;Perception;Pharmaceutical Preparations;Physicians;Positioning Attribute;Public Health;Quality of Care;Randomized;Recording of previous events;Recovery;Relapse;Reporting;Research;Research Personnel;Rewards;Safety;Savings;Self Medication;Services;Site;System;Time;Treatment Cost;United States National Institutes of Health;Universities;Woman;arm;base;community reentry;compare effectiveness;comparison group;cost;cost effectiveness;cost-effectiveness ratio;effectiveness implementation trial;experience;follow-up;high risk;improved;incremental cost-effectiveness;innovation;innovative technologies;intervention cost;member;men;opioid epidemic;opioid exposure;opioid injection;opioid mortality;opioid use disorder;organizational readiness;overdose death;pain sensitivity;peer;prescription opioid;programs;recidivism;safety outcomes;services as usual;telehealth;treatment as usual

public_health_relevance:
PROJECT NARRATIVEThe University of Kentucky proposes to establish the Womens Clinical Research Center as part of the NIDAJustice Community Opioid Innovation Network (W-JCOIN) with the overall goal of increasing initiation andmaintenance of MOUD among high-risk justice-involved women in the transition from jail to the community toreduce opioid relapse and overdose. The KY W-JCOIN has the potential for significant impact on the OUDtreatment field by contributing empirical evidence on the effectiveness and implementation of innovativetechnologies to increase initiation and maintenance of life-saving medications during a critical high-risk time ofcommunity re-entry among vulnerable justice-involved women in both urban and non-urban communities. Thisresearch will impact the field by increasing the capacity of the justice system to respond to the opioid crisisthrough increased access to MOUD treatment to reduce opioid relapse and overdose.


application_id: 10147006
project_number: 5R01DA045023-04
project_title: A translational determination of the mechanisms of maladaptive choice in cocaine use disorder
administering_ic: NIDA
award_notice_date: 2021-04-28
opportunity_number: PA-17-111
application_type: 5
activity_code: R01
ic: DA
serial_number: 045023
program_official: FEDOTA, JOHN RAPHAEL
project_start_date: 2018-07-01
project_end_date: 2023-04-30
study_section: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]
contact_pi_person_id: 8046705
contact_pi: LILE, JOSHUA ANTHONY
other_pis: BECKMANN, JOSHUA ;WESLEY, MICHAEL J
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:
ABSTRACT Cocaine use disorder (CUD) is characterized by the decision to use cocaine at the expense of other activities.Lab-based efforts to address this problem have therefore included cocaine choice self-administration proceduresthat incorporate a non-drug alternative to model this defining feature. Studies using these procedures havetypically scheduled competing reinforcers so that the probabilities are certain. However such deterministicoutcomes are not representative of real-world scenarios in which the consequences from drug-related decisionsare often unpredictable. Importantly decision-making in a dynamic uncertain context significantly alters thevalue of choice options and requires continuous updating of option values which engages learning processesand related corticostriatal networks that might be functioning abnormally in CUD. Decision-making in dynamicenvironments has been successfully modeled using probabilistic reinforcement-learning choice (PRLC) tasks.The integration of these tasks with reinforcement-learning (RL) modeling has been used to capture moment-to-moment changes in the mechanisms of dynamic choice and the application of neuroscience techniques hasbegun to identify the underlying neurobiology. This approach has uncovered biologically-based decision-makingabnormalities in multiple brain disorders but has yet to be systematically applied to the experimental study ofCUD The translation of combined RL and neuroscience approaches to CUD is logical considering themaladaptive choice behavior that typifies the disorder the varying reinforcement probabilities in cocaine usersnatural environments and the learning impairments and neuroadaptations that have been documented inindividuals with CUD. Thus there are critical gaps in our understanding of the mechanisms underlying dynamiccocaine use decisions and a strong scientific premise for applying an RL framework to fill these gaps. Thisproject proposes rigorous PRLC tasks RL modeling neuromodulation/fMRI neuroimaging techniques andcomplementary translational study designs in rats and humans to study dynamic choice in CUD. The first set ofcross-species experiments will demonstrate the impact of problematic cocaine use on dynamic decision-makingand reveal the neurobehavioral and neurobiological processes underlying this abnormal task performance. Thesecond set of experiments will use a PRLC task in which intravenous cocaine is available as an alternative tothe non-drug reinforcer to determine the behavioral and neural profile associated with the decision to usecocaine and reduced cocaine choice during treatment. Amphetamine maintenance and non-drug alternativereinforcer treatments reduce cocaine choice which will be leveraged here to uncover behavioral and neuralmechanisms that can be targeted for future treatment development. This project will have a significant impacton the field by establishing the experimental application of reinforcement-learning theory to the study ofmaladaptive dynamic decision-making in CUD.

project_terms:
Address;Amphetamines;Animals;Back;Behavioral;Behavioral Mechanisms;Biological;Brain Diseases;Brain region;Choice Behavior;Clinical;Clinical Trials;Cocaine;Cocaine Users;Complement;Cues;Data;Decision Making;Disease;Environment;Food;Functional Magnetic Resonance Imaging;Future;Human;Impairment;Individual;Intake;Intervention;Intravenous;Knowledge;Learning;MRI Scans;Maintenance;Methods;Modeling;Nature;Neurobiology;Neurosciences;Outcome;Pharmaceutical Preparations;Postdoctoral Fellow;Probability;Procedures;Process;Psychological reinforcement;Rattus;Recording of previous events;Research;Research Design;Safety;Schedule;Self Administration;Signal Transduction;System;Task Performances;Techniques;Therapeutic Effect;Time;Translating;Translations;Update;base;cocaine self-administration;cocaine use;contingency management;drug of abuse;experimental study;human subject;innovation;nervous system disorder;neuroadaptation;neurobehavioral;neuroimaging;neuromechanism;neuroregulation;non-drug;novel;reinforcer;relating to nervous system;theories;therapy development;translational study

public_health_relevance:
PROJECT NARRATIVE Cocaine use disorder (CUD) is characterized by the decision to use cocaine at the expense of other activitiesbut lab-based studies have not modeled naturalistic dynamic decision-making. This translational rat and humanproject will use an innovative reinforcement-learning approach and neuroscience methods to uncover themechanisms of maladaptive dynamic choice in CUD and the effects of established interventions in order toreveal novel treatment targets.


application_id: 10146204
project_number: 5R01DK115406-04
project_title: CSN8 regulation of S1P-enriched extracellular vesicles to modulate NAFLD by gut-liver axis
administering_ic: NIDDK
award_notice_date: 2021-04-14
opportunity_number: PA-16-160
application_type: 5
activity_code: R01
ic: DK
serial_number: 115406
program_official: GARCIA, MARTHA
project_start_date: 2018-07-20
project_end_date: 2023-04-30
study_section: Hepatobiliary Pathophysiology Study Section[HBPP]
contact_pi_person_id: 11629370
contact_pi: DENG, ZHONG-BIN
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:
The overarching theme of this project is to address the mechanisms underlying gut derived extracellular vesicles(EVs)-induced liver inflammation/injury in Non-alcoholic fatty liver disease (NAFLD). We will determine the roleof sphingolipid metabolites specifically; Sphingosine 1-phosphate (S1P)-enriched gut EVs and pathwayCSN8/SphK1 in the development of NAFLD. The current proposal links gut-derived EVs to macrophage-mediated inflammation by proposing that extracellular vesicles from gut recruit macrophages to the liverresulting in liver injury and inflammation. Our recent work has begun to identify intestinal inflammation-inducedalterations in EVs and shows that gut-derived EVs play a critical role in the regulation of NKT cells and Th17cells in the development of liver inflammation and colon cancer via gut-liver axis. Our preliminary data showsthat LPS promotes Intestinal epithelial cells (IECs) release sphingolipid metabolites-enriched pro-inflammatoryEVs including ceramide and S1P. Our preliminary findings also indicate that CSN8/SphK1 signaling pathwayplays a crucial role in the production of S1P-enriched EVs. Chronic high fat diet consumption leads to increasedgut permeability and expose the liver to gut-derived products including EVs of IECs. Increased S1P-enrichedEVs activate its receptor S1P1 on hepatic macrophages which may promote macrophage chemotaxis into theliver. This has led to the central hypothesis that gut microbiota regulate sphingolipid metabolites-enriched EVs biogenesis and release via gut CSN8/SphK1 pathway and gut EVs carrying sphingolipidmetabolites (ceramide and S1P) translocate to liver which in turn attract macrophages into the liverpromoting liver injury in NAFLD. Importantly the proposal also pursues translational studies that examine theefficacy of nutrition-nanoparticles based therapeutic interventions targeted at gut microbiota and SphK1-S1PR1inhibition in mitigating gut-liver axis changes. To address our hypothesis we propose the following specific aims:Aim 1: Determine whether gut-derived EVs-S1P regulate liver inflammation and injury via CSN8/SphK1 pathwayin NAFLD. Aim 2: Determine whether gut-derived EVs-S1P contribute to liver macrophagesrecruitment/activation by S1PR1-STAT3 in NAFLD. Aim 3: Define molecular mechanisms underlying CSN8 andSphK1 reciprocal regulation and modulation of the CSN8/S1P-S1PR1 signal will prevent macrophagesmediated-liver injury in NAFLD. The proposal will provide a better understanding of diet-gut-liver interactions andmolecular mechanisms contributing to the pathogenesis of EVs-S1P-induced liver inflammation and injury. Thestudy will lead to identification of new therapeutic targets and potential dietary interventions for treating NAFLD.

project_terms:
Address;Affect;Biogenesis;Cell physiology;Cells;Ceramides;Chemotaxis;Chronic;Colitis;Colon Carcinoma;Consumption;Data;Development;Diet;Dietary Intervention;Distant;Enzymes;Epithelial Cells;Hepatic;High Fat Diet;Immune;Inflammation;Inflammatory;Injury;Intestinal permeability;Intestines;Kupffer Cells;Link;Lipids;Liver;Macrophage Activation;Mediating;Molecular;Pathogenesis;Pathogenicity;Pathway interactions;Play;Production;Property;Regulation;Role;SPHK1 enzyme;STAT3 gene;Severities;Signal Pathway;Signal Transduction;Sphingolipids;TLR4 gene;Testing;Therapeutic;Therapeutic Intervention;Up-Regulation;Work;base;ceramide 1-phosphate;dietary;edg-1 Protein;efficacy evaluation;exosome;extracellular vesicles;gut microbiota;gut-liver axis;inflammatory disease of the intestine;interest;intestinal epithelium;liver development;liver inflammation;liver injury;lymphocyte trafficking;macrophage;microorganism antigen;nanoparticle;new therapeutic target;non-alcoholic fatty liver disease;nutrition;prevent;recruit;sphingosine 1-phosphate;translational study

public_health_relevance:
Project NarrativeThis proposal underscores the importance of investigating S1P-enriched extracellular vesicles as a critical gut-derived factor for the development of nonalcoholic fatty liver diseases by regulating the recruitment/activation ofhepatic macrophages. We anticipate that we can abrogate their local and/or distant activities by targetingCSN8/SphK1-S1PR1/Stat3 pathway.


application_id: 10145776
project_number: 5R01HL151419-02
project_title: Biophysical Mechanisms of Hyperoxia-Induced Lung Injury
administering_ic: NHLBI
award_notice_date: 2021-03-17
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: HL
serial_number: 151419
program_official: ZHOU, GUOFEI
project_start_date: 2020-04-15
project_end_date: 2024-03-31
study_section: Lung Injury, Repair, and Remodeling Study Section[LIRR]
contact_pi_person_id: 1860187
contact_pi: WATERS, CHRISTOPHER M
other_pis: Not Applicable
congressional_district: 06
department: PHYSIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Acute lung injury and its more severe form acute respiratory distress syndrome(ARDS) are devastating illnesses with high rates of incidence and mortality. Patientswith acute lung injury are typically provided supplemental oxygen using positivepressure mechanical ventilation but this can lead to additional injury termed ventilator-induced lung injury (VILI). The long term objective of this proposal is to improveunderstanding of the mechanisms by which the combination of exposure to high levelsof oxygen (hyperoxia) and overdistention (or stretch) of lung cells contributes toventilator-induced lung injury. The central hypothesis of this application is thathyperoxia induces structural changes in alveolar epithelial and endothelial cells as wellas macrophages that alter their mechanical properties making them more susceptibleto injury caused by mechanical stretch. Mechanisms of the initiation of cell injury will beinvestigated using primary cultures of mouse alveolar type II (AT2) epithelial cellsprimary human lung endothelial cells mouse alveolar and bone marrow-derivedmacrophages cultures of mouse lung slices and a mouse model of combinedhyperoxia and VILI. In Aim 1 we will test the hypothesis that exposure of cells or lungslices causes changes in cell structural elements that increase the elastic modulus ofthe cells through activation of RhoA. We will measure the Youngs modulus anindication of an objects ability to deform using atomic force microscopy in theindentation mode and we will determine how hyperoxia changes cytoskeletal structuresincluding f-actin microtubules and focal adhesions. In Aim 2 we will investigate howhyperoxia increases stretch-induced cell detachment and injury. In Aim 3 we will testthe hypothesis that RhoA-mediated changes in structure and mechanical propertiesincreases lung injury in mice in a combined model of hyperoxia and VILI. The proposedstudies will investigate the biophysical mechanisms that contribute to lung injury duringmechanical ventilation and provide new insights into mechanotransduction the processof converting mechanical signals to biological signals.

project_terms:
Actins;Acute Lung Injury;Adult Respiratory Distress Syndrome;Alveolar;Animal Model;Antioxidants;Apoptosis;Atomic Force Microscopy;Bacterial Pneumonia;Basement membrane;Biological;Biophysical Process;Biophysics;Bone Marrow;Cell Adhesion;Cell Death;Cell membrane;Cells;Cellular Structures;Clinical;Cultured Cells;Disease;Elements;Endothelial Cells;Endothelium;Epithelial;Epithelial Cells;Exposure to;F-Actin;Focal Adhesions;Gelsolin;Guanosine Triphosphate Phosphohydrolases;Human;Hyperoxia;Incidence;Inflammasome;Inflammation;Inflammatory;Influenza;Injury;Intensive Care Units;Investigation;Knock-out;Lead;Light;Lung;MYLK gene;Masks;Measures;Mechanical ventilation;Mechanics;Mediating;Microtubules;Modeling;Modulus;Mus;Myosin ATPase;Myosin Light Chains;Necrosis;Oxygen;Pathway interactions;Patients;Phosphotransferases;Predisposition;Preparation;Process;Proteins;Resistance;Rho-associated kinase;Rupture;Severities;Signal Pathway;Signal Transduction;Slice;Stretching;Structure;Structure of parenchyma of lung;Testing;Therapeutic Intervention;Tidal Volume;Ventilator-induced lung injury;Work;alveolar bone;alveolar epithelium;biophysical properties;cell injury;ezrin;improved;injured;insight;keratinocyte growth factor;lung injury;macrophage;mechanical pressure;mechanical properties;mechanotransduction;moesin;mortality;mouse model;myosin phosphatase;prevent;radixin protein;response;supplemental oxygen;targeted treatment

public_health_relevance:
Bacterial pneumonia and influenza are common diseases that can lead to severeacute lung injury. Patients with severe acute lung injury require mechanical ventilationand supplemental oxygen and often require extended stays in the intensive care unit.The proposed studies will investigate the biophysical mechanisms that contribute tolung injury during mechanical ventilation and will identify potential targets for therapeuticintervention to reduce injury.


application_id: 10145654
project_number: 5R01DE029650-03
project_title: HPV16 E6 Antibody Detection as an Early Marker for Oropharyngeal Cancer Among Men Living with HIV
administering_ic: NIDCR
award_notice_date: 2021-04-19
opportunity_number: RFA-DE-20-001
application_type: 5
activity_code: R01
ic: DE
serial_number: 029650
program_official: YIN, HONGEN
project_start_date: 2021-02-05
project_end_date: 2025-04-30
study_section: ZDE1-GZ(13)
contact_pi_person_id: 14510566
contact_pi: KUHS, KRYSTLE 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
arra_indicator: N
project_terms:
Acquired Immunodeficiency Syndrome;Address;Affect;Age;Antibodies;Behavioral;Biological Markers;Blood;Blood Banks;Blood specimen;Cancer Center;Cancer Etiology;Clinic;Collection;Comprehensive Health Care;Development;Diagnosis;Early Diagnosis;Eligibility Determination;General Population;HIV;HIV Infections;HIV Seronegativity;HPV-High Risk;Head and Neck Cancer;Head and Neck Surgeon;Head and neck structure;High Prevalence;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Human papilloma virus infection;Human papillomavirus 16;Incidence;Individual;Laryngoscopes;Lesion;Life Expectancy;Malignant Neoplasms;Malignant neoplasm of cervix uteri;Methods;Natural History;Oncoproteins;Oral cavity;Oral health;Palpation;Patients;Persons;Population;Positioning Attribute;Prevalence;Quality of life;Questionnaires;Research;Resources;Risk;Risk Estimate;Risk Factors;Screening for cancer;Screening procedure;Seroprevalences;Sex Behavior;Surrogate Markers;Tennessee;Testing;Time;Tonsil;Ultrasonography;Visit;Visual;Work;aged;antibody detection;base;biobank;cancer risk;chemoradiation;clinical examination;cohort;early detection biomarkers;effective therapy;high risk;improved;malignant oropharynx neoplasm;men;middle age;mortality;novel;oral HPV;oral HPV infection;premalignant;rapid detection;screening;screening guidelines;seropositive


application_id: 10145585
project_number: 5R21AI146945-02
administering_ic: NIAID
award_notice_date: 2021-04-29
opportunity_number: PA-19-053
application_type: 5
activity_code: R21
ic: AI
serial_number: 146945
program_official: GU, XIN-XING
project_start_date: 2020-04-15
project_end_date: 2024-03-31
study_section: Special Emphasis Panel[ZRG1-IDM-B(81)]
contact_pi_person_id: 8869391
contact_pi: KOROTKOVA, NATALIA
other_pis: Not Applicable
congressional_district: 06
department: BIOCHEMISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2021-04-01
project_title:
Mechanisms of resistance against the human group IIA secreted phospholipase A2 in Group B Streptococcus

project_abstract:
Antimicrobial peptides play a major role in humoral innate immunity against microorganisms.Multiple in vivo and in vitro studies highlight the important function of human group IIA secretedphospholipase A2 (hGIIA) in protection against Gram-positive bacterial infection including GroupB Streptococcus (GBS) a leading cause of neonatal sepsis and meningitis. hGIIA kills bacteriaby catalyzing the hydrolysis of the membrane glycerophospholipids. The Gram-positive cellenvelope consisting of multiple peptidoglycan layers decorated with a variety of glycopolymersrepresents a substantial barrier to hGIIA and it is poorly understood how hGIIA gains access tothe bacterial plasma membrane to produce lethal damage. We have recently identified novelbacterial resistance mechanisms against hGIIA in the bacterium closely-related to GBS GroupA Streptococcus (GAS). Our work revised the current models of GAS cell wall architecture andhighlighted the importance of these structural determinants for resistance to hGIIA. InterestinglyGBS is killed by hGIIA at concentrations that are approximately 500-fold lower than the GASstrains. The experiments described in this proposal are designed to understand the underlyingmechanisms for hGIIA potency against GBS. To accomplish our goal we will use twoapproaches. In the first approach we will conduct screens of a recently constructed highlysaturated GBS transposon mutant library using lethal and sub-lethal concentrations of hGIIA.After construction of deletion mutants in the identified genes we will perform antimicrobial andmechanistic assays and transmission electron microscopy analysis of the freeze-substitutedcells to confirm the hGIIA susceptibility phenotype of the mutants and understand themechanisms of resistance/susceptibility. In the second approach we will investigate the role ofthe major peptidoglycan-attached glycopolymer of GBS the Group B Carbohydrate (GBC) inhGIIA susceptibility by swapping GBC with the GAS cell wall glycopolymer in GBS. Successfuloutcomes will guide future efforts for new drug development against GBS.

project_terms:
Acute;Affect;Anti-Bacterial Agents;Antimicrobial Cationic Peptides;Architecture;Bacteria;Bacterial Infections;Biochemical;Biological Assay;Biology;Body Fluids;Candidate Disease Gene;Carbohydrates;Cations;Cell Wall;Cell membrane;Cells;Charge;Chronic Disease;Complex;Data;Elderly;Enzymes;Freeze Substitution;Future;Gene Deletion;Genes;Genetic;Glycerol;Glycerophospholipids;Glycolipids;Goals;Gram-Positive Bacteria;Histones;Human;Hydrolysis;In Vitro;Infection;Inflammation;Knowledge;Libraries;Link;Membrane;Modeling;Modification;Morphology;Muramidase;Natural Immunity;Neonatal meningitis;Newborn Infant;Outcome;Peptidoglycan;Permeability;Phase;Phenotype;Phosphatidylglycerols;Phospholipase A2;Phospholipids;Plasma Cells;Play;Polymers;Polysaccharides;Predisposition;Proteins;Publishing;Research;Resistance;Rhamnose;Role;Serum;Side;Skin;Streptococcus;Streptococcus Group B;Streptococcus mutans;Streptococcus pyogenes;Stress;Structure;Systemic infection;Technology;Testing;Transgenic Mice;Transmission Electron Microscopy;Vertebral column;Work;antimicrobial;antimicrobial peptide;bacterial resistance;base;capsule;cell envelope;cell type;design;drug development;experimental study;extracellular;human pathogen;in vivo;inorganic phosphate;microorganism;mouse model;mutant;neonatal sepsis;novel;novel therapeutics;pathogen;phosphodiester;prevent;resistance mechanism;screening

public_health_relevance:
Streptococcus agalactiae or Group B Streptococcus (GBS) is cause serious infections innewborns as well as in older adults and people with chronic illness. The proposedresearch seeks to determine the mechanisms of resistance/susceptibility to humangroup IIA secreted phospholipase A2 in GBS.


application_id: 10145206
project_number: 1R01CA257370-01
project_title: Targeting AR and AR-Variants in Castration-Resistant Prostate Cancer
administering_ic: NCI
award_notice_date: 2021-01-25
opportunity_number: PA-19-056
application_type: 1
activity_code: R01
ic: CA
serial_number: 257370
program_official: KONDAPAKA, SUDHIR B
project_start_date: 2021-02-01
project_end_date: 2021-03-31
study_section: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]
contact_pi_person_id: 7649061
contact_pi: DAMODARAN, CHENDIL
other_pis: SHARMA, ARUN K
congressional_district: 03
department: UROLOGY
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/AbstractCurrent AR inhibitors (enzalutamide and abiraterone) inhibit either the conversion of androgen todihydrotestosterone (DHT) block androgen binding to androgen receptor (AR) or AR signaling. Althoughinitially effective these treatments eventually fail because of factors such as AR-splice variants (AR-SVs)and AR responding to stimuli other than androgen. An effective way to control the emergence and treatmentof castration-resistant prostate cancer (CRPC) is to develop small molecules that either inhibit AR expressionor promote its degradation. If there is no AR there would be no AR signaling regardless of whether or howmuch androgen or other stimuli of AR signaling are present in CRPC. Our preliminary studies demonstratedthat naturally occurring Urolithin A (UroA) inhibited the AR signaling and selectively suppressed the growth ofAR-positive (AR+: IC50 ~35 M) but not AR-negative (AR-: IC50 ~70 M) CRPC in both in vitro and in vivomodels (50 mg/kg/body weight). As higher concentrations of UroA are required to suppress CRPC growthwe aimed to design and develop potent UroA analogs that could selectively inhibit AR activation at lowerconcentrations (nM) are orally bioavailable and suppress the growth of CRPC. The subsequent developmentof a series of UroA analogs and structure-activity relationship (SAR) studies led to the identification of twonovel lead compounds ASR-600 and ASR-603 (US Provisional 62/941588) which demonstrated betterefficacy (nM) than UroA (ASR-600: >40-fold and ASR-603: >12-fold) in inhibiting AR signaling in CRPC celllines. Molecular studies suggest these two ASRs inhibit both AR and AR-SVs expression via ubiquitinationand degradation within the cytosol. Molecular dynamic (MD) system simulation studies biophysical analysisbased on nuclear magnetic resonance (NMR) and thermal shift assays showed that these small moleculesbind to the N-terminal domain (NTD) of AR and block the activation of both AR and AR-SV. At physiologicallyachievable concentrations ASR-600 abrogated AR+ and AR-SV (C4-2B and 22Rv1) tumor growth inxenografts. Based on our preliminary results we hypothesized that Rationally designed ASRs will effectivelyinhibit and/or promote the degradation of both AR and AR-SV expression by directly targeting the AR-NTDand inhibit the growth of CRPC. We will test this hypothesis with the following specific aims. Aim1. Investigate the mechanism of action of ASRs on AR+ CRPC cells. Aim 2. Determine in vivo signalingmechanism of AR and AR-SVs expression and optimize the dose of ASRs. Aim 3. Determine the therapeuticefficacy of the ASRs to inhibit CRPC growth in orthotopic and patient-derived xenograft (PDX) models. Theproposed studies will elucidate the mechanism of action of the ASRs and lead to a better understanding ofthe chemotherapeutic properties of these compounds against CRPC.

project_terms:
Acute;Androgen Receptor;Androgens;Binding;Binding Sites;Bioavailable;Biological Assay;Body Weight;Calorimetry;Cancer Patient;Cell Death;Chemicals;Cytosol;Development;Dose;Foundations;Goals;Growth;Histopathology;In Vitro;Label;Lead;Maximum Tolerated Dose;Mediating;Modeling;Molecular;Mus;N-terminal;Nuclear Magnetic Resonance;Oral;Oral Administration;Outcome;Pattern;Phase I Clinical Trials;Physiological;Pre-Clinical Model;Property;RNA Splicing;Receptor Activation;Receptor Signaling;Research;Resistance;Series;Signal Transduction;Site;Solubility;Stanolone;Stimulus;Structure-Activity Relationship;Tertiary Protein Structure;Testing;Titrations;Toxic effect;Treatment Efficacy;Tumor Tissue;Ubiquitination;Urology;V1 Receptors;Variant;Xenograft procedure;abiraterone;advanced prostate cancer;analog;androgen deprivation therapy;base;biophysical analysis;castration resistant prostate cancer;chemotherapy;design;dynamic system;effective therapy;efficacy evaluation;implantation;in vivo;in vivo Model;inhibitor/antagonist;next generation;novel lead compound;patient derived xenograft model;pharmacokinetics and pharmacodynamics;pro-apoptotic protein;prostate cancer cell;prostate cancer cell line;prostate cancer progression;protein expression;receptor expression;simulation;small molecule;tumor growth

public_health_relevance:
Project NarrativeThe advanced prostate cancer (CaP) is initially amenable for androgen deprivation therapy (ADT) andeventually there is an emergence of CRPC. Next-generation ADT agents (abiraterone andenzalutamide) and chemotherapy are not curative of CRPC. Hence the overall goal of the proposal isto determine the mechanism by which our small molecules (ASR-600 & ASR-603) target androgenreceptor (AR) and androgen receptor splice -variants (AR-SV) in castration-resistant prostate cancer.


application_id: 10145096
project_number: 5F32NS111241-03
project_title: Role of Age on Anti-oxidant Defense in Spinal Cord Injury: Physiological Changes and Intervention
administering_ic: NINDS
award_notice_date: 2021-04-05
opportunity_number: PAR-16-458
application_type: 5
activity_code: F32
ic: NS
serial_number: 111241
program_official: BAMBRICK, LINDA LOUISE
project_start_date: 2019-04-01
project_end_date: 2021-10-31
study_section: NST-2 Study Section [NST-2]
contact_pi_person_id: 15507155
contact_pi: STEWART, ANDREW NATHANIEL
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:
Since the 1970s the average age that a spinal cord injury (SCI) occurs has shifted towards older populationsfrom age 29 to 42. Further both clinical and pre-clinical reports reveal age as an important predictor offunctional recovery following SCI. Despite this the use of younger adult animals prevails in pre-clinical SCImodels. Increasingly age-dependent inflammatory responses and reactive oxygen species-mediated damageare implicated in the pathophysiology of SCI deficits. Although not yet explored in the context of SCI agereduces cellular anti-oxidant capacity through diminished levels of glutathione a critical anti-oxidant regulatingredox balance within all cells. Collectively an increase in ROS production with a decrease in anti-oxidantdefense leaves aged cells more susceptible to ROS-mediated damage and can result in cell death.Characterization of redox balance within the aged spinal cord before and after injury is needed to evaluate thetherapeutic potential of strategies aimed at increasing cellular anti-oxidant defense. One such strategy istreatment using N-acetylcysteineamide (NACA) which increases intracellular glutathione and results in anti-oxidant protection against ROS. Treatment using NACA or similar analogs have demonstrated therapeuticefficacy in animal models of SCI when used to treat young SCI conditions. The proposed work will determinethe anti-oxidant capabilities and redox state of aged and young spinal cords before and after SCI as well astest the efficacy of NACA as a free radicle scavenging treatment to restore function and improve outcomes in acontusive mouse model of SCI. The specific hypotheses are two-fold: 1) intracellular anti-oxidant capacitywithin the spinal cord diminishes with age and is further reduced as a consequence of SCI and 2) treatmentefficacy using NACA is age-dependent following SCI and will elicit a larger therapeutic response in aged mice.Aim 1 will determine the extent that intracellular anti-oxidant defense mediates protection against ROS in agedand young spinal cords. Aim 2 will determine the extent to which the therapeutic efficacy of ROS scavengingafter spinal cord contusion is age-dependent. Collectively the data from these studies will aid in thedevelopment of therapies to treat SCI individuals of all ages. Further elucidating the mechanisms of age-related neurodegeneration will advance the fields of aging and neuroscience.

project_terms:
Affect;Age;Aging;Animal Model;Animals;Antioxidants;Biochemical Process;Biological Assay;Buthionine Sulfoximine;Cell Death;Cells;Clinical;Contusions;Data;Defense Mechanisms;Dependence;Dose;Enzymes;Equilibrium;Exposure to;Fostering;Free Radicals;Functional disorder;Glutathione;Histologic;Homeostasis;Human;Individual;Inflammation;Inflammatory Response;Injury;Intervention;Knowledge;Laboratories;Measures;Mediating;Mediator of activation protein;Mission;Modeling;Motor;Mus;N-Acetylcysteinamide;NADPH Oxidase;Neurosciences;Nitrogen Dioxide;Older Population;Outcome;Oxidation-Reduction;Physiological;Pre-Clinical Model;Production;Public Health;Rattus;Reactive Oxygen Species;Recovery of Function;Reduced Glutathione;Reporting;Research;Role;Spinal Cord;Spinal Cord Contusions;Spinal cord injury;Testing;Therapeutic;Tissues;Translations;Treatment Efficacy;United States National Institutes of Health;Work;acetovanillone;age effect;age related;age related neurodegeneration;aged;analog;base;cell age;disability;efficacious treatment;efficacy testing;experience;experimental study;functional outcomes;functional restoration;improved;improved outcome;inhibitor/antagonist;juvenile animal;mature animal;mouse model;nervous system disorder;neuropathology;neuroprotection;pre-clinical;targeted treatment;therapy development;translational impact;treatment response;young adult

public_health_relevance:
The proposed research is relevant to public health because determining the extent to which age affect the efficacy of therapies for SCI will facilitate the successful translation of treatments to a growing aging SCI demographic. Moreover understanding the mechanisms that contribute to age-related neurodegeneration is important for a number of neuropathologies. Therefore the proposed research is relevant to the part of the NIH mission that pertains to developing fundamental knowledge and applying that knowledge to foster research strategies to reduce the burden of human disabilities.


application_id: 10145002
project_number: 5R01ES019217-09
project_title: Endothelial Progenitor Cells and Particulate Air Pollution
administering_ic: NIEHS
award_notice_date: 2021-03-17
opportunity_number: PA-16-160
application_type: 5
activity_code: R01
ic: ES
serial_number: 019217
program_official: NADADUR, SRIKANTH
project_start_date: 2011-09-23
project_end_date: 2023-03-31
study_section: Special Emphasis Panel[ZRG1-CVRS-C(02)]
contact_pi_person_id: 8911484
contact_pi: O'TOOLE, TIMOTHY E
other_pis: BHATNAGAR, ARUNI ;POPE, ARDEN
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:
ABSTRACTMultiple epidemiological and experimental studies report that acute or chronic exposure to air pollution isassociated with adverse cardiovascular events including myocardial ischemia stroke arrhythmias heart failuresudden cardiac arrest and atherogenesis. These effects of air pollution are most strongly correlated with fineparticulate matter (PM2.5) fraction which is generated directly from the combustion of fossil fuels and is found inautomobile exhaust wood or coal smoke and industrial emissions. However the mechanisms by which PM2.5induces cardiovascular injury remain unclear and the pathophysiological conditions and co-exposures thatdetermine individual susceptibility to PM2.5 toxicity have not been identified. Our previous work has shown thatin young healthy adults exposure to PM2.5 is associated with inflammation decreases in vascular reparativecirculating angiogenic cells (CACs) and changes in cytokine/growth factor profiles consistent with an inhibitionof angiogenesis. In addition we found increased levels of circulating endothelial microparticles evidence ofsubclinical vascular injury. We obtained similar results in mouse exposure studies which show that exposure toconcentrated ambient particles depletes circulating angiogenic cells and leads to defective hematopoiesis andfunctional defects in bone marrow-derived cells. In pilot experiments we have found that these PM2.5-induceddefects in mice could be prevented by treatment with the endogenous nucleophile carnosine which quenchesreactive oxygen species and removes toxic products of lipid peroxidation. Furthermore in a human cohort withmild-to-moderate CVD risk we also found that those with high CVD risk are more susceptible to the effects ofPM2.5 and that individuals with high carnosine levels are relatively impervious to the adverse cardiovasculareffects of PM2.5 exposure. Thus we hypothesize that individual risk factors determine cardiovascular susceptibilityto PM2.5 and that means to limit electrophiles/oxidative stress will mitigate the adverse consequences of PM2.5exposure. These ideas will be tested in three Aims. In the first we will assess the impact of PM2.5 exposure onvascular function (arterial stiffness flow-mediated dilation peripheral artery tone) in a population with mild-to-moderate CVD risk and determine whether exposure exacerbates composite CVD risk and whether changesinflammation oxidative stress or thrombosis are associated with PM2.5-induced vascular dysfunction. In thesecond Aim we will determine whether the relationship between vascular injury and dysfunction is mediated byindividual-level demographic characteristics (e.g. sex age ethnicity) co-exposure to gaseous pollutants orsystemic levels of carnosine. In the third Aim we will enroll a subset of individuals with inherently low carnosinelevels and determine whether daily oral supplementation with carnosine attenuates the association betweenPM2.5 exposure and vascular dysfunction as well as PM2.5 -induced changes in biomarkers of cardiovascularinjury and indices of cardiovascular function. The results of this project will provide better estimates of CVDburden due to PM2.5 exposure identify specific risk factors that increase susceptibility to PM2.5-induced injuryand assess the efficacy of carnosine in attenuating PM2.5 toxicity. Findings of this project could potentially leadto the development of a novel and practical therapeutic intervention to prevent PM2.5 toxicity.

project_terms:
Acute;Adult;Adverse effects;Affect;Age;Air Pollution;Angiogenesis Inhibition;Animal Model;Antioxidants;Arrhythmia;Arteries;Atherosclerosis;Attenuated;Automobile Exhaust;Biological Markers;Blood Vessels;Bone Marrow;Cardiovascular Diseases;Cardiovascular Physiology;Cardiovascular system;Carnosine;Cell physiology;Cells;Characteristics;Chronic;Clinical Trials;Coal;Defect;Development;Dipeptides;Double-Blind Method;Endothelium;Enrollment;Ethnic Origin;Event;Exposure to;Fossil Fuels;Grant;Growth Factor;Guidelines;Health;Heart Arrest;Heart failure;Hematopoiesis;Human;Impairment;Individual;Industrialization;Inflammation;Inflammatory Response;Injury;Insulin Resistance;Intervention;Lead;Link;Lipid Peroxidation;Measures;Mediating;Mediator of activation protein;Mus;Myocardial Infarction;Myocardial Ischemia;Oxidative Stress;Participant;Particulate;Particulate Matter;Peripheral;Placebos;Population;Populations at Risk;Predisposing Factor;Predisposition;Reactive Oxygen Species;Reporting;Risk;Risk Factors;Smoke;Socioeconomic Status;Stroke;Testing;Therapeutic Intervention;Thrombosis;Toxic effect;Vascular Diseases;Wood material;Work;adverse outcome;ambient particle;arterial stiffness;atherogenesis;base;biological adaptation to stress;burden of illness;cardiovascular disorder risk;cardiovascular effects;cardiovascular injury;cohort;cytokine;design;efficacy evaluation;endothelial stem cell;epidemiology study;experimental study;fine particles;indexing;mortality;novel;oral supplementation;pollutant;prevent;randomized trial;repaired;sex;sudden cardiac death;vascular injury;volatile organic compound

public_health_relevance:
PROJECT NARRATIVEAcute exposure to particulate matter (PM) air pollution produces oxidative stress and inflammatory responsesin young healthy adults and chronic exposures are strongly correlated with the progression of atherosclerosisincreased thrombosis myocardial infarction and stroke. In this proposal we determine if the effects of PM aremore pronounced in unhealthy at risk populations with impaired anti-oxidant capacity and whether theseeffects can be limited by a simple anti-oxidant intervention.


application_id: 10144998
project_number: 5R01DK122811-02
project_title: Diabetes glucose metabolism and neuroplasticity in the vagal complex
administering_ic: NIDDK
award_notice_date: 2021-02-26
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: DK
serial_number: 122811
program_official: COOKE, BRAD
project_start_date: 2020-04-15
project_end_date: 2021-07-31
study_section: Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section[NNRS]
contact_pi_person_id: 1911523
contact_pi: SMITH, BRET N
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 SummaryDiabetes mellitus is a major health concern affecting over 30 million people in the United States. Seriouscomplications resulting from diabetes including include heart disease stroke hypertension blindness nervoussystem damage and autonomic dysfunction. A major impediment to developing successful diabetestreatments (versus treating symptoms) is the relative knowledge gap regarding the multifaceted and redundantsystems that are affected by and contribute to control of metabolic homeostasis. This proposal investigatesdisease-related plasticity of central neural circuitry controlling autonomic function. Experiments utilize murinemodels of type 1 and type 2 diabetes. Second-order viscerosensory neurons in the nucleus tractus solitarius(NTS) are glucosensors and contribute significantly to autonomic regulation of glucose homeostasis bysignaling integrated visceral and humoral signals to brain areas that directly regulate systemic glucose levelsincluding the dorsal motor nucleus of the vagus nerve (DMV) which contains vagal motor neurons. Vagalmotor function is altered in diabetes leading to autonomic dysregulation including excess hepatic glucoseproduction and gastric motility dysfunction. We have found that changes in activity of GABA neurons or alteringglucose pathways in the NTS affect systemic [glucose]. Glutamate and GABA receptors are reorganized andsynaptic excitation of NTS GABA neurons is persistently increased in the vagal complex after a few days ofhyperglycemia in a model of type 1 diabetes. The majority of GABA neurons in the NTS is responsive toelevated [glucose] being either excited or inhibited but glucose-excitatory responses are blunted in diabeticmice. Vertical sleeve gastrectomy rapidly improves glycemic index in patients and animal models of diabetesindependent of weight loss; convergent data suggest the brainstem dorsal vagal complex (DVC) is integral tothis response. Electrophysiological recordings from NTS neurons in slices chemogenetic and pharmacologicalmanipulation of NTS neuron activity and direct glutamate and glucose measurements from the NTS of controland diabetic mice will be used to obtain functional cellular and molecular data relevant to the contribution of theNTS to glucose metabolism in the streptozotocin-treated mouse and the BKS-db mouse models of type 1 andtype 2 diabetes respectively. The broad hypothesis of this proposal is that altered neural function in the vagalcomplex reflects a neurogenic component of diabetic pathology. The experiments in this proposal aim to: 1)Identify cellular outcomes of glucose responsiveness in the caudal DVC associated with diabetes; 2);Determine effects of DVC manipulation on systemic glucose metabolism; and 3) Determine effects of bariatricsurgery on diabetes-related neuroplasticity in the vagal complex. Results will guide future development ofnovel disease-modifying therapies based on modulating specific neural functions in the vagal system toaddress diabetes-related glycemic dysregulation in patients.

project_terms:
Address;Affect;Animal Model;Area;Autonomic Dysfunction;Blindness;Blood Glucose;Body Weight decreased;Brain;Brain Stem;Brain region;Cell Nucleus;Chronic;Complex;Data;Development;Diabetes Mellitus;Diabetic mouse;Disease;Dorsal;Electrophysiology (science);Functional disorder;Future;GABA Receptor;Gastrectomy;Gastrointestinal tract structure;Glucose;Glutamate Receptor;Glutamates;Glycemic Index;Goals;Health;Heart Diseases;Hepatic;Homeostasis;Human;Hyperglycemia;Hypertension;Ingestion;Insulin-Dependent Diabetes Mellitus;Knowledge;Lead;Liver;Measurement;Mediating;Metabolic Control;Modeling;Modification;Molecular;Monitor;Motor;Motor Neurons;Mus;N-Methyl-D-Aspartate Receptors;Nervous System Trauma;Neuronal Plasticity;Neurons;Neurophysiology - biologic function;Non-Insulin-Dependent Diabetes Mellitus;Nutrient;Outcome;Output;Palliative Care;Pancreas;Pathology;Pathway interactions;Patients;Peripheral;Pharmacology;Phenotype;Physiological;Play;Public Health;Regulation;Role;Signal Transduction;Slice;Stomach;Streptozocin;Stroke;Symptoms;Synapses;System;United States;Vagus nerve structure;Viscera;Visceral;bariatric surgery;base;blood glucose regulation;cell motility;curative treatments;diabetes mellitus therapy;diabetic;dorsal motor nucleus;experimental study;gamma-Aminobutyric Acid;gastrointestinal;glucose metabolism;glucose production;improved;in vivo;inhibitory neuron;mouse model;nerve supply;neural circuit;neurochemistry;novel;relating to nervous system;response;symptom treatment;synaptic function;trafficking

public_health_relevance:
Project NarrativeInvolvement of the brain in glycemic regulation has important implications for controlling diabetes a growingand potentially devastating public health issue yet how brain regions that regulate whole-body glucosehomeostasis are affected by and contribute to diabetes are not well-understood. This proposal will identifymechanisms by which brainstem neurons that directly monitor both nutrient ingestion and blood glucoseconcentration are altered in diabetes and how bariatric surgery might influence brain function to modify diabetichyperglycemia.


application_id: 10144836
project_number: 5R01HD096077-03
project_title: The Role of FOS in the Ovary
administering_ic: NICHD
award_notice_date: 2021-02-24
opportunity_number: PA-18-484
application_type: 5
activity_code: R01
ic: HD
serial_number: 096077
program_official: TAYMANS, SUSAN
project_start_date: 2019-05-06
project_end_date: 2025-02-28
study_section: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]
contact_pi_person_id: 8244639
contact_pi: JO, MISUNG
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:
Abstract Understanding the cellular events underlying ovulation and subsequent corpus luteum (CL) formation iscritically important because these biological processes provide the foundation of our ability to regulate femalefertility. A fundamental cornerstone of the cellular events induced by the preovulatory gonadotropin surge vitalfor ovulation and CL formation is the expression of specific transcription factors. However our knowledge ofthe identity and regulatory actions of gonadotropin-induced key transcription factors remains limited. A recent study has shed light on a member of the activator protein-1 (AP-1) transcription factor family FOS(a.k.a. c-fos) as a key transcription factor involved in follicular development ovulation and luteal formation.Fos-deficient mice failed to ovulate and form CL even when exogenous gonadotropins were administered (1)indicating that the ovarian expression of Fos is necessary for normal ovulation and luteinization. However littleto nothing is known exactly how the FOS/AP-1 transcription factor affects these processes in the ovary. Ourpreliminary study revealed for the first time that the expression of FOS is highly up-regulated in dominantfollicles collected after hCG administration from normally cycling women and in preovulatory follicles after hCGadministration in mice. Moreover we demonstrated that FOS regulated the hCG-induced increase in theexpression of key ovulatory genes in human granulosa cells by directly binding to the promoters of thesegenes. Based on these novel findings we hypothesized that FOS/AP-1 plays essential roles in ovulation andluteal formation/function both in humans and mice. Fos null mice displayed a pleiotropic phenotype with significant loss of viability at birth. To determine theovary-specific function/action of FOS/AP-1 we propose to establish novel transgenic mouse models in whichFos expression is ablated in an ovarian cell-specific manner. These mutant mice will be used to assess theovarian phenotype including follicular development ovulation luteal development and fertility as well as toidentify downstream target genes of FOS/AP-1 in ovarian cells (Specific Aim #1). To relate and compare thefindings from mice to humans we will first characterize the spatiotemporally regulated expression of all FOSand JUN family members in ovulatory follicles obtained before and throughout the periovulatory period fromnormally cycling women. The specific role of FOS/AP-1 in human ovaries will also be determined by identifyingdownstream target genes of FOS/AP-1 and assessing the cellular impact(s) of FOS' action (Specific Aim #2). The information obtained from the proposed studies will not only advance our understanding of themechanism necessary for successful ovulation and luteinization but also be instrumental for futuretranslational/clinical application thus leading to improved management of fertility in vivo and in vitro.

project_terms:
Address;Affect;Albers-Schonberg disease;Binding;Binding Sites;Biological Process;Birth;Cell Culture Techniques;Cells;DNA Binding;Data;Development;Event;Exhibits;FOS gene;Family;Family member;Fertility;Foundations;Future;Gene Expression;Genes;Gonadotropins;Hour;Human;Human Chorionic Gonadotropin;In Vitro;JUNB gene;Knockout Mice;Knowledge;Light;Luteinization;Mediating;Mus;Mutant Strains Mice;Ovarian;Ovarian Tissue;Ovary;Ovulation;PMSG (Gonadotropins);Pathway interactions;Phenotype;Physiological;Physiology;Pilot Projects;Play;Process;Progesterone Receptors;Prostaglandins;Reporting;Reproductive Health;Role;Time;Transcription Factor AP-1;Transgenic Mice;Woman;base;clinical application;corpus luteum;design;female fertility;granulosa cell;human tissue;improved;in vivo;insight;jun Oncogene;member;mouse model;novel;prevent;promoter;recombinase-mediated cassette exchange;spatiotemporal;transcription factor

public_health_relevance:
Narrative Successful ovulation and subsequent corpus luteum formation and development are essential for femalefertility. In the present proposal we will demonstrate for the first time that the FOS/AP-1 transcription factorplays an essential role in ovulation and corpus luteum formation in both humans and mice. Information derivedfrom the present proposal will provide novel insights into the mechanism(s) underlying ovulation and lutealformation and can be applied for promoting and inhibiting the critical facet of ovarian physiology therebyallowing us to effectively manage fertility in women.


application_id: 10144830
project_number: 5R01ES027881-05
project_title: Air Pollution Circadian Rhythm Disruption and Cardiometabolic Disease
administering_ic: NIEHS
award_notice_date: 2021-04-14
opportunity_number: PA-16-160
application_type: 5
activity_code: R01
ic: ES
serial_number: 027881
program_official: SCHUG, THADDEUS
project_start_date: 2017-05-01
project_end_date: 2024-04-30
study_section: Systemic Injury by Environmental Exposure[SIEE]
contact_pi_person_id: 11375489
contact_pi: HABERZETTL, PETRA
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:
AbstractExposure to ambient air pollution has been linked to annually 7 million premature deathsworldwide and 200000 in the US and the global burden of air pollution is likely to increase dueto increasing urbanization and industrialization. Extensive research has shown that exposure toparticulate air pollution and specifically fine particulates (PM2.5) increase the risk ofcardiovascular disease and diabetes. However despite this extensive evidence it is unclearhow PM2.5 exposure increases the cardiometabolic risk and which susceptible states increasethe sensitivity to vascular and cardiometabolic injury due to PM2.5 exposure. In our proposedstudies we attempt to disentangle the mechanism leading to the toxicity of PM2.5 by testing thenovel hypothesis that PM2.5 disrupts vascular circadian rhythms and that this contributes to thedevelopment of cardiometabolic disease in a new susceptibility state of circadian dyssynchrony.This hypothesis is supported by our preliminary data showing that that exposure to concentratedambient PM2.5 (CAP) alters the rhythmic expression of clock genes in the murine aorta andincreases insulin resistance in mice with the disturbed light/dark cycle (circadian dyssynchrony).As this models a real-world scenario in which individuals with disturbed light cycle (e.g. due tolight pollution sleep deprivation) are exposed to air pollution it is of high relevance to ourmodern urban 24 h lifestyle associated with air and light pollution and changes in sleepbehavior. Successful completion of this project will identify new targets of and novelsusceptibility states (circadian dyssynchrony and chronotoxicity) for PM2.5 toxicity. Results oftheses studies will be of significance in understanding the adverse health effects originated fromour modern lifestyle and could ultimately lead to the development of evidence-based guidelinesand policies to minimize the cardiometabolic effects of urbanization and pollutant exposure.

project_terms:
ARNTL gene;Aerosols;Affect;Air;Air Pollution;Animal Model;Aorta;Attenuated;Biochemical Process;Biological;Biological Availability;Blood Pressure;Blood Vessels;Cardiometabolic Disease;Cardiovascular Diseases;Cardiovascular system;Cessation of life;Characteristics;Circadian Dysregulation;Circadian Rhythms;Data;Deposition;Development;Diabetes Mellitus;Diet;Eating;Endothelium;Exposure to;Gene Expression;Genes;Goals;Health;Human;Individual;Industrialization;Injury;Insulin Resistance;Knockout Mice;Laboratories;Lead;Life Style;Light;Link;Lung;Mediating;Metabolism;Modeling;Modernization;Mus;Nitric Oxide Synthase;Non-Insulin-Dependent Diabetes Mellitus;Oxidation-Reduction;Oxidative Stress;Particulate;Periodicity;Peripheral;Phase;Physiological Processes;Policies;Pollution;Post-Translational Protein Processing;Predisposition;Prevention strategy;Research;Sleep Deprivation;System;Testing;Toxic effect;Transcriptional Regulation;Urbanization;Work;air filter;ambient air pollution;atherogenesis;base;cardiometabolic risk;cardiometabolism;cardiovascular disorder risk;chemical property;circadian;diabetes risk;epidemiologic data;evidence based guidelines;fine particles;mortality;mouse model;novel;overexpression;particle;physical property;pollutant;premature;prevent;response;sleep behavior;vascular injury

public_health_relevance:
NarrativeGoal of this project is to test the novel hypothesis that air pollution exposure a major healthconcern worldwide that increase the risk of cardiovascular disease and diabetes disruptsvascular circadian rhythms and that this exacerbates cardiometabolic injury in the newsusceptibility state of circadian dyssynchrony. Results of this project will be of significance inunderstanding and preventing the adverse health effects originated from air pollution exposure.


application_id: 10144538
project_number: 3R01GM130954-01A1S1
project_title: Insulin Degrading Enzyme: Physiological Function and its Spatial and Activity Modulation
administering_ic: NIGMS
award_notice_date: 2020-06-02
opportunity_number: PA-18-591
application_type: 3
activity_code: R01
ic: GM
serial_number: 130954
suffix: A1S1
program_official: BARSKI, OLEG
project_start_date: 2019-09-01
project_end_date: 2023-07-31
contact_pi_person_id: 7875201
contact_pi: LOUIS HERSH, LOUIS HERSH LOUIS HERSH
other_pis: RODGERS, DAVID W
congressional_district: 06
department: BIOCHEMISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
An administrative supplement to support an undergraduate summer research experience forrising senior Sarah Sprigg is requested. Sarah will carry out some of the investigationsproposed in Aims 1 and 2 of the parent grant. Specifically she will explore the utility of afluorescent fusion construct of insulin-degrading enzyme (IDE) in following enzyme localizationin cultured live cells. She will also use the construct to evaluate potential non-localizing mutantsand the proposed close interaction with insulin in endosomes. This research experience willprovide many opportunities for Sarah to enhance her scientific communication and career skills.She will follow a structured protocol in designing experiments aimed at giving her experience indeveloping and testing hypotheses and gain further experience in documenting her researchactivities. She will learn mammalian cell culture techniques sophisticated light microscopyCRISPR/Cas9 technology as well as the use of FRET to demonstrate the close proximity ofmolecules in cells. Sarah will present her work in regular group meetings our university'sshowcase of undergraduate scholars and the annual state undergraduate research event. Inaddition Sarah will participate in a student led journal club in the department write up hersummer studies in the form of a manuscript and submit her work for presentation at theNational Conference of Undergraduate Research. Finally Sarah will register with andparticipate in programs provided by our Office of Undergraduate Research which will furtherexpand her contact with students interested in research and career mentors.

project_terms:
Administrative Supplement;Affect;Affinity;Alzheimer's Disease;Amyloid beta-Protein;Binding;Binding Sites;Biological Assay;CRISPR/Cas technology;Catabolism;Cell Culture Techniques;Cell Fractionation;Cell physiology;Cells;Communication;Cultured Cells;Development;Diabetes Mellitus;Disease;Endosomes;Enzyme Activation;Enzymes;Event;Fluorescence Resonance Energy Transfer;Goals;Group Meetings;Inositol Phosphates;Insulin;Insulinase;Investigation;Journals;Knowledge;Learning;Ligands;Lipids;Mammalian Cell;Manuscripts;Membrane;Mentors;Microscopy;Monitor;Peptide Hydrolases;Peptides;Phosphatidylinositols;Physiological;Play;Professional Competence;Protocols documentation;Research;Research Activity;Role;Signal Transduction;Structure;Students;Techniques;Testing;Universities;Work;Writing;Yeasts;base;career;design;endosome membrane;enzyme activity;enzyme substrate;experience;experimental study;human disease;inhibitor/antagonist;innovation;interest;light microscopy;mutant;parent grant;phosphatidylinositol 3-phosphate;polyanion;programs;receptor internalization;receptor mediated endocytosis;summer research;symposium;undergraduate research;undergraduate student

public_health_relevance:
From parent grant:Insulin Degrading Enzyme (IDE) plays an important role in regulating the levels of a number ofphysiological peptides involved in human disease including insulin involved in diabetes andamyloid beta peptide involved in Alzheimer's disease. This project will focus on how thephysiological functions of Insulin Degrading Enzyme are affected by its intracellular localizationand by activation by polyanions.


application_id: 10144289
project_number: 1R13ES032657-01
administering_ic: NIEHS
award_notice_date: 2021-02-22
opportunity_number: PA-18-648
application_type: 1
activity_code: R13
ic: ES
serial_number: 032657
program_official: O'FALLON, LIAM
project_start_date: 2021-03-01
project_end_date: 2024-02-29
study_section: Special Emphasis Panel[ZES1 LWJ-S (13)]
contact_pi_person_id: 14360895
contact_pi: MARION, JASON WAYNE
other_pis: Not Applicable
congressional_district: 06
department: NONE
primary_duns: 074051269
primary_uei: K69HFP3FKJ11
duns_number: 074051269
uei: K69HFP3FKJ11
fips: US
organization_id: 2274301
organization_name: EASTERN KENTUCKY UNIVERSITY
organization_city: RICHMOND
organization_state: KY
organization_type: SCH ALLIED HEALTH PROFESSIONS
organization_zip: 404753100
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2021-03-01
project_title:
Integrating U.S. Environmental Health Research and Practice into the Global One Health Framework: The One Health - One Global Environment Conference

project_abstract:
PROJECT SUMMARYThe proposed conference support will add substantial value in strengthening U.S.partnerships with scientists and environmental health practitioners in Jamaica andbeyond on topics related to emerging multidisciplinary multination environmental healththreats. The conference support will enable two leading women in environmental healthscience to engage with six sponsored junior scientists at least 300 attendees roughly30 undergraduate EHS students and many livestream participants. The One HealthOne Global Environment Conference in 2017 included leadership from the One HealthCommission the U.S. Armys food safety program national practitioner associationsfrom six continents and scientists from environmental and veterinary public health. In2017 key thematic areas emerged as threats to U.S. and global environmental healthsecurity mostly in infectious disease prevention and research capacity. The aims of thisproposal are to 1) identify and address environmentally- and occupationally-mediatedinfectious disease risks (including COVID-19) impacting low- and middle- incomenations and 2) to enhance the capacity and resource-sharing among universities andenvironmental health organizations to address emerging infectious disease threats inenvironmentally-impacted landscapes and workplaces. Project activities will include a1.0-day of information exchange between selected participants through a dedicatedtrack while supporting 2.0  2.5 additional presentation days to 30 undergraduatestudents and 300 attendees of the Jamaica Association of Public Health Inspectors jointmeeting with the One Health One Global Environment Conference. The proposal seeksto leverage the expertise (including pandemic disease prevention/response expertise) ofspeakers to facilitate discussion. Funding will enable greater representation of women inscientific leadership positions enhancement of the career pipeline and knowledge toaction. The support will promote translation through action-oriented partnerships withCaribbean (and other international) researchers and practitioners lacking resources forsuch a conference. We are committed to promoting translation through greater researchengagement and partnership in the Caribbean (and beyond) on addressing emergingborderless environmental health threats as all five keynotes will be livestreamed viasocial media (at no charge). Support will also enhance the EHS career pipeline byengaging a diverse group of junior EHS scientists in collaborative global health science.

project_terms:
Address;American;Americas;Antimicrobial Resistance;Area;Award;COVID-19;Caribbean region;Charge;Chemicals;Communicable Diseases;Communities;Consequentialism;Data;Discipline;Emerging Communicable Diseases;Environment;Environmental Health;Environmental Pollution;Epidemiologist;Event;Food Safety;Foundations;Funding;Future;Goals;Health;Health Sciences;Human;Income;Institutes;International;Intervention;Jamaica;Joints;Journals;Knowledge;Leadership;Livestock;Longevity;Mediating;Methods;Molecular;National Institute of Environmental Health Sciences;Occupational;Outcome;Participant;Persons;Play;Positioning Attribute;Prevention Research;Process;Public Health;Research;Research Personnel;Resistance development;Resource Sharing;Resources;Role;Science;Scientist;Security;Senior Scientist;Site;Strategic Planning;Students;System;Time;Training;Translating;Translations;United States National Institutes of Health;Universities;Woman;Workplace;beneficiary;biosecurity;career;career development;cost;disorder prevention;disorder risk;gender diversity;global environment;global health;health organization;improved;interest;international partnership;live stream;meetings;microbiome research;multidisciplinary;outreach;pandemic disease;pathogen;prevent;programs;response;social media;support network;symposium;transmission process;undergraduate student

public_health_relevance:
PROJECT NARRATIVERecent Academic World Conferences of the International Federation of EnvironmentalHealth revealed opportunities for enhancing global engagement among environmentalhealth science (EHS) practitioners and One Health researchers through the use of EHSexposure assessment methods in chemically contaminated landscapes or workplacesthat have substantial human wildlife and/or livestock interaction. With support for theOne Health  One Global Environment meeting we will engage a diverse pool of juniorand senior scientists in characterizing research needs and intervention opportunitiesrelated to environmental contaminants that may be facilitating antimicrobial resistancedevelopment and/or altering pathogen transmission dynamics between reservoirs andhuman hosts. Our ultimate objective is to enhance diversity in the pipeline ofcollaborative global health scientists focused on preventing and managing emergingenvironmentally-mediated infectious disease threats including possible pandemicpathogens.


application_id: 10143668
project_number: 1R13ES032658-01
project_title: 2021 Central and Eastern European Conference on Health and the Environment
administering_ic: NIEHS
award_notice_date: 2021-09-01
opportunity_number: PA-18-648
application_type: 1
activity_code: R13
ic: ES
serial_number: 032658
program_official: TROTTIER, BRITTANY
project_start_date: 2021-09-01
project_end_date: 2024-08-31
study_section: Special Emphasis Panel[ZES1 LWJ-S (13)]
contact_pi_person_id: 12547580
contact_pi: GUTIERREZ, ANGELA MARIA
other_pis: Not Applicable
congressional_district: 06
department: VETERINARY 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: EARTH SCIENCES/RESOURCES
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY/ABSTRACTThe seventh Central and Eastern European Conference on Health and the Environment (CEECHE) will beheld at Vytautas Magnus University Kaunas Lithuania. CEECHE is an important platform for continuingcoordination of U.S. and Central and Eastern European (CEE) stakeholder expertise directed at multiple facetsof environmentally induced diseases. This proposed meeting builds on 30 years of international interactionsdedicated to building a network of scientists health experts and federal and private stakeholders poised toaddress a central problem: environmental insults linked to comprised health. Major concerns of environmentalpollution in Baltic states such as Lithuania and CEE stakeholders include air pollution water pollution and thethreat of nuclear contamination. Thus the goal of CEECHE 2021 is to explore promote support and providethe resources to representative individuals across Central Eastern and Northern Europe with a focus on healthand environment. Key areas of focus will include emerging (and ongoing) issues for water resources thatimpact drinking water sources indoor and outdoor air pollution health effects and mitigation approachesenvironmental disease prevention strategies including lifestyle factors public policy implications and next-generation scientific leadership. Collaboration between the US and Lithuanian scientists through previousCEECHE meetings have established opportunities to explore new ideas for addressing common environmentalchallenges such as water and indoor and ambient air pollution. The University of Kentucky SuperfundResearch Center Lexington Kentucky proposes to partner with the Vytautas Magnus University to organizeand implement the CEECHE 2021 in Kaunas Lithuania June 6-10 2021. Conference objectives are centeredon the conference theme of Seeking Solutions for Environmental Exposures and Disease Risks and are to: 1)provide an intellectual exchange between scientists and trainees in the field of environmental pollutantexposure and disease risks by exploring sustainable strategies for environmental detection and remediation ofhazardous pollutants; 2) review environmental insults related to water and air pollution on population health asa variant of disease by including studies related to persistent organic pollutants metals mixtures and new andemerging pollutants; 3) compare understand and assess population health impacts associated with exposurescience and prevention of environmental disease through positive lifestyle modifications and new riskassessment paradigms; and 4) provide a platform to strengthen the relation and collaboration between traineesand young environmental scientists from the US CEE and Baltic regions relative to environmental challengesin the 21st century and beyond. CEECHE meetings have focused on highly contaminated geographicenvironments in CEE that pose severe multinational health threats. There are few if any other internationalvenues that bring together CEE and U.S. scientists. The conference site in Kaunas Lithuania will facilitatemaximum participation of European Union and other CEE scientists and stakeholders with their U.S.counterparts to promote productive scientific discussions and collaborations focused on emerging globalpriorities including air and water pollution and associated challenges in the area of environmentally induceddisease.

project_terms:
Address;Air;Air Pollution;Area;Baltic States;Biological;Cessation of life;Chemicals;Collaborations;Communities;Complex;Country;County;Czech Republic;Deposition;Detection;Discipline;Disease;Eastern Europe;Education;Environment;Environmental Exposure;Environmental Health;Environmental Pollutants;Environmental Pollution;European;European Union;Event;Fire - disasters;Funding;Geographic Locations;Geography;Goals;Government Officials;Health;Human;Individual;Institution;International;Intervention;Kentucky;Knowledge;Leadership;Life Style Modification;Link;Lithuania;Location;Longevity;Metals;Minority;National Institute of Environmental Health Sciences;Northern Europe;Nuclear;Pathway interactions;Personal Satisfaction;Poland;Predisposition;Prevention;Prevention strategy;Privatization;Public Policy;Publications;Research;Research Personnel;Residual state;Resources;Risk Assessment;Romania;Science;Scientist;Sea;Site;Soil;Source;Students;Superfund;Training;Travel;Universities;Variant;Water;Water Pollution;Woman;ambient air pollution;career;contaminant transport;contaminated water;cost;disorder prevention;disorder risk;drinking water;environmental transport;exposed human population;fighting;health disparity;health literacy;improved;lifestyle factors;meetings;next generation;persistent organic pollutants;policy implication;pollutant;population health;remediation;symposium

public_health_relevance:
PROJECT NARRATIVECentral and Eastern European Conference on Health and the Environment (CEECHE) 2021 SeekingSolutions for Environmental Exposures and Disease Risks will provide a diverse and engaging platform forinternational scientists to discuss 21st century environmental health challenges. Conference sessions will focuson prevention/intervention approaches to reduce disease risks associated with environmental insults. Theconference will also include scientific presentations on water and indoor/ambient air pollution which do notrecognize country boundaries as pollutants migrate and pose adverse health effects on communities.


application_id: 10142529
project_number: 5K01MH119942-02
project_title: Examining HIV-related Stigma and HIV Testing Among Formerly Incarcerated African American Youth
administering_ic: NIMH
award_notice_date: 2021-04-07
opportunity_number: PA-19-126
application_type: 5
activity_code: K01
ic: MH
serial_number: 119942
program_official: GREENWOOD, GREGORY LOUIS
project_start_date: 2020-05-01
project_end_date: 2024-04-30
study_section: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH]
contact_pi_person_id: 12373928
contact_pi: KERR, JELANI
other_pis: Not Applicable
congressional_district: 03
department: PSYCHOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF PUBLIC HEALTH
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/AbstractPersistent HIV health disparities impacts African Americans and are a public health priority. Despite decliningHIV rates nationally African American communities continue to experience disproportionate HIV burden andincreasingly account for the largest share of HIV-related morbidity and mortality in the United States. Theseconcerning disparities necessitate research to inform robust responses that target priority subgroups within thispopulation. High rates of incarceration in many African American communities contribute to high HIV riskenvironments where the risks persist after release from the criminal justice system. Formerly incarceratedAfrican American youth (FIAAY ages 18-24 years) in particular are at heightened risk in terms of sexualbehavior illicit drug use and challenged rates of HIV testing behavior after release. A prominent barrier to HIVtesting and timely diagnosis in this and other vulnerable populations is HIV-related stigma. Thus moreresearch needs to not only examine stigma-related factors that reduce HIV testing behavior but also create abasis for interventions that can reduce stigma and increase HIV testing and HIV preventive behaviors in prioritypopulations such as FIAAY. Towards these goals my proposed study focusing on FIAAY in LouisvilleKentucky will allow me to: 1) develop a risk profile of HIV-negative or HIV status unknown FIAAY at greaterlikelihood of having stigmatizing beliefs related to HIV infection and longitudinally examine the likelihood of HIVtesting based on this profile and 2) delineate mediating and moderating mechanisms by which stigma reducesHIV testing in this population. These actions will help generate knowledge for the development of a multilevelintervention targeting individual and structural factors to reduce HIV-related stigma and increase HIV testingand prevention among this population of vulnerable youth. This Career Development Award will provide thenecessary knowledge and skills to conduct this and future research with criminal justice-involved populations.This entails enhancing my skills in advanced statistical methods such as survival analysis and structuralequation modeling. In addition it will foster content expertise in decision science and the criminal justicesystem which will help inform intervention development. Study methods will include longitudinal survey datacollection (baseline 12-months 24-months) from 274 FIAAY in Louisville KY. This research will inform thedevelopment of stigma-related HIV-risk profiles for FIAAY who are less likely to test and delineate mediatorsand moderators of the stigma-HIV testing relationship. If a relationship between stigma and testing is notdetected other psychosocial factors will be examined to determine mediators and moderators of HIV testing.This study has important downstream benefits for HIV prevention and treatment in this highly vulnerablepopulation.

project_terms:
AIDS prevention;Address;Affect;African American;Age;Behavior;Behavior Therapy;Behavioral;Belief;Caring;Characteristics;Communities;Criminal Justice;Data;Data Collection;Demographic Factors;Development;Diagnosis;Drug usage;Early Diagnosis;Environment;Equation;Exhibits;Fostering;Fright;Gender;Gender Identity;General Population;Goals;HIV;HIV Infections;HIV Seronegativity;HIV diagnosis;HIV risk;Health;Health behavior;Homophobia;Human immunodeficiency virus test;Imprisonment;Individual;Intervention;K-Series Research Career Programs;Kentucky;Knowledge;Longitudinal Surveys;Mediating;Mediator of activation protein;Methods;Modeling;Morbidity - disease rate;Neighborhoods;Participant;Pathway interactions;Persons;Population;Poverty;Predisposition;Prevention;Prevention strategy;Preventive;Psychosocial Factor;Public Health;Recording of previous events;Research;Research Personnel;Research Project Grants;Risk;Risk Behaviors;Science;Sex Behavior;Sex Orientation;Statistical Methods;Stereotyping;Stigmatization;Structure;Subgroup;Survival Analysis;System;Testing;Time;Translational Research;Unemployment;United States;Vulnerable Populations;Work;Youth;aged;base;behavior test;care systems;career development;condoms;experience;health disparity;illicit drug use;improved;male;mortality;pre-exposure prophylaxis;prediction algorithm;prevent;prevention service;psychologic;public health priorities;racial and ethnic disparities;racial disparity;response;sexual risk behavior;skills;social stigma;substance use;testing uptake;therapy development;treatment disparity;uptake

public_health_relevance:
Project NarrativeAfrican American youth with a history of incarceration are at heightened HIV risk thus early detection amongthis group is critical for linkage to prevention and care services improving survival prospects and reducingracial disparities in HIV. Despite the benefits of testing HIV-related stigma remains a significant barrier totimely HIV diagnosis however little research examines the mechanisms by which HIV-related stigma inhibitstesting behavior. This study will delineate the relationships between stigma stigma-related factors and HIVtesting and the information will be used to help generate knowledge for intervention development to improveHIV testing and stigma-reduction for formerly incarcerated African American youth.


application_id: 10142519
project_number: 5R01HD101508-02
project_title: Noninvasive Noncontact High-Density Optical Imaging of Neonatal Intraventricular Hemorrhage
administering_ic: NICHD
award_notice_date: 2021-03-31
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: HD
serial_number: 101508
program_official: KING, TRACY
project_start_date: 2020-04-10
project_end_date: 2025-03-31
study_section: Imaging Technology Development Study Section[ITD]
contact_pi_person_id: 8252681
contact_pi: YU, GUOQIANG
other_pis: Not Applicable
congressional_district: 06
department: BIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_terms:
Acute;Aftercare;Autopsy;Biological Markers;Birth;Blood;Blood Vessels;Brain;Brain Injuries;Brain imaging;Calibration;Case Study;Cephalic;Cerebral Ventricles;Cerebrospinal Fluid;Cerebrospinal fluid shunts procedure;Cerebrovascular Circulation;Cerebrum;Chronic Phase;Clinical;Complication;Coupled;Coupling;Critical Care;Critical Illness;Detection;Development;Devices;Diffuse;Effectiveness of Interventions;Evaluation;Fiber;Functional Imaging;Goals;Guidelines;Head;Histologic;Homeostasis;Human;Hydrocephalus;Image;Imaging Device;Imaging Techniques;Impairment;Inflammation;Injury;Intervention;Intracranial Hypertension;Intracranial Pressure;Ischemic Brain Injury;Laboratories;Lead;Legal patent;Low Birth Weight Infant;Magnetic Resonance Imaging;Measurement;Measures;Medical;Metabolic;Metabolism;Methods;Modeling;Monitor;Multi-modal optical imaging;Mus;Near-Infrared Spectroscopy;Neonatal;Neonatal Brain Injury;Neonatal Intensive Care Units;Neonatology;Neurologic Deficit;Neurological outcome;Neurosciences Research;Observational Study;Optics;Outcome;Outcome Measure;Outcome Study;Oxygen;Oxygen Consumption;Premature Birth;Premature Infant;Property;Rattus;Recovery;Research;Resolution;Safety;Scalp structure;Signal Transduction;Source;Structure;Survival Rate;System;Technology;Testing;Three-Dimensional Imaging;Time;Tissues;Ultrasonography;algorithmic methodologies;brain health;brain tissue;cerebral hemodynamics;cerebrovascular;clinical application;clinical outcome assessment;cranium;density;design;detector;functional disability;high risk;human imaging;imager;imaging modality;improved;in vivo;injury recovery;innovation;intraventricular hemorrhage;metabolic rate;multimodality;neonatal brain;neonate;neuroimaging;novel;optical imaging;portability;pre-clinical;premature;preservation;preterm newborn;prevent;standard care;standard of care;tissue injury;tissue phantom;tomography;tool


application_id: 10142414
project_number: 5UM1DA049406-03
project_title: Kentucky CAN HEAL (Communities and Networks Helping End Addiction Long-term)
administering_ic: NIDA
award_notice_date: 2021-04-08
opportunity_number: RFA-DA-19-016
application_type: 5
activity_code: UM1
ic: DA
serial_number: 049406
program_official: HIGHSMITH, KEISHER S
project_start_date: 2019-04-17
project_end_date: 2023-03-31
study_section: ZDA1-TXW-S(16)R
contact_pi_person_id: 1877426
contact_pi: WALSH, SHARON L.
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:
ABSTRACTThe Kentucky CAN (Communities and Networks) HEAL (Helping End Addiction Long-term) [KCH] study is alarge-scale community intervention project submitted in response to the HEALing Communities request forproposals to test the immediate impact of implementing an integrated set of evidence-based interventionswith the aim of reducing opioid overdose deaths by 40% in three years. KCH represents a partnership betweenthe University of Kentucky Kentucky State government officials and numerous community organizations. Thisproject will employ an incomplete stepped-wedge cluster randomized design to deploy an integrated set ofevidence-based practices in 17 highly affected counties in Kentucky in two waves of assignment. Highlyaffected counties were identified through an empirical algorithm that incorporated the requisite epidemiologicalcriteria for opioid overdose and structural systems in place to support the deployment of evidence-basedinterventions (EBIs). Prior to randomization a systematic implementation science-based approach will be usedto assess barriers attitudes and assets and to enhance implementation of EBIs. Primary intervention aims areto improve and expand treatment with medications for opioid use disorder (MOUD) by increasing capacityentry and retention expand overdose prevention approaches in the community and reduce opioid supply bydecreasing high risk prescribing and increasing safe drug disposal. Community partners include thoserepresenting behavioral health healthcare public health criminal justice and community coalitions.Interventions will include those focused on 1) development of a Care Navigation network in MOUD treatmentprograms (FQHCs OTPs and OBOT providers) syringe service programs jails and parole and probationoffices to increase the number of individuals screened referred to initiating evidence-based care retained intreatment and receiving ancillary recovery support services; 2) enhancing and expanding the treatmentworkforce through increased DATA 2000 waiver trainings and weekly support through expert telehealthguidance using the ECHO model; 3) increasing overdose education and naloxone distribution in treatmentsettings syringe services programs jails parole and probation; and the community; 4) increasing access tosyringe services programs; 5) reducing risky opioid prescribing and dispensing; and 6) enhancing drugdisposal. By targeting individuals who are at highest risk (e.g. out of treatment reentering the community) anddeploying a community-wide health communication strategy to increase awareness and demand for EBIs wehypothesize that KCH will reduce overdose deaths by 40% in three years. KCH will leverage existing fundingand resources to enhance its effectiveness and the health economics of these interventions will be evaluatedin order to have meaningful and translatable impact on public policy.

project_terms:
Address;Affect;Age;Algorithms;Attitude;Awareness;Benzodiazepines;Buprenorphine;Caring;Cessation of life;Communities;Community Networks;County;Criminal Justice;Data;Death Rate;Development;Diagnosis;Education;Effectiveness;Emergency Situation;Ensure;Epidemiology;Evidence based intervention;Evidence based practice;Fentanyl;Funding;Government Agencies;Government Officials;Guidelines;Health Professional;Health Services Accessibility;Healthcare;Helping to End Addiction Long-term;Heroin;Individual;Intervention;Jail;Kentucky;Life Expectancy;Methadone;Modeling;Naloxone;Needle-Exchange Programs;Opioid;Opioid Antagonist;Outcome;Overdose;Pharmaceutical Preparations;Pharmacists;Phase;Policies;Prevention;Prevention approach;Professional Education;Provider;Public Health;Public Policy;Randomized;Recovery;Request for Proposals;Research;Resources;Rural;Services;Site;State Government;Structure;System;Testing;Training;Training Support;United States;Universities;Work;barrier to care;base;behavioral health;community based participatory research;community center;community intervention;community organizations;cost;design;evidence base;experience;healing;health communication;health economics;high risk;illicit drug use;implementation facilitators;implementation science;implementation strategy;improved;metropolitan;mortality;opioid disposal;opioid epidemic;opioid misuse;opioid mortality;opioid overdose;opioid use disorder;overdose death;overdose prevention;parole;prescription monitoring program;prescription opioid;probation;programs;response;screening;social stigma;stem;synthetic opioid;telehealth;test strip;theories;treatment program;waiver

public_health_relevance:
PROJECT NARRATIVEThe Kentucky CAN HEAL (Communities and Networks Helping End Addiction Long-Term) project aims toreduce opioid overdose deaths by 40% within three years. This initiative is a partnership between theUniversity of Kentucky and the Commonwealth of Kentucky along with numerous other academic andcommunity partners. This large-scale community-based project will leverage many evidence-basedinterventions to reduce overdose including expanding access to treatment overdose prevention trainingnaloxone distribution improving opioid prescribing practices and safe disposal of opioids.


application_id: 10142341
project_number: 5R01AG066653-02
project_title: Aberrant Glycogen Modulates Cerebral Glucose Metabolism in Aging and Alzheimer's Disease
administering_ic: NIA
award_notice_date: 2021-03-18
opportunity_number: PAR-17-031
application_type: 5
activity_code: R01
ic: AG
serial_number: 066653
program_official: BARRETT, PAUL JOHN
project_start_date: 2020-04-15
project_end_date: 2025-03-31
study_section: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]
contact_pi_person_id: 11838914
contact_pi: SUN, RAMON C.
other_pis: Not Applicable
congressional_district: 06
department: BIOCHEMISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Abstract:The onset of Alzheimer's disease (AD) increases in incidence with age and an increasing aging demographicmeans the number of individuals suffering from AD is expanding rapidly. Changes in cerebral metabolism arehallmarks of aging therefore it is reasonable to hypothesize that age-associated change in metabolism playmajor roles in AD progression. AD brains show clear metabolic impairments and studies suggest that alteredmetabolism drives a cascade of events leading to AD onset. The mechanisms initiating these metabolicimpairments remain a critical knowledge gap in AD research. We recently discovered that aberrant glycogenaggregates (AD-glycogen) are a universal feature of AD in both human and mice. Increases in AD-glycogencorrelated with higher Braak staging and lower glucose levels in patient specimens. AD-glycogen is bothhyper-phosphorylated and hyper-branched making them architecturally distinct from normal glycogen. Wepresent strong evidence showing that AD-glycogen modulate brain metabolism through direct binding andinactivation of the AMP-activated protein kinase (AMPK) a master regulator of central carbon metabolism. Wewill first elucidate the molecular events leading to abnormal AD-glycogen formation in vitro and in vivo (Aim 1)then we will interrogate the impact of AD-glycogen on cerebral metabolism during aging (Aim 2). Finally wewill assess the efficacy of a novel glycogen-clearing enzyme therapy on brain metabolism cognition and ADneuropathology in vivo (Aim 3). The PI has assembled a multi-disciplinary team of investigators withcomplementary skillsets and state-of-art high resolution and Omic-based techniques to discover potentialtherapeutic options and possibly treat the onset of AD.

project_terms:
5'-AMP-activated protein kinase;Ablation;Age;Aging;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease patient;Anabolism;Antibodies;Architecture;Astrocytes;Autopsy;Behavior;Binding;Biochemical;Brain;Carbon;Cerebrum;Characteristics;Clinical;Cognition;Cyclic AMP-Dependent Protein Kinases;Data;Disease Progression;Enzymes;Event;Glucose;Glycogen;Glycogen Storage Disease;Human;Impairment;In Vitro;Incidence;Individual;Kentucky;Knowledge;Lead;Learning;Mass Spectrum Analysis;Measures;Memory;Metabolic;Metabolic Pathway;Metabolism;Methods;Molecular;Mus;Nerve Degeneration;Neurons;Onset of illness;Pathogenesis;Pathologic;Patients;Play;Polysaccharides;Positioning Attribute;Premature aging syndrome;Process;Protein Kinase;Reporting;Research;Research Personnel;Resolution;Rodent;Role;Sampling;Severities;Specimen;Staging;Structure;Symptoms;System;Tauopathies;Techniques;Testing;Therapeutic;Transgenes;Universities;age related;aging brain;aging demographic;aging population;amyloid pathology;base;brain metabolism;design;enzyme therapy;glucose metabolism;glycogen metabolism;improved;in vitro Model;in vivo;metabolomics;mouse model;multidisciplinary;mutant;neuropathology;novel;novel therapeutics;pre-clinical;stable isotope;therapeutic target

public_health_relevance:
Project NarrativeCerebral glucose hypometabolism is now considered one of the hallmarks of Alzheimers disease (AD) clinicalAD symptoms almost never occur in the absence glucose hypometabolism and the extent of the metabolicchanges measured strongly correlate with the severity of clinical symptoms. The mechanism(s) that driveglucose hypometabolism remain a critical knowledge gap in AD research. This proposal aims to examine age-related changed in cerebral glucose metabolism in both healthy and AD mouse models to 1) improve ourunderstanding in the metabolic aging process and 2) to identify divergent events that result in the onset of ADfrom the aging population.


application_id: 10142117
project_number: 3T32DA016176-15S1
project_title: Administrative Supplement: Training in Drug Abuse Related Research
project_terms: Administrative Supplement;Drug abuse;Research;Training
administering_ic: NIDA
award_notice_date: 2020-04-17
opportunity_number: PA-18-591
application_type: 3
activity_code: T32
ic: DA
serial_number: 016176
suffix: S1
program_official: BABECKI, BETH
project_start_date: 2004-07-01
project_end_date: 2021-06-30
contact_pi_person_id: 1878605
contact_pi: DWOSKIN, LINDA P
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
PROJECT SUMMARYT32 Training Grant supplement entitled Training in Drug Abuse Related Research requests 1 year of supportfor a highly collaborative translational program in broad-based contemporary aspects of substance usedisorder (SUD) research. Training the next generation of SUD researchers is critical to current and futurepublic health challenges associated with SUD. The overarching goal is to prepare trainees for successfulcareers in SUD research. The overarching theme is that abused substances alter fundamental cellular andmacromolecular proteins and signaling processes in brain resulting in long term changes in neural plasticityand behavior and that these macromolecular proteins serve as targets for novel therapeuticdiscovery/development that ultimately will be effective in mitigating harm to the individual and the population.The program will: 1) foster the development of essential experimental and critical thinking skills; 2) provideopportunities to gain an in depth understanding of and expertise in molecular/cellular aspects ofreceptors/brain signaling mechanisms mediating the behavioral response to abused drugs; 3) becomeimmersed in the pathway of discovery/development/translation/implementation of medications to treat SUD;and 4) understand population-level pharmaceutical outcomes of these interventions. We propose to continue tosupport 2 predoctoral trainees for 1 year. In the upcoming period we propose to continue our record ofsuccess in developing ethical SUD researchers who will move the SUD field forward.

public_health_relevance:
PROJECT NARRATIVEThe goal of this training program is to prepare promising predoctoral and postdoctoral trainees forproductive and successful careers in drug abuse research a critical endeavor for current and future publichealth challenges associated with drug addiction. The program fosters the development of essentialexperimental and critical thinking skills and focused expertise on the interrelationships of cellular andmolecular aspects of receptors and signaling mechanisms involved in the response to drugs of abusewithin the context of drug discovery and development of novel treatments for drug abuse. Our programprovides a highly collaborative environment of interdisciplinary and translational training in drug abuseresearch coupled with opportunities for networking and collaboration to advance our trainees towardsindependent investigator status in drug abuse research.


application_id: 10141237
project_number: 5T35EY026509-05
project_title: Summer Vision Sciences Training Program
administering_ic: NEI
award_notice_date: 2021-04-12
opportunity_number: PA-16-151
application_type: 5
activity_code: T35
ic: EY
serial_number: 026509
program_official: CLAYTON, EDWIN C
project_start_date: 2017-07-01
project_end_date: 2022-04-30
study_section: ZEY1-VSN(03)
contact_pi_person_id: 1925445
contact_pi: CERESA, BRIAN P.
other_pis: GUIDO, WILLIAM
congressional_district: 03
department: PHARMACOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/Abstract This application is a resubmission for a T35 summer medical student training program invision research with two Specific Aims: 1) To provide hands-on training in basic and clinicalvision research to medical students in a structured mentored environment and 2) To provide aninteractive educational experience that introduces medical students the fundamental skillsnecessary for basic translational and clinical research in vision biology. The co-directors of thisprogram request support for 6 second-year medical students each summer in vision relatedresearch laboratories that focus on topics such as visual circuitry retinal degeneration cornealepithelial homeostasis uveitis and development of the visual system. Trainees will be selectedfrom the first year class at University of Louisville School of Medicine. Students will reviewresearch projects submitted by 19 faculty funded by the NEI or vision related foundations. Thedirectors will make a special effort to recruit students from ethnic minorities and disadvantagedbackgrounds. Students will review the available projects and enter their 1st-3rd choices allowingmatching of trainees with mentors. Final decisions will be made based on interviews betweenmentors and Trainees. During the 10-week summer training students work with mentors ontheir research project in clinical or laboratory settings complete training in the ResponsibleConduct of Research including topics such as fabrication and falsification of data plagiarismmanaging scientific data publication practices and responsible authorship mentorshipstewardship and conflict of interest. Trainees will complete human subject IRB training andanimal care and handling as required by their specific research projects. All Trainees will attenda 2-hour weekly Vision Sciences Research Training Seminar designed to introduceclinical/translational research in Ophthalmology led by mentors in this T35 program. Theseminar series will culminate with each Trainee presenting his/her research project to peers andmentors. Trainees present the results of their research as posters with peers at a School ofMedicine-wide week-long celebration of research that includes nationally recognized physician-scientists as keynote speakers. Trainees will be encouraged to continue research as part of theDistinction in Research track that is an enrichment program focusing on providing meaningfuland productive research experiences throughout second through fourth years of medical schoolwith ongoing presentations by students with mentors and 4+ weeks of research time in thefourth year toward the goal of developing clinician-researchers. Trainees will be tracked toassess the impact of this T35 program on careers as physician-scientists.

project_terms:
Authorship;Basic Science;Biology;Clinical;Clinical Research;Conflict of Interest;Data;Environment;Faculty;Foundations;Funding;Goals;Homeostasis;Hour;Institutional Review Boards;Interview;Laboratories;Laboratory Research;Medical Students;Mentors;Mentorship;Ophthalmology;Physicians;Plagiarism;Publications;Research;Research Personnel;Research Project Grants;Research Training;Retinal Degeneration;Scientist;Series;Structure;Student recruitment;Students;Time;Training;Training Programs;Translational Research;Universities;Uveitis;Vision;Vision research;Visual;Work;animal care;base;career;corneal epithelium;design;disadvantaged background;ethnic disadvantage;ethnic minority population;experience;human subject;medical schools;peer;peer coaching;posters;programs;responsible research conduct;skills;vision development;vision science

public_health_relevance:
Program Narrative:This new NEI Short-Term Institutional Training Grant application is to request 5 years of support for 6 risingsecond year Medical Student trainees in our Vision Science laboratories for a 10 week research experience.We will focus on recruitment of under-represented trainees into this program to enhance the diversity of ourmedical workforce. The T35 training grant will be used to entice our medical students into our new Distinctionin Research Track a program that encourages students to participate in laboratory research in years 2-4 ofmedical school with an eye toward scholarly activities in academic medicine to continue to build a pipeline oftranslational clinician-researchers in the future.


application_id: 10140944
project_number: 3RF1AG062480-01S1
administering_ic: NIA
award_notice_date: 2020-08-14
opportunity_number: PA-18-817
application_type: 3
activity_code: RF1
ic: AG
serial_number: 062480
suffix: S1
program_official: ARUNKUMAR, NANDINI
project_start_date: 2019-05-01
project_end_date: 2021-08-01
contact_pi_person_id: 10518078
contact_pi: LIN, AI-LING
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2020-08-15
project_title:
Supplement to Prebiotics Intervention to Reduce Alzheimer's Disease Risk via Brain-Gut Axis in an APOE4 Mouse Model

project_abstract:
Project SummaryTraumatic brain injury (TBI) currently affects 1.6-3.8 million people in the US annually. Over the past 30 yearsresearch has linked TBI to a greater risk of developing Alzheimers disease (AD) or another dementia yearsafter the original head injury. More recently emerging evidence shows that TBI increases intestinalpermeability and alters gut microbiome composition that further exacerbate inflammation brainvascular/metabolic dysfunctions and perpetuate long-term secondary sequelae. Therefore the presumption isthat having a pre-existing healthy gut microbiome composition/diversity may be critical for protecting brainfunctions after TBI and potentially prevent the further development of cognitive impairment. In this study ourgoal is to determine if AD risk can be reduced by administrating prebiotic Inulin diet before TBI in young miceto protect the brain vascular metabolic and white matter (WM) integrity and reduce neuroinflammation throughgut microbiome modulation. The central hypothesis is that mice with inulin diet before TBI will have healthiergut microbiome profile and better protection for brain vascular metabolic and WM integrity after TBI and thusprotect the cognitive function. We will test the hypothesis by pursuing the following two Specific Aims: (i)Determine Inulin effects on the gut microbiome and SCFAs production for protecting TBI; (ii) Identify Inulineffects on brain functions and neuroinflammation for protecting TBI. This project is innovative because it is oneof the first studies to identify the protective effects of prebiotic Inulin for TBI via gut-brain axis. It is alsoinnovative because it challenges the current standing of the field of TBI. Instead of trying to reduce theneurological and systemic effects of injury after it occurs we shift the focus to mitigation of the injury cascadein populations already known to be at risk such as military personnel and athletes. The success of the studywould enhance our understanding of CNS-peripheral interactions in TBI and identify potential effective dietaryintervention for preventing AD in a younger population. As Inulin-related diets are commercially available andMRI neuroimaging and gut microbiome analyses are readily to be used for humans our approaches are highlytranslational; if we are able to show that we can use diet as a measure to mitigate secondary sequelae in micewed be able to rapidly transition to studies with humans.

project_terms:
Acetates;Acute;Affect;Age;Age-Months;Alzheimer's Disease;Alzheimer's disease risk;Applications Grants;Award;Bacteria;Biochemical;Biological Assay;Blood;Blood Vessels;Brain;Brain Injuries;Butyrates;C57BL/6 Mouse;Cecum;Centers for Disease Control and Prevention (U.S.);Cerebrovascular Circulation;Clinical Research;Cognition;Craniocerebral Trauma;Dementia;Development;Diet;Dietary Intervention;Early Intervention;Effectiveness;Future;Gene Expression;Goals;Human;Image;Immune response;Impaired cognition;Impairment;Inflammation;Injury;Intervention;Intestinal permeability;Inulin;Light;Link;Magnetic Resonance Imaging;Measures;Metabolic;Metabolic dysfunction;Metabolism;Military Personnel;Mus;Neurologic;Paper;Parents;Patients;Peripheral;Phase;Physiological;Physiology;Play;Population;Production;Propionates;Public Health;Publishing;Reporting;Research;Research Personnel;Risk;Role;Sampling;Sports;Taxonomy;Testing;Traumatic Brain Injury;Volatile Fatty Acids;aging population;behavior test;brain metabolism;brain tissue;cognitive development;cognitive function;cytokine;dietary supplements;disability;dysbiosis;feeding;genetic risk factor;gut microbiome;gut microbiota;gut-brain axis;innovation;insight;metabolic profile;microbiome analysis;microbiome composition;mouse model;neuroimaging;neuroinflammation;parent grant;prebiotics;preservation;prevent;protective effect;success;white matter;young adult

public_health_relevance:
NarrativeThe proposed research is relevant to public health because we will identify the effectiveness of prebiotic inulindiet for protecting brain functions under traumatic brain injury (TBI) through gut microbiome modulation. Thesuccess of the study will bring insight for potential usefulness of dietary interventions to preserve brainphysiological and cognitive functions against TBI.


application_id: 10140325
project_number: 5R21DE028506-02
project_title: Filifactor alocis-tobacco interactions
administering_ic: NIDCR
award_notice_date: 2021-03-15
opportunity_number: PA-19-053
application_type: 5
activity_code: R21
ic: DE
serial_number: 028506
program_official: MCNEALY, TAMARA L
project_start_date: 2020-04-07
project_end_date: 2023-03-31
study_section: Special Emphasis Panel[ZRG1-MOSS-S(02)M]
contact_pi_person_id: 7338645
contact_pi: SCOTT, DAVID A
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARYTobacco smoking is the leading environmental cause of chronic periodontitis and other bacterial-induced periodontal diseases. Some components of dental plaque are highly resistant to the plethoraof toxic insults contained in cigarette smoke. One such species is the emergent oral pathogen Filifactoralocis. F. alocis has been consistently associated with periodontal diseases epidemiologically; thrivesin tobacco-rich environments both in vitro and in vivo; and is one of the most transcriptionally activebacterial species found in the disease-associated microbiome. We will identify (RNAseq) validate(qPCR) and classify (KEGG DAVID etc) those genes that are significantly regulated by cigarettesmoke exposure in three strains of F. alocis. We will then assess in vivo relevance in a germ-free F.alocis infection smoke exposure model. We shall generate some of the first information to explain howthis emergent periodontopathogen may survive and persist in the oral cavity of smokers. The smokeexposure chamber will also facilitate the development of a reproducible model of tobacco-inducedand/or exacerbated bacteria-associated periodontitis. This will represent a much needed tool to thefield.

project_terms:
Address;Adult;Anaerobic Bacteria;Animal Model;Architecture;Bacteria;Bacterial Infections;Cigarette;Classification;Clinical;Communicable Diseases;Complex;Data;Dental Plaque;Developed Countries;Development;Disease;Disease Progression;Disease model;Dose;Environment;Epidemiology;Etiology;Genes;Genetic Screening;Genetic Transcription;Germ-Free;Gingiva;Gram-Positive Bacteria;Health;Hemorrhage;In Vitro;Infection;Inflammatory;Lesion;Literature;Mainstreaming;Meningeal Tuberculosis;Microbe;Modeling;Mus;New Zealand;Nomenclature;Oral cavity;Periodontal Diseases;Periodontitis;Persons;Physiology;Pneumonia;Population;Porphyromonas gingivalis;Refractory Disease;Reproducibility;Research;Resistance;Risk;Risk Factors;Rod;Role;Scandinavia;Severity of illness;Sexual Transmission;Smoke;Smoker;Smoking;System;Technology;Tissues;Tobacco;Tobacco smoke;Tobacco smoking behavior;Tobacco use;Tooth structure;Virulence;Virulence Factors;arm;base;bone loss;cigarette smoke;cigarette smoking;environmental stressor;exposure to cigarette smoke;high risk;in vivo;insight;microbial;microbiome;non-smoker;novel;oral biofilm;oral pathogen;pathogen;periodontopathogen;theories;tool;transcriptome;transcriptome sequencing

public_health_relevance:
PROJECT NARRATIVEFilifactor alocis is a Gram positive anaerobic and assacharolytic microbe that has recently emerged asa key etiological agent of periodontal diseases. Cigarette use is a risk factor for gum diseases while F.alocis is particularly well adapted to tobacco-rich environments and is one of the most genetically activebacteria in dental plaque. We will identify confirm and classify those F. alocis genes that are activatedor repressed during cigarette smoke exposure in vitro and in vivo. Therefore we will begin tounderstand how F. alocis survives and thrives in the oral cavity of smokers. The in vivo arm will employa murine smoke exposure chamber which will facilitate the development of a much needed animalmodel of tobacco-induced periodontitis.


application_id: 10139387
project_number: 1R41MD015915-01
administering_ic: NIMHD
award_notice_date: 2020-09-23
opportunity_number: PA-19-270
application_type: 1
activity_code: R41
ic: MD
serial_number: 015915
program_official: DAGHER, RADA K
project_start_date: 2020-09-23
project_end_date: 2021-08-31
study_section: Special Emphasis Panel[ZRG1 RPHB-A (11)]
contact_pi_person_id: 16414967
contact_pi: SHAH, SWATI
other_pis: Not Applicable
congressional_district: 04
department: Unavailable
primary_duns: 081302037
primary_uei: D263NL49YK14
duns_number: 081302037
uei: D263NL49YK14
fips: US
organization_id: 10059076
organization_name: FETAL LIFE, LLC
organization_city: PROSPECT
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 400598112
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2020-09-23
project_title:
Portable Affordable Innovative and Smart Device-Coupled Electronic Fetal Monitoring System to Improve Rural Access to Obstetrics Services and Improve Outcomes in Rural Communities

project_abstract:
Obstetricians measure fetal heartrate (FHR) and uterine contractions to evaluate fetal health during pregnancyand labor. This monitoring is performed to decrease the development of complications while minimizing the needfor unnecessary obstetric interventions and is especially important for women with high-risk pregnancies.However many women especially in rural areas do not have the time or resources to reach an obstetrician andthe lack of monitoring increases the risk of morbidity mortality and poor infant outcomes. Thus there is asignificant need for improved access to specialized healthcare providers like obstetricians.Because FHR and contractions are detected in separate locations of the mothers abdomen two separatedevices are required- a tocometer to measure contractions and an FHR monitor. In the hospital both are usedto simultaneously measure contractions and FHR and the data is fed to and displayed on a large and separatemachine called the cardiotocograph (CTG). Meanwhile current monitors for home use can measure only 1parameter because there is no method to simultaneously read data from 2 separate devices on an app.Additionally these home devices are not approved for clinical decision-making. Fetal Life developed a patent-pending engineering design for a tocometer that is significantly smaller and more affordable than those in clinicaluse. To build upon this Fetal Life will develop a portable and affordable system with its existing tocometer andan FHR monitor for at-home use that can send both sets of data to a hub that will be able to simultaneously sendthe data to an app on a commercial tablet to a remote obstetrician for real time monitoring. The development ofthe novel tocometer and the use of a tablet eliminates the need for a separate CTG which will reduce overallcost and size. In addition to increasing access to necessary healthcare this product will reduce cost and timerequired for healthy mothers and redirect resources to mothers with high-risk pregnancies.The goal of this Phase I STTR proposal is to develop the system of products and evaluate its usability for at-home use. This will be accomplished through the execution of 3 aims. In Aim 1 Fetal Life will repackage aconsumer FHR monitor to be of similar size to the tocometer and incorporate a serial port onto each device thatwill send continuous data to a hub device through a cable and redesign the cases to be appropriate for use witha belt. In Aim 2 we will build a hub with two serial inputs to receive FHR and contraction data and develop itssoftware to integrate the data and display it on a single app (iOS and Android) on commercial tablets. In Aim 3we will perform a small proof-of-concept human subject to demonstrate feasibility with 5 pregnant women andevaluate its usability in an at-home context through surveys. This Phase I program will develop the prototypeand provide necessary proof-of-concept data to support further development and a larger Phase II clinical trialthat will center on its accuracy and efficacy.

project_terms:
Abdomen;Android;Bluetooth;Clinic;Clinical;Clinical Research;Computer software;County;Coupled;Data;Data Display;Data Set;Development;Devices;Diabetes Mellitus;Discipline of obstetrics;Electronics;Engineering;Ensure;Fetal Monitoring;Fetal health;Goals;Gynecology;Health Personnel;Healthcare;High-Risk Pregnancy;Home environment;Hospitals;Housing;Improve Access;Intervention;Legal patent;Life;Location;Low income;Measures;Methods;Modification;Monitor;Morbidity - disease rate;Mothers;Outpatients;Patient-Focused Outcomes;Patients;Personal Satisfaction;Phase;Phase II Clinical Trials;Pregnancy;Pregnant Women;Procedures;Reporting;Resources;Risk;Risk Factors;Rural;Rural Community;Safety;Services;Signal Transduction;Skin;Small Business Technology Transfer Research;Social Distance;Surveys;System;Tablets;Technology;Time;Triage;Ultrasonic Transducer;Ultrasonography;United States;Universities;Uterine Contraction;Validation;Woman;analog;barrier to care;base;clinical decision-making;clinical practice;cost;design;digital;engineering design;fetal;health care availability;human subject;improved;improved outcome;infant outcome;innovation;instrument;maternal health care;mortality;novel;pandemic disease;portability;programs;prototype;real time monitoring;recruit;remote health care;rural area;rural healthcare;software development;telehealth;usability;wireless fidelity

public_health_relevance:
PROJECT NARRATIVEMeasuring fetal heartrate and uterine contractions is a common procedure performed by obstetricians to ensuremother and fetal health during pregnancy and labor. However many pregnant mothers especially in rural areasdo not have the resources or time to reach an obstetrician and currently available at-home products are not usedto make clinical decisions. Fetal Health will lower the barriers to healthcare access for rural mothers bydeveloping a portable and affordable telemonitoring product that can measure fetal heartrate and uterinecontractions and simultaneously send both sets of data to a remote doctor to make critical decisions in real timethat will ultimately improve mother and fetal health.


application_id: 10139082
project_number: 5R01HL125877-05
project_title: A novel mechanism of stromal cell-derived factor 1 protection against diabetic cardiomyopathy
administering_ic: NHLBI
award_notice_date: 2021-02-25
opportunity_number: PA-16-160
application_type: 5
activity_code: R01
ic: HL
serial_number: 125877
program_official: BUXTON, DENIS B
project_start_date: 2017-05-01
project_end_date: 2023-02-28
study_section: Myocardial Ischemia and Metabolism Study Section[MIM]
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:
Diabetic cardiomyopathy (DCM) is one of the major chronic complications in diabetic patients. Conventionaltherapies for treatment of DCM include glycemic control management of hypertension lowering lipid andlife-style management. However there are no treatment strategies available that specifically target thepathogenesis of DCM. Greater understanding of the pathogenic mechanism of DCM is needed to developimproved therapeutic strategies.Stromal cell-derived factor-1 (SDF-1) belongs to C-X-C motif chemokine family. It controls diverse cellfunctions by interacting with its receptors CXCR4 and CXCR7. Myocardial SDF-1 is transiently up-regulatedduring ischemia or after infarction and can attract stem cells to the injury site contributing to cardiacregeneration and angiogenesis. Exogenous SDF-1 can help prevent myocardial infarction andischemia/reperfusion injury through stem cell-dependent and -independent mechanisms. However the roleand mechanism of the SDF-1-CXCR4/CXCR7 system in DCM has not been established.Accumulating evidence indicates that diabetes-induced deficiency of growth factors such as SDF-1 isassociated with diabetic cardiovascular complications. In a preliminary study the PI showed that theexpression of SDF-1 is notably down-regulated in the cardiac tissue of mice with type 1 and type 2 diabeteswhile the receptor expression levels are unaffected. The PI considered that lack of cardiac SDF-1 maycontribute to DCM and supplementary SDF-1 may provide direct cardiomyocyte protection. As an initial testcultured cardiac cells were exposed to palmitate-mimicked diabetic lipotoxicity with SDF-1 pretreatment.These studies showed that SDF-1 protected against palmitate-induced cell death via CXCR7- but notCXCR4- mediated AMP-activated protein kinase (AMPK) activation. The results are of great significancesince they demonstrate SDF-1 can provide direct protection against diabetic cardiac cell death independentof stem cells. Therefore it is critical to determine if in vivo protection involves the same direct actions bySDF-1 identified on isolated cardiomyocytes. Based on the critical role of CXCR4 and CXCR7 incardiovascular diseases it is hypothesized that SDF-1 treatment of diabetic mice directly protects againstdiabetes-induced cardiomyocyte death and cardiac remodeling via CXCR7-mediated activation of AMPKand that SDF-1 treatment can ultimately prevent DCM.This hypothesis will be tested through three specific aims: (1) to determine the direct cardiomyocyte effectsof SDF-1 in protection against DCM; (2) to determine whether SDF-1 signaling through CXCR7 mediatesprotection against DCM independently of CXCR4; (3) to determine whether AMPK mediates SDF-1/CXCR7protection against DCM.This project will provide fundamental evidence for the interaction of SDF-1-CXCR4 and/or -CXCR7 at thecardiomyocyte as a new therapeutic target for the prevention of DCM in future clinical investigations.

project_terms:
5'-AMP-activated protein kinase;Adhesions;Apoptosis;Bone Marrow;CXCR4 Receptors;CXCR4 gene;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;Cardiovascular system;Catalytic Domain;Cell Death;Cell physiology;Cells;Cessation of life;Chemotaxis;Chronic;Cytoskeletal Modeling;Data;Development;Diabetes Mellitus;Diabetic Angiopathies;Diabetic mouse;Dysplasia;Exposure to;Family;Future;GTP-Binding Proteins;Genes;Growth Factor;Heart;High Fat Diet;In Vitro;Infarction;Injections;Injury;Insulin-Dependent Diabetes Mellitus;Interleukin-6;Ischemia;Knock-out;Knockout Mice;Life Style;Lipids;MAP Kinase Gene;Mediating;Modeling;Mus;Myocardial;Myocardial Infarction;Myocardial Ischemia;Non-Insulin-Dependent Diabetes Mellitus;Oxidative Stress;Palmitates;Paper;Pathogenesis;Pathogenicity;Pathologic;Pathology;Phosphorylation;Phosphotransferases;Prevention;Process;Production;Protein Kinase;Reperfusion Injury;Role;Signal Pathway;Signal Transduction;Site;Streptozocin;Stromal Cell-Derived Factor 1;System;Testing;Therapeutic;Tissues;Transgenes;Transgenic Organisms;Transplantation;Ventricular septum;antioxidant therapy;base;beta-arrestin;cardiac angiogenesis;cardiac regeneration;chemokine;clinical investigation;clinical practice;conditional knockout;conventional therapy;diabetic;diabetic cardiomyopathy;diabetic patient;glycemic control;heart damage;hypertension control;improved;in vivo;insight;new therapeutic target;novel;p38 Mitogen Activated Protein Kinase;prevent;receptor;receptor expression;stem cells;treatment strategy

public_health_relevance:
The objective of this study is to test our hypothesis that SDF-1 treatment of diabetic mice directly protectsagainst diabetes-induced cardiomyocyte death and cardiac remodeling via CXCR7-mediated activation ofAMPK and that SDF-1 treatment can ultimately prevent diabetic cardiomyopathy. We will first determine thedirect cardiomyocyte effects of SDF-1 in protection against diabetic cardiomyopathy in type 2 diabetes. Nextwe will determine which receptor mediates SDF-1's cardiomyocyte protection and the specific cell signalingpathway responsible. This project will reveal new insight into the underlying mechanism behind SDF-1protection against diabetic cardiomyopathy as well as provide fundamental evidence supporting the SDF-1/CXCR7 axis as a novel therapeutic target for the prevention of diabetic cardiomyopathy in future clinicalpractice.


application_id: 10138976
project_number: 5R21AI149366-02
administering_ic: NIAID
award_notice_date: 2021-04-29
opportunity_number: PA-19-053
application_type: 5
activity_code: R21
ic: AI
serial_number: 149366
program_official: GU, XIN-XING
project_start_date: 2020-04-06
project_end_date: 2023-03-31
study_section: Special Emphasis Panel[ZRG1-IDM-B(81)]
contact_pi_person_id: 8869391
contact_pi: KOROTKOVA, NATALIA
other_pis: Not Applicable
congressional_district: 06
department: BIOCHEMISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2021-04-01
project_title:
Identification of the factors contributing to resistance of Group A Streptococcus to human group IIA secreted phospholipase A2

project_abstract:
Human Group IIA secreted phospholipase A2 (hGIIA) is a highly cationic small protein!important for the innate immune defense against Gram-positive bacteria. The enzyme traversesthe thick peptidoglycan layer of Gram-positive bacteria to reach the phospholipid membranewhere it catalyzes the hydrolysis of phosphatidylglycerol ultimately leading to bacterial deaththrough lysis. In comparison to other Gram-positive bacteria Group A Streptococcus (GAS) orStreptococcus pyogenes is remarkably resistant to hGIIA activity. GAS transposon libraryscreens designed to identify the genes that provide susceptibility/resistance to hGIIAuncovered a number of genes involved in biosynthesis and modification of Lancefield group Acarbohydrate (GAC) and lipoteichoic acid (LTA) two crucial cell envelope constituents of GAS.GAC is a rhamnose-containing glycopolymer covalently attached to peptidoglycan. Modificationof GAC with negatively charged glycerol phosphate as well as the absence of positively-chargedD-alanine modifications in LTA drastically compromise GAS survival when challenged withhGIIA. This project seeks to identify the functions of two previously uncharacterized proteinsidentified by an hGIIA sensitivity screen a putative GAC hydrolase GacM and a GT-C typemembrane glycosyltransferase PgtC. Additionally we uncovered a GT-A type membraneglycosyltrasferase PgtA that might participate together with PgtC in a protein glycosylationpathway in GAS. We will define the biological functions of these three proteins and their roles inantimicrobial resistance and virulence using a range of genetic biochemical and analyticalapproaches. Functional characterization of these novel targets will lead to an increasedunderstanding of how antimicrobial resistance is regulated in all Gram-positive bacteria and howresistance to antimicrobials is emerging among Gram-positive pathogens.

project_terms:
Acute;Affect;Affinity Chromatography;Alanine;Anabolism;Anti-Bacterial Agents;Antibiotics;Antimicrobial Resistance;Bacteria;Binding;Biochemical;Biological;Biological Process;Body Fluids;Carbohydrates;Cations;Cell Wall;Cell membrane;Cells;Cessation of life;Charge;Complex;Control Groups;Cytolysis;Data;Development;Divalent Cations;Enzymes;Eukaryota;Gene-Modified;Genes;Genetic;Glycerol;Glycopeptides;Glycoproteins;Glycoside Hydrolases;Goals;Gram-Positive Bacteria;Grouping;Histones;Human;Hydrolase;Hydrolysis;Immune;Infection;Inflammation;Ions;Lectin;Libraries;Mediating;Membrane;Modification;Muramidase;Outcome;Outcome Study;Pathway interactions;Penetration;Peptidoglycan;Permeability;Phase;Phosphatidylglycerols;Phospholipase A2;Phospholipids;Polysaccharides;Predisposition;Protein Family;Protein Glycosylation;Proteins;Proteome;Publishing;Regulation;Research Personnel;Resistance;Rhamnose;Role;Serology;Serum;Side;Skin;Stains;Streptococcal Infections;Streptococcus;Streptococcus Group B;Streptococcus pyogenes;Structure;Thick;Transcription Repressor;Transgenic Mice;Vaccine Design;Virulence;antimicrobial;antimicrobial peptide;base;cell envelope;cell type;design;extracellular;glycosylation;glycosyltransferase;human pathogen;improved;in vivo;inorganic phosphate;link protein;lipoteichoic acid;mouse model;mutant;neutrophil;novel;novel strategies;pathogen;resistance mechanism

public_health_relevance:
The goal of this project is to identify the functions of two enzymes that provide resistance ofGroup A Streptococcus (GAS) to Human Group IIA secreted phospholipase A2. Understandingthe resistance mechanisms used by GAS will allow developing the novel strategies against GASinfections.


application_id: 10138375
project_number: 1F31NS116935-01A1
project_title: The effects of activity on propriospinal neuron morphology and connectivity
administering_ic: NINDS
award_notice_date: 2020-09-21
opportunity_number: PA-19-195
application_type: 1
activity_code: F31
ic: NS
serial_number: 116935
suffix: A1
program_official: BAMBRICK, LINDA LOUISE
project_start_date: 2020-12-01
project_end_date: 2023-09-30
study_section: Special Emphasis Panel[ZRG1 F01A-F (20)]
contact_pi_person_id: 16080666
contact_pi: BROWN, BRANDON LEE
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
project_abstract:
Project Summary. The majority of human spinal cord injuries (SCI) are anatomically incomplete potentiallyleaving propriospinal pathways which may relay information past the injury epicenter intact. Following SCI inrodents descending motor tracts sprout and increasingly contact descending propriospinal neurons (DPNs)forming detour circuits to relay signals caudal to the injury. However no studies have evaluated the potentialfor ascending PNs to form bottom-up detour circuits post-SCI. We previously found that silencing longascending PNs (LAPNs) which directly connect the lumbar and cervical spinal enlargements disruptedcoordination at each limb girdle. Surprisingly silencing this anatomically intact pathway post-SCI improvedlocomotor function. Thus it is critical to evaluate LAPN plasticity and determine how this plasticity might berefined by therapeutic interventions. To do so LAPN somatic and dendritic morphology will be characterizedusing a dual-viral system to specifically label LAPNs. We will also use a multi-viral system with a highlymodified rabies virus to identify the sources of direct synaptic input to LAPNs. Increased physical activity andrehabilitative training are known to improve locomotor function and anatomical outcomes post-SCI. To evaluatethe impact of physical activity and rehabilitative training on LAPN plasticity and locomotor function post-SCIwe will alter activity levels by housing animals in tiny cages or in large cages to restrict or facilitate activity.Animals in large cages will also receive rehabilitative training which mimics clinical rehabilitation. Furtherunderstanding SCI-induced neuroplasticity and how physical activity and rehabilitative training impact thisplasticity will further our understanding of SCI pathology and provide new therapeutic targets. Working closelywith my mentors we have developed a training plan that will broaden my scientific skills facilitate independentscientific thought and cultivate skills needed to be a productive postdoctoral fellow. The Kentucky Spinal CordInjury Research Center provides clinical and scientific expertise in SCI and related fields and has a history ofsuccessfully preparing trainees for current and next stages in their careers.Hypothesis. Pre-SCI we hypothesize that DPNs reticulospinals and sensory afferents will provide input toLAPNs. Post-SCI we anticipate 1) LAPN dendrite orientation change 2) LAPNs will be increasingly contactedby sensory afferents to form bottom-up detour circuits and 3) increased activity plus rehabilitative training post-SCI will improve locomotor function impact dendrite reorganization and refine detour circuits.Aim 1. Characterize the somatic and dendritic morphology of LAPNs and identify the sources of directsynaptic input onto LAPNs.Aim 2. Evaluate the effects of activity and rehabilitative training on locomotor function LAPN morphology andthe sources of direct synaptic inputs to LAPNs after T10 contusive spinal cord injury.

project_terms:
Anatomy;Animal Housing;Animal Model;Animals;Area;Axon;Behavior;Behavioral;Behavioral Assay;Breathing;Cells;Cervical;Chest;Clinical;Data;Dendrites;Dependovirus;Ensure;Enterobacteria phage P1 Cre recombinase;Forelimb;GTP-Binding Proteins;Gait;Genes;Genetic Transcription;Growth and Development function;Hindlimb;Human;Injections;Injury;Kentucky;Label;Lateral;Limb structure;Locomotion;Locomotor Recovery;Mentors;Messenger RNA;Morphology;Motor;Muscle;Nervous system structure;Neuraxis;Neuronal Plasticity;Neurons;Ontology;Outcome;Output;Pathology;Pathway interactions;Pattern;Periodicity;Physical Rehabilitation;Physical activity;Positioning Attribute;Postdoctoral Fellow;Presynaptic Terminals;Rabies;Rabies virus;Recording of previous events;Recovery of Function;Regulation;Rehabilitation therapy;Research;Rodent;Role;Sensory;Signal Transduction;Source;Specificity;Spinal;Spinal Cord Contusions;Spinal Ganglia;Spinal cord injury;Subfamily lentivirinae;Synapses;System;Therapeutic Intervention;Training;Transcriptional Regulation;Vertebrates;Viral;base;career;central pattern generator;improved;kinematics;neuronal excitability;neuroregulation;new therapeutic target;receptor;reconstruction;skills;transcriptome sequencing;white matter

public_health_relevance:
This project aims to evaluate spinal cord injury (SCI)-induced neuroplasticity and how rehabilitative trainingalters this plasticity. By characterizing the morphology of and inputs to long ascending propriospinal neurons(LAPNs) before SCI we will be able to assess SCI induced changes to LAPN morphology determine the roleof LAPNs in forming de novo spinal circuits post-SCI and determine the potential for rehabilitative training torefine these newly formed spinal circuits. Elucidating this will enhance our understanding of SCI pathology andprovide new targets for neuromodulatory and rehabilitative therapies.


application_id: 10137855
project_number: 5R44AA025804-04
project_title: Novel modulators of the dopamine transporter for alcohol and nicotine use disorders
administering_ic: NIAAA
award_notice_date: 2021-04-09
opportunity_number: PA-19-272
application_type: 5
activity_code: R44
ic: AA
serial_number: 025804
program_official: PATTERSON, JENICA DAWN
project_start_date: 2016-09-22
project_end_date: 2023-03-31
study_section: Special Emphasis Panel[ZRG1-ETTN-B(18)B]
contact_pi_person_id: 1970787
contact_pi: LITTLETON, JOHN M.
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
project_abstract:
AbstractSubstance use disorders (SUDs) are at epidemic levels in the US [Mack et al 2017] and this has acceleratedefforts to find effective pharmacotherapies. All SUDs are associated with increased synaptic dopamine in themesolimbic pathway. This makes the dopamine transporter (DAT) a primary molecular target and atypicalDAT inhibitors with low abuse potential are the most promising therapeutic candidates [Reith et al 2015].Lobinaline a complex alkaloid from Lobelia cardinalis is a novel atypical DAT inhibitor [Brown et al 2015] andis a lead for pharmacotherapy of SUDs. However chemical synthesis of lobinaline is challenging so theapplicants used a proprietary technology to optimize this lead in mutant L. cardinalis plant cells [Brown et al2016]. This identified two lobinaline N-oxides that are more water soluble than lobinaline and also modulatethe DAT in a different way. Like lobinaline they are competitive inhibitors of the DAT but paradoxically andunlike lobinaline they also increase DA uptake capacity. This unique combination of actions is ideally suited toreversing effects on synaptic DA associated with SUDs without intrinsic reinforcing effects or precipitatingwithdrawal. Thus lobinaline and its N-oxides are potential therapeutic agents for all SUDs. However inaddition to activity on the DAT lobinaline has partial agonist activity at nicotinic receptors [Brown et al 2015]which suggests specific value in nicotine and alcohol use disorders [Rahman et al 2016]. These are currentlythe most damaging SUDs worldwide [Peacock et al 2018] and smoking cessation is also the most profitablemarket in SUD therapeutics. The potential value of lobinaline and the N-oxides in these SUDs was supportedby activity in simple animal models and this phase IIB SBIR proposal is to begin their development astherapeutics. The aims are; (1) to test lobinaline and the N-oxides for off-target activity and to assess theirsingle dose pharmacokinetics and toxicity in rodents (2) to evaluate them more fully in animal models(including a novel rat model of nicotine plus alcohol self-administration) (3) to scale-up methods forbiosynthesis of lobinaline and its chemical conversion to the N-oxides. The commercial objectives are: (a) toevaluate these novel biosynthetics as potential medications for nicotine and alcohol use disorders and (b) toleverage this into the commercialization of Naprogenix biotechnology as a plant lead discovery platform. Bothobjectives will require partnership with a major pharmaceutical or biotechnology company in phase III.

project_terms:
Agonist;Alcohol abuse;Alcohol consumption;Alcohol dependence;Alcohols;Alkaloids;Anabolism;Animal Model;Animals;Biotechnology;Bupropion;Cell Culture Techniques;Cells;Chemicals;Commercial Sectors;Complex;Development;Directed Molecular Evolution;Disclosure;Dopamine;Dose;Drug Addiction;Drug Kinetics;Epidemic;FDA approved;Human;Intention;Lead;Libraries;Lobelia;Methods;Modeling;Molecular Target;Morbidity - disease rate;Mutagenesis;Nicotine;Nicotine Use Disorder;Nicotinic Receptors;Oxides;Parents;Pathway interactions;Pharmaceutical Preparations;Pharmacologic Substance;Pharmacology;Pharmacotherapy;Phase;Plants;Production;Proteins;Rattus;Recording of previous events;Research;Rodent;Self Administration;Small Business Innovation Research Grant;Smoking;Smoking Cessation Intervention;Structure;Substance Use Disorder;Synapses;Technology;Technology Transfer;Testing;Therapeutic;Therapeutic Agents;Therapeutic Human Experimentation;Toxic effect;Water;Withdrawal;Work;alcohol abuse therapy;alcohol use disorder;base;cathinone;chemical synthesis;commercialization;conditioned place preference;cost;cytisine;dopamine transporter;drug discovery;effective therapy;in vitro testing;inhibitor/antagonist;interest;invention;lead optimization;monoamine;mouse model;mutant;nicotine use;novel;novel therapeutics;product development;receptor;scale up;screening;smoking cessation;social;success;therapeutic candidate;therapeutic target;uptake;varenicline

public_health_relevance:
Project narrativeThe company has used a new biotechnology to discover novel plant drugs that could be effective treatments forall forms of drug dependence. However the way these compounds work suggests that they should be mosteffective against smoking and alcohol abuse so the company will develop them for these uses first. This proposalis to test these plant compounds for their potential as drugs including their ability to reduce alcohol and nicotineself-administration in animals and to begin development of them as medications for alcohol and nicotine usedisorders.


application_id: 10137803
project_number: 5P42ES023716-05
project_title: Superfund Training Core
administering_ic: NIEHS
award_notice_date: 2021-03-16
opportunity_number: RFA-ES-15-019
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2020-04-01
project_end_date: 2022-08-31
study_section: ZES1-LKB-K
subproject_number: 7663
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:
Abstract: Interdisciplinary research remains an important feature of the NIH Roadmap. An integrated investigation of chemicals in Louisville will address the effects of exposure on health outcomes related to cardiometabolic disease. The central hypothesis of the UofL Superfund Hazardous Substance Research and Training Project is that exposure to the environmental chemicals volatile organic compounds (VOCs) causes/exacerbates insulin resistance leading to cardio-metabolic disease. Preliminary results from our biomedical projects provide evidence that obesity places individuals at higher risk to adverse health outcomes related to VOCs exposures while our non-biomedical projects will address the lack of methods to systematically measure exposure to these chemicals in residents distal and proximal to industrial areas. This Training Core will train our pre- and post-doctoral fellows not only in laboratory-based research but also in effective communication of the research findings to others in the Superfund Research Projects as well as to the Community at large. The Training Core will develop graduate courses for our Trainees to be shared with the UofL Schools of Engineering Dentistry Medicine and Nursing and the College of Arts & Sciences providing the latest information about the chemistry and human health effects of volatile organic compounds. The Training Core also will contribute to the professional and undergraduate training programs by providing our trainees as seminar speakers or lecturers to UofL undergraduate Biology & Chemistry honors students to nursing dentistry and medical students and to teachers and high school students in the Jefferson County School System to communicate the role of chemical exposure in human disease. Finally our trainees will participate in meetings with the West Louisville Task Force and the Metro Louisville Public Health and Wellness Department with our Community Engagement and Research Translation Cores to engage in discussion and answer questions about the Superfund research projects. Each trainee will be assigned a specific project that each trainee will develop in order to experience how to translate research findings into concepts that can be transmitted effectively to the community various local/state agencies and university audiences alike.

project_terms:
Address;Advisory Committees;Area;Arts;Biology;Cardiometabolic Disease;Chemical Exposure;Chemicals;Chemistry;Communication Research;Communities;County;Dentistry;Discipline of Nursing;Distal;Engineering;Environmental Exposure;Exposure to;Hazardous Substances;Health;High School Student;Human;Individual;Industrialization;Insulin Resistance;Interdisciplinary Study;Investigation;Laboratories;Measures;Medical Students;Medicine;Methods;Obesity;Outcome;Postdoctoral Fellow;Public Health;Research;Research Project Grants;Role;Schools;Science;Students;Superfund;System;Training;Training Programs;Translating;Translational Research;United States National Institutes of Health;Universities;base;college;community based participatory research;community engagement;environmental chemical;experience;high risk;human disease;lecturer;meetings;pre-doctoral;teacher;training project;undergraduate student;volatile organic compound


application_id: 10137802
project_number: 5P42ES023716-05
project_title: Characterizing Urban- and Finer-Scale Spatial Variability for Select VOC Superfund Compounds
administering_ic: NIEHS
award_notice_date: 2021-03-16
opportunity_number: RFA-ES-15-019
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2022-08-31
study_section: ZES1-LKB-K
subproject_number: 5123
contact_pi_person_id: 10828196
contact_pi: TURNER, JAY ROBERT
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:
SUMMARY  Project 4 Hazardous volatile organic compounds (VOC) have adverse impacts on human health.These compounds likely exhibit high spatial variability in urban areas because of the numerousemission sources (e.g. industrial commercial residential traffic) and complex dispersionpatterns. Thus tools are needed to characterize the small-area variation of intra-urban VOCconcentrations. Land use regression (LUR) modeling is a powerful tool for assessing spatialvariability. It relies upon ambient measurements at a large number of sites and has beenextensively used for pollutants such as nitrogen dioxide and particulate matter. Howeverrelatively few studies have built LUR models for VOCs and in most cases the focus was trafficrelated emissions of benzene and other compounds emitted by vehicles. Mobile platformmeasurements have recently been used to collect air quality data for LUR model-building.However mobile monitoring of VOCs has not been used in LUR modeling because ofmeasurement challenges. This project will develop a portable VOC monitor suitable for mobileplatform measurements. Field studies will be conducted at urban- and neighborhood scales andthe VOC data will be used for LUR model-building. LUR results will be used by another Centerproject to evaluate relationships between ambient VOCs and cardiometabolic disease. LURresults will also be used to examine relationships between VOC air quality and proximity togreen space which might be an effective VOC remediation strategy. New tools will bedeveloped to use mobile platform measurements to identify the location and strength ofemission sources. This project is closely coupled to the Centers primary objective to examinecardiometabolic effects of exposure to VOC Superfund chemicals. It will also have broaderimpacts on air quality monitoring and exposure assessment.

project_terms:
Air;Automobile Driving;Benzene;Cardiometabolic Disease;Categories;Complex;Coupled;Data;Data Analyses;Development;Disease Progression;Ecology;Environment;Environmental Engineering technology;Environmental Exposure;Equipment and supply inventories;Etiology;Exhibits;Exposure to;Future;Gases;Geography;Goals;Green space;Health;Heart;Housing;Human;Industrialization;Location;Measurement;Modeling;Monitor;Neighborhoods;Nitrogen Dioxide;Participant;Particulate Matter;Pattern;Proxy;Research Project Grants;Resolution;Route;Sampling;Scheme;Seasons;Site;Small-Area Variations;Source;Superfund;Testing;Time;Variant;Work;cardiometabolism;density;design;design and construction;field study;insight;land use;metropolitan;miniaturize;mobile computing;model building;novel;pollutant;portability;remediation;sample collection;spatial relationship;study population;superfund chemical;tool;urban area;urban setting;urinary;volatile organic compound

public_health_relevance:
RELEVANCE  Project 4This environmental science and engineering research project will develop a novel portablevolatile organic compound (VOC) monitor suitable for mobile platform measurements andconduct monitoring for land use regression model-building. The project will determine the small-scale variation of intra-urban VOC concentrations which will be used by another Center projectto examine the impact of VOCs on cardiometabolic disease. Relationships between VOCconcentrations and proximity to green space will be examined towards evaluating whethergreening could be an effective remediation strategy. Tools will be developed to use mobilemonitoring data to identify emission sources of ambient VOCs.


application_id: 10137800
project_number: 5P42ES023716-05
project_title: Development of Novel Ultrasensitive Devices for the Measurement of VOCs
administering_ic: NIEHS
award_notice_date: 2021-03-16
opportunity_number: RFA-ES-15-019
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2022-08-31
study_section: ZES1-LKB-K
subproject_number: 5122
contact_pi_person_id: 9972311
contact_pi: NANTZ, MICHAEL H
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:
Hazardous volatile organic compounds (VOCs) in environmental air have both acute andchronic effects on human health. Gas chromatography coupled with a mass spectrometer (GC-MS) is the most common technology used for analysis of airborne VOCs. However GC-MS isnot effective for on-site measurement of trace VOCs at Superfund sites. The overall goal of thisenvironmental science research project is to develop novel technologies for quantitativeanalysis of trace VOCs in both the lab and for on-site measurement of toxic airborne VOCs.We will focus on measurements of acrolein vinyl chloride benzene and 13-butadiene. Theapproach is to investigate chemoselective microreactors for capture of Superfund VOCs.Microreactors provide superior advantages of miniaturized device size very low cost and fastdetection over current sorbent-based tube preconcentrators. We also will develop thiol-modifiedgold nanoparticle gas sensor arrays for on-site detection of these VOCs. Functionalized thiolswill be synthesized to detect target VOCs at a concentration range from sub-ppb to a few ppm.The thiols proposed for modification of gold nanoparticles will have functional groups andstructural motifs to specifically promote interaction with and recognition of target VOCs thussignificantly increasing sensing selectivity and sensitivity. The sensors will work at ambienttemperature. This research project will lead to transformational technologies for quantitativeanalysis of trace VOCs. The research is directly related to the overall goals of the Center forinvestigating the effects of exposure to VOCs on inducing/exacerbating cardiometabolicdisease. The project will also have significant broader impacts on monitoring environmental airand on promoting homeland security.

project_terms:
13-Butadiene;Acrolein;Acute;Adsorption;Air;Benzene;Biomedical Research;Butadiene;Cardiometabolic Disease;Chemicals;Chronic;Complex;Coupled;Custom;Detection;Development;Devices;Ecology;Electrodes;Engineering;Environmental Exposure;Environmental Monitoring;Environmental Pollutants;Exposure to;Face;Gas Chromatography;Gases;Goals;Gold;Group Structure;Health;High Pressure Liquid Chromatography;Human;Insulin Resistance;Ions;Liquid substance;Mass Spectrum Analysis;Measurement;Measures;Methods;Modification;Normal Range;Oxidants;Pattern;Process;Research;Research Project Grants;Security;Signal Transduction;Silicon;Site;Sulfhydryl Compounds;Superfund;Surface;System;Techniques;Technology;Temperature;Tube;Vinyl Chloride;Work;adduct;air sampling;base;carbonyl compound;cost;design;detection limit;functional group;glycolaldehyde;improved;liquid chromatography mass spectrometry;mass spectrometer;metal oxide;microsensor;miniaturize;nanoGold;new technology;novel;sensor;simulation;superfund site;vascular inflammation;volatile organic compound

public_health_relevance:
NarrativeThe overall goal of this environmental science research project is to develop novel microsensorsfor quantitation of volatile organic compounds (VOCs) for on-site measurement of toxic airborneVOCs. The research is directly related to the overall goals of the Superfund Center forinvestigating the effects of exposure to VOCs on inducing/exacerbating cardiometabolicdisease.


application_id: 10137799
project_number: 5P42ES023716-05
project_title: Molecular and Cellular Mechanisms of Cardiometabolic Toxicity of VOCs
administering_ic: NIEHS
award_notice_date: 2021-03-16
opportunity_number: RFA-ES-15-019
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2022-08-31
study_section: ZES1-LKB-K
subproject_number: 5121
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. While the healthof effects of ubiquitous environmental substances such as tobacco smoke and particulate matter are morewell-studied less is known about how volatile organic chemicals (VOC)a class of toxicants associated withhigher prevalence of type 2 diabetes (T2D) and strokepromote the development of cardiometabolic disease(CMD). Understanding how VOC affect CMD is important because obesity and T2D are rapidly growing globalhealth crises. Accordingly the overarching goals of this Superfund project are to determine the mechanisms bywhich VOCs negatively impact cardiovascular health and metabolism identify biomarkers for VOC exposureand vascular injury and test therapeutic strategies to minimize VOC-induced CMD. Our preliminary datasuggest that VOC such as acrolein promote endoplasmic reticulum (ER) stress and trigger the unfolded proteinresponse (UPR) in endothelial cells resulting in insulin resistance. In addition we find that individuals exposedto VOC such a vinyl chloride develop symptoms of CMD that could be instigated at the molecular level byVOC-induced ER stress. Specifically we hypothesize that aldehyde metabolites of VOC which are generallymore toxic than their parent compound diminish insulin sensitivity in vascular tissues by inducing ER stresswhich triggers metabolic changes that accelerate ectopic lipid deposition and promote cardiometabolicdysfunction. To test this hypothesis we will: (1) examine the effects of VOC exposure on endothelial functionand insulin resistance; (2) delineate the contribution of endothelial UPR to the cardiometabolic toxicity of VOC;and (3) elucidate the role of VOC-derived aldehydes in exacerbating CMD. The design of these studiesincludes molecular and pharmacological interventions designed to detoxify or quench the reactiveintermediates evoked by VOC exposure as well as studies that could lead to the identification of novelsensitive and robust biomarkers of both VOC exposure and vascular injury. These studies were designed tosynergize with and provide biological plausibility for the associations identified in Project 1. Successfulcompletion of this project will lead to identification of the underlying cellular and molecular mechanisms bywhich VOC affect insulin sensitivity and cardiometabolic function and provide insights into how VOC toxicitycould be prevented or therapeutically minimized by targeting aldehydes or protein-folding pathways.

project_terms:
ATF6 gene;Acids;Acrolein;Adipose tissue;Adult;Affect;Aldehydes;Apoptosis;Atherosclerosis;Attenuated;Benzene;Biochemical Pathway;Biological;Biological Markers;Blood Vessels;Body Burden;Butyric Acids;Cardiometabolic Disease;Cardiovascular Diseases;Cardiovascular system;Carnosine;Cell Respiration;Chemical Exposure;Chemical Injury;Chemicals;Chronic Disease;Data;Deposition;Development;Diabetes Mellitus;Disease;Disease Resistance;Dyslipidemias;Endoplasmic Reticulum;Endothelial Cells;Endothelium;Environmental Exposure;Environmental Impact;Enzymes;Exposure to;Fatty Liver;Fatty acid glycerol esters;Functional disorder;Goals;Hazardous Chemicals;Hazardous Substances;Health;Hepatic;High Prevalence;Individual;Inflammatory;Insulin Resistance;Investigation;Lead;Link;Lipids;Measures;Mediator of activation protein;Metabolic;Metabolism;Molecular;Molecular Chaperones;Mus;Myocardial Infarction;Non-Insulin-Dependent Diabetes Mellitus;Nutritional status;Obesity;Oxidative Stress;Parents;Particulate;Particulate Matter;Pathway interactions;Pharmacology;Phase;Plants;Plasma;Poison;Polyvinyl Chloride;Process;Production;Proteins;Protocols documentation;Reporting;Risk;Role;Series;Signal Transduction;Stress;Stroke;Superfund;Surveys;Symptoms;Testing;Therapeutic;Tissues;Tobacco smoke;Toxic effect;Vinyl Chloride;Work;aldehyde dehydrogenases;ambient air pollution;cardiometabolism;cardiovascular disorder risk;cardiovascular health;design;diet-induced obesity;endoplasmic reticulum stress;global health;insight;insulin sensitivity;metabolomics;mouse model;novel;overexpression;oxidized lipid;prevent;protein folding;response;superfund site;tauroursodeoxycholic acid;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 insulin resistance obesity anddiabetes as well as to develop therapeutic strategies to minimize these affect after exposure to toxiccompounds.


application_id: 10137798
project_number: 5P42ES023716-05
project_title: Environmental Exposure and Cardiometabolic Disease
administering_ic: NIEHS
award_notice_date: 2021-03-16
opportunity_number: RFA-ES-15-019
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2022-08-31
study_section: ZES1-LKB-K
subproject_number: 5120
contact_pi_person_id: 1902075
contact_pi: MCCLAIN, CRAIG J.
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
The overall goal of this project is to examine whether exposure to environmental pollutants specifically volatileorganic compounds (VOCs) induces/exacerbates cardiometabolic disease (CMD) by causing systemic insulinresistance and low grade inflammation. Insulin is a master regulator of metabolism and energy disposition anddysregulation of insulin signaling is associated with the development of obesity and Type 2 diabetes (T2D)which are robust contributors to atherogenesis and heart disease. Recent research has identified a pathogeniccontinuum between the development of insulin resistance hepatic steatosis dyslipidemia and cardiovasculardisease. We postulate that environmental pollutants/toxins can either directly cause CMD or interact withobesity and poor nutrition to cause/exacerbate CMD. We have published initial experimental human/rodentdata to support this concept and further preliminary animal data are presented in Project #2. Here we presentimportant human preliminary results from a unique database/specimen bank of plant workers exposed to highlevels of certain VOCs especially vinyl chloride. The Toxicology Specimen and Databank provides theopportunity for a novel cross-sectional study evaluating the effects of vinyl chloride and other VOCs on thedevelopment of insulin resistance and fatty liver (Aim 1a). We will examine our death certificate data toevaluate the effects of VOC exposure on all cause and cardiac deaths (Aim 1b). We will also perform aretrospective/prospective study using samples obtained over a ~40-year period of time to correlate thedevelopment of insulin resistance with outcome measures of the CMD and predictors of risk (includingoccupational exposure personal exposure and novel markers of metabolic injury that we have developedAim 1c). We will also be able to enroll residents from VOC "hot spots" including the Lees Lane superfund sitein a prospective longitudinal evaluation of the impact of lower levels of exposure and the impact ofobesity/nutrition on the progression of CMD (Aim 2). We are able to perform these studies because of anestablished database continued linkages with industry for nearly 40 years and ongoing interactions withcommunity leaders and residents which provide a highly-novel opportunity to assess the cardiometaboliceffects of VOCs over a range of exposures.

project_terms:
Air;Area;Arsenic;Attention;Benzene;Biochemical Pathway;Biological Markers;Biological Specimen Banks;Biological Specimen database;Blood;Blood Coagulation Factor;Blood Platelets;Cardiac Death;Cardiometabolic Disease;Cardiovascular Diseases;Cardiovascular system;Cause of Death;Cell physiology;Cessation of life;Chronic;Clinical;Collaborations;Communities;Controlled Study;Cross-Sectional Studies;Cytokeratin 18;Data;Databases;Death Certificates;Development;Disease;Disease Progression;Dyslipidemias;Endocrine Disruptors;Endothelial Cells;Endothelium;Enrollment;Environment;Environmental Exposure;Environmental Pollutants;Environmental Risk Factor;Event;Exposure to;Fatty Liver;Geography;Glucose Intolerance;Goals;Heart;Heart Diseases;Hot Spot;Human;Hydroxyeicosatetraenoic Acids;Impact evaluation;Individual;Industrialization;Industry;Inflammation;Injury;Insulin;Insulin Resistance;Lipids;Liver diseases;Longitudinal prospective study;Measures;Medical;Medical History;Metabolic;Metabolic Marker;Metabolism;Modeling;Monitor;Non obese;Non-Insulin-Dependent Diabetes Mellitus;Nutritional status;Obesity;Occupational;Occupational Exposure;Outcome Measure;Participant;Particulate;Pathogenicity;Pathway interactions;Plants;Plasma;Population;Prevalence;Process;Prospective Studies;Publishing;Research;Resources;Retrospective Studies;Risk;Rodent;Role;Sampling;Serum;Severities;Specimen;Superfund;Testing;Time;Toxicology;Toxin;Urine;Vinyl Chloride;Work;adipokines;animal data;atherogenesis;base;biobank;blood glucose regulation;cardiometabolism;cardiovascular disorder risk;cardiovascular injury;cohort;cytokine;data management;data repository;endoplasmic reticulum stress;endothelial dysfunction;exposed human population;insulin signaling;monocyte;novel;novel marker;nutrition;obese person;obesity development;pollutant;primary outcome;prospective;stem cells;superfund chemical;superfund site;translational study;urinary;volatile organic compound

public_health_relevance:
The overall goal of this project is to examine whether exposure to environmental pollutants particularly volatileorganic compounds (VOCs) causes or makes worse a group of disease processes known as cardiometabolicdisease (CMD). These processes include type 2 diabetes cardiovascular disease and fatty liver disease. Allof these conditions seem to be regulated through insulin resistance. We hypothesize that environmentalpollutants/toxins can either directly cause CMD or interact with obesity and poor nutrition to cause CMD ormake it worse. In this project we will investigate subjects from two ongoing studiesOccupational ToxicologyData and Specimen Bank and the Louisville Healthy Heart Studyto determine if exposure to pollutants leadsto insulin resistance and subsequent CMD. We are able to perform these studies because of an establisheddatabase continued linkages with industry for nearly 40 years and ongoing interactions with communityleaders and residents which provide a highly-novel opportunity to assess the effects of pollutants in bothworkers and a residential population from the same West Louisville area.


application_id: 10137797
project_number: 5P42ES023716-05
project_title: Sample and Data Management Core
administering_ic: NIEHS
award_notice_date: 2021-03-16
opportunity_number: RFA-ES-15-019
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2022-08-31
study_section: ZES1-LKB-K
subproject_number: 5119
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:
ABSTRACTThe primary objective of the Sample and Data Management Core (SDMC) is to provide support to each of thefour projects of the Louisville Superfund Center. The functions of the Core are matched to the needs of eachproject and cover a full range of services from collaboration and routine service to protocol preparation toprocedural review and oversight. The Core will provide two main services: it will establish a repository for thelong-term storage and archiving of samples and data; and it will assist Center investigators in the statisticalanalysis of their results. The core will assure the authenticity and quality of these specimens and it will preparethese samples for long-term storage or dispense samples as needed. The Core will also provide scientificallyvalid and rigorous statistical analysis of data and support the development of innovative methods to enhance thebasic and translational research efforts of Center investigators. The Core will provide state-of-the-art biostatisticsand bioinformatics expertise and analytical support. Core biostatisticians will also develop new statisticalmethods such as quantitative risk assessment models for estimating cardiometabolic disease risk in exposedpopulations and for the analysis and evaluation of exposures and health consequences. In addition the corewill develop novel methods for the analysis of multi-pollutant exposures as they relate to health outcomes. Thecore will serve as a unique educational resource for training graduate students post-doctoral fellows residentsand junior faculty and in collaboration with the Training and Administration Cores. This Core will allow Centerinvestigators easy access to high quality centralized data management and statistical services and thereby willstrengthen the organizational cohesion of the Center. This comprehensive and integrated service permits oneor more biostatisticians to be involved from the initial planning stage of a project (when statistical consultation ismost beneficial) throughout its implementation analysis and completion. The Core will provide a stable andcollegial environment that fosters long-term working relationships between biostatisticians and investigators andcontinues to promote sophisticated approaches to experimental design and analysis. The biostatisticians of thisCore are knowledgeable about clinical research and have broad expertise in statistical applications forepidemiological investigations clinical trials pre-clinical studies and prevention and control research. Theirinterdisciplinary interactions with basic scientists and clinical investigators will add a new dimension to theinterpretation of experimental results one that is only possible when collaborators share a mutual appreciationof problems and issues.

project_terms:
Animals;Annual Reports;Basic Science;Bioinformatics;Biological;Biometry;Biostatistical Methods;Cardiometabolic Disease;Cataloging;Clinical Investigator;Clinical Research;Clinical Trials;Collaborations;Collection;Communities;Consultations;Continuing Education;Data;Data Analyses;Development;Dimensions;Educational workshop;Elements;Ensure;Environment;Environmental Exposure;Evaluation;Experimental Designs;Exposure to;Faculty;Fostering;Future;Goals;Hazardous Chemicals;Hazardous Substances;Health;Human Resources;Individual;Journals;Metabolism;Methods;Modeling;Outcome;Population Analysis;Postdoctoral Fellow;Preparation;Prevention;Procedures;Productivity;Protocols documentation;Publications;Records;Reproducibility;Research;Research Activity;Research Design;Research Personnel;Resources;Risk;Risk Assessment;Sampling;Scientist;Services;Signal Recognition Particle;Source;Specimen;Statistical Data Interpretation;Statistical Methods;Students;Superfund;System;Technology;Testing;Tissues;Toxic effect;Training;Translational Research;Universities;Work;archive data;archived data;base;biobank;career development;cohesion;cohort;data exchange;data management;design;disorder risk;education resources;efficacy testing;epidemiology study;experience;experimental analysis;graduate student;innovation;meetings;member;novel;operation;pollutant;preclinical study;programs;quality assurance;radio frequency;repository;sample archive;statistical service;tool;usability

public_health_relevance:
RELEVANCEBy ensuring proper study designs and supporting appropriate data analysis the core will help in theunderstanding of risk sources and cardiometabolic disease risk estimation due to exposure to hazardouschemicals. Long-term storage and archiving of data and samples within the Core will facilitate future studies.


application_id: 10137796
project_number: 5P42ES023716-05
project_title: Metabolism and Toxicity Core
administering_ic: NIEHS
award_notice_date: 2021-03-16
opportunity_number: RFA-ES-15-019
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2022-08-31
study_section: ZES1-LKB-K
subproject_number: 5118
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:
ABSTRACTThe function of the Metabolism and Toxicity Core is to provide intellectual input high quality analytical servicesand validated data in support of all projects in this Superfund Center. Furthermore its support and interactionwith all other components of this Center will assure the overall success of these endeavors. While it is chargedto satisfy the existing needs of the current projects the scope of the Core services will not be limited to therequirements of these projects. The Core will endeavor to develop leading edge technologies and use them toestablish a variety of validated endpoints including exposure biomarkers disease prognosticators andtherapeutic interventions. This Core will be comprised of three discrete technology-centric components includingFlow Cytometry Metabolism and Pathology that nevertheless will function seamlessly and efficiently together toensure that the projects progress smoothly. In addition this Core will strive to educate and train its users throughtechnical seminars and hands-on operation. It will also organize informal meetings which will serve as forumsfor bringing together users to initiate discussion of novel procedures applications and approaches. Finally theMetabolism and Toxicity Core intends to expand its operations not only to support the multidimensional needsof the proposed projects but also to facilitate interactions with additional UofL faculty investigators and with otherSuperfund Centers. Thus the highly diverse yet integrated services and expertise of this Core are essential toachieve the goals of the Superfund center and help make progress with regards to understanding the likelydiverse pathological consequences of VOC exposures and the mitigation of these consequences.

project_terms:
Address;Analytical Chemistry;Animals;Biochemistry;Biological Assay;Biological Markers;Biology;Cardiometabolic Disease;Cells;Charge;Chemical Exposure;Clinical;Communities;Complex;Continuing Education;Data;Detection;Development;Disease;Ensure;Environmental Exposure;Equipment;Extramural Activities;Faculty;Felis catus;Flow Cytometry;Future;Goals;Histologic;Human;Human Resources;Informatics;Infrastructure;Measurement;Metabolic;Metabolism;Mission;Mus;Pathologic;Pathology;Physiological;Population;Postdoctoral Fellow;Procedures;Property;Proteomics;Protocols documentation;Research;Research Personnel;Resolution;Resources;Role;Sampling;Services;Signal Transduction;Superfund;Techniques;Technology;Testing;Therapeutic Intervention;Toxic effect;Toxicology;Toxin;Training;Universities;Validation;cardiometabolism;career development;flexibility;graduate student;interest;investigator training;meetings;member;metabolomics;novel;operation;response;success;superfund chemical;systemic toxicity;volatile organic compound

public_health_relevance:
NARRATIVEThe primary role of the Metabolism and Toxicity Core is to provide high quality validated data in support of allprojects in this Superfund Center. This Core has appropriate state-of-the art equipment and highly trainedtechnical personnel to carry out this mission. In addition this Core will strive to educate and train its users throughtechnical seminars and hands-on operational training. The highly diverse yet integrated services and expertiseof this Core are essential to achieve the goals of the Superfund center and help make progress with regards tounderstanding the diverse pathological consequences of VOC exposures.


application_id: 10137795
project_number: 5P42ES023716-05
project_title: Research Translation Core
administering_ic: NIEHS
award_notice_date: 2021-03-16
opportunity_number: RFA-ES-15-019
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2022-08-31
study_section: ZES1-LKB-K
subproject_number: 5117
contact_pi_person_id: 1885223
contact_pi: BHATNAGAR, ARUNI
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:
ABSTRACTThe overall goal of the Research Translation Core (RTC) is to disseminate scientific knowledge acquired fromthe Louisville Superfund Basic Research Program (SBRP) in a timely manner to key constituencies in formsthat are targeted and useful to our audience. Our primary target audience are: (a) our local community andcommunity-based groups involved in protecting human health and the environment; (b) scientists and publichealth professionals working at other academic institutions and at local and federal agencies including theNIEHS itself and the broader SBRP community; (c) local state and federal policy makers and non-governmental organizations that contribute to the development of environmental regulations and policies; and(d) local media and press. We will tailor messages to appropriate audiences and use conventional andinnovative tools such as social media blogs and tweets to communicate with our audience aboutenvironmental issues of mutual interest. Our intent is to cultivate an informed participatory audience as well asto enhance awareness and understanding of our Superfund team of environmental issues of interest andconcern to both local and national stakeholders. Serving as a multi-directional bridge the RTC will facilitatemaximize and optimize interactions between our Superfund team and its wider audience. This arrangementwill ensure that environmental issues particularly those related to VOC exposure and cardiometabolic healthinform our research activities and that the findings of our research are appropriately disseminated. It will alsoensure that knowledge generated by our program contributes substantially to practices and policies relevant toenvironmental health across Kentucky and the nation. The RTC will serve as bidirectional bridge between thecommunity and the Louisville Superfund Program and develop effective and contextually appropriatecommunication strategies and tools. The core personnel will communicate routinely with policy makers andpublic health organizations and assist Center investigators in their efforts in disseminating research findingsand facilitate intellectual and technology transfer of promising scientific and engineering applications topromote timely application of research. The RTC will working closely with the Community Engagement Core tofurnish educational information to be incorporated in their community and trainee education activities andprovide a venue for Training Core participants to experience and learn research translation and regulatoryscience. The Core will also evaluate its effectiveness in facilitating communication between the program andits broad audience and in facilitating technology transfer and enabling educational activities.

project_terms:
Administrator;Affect;Area;Awareness;Basic Science;Cardiometabolic Disease;Cardiovascular Diseases;Chemical Exposure;Chemicals;Collaborations;Communication;Communities;Consequentialism;Data;Decision Making;Detection;Development;Devices;Diabetes Mellitus;Education;Educational Activities;Educational Materials;Educational Technology;Effectiveness;Emergency response;Engineering;Ensure;Environment;Environmental Exposure;Environmental Health;Evaluation;Exposure to;Federal Government;General Population;Goals;Government;Government Agencies;Government Officials;Health;Health Policy;Health Professional;Human;Human Resources;Information Dissemination;Institution;Intellectual Property;Kentucky;Knowledge;Learning;Link;Liver diseases;Local Government;Medical emergency;Methods;National Institute of Environmental Health Sciences;Newsletter;Nongovernmental Organizations;Participant;Pathway interactions;Policies;Policy Maker;Population;Process;Public Health;Regulation;Research;Research Activity;Research Personnel;Risk Estimate;Science;Scientist;State Government;Students;Superfund;Technology;Technology Transfer;Time;Training;Translating;Translational Research;Work;base;cardiometabolism;community engagement;effectiveness evaluation;experience;federal policy;health organization;innovation;interest;meetings;member;news;novel;programs;public health relevance;social media;superfund chemical;superfund site;symposium;tailored messaging;tool;volatile organic compound;web site;webinar

public_health_relevance:
Project Narrative:The Research Translational Core (RTC) will provide a communication pathway linking the community atSuperfund site and other areas of high exposure to volatile organic chemicals (VOCs) with investigators at theLouisville Superfund Center (LSC). Working with both the Community Engagement Core and theAdministrative Core the RTC will organize Town Hall Meeting symposia informal meeting round tablediscussions between the community residents and leaders subject matter experts LSC researchers membersof governmental agencies and other stakeholders. The Core will develop communication strategies to targetspecific audiences and disseminate research findings and environmental health relevant information incontextually appropriate formats. Core personnel will communicate regularly with governmental organizationsand other interested parties to Louisville Superfund Center to provide assessments and risk estimates of VOCexposure in affected communities. The RTC will strive to identify the barriers to communication betweenresearchers and policy makers and work toward eliminating or ameliorating those barriers. The Core will alsofacilitate transfer of intellectual property and technology to ensure that the research and technology developedby LSC members finds appropriate and timely application. In collaboration with the Community EngagementCore and the Training Core the RTC will develop educational material for community forums and for traineesand students. The Core will gather data on its effectiveness in enabling communication between the programand its broad audience and provide an evaluation of its activities.Public Health RelevanceLittle is known about the health effects of volatile organic chemicals (VOCs) an important class of SuperfundChemicals on cardiovascular disease liver disease or diabetes. The Core will assist in understanding theimpact of these chemicals in affected populations facilitate the dissemination of this information and translatethis knowledge into formats that would be readily accessible to policy makers and regulators. During thisprocess the Core will ensure that the technologies and research developed by LSC researcher finds timelyapplications and that the activities of the Center are fully understood by its participants trainees governmentagencies and the general public.


application_id: 10137794
project_number: 5P42ES023716-05
project_title: Community Engagement Core
administering_ic: NIEHS
award_notice_date: 2021-03-16
opportunity_number: RFA-ES-15-019
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2022-08-31
study_section: ZES1-LKB-K
subproject_number: 5116
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_abstract:
Abstract: Residents of Kentucky suffer disproportionately from many chronic diseases and exposure to toxics in theirenvironment. Dangerously high rates of obesity hypertension diabetes and cancer in Kentucky have beenwell documented. Our areas of focus are West Louisville encompassing six zip codes within the larger Metroarea. In West Louisville neighborhoods 61.1% of residents are black/African Americans and 55% of childrenunder age 18 live in poverty. Our preliminary assessments suggest that residents living near the Lees Lanelandfill in West Louisville Rubbertown a heavily industrialized residential area and Oakdale a neighborhoodnear Churchill Downs have high in VOC exposures. The Louisville medical community has a long history of bi-directional interactions with active communityinvolvement in health care delivery and research. These interactions date back to the creation of the MarineHospital in 1823 to treat riverboat workers continues in the 1970s with partnerships with industries to establishthe ongoing surveillance program of workers with hepatic hemeangiosarcoma associated with their exposureto vinyl chloride and more recently is highlighted by the partnership between Louisville Metro Department ofPublic Health and Wellness along with UofL and other community partners to fight obesity and chronic diseaseunder the CDC Communities Putting Prevention To Work (CPPW) grant and to mitigate the effects of airpollution exposure by planting trees under the Funders Network for Smart Growth and Livable CommunitiesPartner-for-Places grant. The overarching goal of the CEC is to support community and academicscientists/educators in transdisciplinary research that incorporates best practices in community engagement byfacilitating beneficial and bidirectional interactions between residents industry policy makers and SuperfundCenter interdisciplinary investigators. We will achieve this through the following Specific Aims: 1. Augment community and investigator capacity for transdisciplinary research focused on exposure to Superfund contaminants through facilitating Community Environmental Quality Resource Exchange Sessions (CEQRES) and establishing a Sustainable InstitutionalizedCollaborative Framework through the Louisville Superfund Center Community Advisory Board (LSC-CAB). 2. Support and facilitate project- and core-specific community engagement activities 3. Support a community project aimed at mitigating the effects of exposures to Superfund VOCs 4. Assess change in perception and knowledge of community participants and investigators as a result of engaging in specific Superfund Center activities.Through regular public forums and board meetings support of specific Superfund research projects andtraining community engaged intervention assessment of community and investigator perceptions andknowledge and substantive interactions with other project Cores particularly the Research Translation Core(RTC) the CEC will provide content and structural support necessary for ongoing community engagedresearch aimed at evaluating the health effects of pollutant exposure and reducing exposures to and negativeimpacts of Superfund toxic emissions.

project_terms:
Address;Adult;Affect;African American;Age;Air;Air Pollution;Area;Awareness;Back;Belief;Cardiometabolic Disease;Centers for Disease Control and Prevention (U.S.);Child;Chronic;Chronic Disease;Code;Communities;Dangerousness;Data;Death Rate;Development;Diabetes Mellitus;Elements;Ensure;Environment;Environmental Exposure;Environmental Health;Equipment;Evaluation;Exposure to;Fatty Liver;Feedback;Future;Goals;Government;Grant;Green space;Growth;Health;Health Food;Health Sciences;Heart Diseases;Hepatic;Home;Hospitals;Hot Spot;Housing;Hypertension;Industrialization;Industry;Intervention;Kentucky;Knowledge;Liver diseases;Love;Malignant Neoplasms;Measures;Medical;Monitor;Natural Sciences;Neighborhoods;Obesity;Participant;Patient Recruitments;Perception;Plants;Play;Policy Maker;Population;Poverty;Prevention;Process;Public Health;Recording of previous events;Research;Research Personnel;Research Project Grants;Resources;Risk;Role;Scientist;Social Sciences;Source;Structure;Superfund;Surveillance Program;Syndrome;Toxic effect;Training;Transcend;Translational Research;Transportation;Trees;Vinyl Chloride;Work;attributable mortality;biological systems;cardiometabolism;community center;community engaged research;community engagement;community involvement;feasibility testing;fighting;health care delivery;health disparity;landfill;meetings;member;pollutant;preventive intervention;public health relevance;racial disparity;social;superfund site;therapy design;toxicant

public_health_relevance:
Project Narrative:Residents of Kentucky are disproportionately affected by many chronic diseases and exposure to toxics in theirenvironment. Dangerously high rates of obesity hypertension diabetes and cancer in Kentucky have beenwell documented. Health disparities by race and class persist across Louisville Metro. Our areas of focus areWest Louisville neighborhoods where 61% of the population is black/African American. This area includesboth the Lees Lane Superfund site and Rubbertown. A nearby neighborhood Oakdale also is a hot spot.All of these areas have excessive exposure to Superfund VOCs. Within the West Louisville neighborhoods thepercentage of children under age 18 who live in poverty is 55% and the rates of deaths attributable to povertyfor adults over 25 are 4%-24% higher than in other Louisville Metro neighborhoods. West Louisville is alsohome to a very high number of industries (located very near residential areas) that are major sources of toxicair emissions numerous brownfields and a superfund designated land-fill. In addition area residents strugglewith poor access to greenspace inadequate transportation lack of affordable safe housing and limited accessto healthy food options. The CEC goal is to support transdisciplinary research that incorporates best practicesin community engagement by facilitating beneficial bi-directional interactions between residents industrypolicy makers and Superfund Center interdisciplinary investigators building all stakeholders capacities tocollaboratively understand reduce exposure to and address the negative impacts of contaminants initiallyfocused on VOCs from Superfund sites and industrial activities in West Louisville.Public Health Relevance:We are beginning to understand that exposure to toxicants can initiate/exacerbate multiple health problemsespecially cardiometabolic diseases. Kentuckians are disproportionately affected by many chronic diseasesincluding obesity hypertension heart disease diabetes fatty liver disease etc. which are all aspects of thecardiometabolic syndrome. Certain communities are more highly impacted than others and it is critical tounderstand why. It is our hypothesis that exposure to toxics specifically VOCs initiates/exacerbates theseconditions. It is fundamental to our understanding of the effects of these toxics to engage the communitiesmost deeply affected by exposure to these pollutants and to try to mitigate the effects of these exposures.Thus determining the influence of pollutant exposure on the development/progression of these chronicconditions is vital.


application_id: 10137793
project_number: 5P42ES023716-05
project_title: Administrative Core
administering_ic: NIEHS
award_notice_date: 2021-03-16
opportunity_number: RFA-ES-15-019
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
project_start_date: 2017-09-01
project_end_date: 2022-08-31
study_section: ZES1-LKB-K
subproject_number: 5115
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 and to maximize the dissemination and application of research findingsthrough the Community Engagement Core and the Research Translation Core. To assist in the planning andcoordination of research and core activities the Core personnel will organize scientific work-in-progress sessionsbiweekly meetings relevant focus groups and frequent formal and informal interactions. To integrate cross-disciplinary research the Core will provide leadership and administrative support needed for integration andcoordination of research. The Core will leverage existing resources on campus to optimize the productivity ofthe Center and will seek input from both an Internal Advisory Committee and an External Advisory Committeein evaluating progress and in maintaining the relevance of Center activities to the Superfund Research Programmandate. Core leaders will maintain close contact with NIEHS program officials and with UofL administration.Core administrators will also manage the finances and resources of the Center to optimize usage and appropriateallocation. They will also coordinate the timely development of progress reports and financial statements. Toensure quality management the Core will monitor and facilitate attainment of Center objectives in researchtraining education and community engagement and ensure compliance with state and federal regulations.These activities will minimize administrative burden on Center members promote communication andcollaboration among investigators and facilitate the sharing of reagents tools specimens and data to ensurethe most effective allocation and use of Center funds. The Administrative Core will be the go-to place for studentsand trainees community members public media and press so that all such activities can be appropriatelyfacilitated and coordinated.

project_terms:
Administrator;Advisory Committees;Cardiometabolic Disease;Collaborations;Communication;Communities;Consultations;Core Facility;Counseling;Data;Development;Development Plans;Diabetes Mellitus;Discipline;Ensure;Environment;Environmental Exposure;Evaluation;Focus Groups;Funding;Future;Goals;Hazardous Chemicals;Heart Diseases;Human Resources;IACUC;Individual;Institutional Review Boards;Leadership;Link;Liver diseases;Logistics;Mentors;Monitor;National Institute of Environmental Health Sciences;Productivity;Progress Reports;Protocols documentation;Quality Control;Reagent;Regulation;Research;Research Personnel;Research Project Grants;Research Training;Resource Sharing;Resources;Scientific Evaluation;Selection Criteria;Signal Recognition Particle;Specimen;Students;Superfund;Time;Training;Training Activity;Training and Education;Translational Research;Universities;Work;community based participatory research;community engagement;effectiveness research;experimental study;meetings;member;operation;programs;tool;training opportunity;web site


application_id: 10137789
project_number: 5P42ES023716-05
project_title: Environmental Exposure and Cardiometabolic Disease
administering_ic: NIEHS
award_notice_date: 2021-03-16
opportunity_number: RFA-ES-15-019
application_type: 5
activity_code: P42
ic: ES
serial_number: 023716
program_official: CARLIN, DANIELLE J
project_start_date: 2017-09-01
project_end_date: 2022-08-31
study_section: ZES1-LKB-K(S)
contact_pi_person_id: 6871611
contact_pi: SRIVASTAVA, SANJAY
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 (Overall)This proposal is to establish a Superfund Center at the University of Louisville. This Center will support researchon the cardiometabolic effects of volatile organic chemicals (VOCs) that are of high relevance to the SuperfundProgram. Center investigators will conduct mode-of-action research to unravel critical pathways of toxicity andto identify toxicological end-points (cardiometabolic changes) of chemicals (VOCs) found at Superfund andrelated sites. Using high throughput metabolomic and mass spectrometry approaches animal experiments andhuman population studies Center investigations will aid in the discovery and validation of novel biomarkers ofboth exposure and cardiometabolic injury that would lay the foundation for future remediation strategies. Thesestudies will employ state-of-the-art tools to develop pollutant atmospheres for animal exposure and to measureunique and sensitive biological endpoints reflective of cardiometabolic injury. In addition work supported by theCenter will lead to the development of new methods and devices for quantifying atmospheric levels of VOCs thatwill employ advanced technologies and offer precise but low-cost measurements of hazardous waste sites. Themajor objectives of the Center are to conduct state-of-the-art research on the cardiometabolic toxicity of VOCsand to determine how they affect cardiometabolic disease (CMD) prevalence and severity in exposedpopulations. These studies will be complemented by mode-of-action mechanistic studies in animals to identifythe molecular and cellular mechanisms that contribute to VOC toxicity. Center investigators will also identifyspecific conditions such as nutritional status and obesity and increase susceptibility to VOC toxicity and testtherapeutic interventions that can attenuate acute and chronic cardiometabolic effects of VOC exposures. Thefindings of these studies will contribute to both the discovery and the validation of sensitive and robust biomarkersthat could be used to assess the extent of exposure metabolism and toxicity. Center investigators will createnew technologies for detecting VOCs at low environmental levels to enable future exposure assessmentactivities. Senior Center members will educate and train junior investigators graduate students and post-doctoralFellows in the field of environmental science and promote relevant community awareness and participation toenhance mutual bidirectional understanding of exposure risk and the health effects of exposure. The findingsand discoveries of the Center will be transferred to affected communities end users in public and private sectorsand other stakeholders. For future use and analysis all samples of human and animal tissues and all datacollected during Center investigations will be stored in a computer-coded biorepository. Collectively Centeractivities will lead to rigorous evaluation and better understanding of the effects of these hazardous chemicalson obesity diabetes and cardiovascular disease.

project_terms:
Action Research;Acute;Advanced Development;Affect;Animal Experiments;Animal Model;Animals;Area;Atmosphere;Attenuated;Awareness;Biological;Biological Markers;Cardiometabolic Disease;Cardiovascular Diseases;Cause of Death;Chemical Exposure;Chemicals;Chemistry;Chronic;Communities;Community Outreach;Complement;Cost Measures;Critical Pathways;Data;Decision Making;Development;Devices;Diabetes Mellitus;Disease Pathway;Ecology;Education and Outreach;Ensure;Environment;Environmental Exposure;Epidemic;Epidemiology;Etiology;Evaluation;Exposure to;Fatty Liver;Foundations;Future;Goals;Hazardous Chemicals;Hazardous Substances;Hazardous Waste Sites;Health;Heart Diseases;Human;Incidence;Industrialization;Injury;Investigation;Knowledge;Liver diseases;Mass Spectrum Analysis;Measures;Medical;Metabolism;Methods;Molecular;Monitor;Non-Insulin-Dependent Diabetes Mellitus;Nutritional;Nutritional status;Obesity;Pathway interactions;Population;Postdoctoral Fellow;Predisposition;Prevalence;Private Sector;Public Health;Public Sector;Research;Research Infrastructure;Research Personnel;Research Project Grants;Research Support;Research Training;Resources;Risk;Sampling;Science;Severities;Site;Superfund;Technology;Testing;Therapeutic Intervention;Time;Tissue Sample;Toxic effect;Toxicity Tests;Toxicology;Training;Training Programs;Translational Research;Universities;Validation;Work;animal tissue;base;biobank;cardiometabolism;community engagement;computer code;data archive;data management;data sharing;detection method;education resources;experience;exposed human population;graduate student;human population study;human tissue;innovation;interest;member;metabolomics;multidisciplinary;new technology;novel marker;obesity development;outreach program;pollutant;programs;remediation;repository;resilience;response;superfund chemical;superfund site;tool;translational medicine;volatile organic compound

public_health_relevance:
RELEVANCEThis proposal is to establish a Center to support research on the health effect of hazardous Superfund chemicals.Work in this Center will help in evaluating the health impact of several hazardous chemicals that are present inthe environment and in understanding how exposure to chemicals could contribute to the risk and developmentof obesity diabetes and heart disease which despite recent medical advances remain the leading causes ofdeath worldwide.


application_id: 10135072
project_number: 5P30ES026529-05
project_title: Pilot Project Program
administering_ic: NIEHS
award_notice_date: 2021-04-01
opportunity_number: RFA-ES-16-001
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
project_start_date: 2017-05-01
project_end_date: 2023-05-31
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 7095
contact_pi_person_id: 1896366
contact_pi: CURRY, THOMAS E
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY  Pilot Project ProgramThe overall goal of the pilot program of the University of Kentucky Center for Appalachian Research andEnvironmental Science (UK-CARES) is to provide new opportunities and resources to support highlyinnovative and collaborative research studies that will enhance the ability to identify and capitalize on emergingenvironmental issues. This will be accomplished by providing developmental and pilot funds for innovativetime-sensitive pilot studies that improve our understanding of the relationships among environmentalexposures human biology and disease. Specifically the goals of the UK-CARES Pilot Program are to:1. Expand the research mission of UK-CARES by supporting new and novel areas of investigation in promising transdisciplinary areas of environmental health research and environmental medicine.2. Provide research support for early career faculty to establish competitive research programs in environmental health science and environmental medicine.3. Provide support for faculty to explore new and innovative directions representing a significant departure from ongoing funded research into the environmental health sciences discipline.4. Enhance the interactions and expand the critical mass of investigators with expertise and experience in transdisciplinary translational environmental health and environmental medicine research on the UKcampus.5. Foster opportunities that meet goals and research interest areas relevant to NIEHS.The pilot program will contribute to creating synergy across the proposed UK-CARES Projects enhancing theeducational component as well as initiating interactions among UK-CARES investigators and otherresearchers at the University of Kentucky. The Pilot Program will actively facilitate research support newlyemerging technologies and focus on the development of the next generation of environmental healthscientists.

project_terms:
Advertisements;Advertising;Appalachian Region;Area;Award;Budgets;Categories;Clinical Sciences;Collaborations;Communities;Data;Development;Dimensions;Discipline;Disease;Ecology;Electronic Mail;Emerging Technologies;Ensure;Environmental Exposure;Environmental Health;Environmental Medicine;Evaluation;Faculty;Fostering;Funding;Funding Opportunities;Generations;Goals;Grant;Human Biology;IACUC;Institutional Review Boards;Investigation;Kentucky;Leadership;Legal patent;Manuscripts;Mission;Monitor;National Institute of Environmental Health Sciences;Pilot Projects;Publishing;Research;Research Personnel;Research Support;Resources;Scientist;Supervision;System;Time;Translational Research;United States National Institutes of Health;Universities;Work;career;clinical center;community organizations;design;early-career faculty;electronic data;experience;faculty support;health science research;high risk;improved;innovation;interest;meetings;new technology;next generation;novel;programs;research study;success;synergism;web site


application_id: 10135071
project_number: 5P30ES026529-05
project_title: Community Outreach and Engagement Core
administering_ic: NIEHS
award_notice_date: 2021-04-01
opportunity_number: RFA-ES-16-001
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
project_start_date: 2017-05-01
project_end_date: 2023-05-31
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 7094
contact_pi_person_id: 1906116
contact_pi: HAHN, ELLEN J
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY  Community Outreach and Engagement CoreThe aims of the UK Center for Appalachian Research in Environmental Sciences (UK-CARES) CommunityOutreach and Engagement Core (COEC) are to: 1) Increase awareness and knowledge among communitypartners about the environmental health research being conducted at the Center across the entire spectrumfrom basic science to community and population health research; 2) Increase community and stakeholderparticipation in community-engaged research to identify and communicate environmental concerns to UK-CARES investigators; and 3) Increase enrollment in citizen and academic training in science communication toleverage community-academic environmental health science partnerships. In Aim 1 we use multi-modaloutreach strategies (e.g. community events media advocacy social media written materials/website) thatengage community partners in developing dissemination plans and culturally appropriate outreach andmessaging approaches. Aim 2 uses multi-directional channels through which researchers can listen to theneeds and concerns of local residents and community stakeholder organizations. Strategies includeconducting focus groups with community health coalitions environmental activists work groups ad hoccommunity groups and healthcare entities. In Aim 3 we adapt evaluate and integrate sciencecommunication workshops into our career development activities and ensure effective science communicationwith community stakeholders and recognize excellence in community engagement. UK-CARES COEC isuniquely positioned to lead this effort due to our longstanding community-engaged research partnerships withcitizens and community stakeholder organizations in three contiguous Area Development Districts located insoutheastern Kentucky: Big Sandy Kentucky River and Cumberland Valley. Community members identify airand water quality impacts due to mining and fracking as critical concerns. We partner with five majorcommunity stakeholder organizations (Appalachian Citizens Law Center Appalachian Voices Area HealthEducation Centers Center for Rural Strategies and Headwaters Inc.) and five community residents to advisethe COEC. The COEC values the complex heterogeneous nature of the communities of AppalachianKentucky and their rich heritage self-reliance and pride of place. The COEC is tightly integrated into theorganizational structure of UK-CARES with direct impact on community-informed Center decision making. Thelong-term goal is to create a strong sustained community-academic partnership to support meaningfulcommunity engagement and environmental health literacy leveraging these community perspectives tofacilitate new understandings of environmental factors in disease initiation progression outcomes andcommunity impacts.

project_terms:
Academic Training;Acute;Address;Advocacy;Air;Appalachian Region;Area;Area Health Education Centers;Awareness;Basic Science;Cardiovascular Diseases;Chemicals;Child Health;Chronic Obstructive Airway Disease;Colorectal Cancer;Communication;Communities;Community Health;Community Outreach;Complex;Decision Making;Development;Diabetes Mellitus;Disease;Ecology;Educational Background;Educational workshop;Employment;Enrollment;Ensure;Environmental Exposure;Environmental Health;Environmental Risk Factor;Event;Exposure to;Focus Groups;Goals;Healthcare;Heavy Metals;Interest Group;Kentucky;Knowledge;Laws;Lead;Link;Malignant Neoplasms;Malignant neoplasm of lung;Metabolic Diseases;Mining;Mission;Modeling;Nature;Obesity;Outcome;Particulate;Plague;Positioning Attribute;Poverty;Pulmonary Heart Disease;Radon;Recording of previous events;Research;Research Personnel;Resources;Rivers;Rural;Science;Trust;Voice;Work;career development;community engaged research;community engagement;community involvement;dissemination research;early life exposure;health literacy;hydraulic fracturing;malignant breast neoplasm;member;multimodality;operation;organizational structure;outreach;population health;programs;self reliance;social media;success;water quality;web site;working group


application_id: 10135070
project_number: 5P30ES026529-05
project_title: Analytical Services Core
administering_ic: NIEHS
award_notice_date: 2021-04-01
opportunity_number: RFA-ES-16-001
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
project_start_date: 2017-05-01
project_end_date: 2023-05-31
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 7093
contact_pi_person_id: 1879477
contact_pi: MORRIS, ANDREW J
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY- ANALYTICAL COREThe overarching goal of the Analytical Core is to improve the capacity quality efficiency and cost-effectiveness of environmental disease research at the University of Kentucky (UK). This will be achieved byproviding UK-Center for Appalachian Research in Environmental Science (UK-CARES) researchers withpremium access to expert advice consultation and technical support to develop and validate analyticalmethods using state-of-the-art technologies for studies spanning the range of environmental disease researchareas represented in the center. These services are needed to detect and measure environmental pollutantsand biomarkers of environmental exposures which requires sophisticated instrumentation and technicalexpertise that is unavailable to individual investigators. Our partner facility cores the Small Molecule MassSpectrometry Core laboratory (SMMSC) and Resource Center for Stable Isotope Resolved Metabolomics (RC-SIRM) can provide the entire range of analytical capabilities required for state-of-the-art environmentaldisease research. However effective use of these facilities by environmental disease researchers oftenrequires new method development validation and pilot studies to establish analyte levels and technicalreproducibility. The properties of the target analytes and the need to measure them at low levels inenvironmental and biological samples frequently present unique challenges for sample preparation. Withvalidated analytical methods in hand data analysis can be challenging particularly since biological and healthoutcomes are dictated by exposures to multiple agents often requiring precise accurate and simultaneousmeasurements of multiple analytes or biomarkers of environmental exposures and informatics approaches toenable integrated analysis of large data sets. The Analytical Core addresses these limitations by providingconsultation in the design execution and interpretation of studies that require use of advanced analyticalinstrumentation for environmental disease research. The core staff will then develop and validate samplepreparation and analytical methods for detection and quantitation of environmental pollutants and biomarkersin complex samples and provide consultation and assistance with statistical methods for the analysis ofdatasets generated using these analytical methods. Finally the Analytical Core will provide education andtraining in analytical and data analysis methods for environmental disease research through personal outreachcourses and workshops enabling integration of analytical and metabolomics technologies into the research ofUK-CARES members. Overall the Analytical Core will add considerable value to environmental diseaseresearch at UK by leveraging existing institutional and NIH investments in research infrastructure to achievethe goals of our UK-CARES research team.

project_terms:
Address;Analytical Chemistry;Appalachian Region;Area;Award;Big Data;Biological;Biological Assay;Biological Markers;Biometry;Complex;Consultations;Core Facility;Coupled;Data;Data Analyses;Data Analytics;Data Set;Detection;Diet;Disease;Ecology;Educational workshop;Ensure;Environmental Exposure;Environmental Pollutants;Evaluation;Exposure to;Feasibility Studies;Flame Retardants;Funding;Goals;Grant;Hand;Health;Individual;Informatics;Investments;Ions;Kentucky;Laboratories;Life Style;Mass Spectrum Analysis;Measurement;Measures;Metal exposure;Methods;Monitor;Outcome;Pesticides;Pharmacologic Substance;Pilot Projects;Plastics;Polychlorinated Biphenyls;Polymers;Preparation;Property;Quality Control;Reproducibility;Research;Research Design;Research Infrastructure;Research Personnel;Resources;Sampling;Schedule;Services;Smoking;Statistical Data Interpretation;Statistical Methods;Technical Expertise;Technology;Training;Training and Education;United States National Institutes of Health;Universities;Use Effectiveness;advanced analytics;analytical method;archive data;cost effectiveness;data archive;design;detection method;disorder risk;experience;improved;in vitro Model;instrument;instrumentation;large datasets;member;metabolomics;method development;outreach;pollutant;programs;quality assurance;small molecule;stable isotope;statistics;validation studies


application_id: 10135069
project_number: 5P30ES026529-05
project_title: Integrative Health Sciences Facility Core
administering_ic: NIEHS
award_notice_date: 2021-04-01
opportunity_number: RFA-ES-16-001
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
project_start_date: 2017-05-01
project_end_date: 2023-05-31
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 7092
contact_pi_person_id: 6457660
contact_pi: BAUER, JOHN ANTHONY
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY  Integrative Health Sciences Facility CoreThe University of Kentucky Center for Appalachian Research in Environmental Sciences (UK-CARES) isdesigned to facilitate discovery and new understandings of environmental factors in disease initiationprogression and outcomes as well as their community impacts and to advance the careers of scientists whoare interested in tackling challenging environmental health questions. A critical element to this endeavor isdevelopment of a well-equipped Integrative Health Sciences Facility Core (IHSFC) to facilitate and enable thedevelopment and conduct of translational studies based on the current environmental health research baseand on emerging new scientific directions as well. The Center draws its theme in part from the challengesendemic to the disadvantaged rural population in southeastern Kentucky and the documented healthdisparities in this area of Appalachian Kentucky that have been linked to environmental factors. The proposedIHSFC serves as the primary institutional access point to specifically facilitate environmentally relatedtranslational and clinical studies providing the critical central infrastructure to enable transformation andexpansion of a portfolio of projects focused on environmental health. The IHSFC offers investigators guidanceassistance and operational support for multi-directional translational and clinical research development. Todeliver this support effectively the Core will also function as a model for integration of other UK-CARES coreresources and of cooperating UK campus centers to meet the needs of Center investigators. Further theIHSFC will leverage resources relevant to our target communities. Thus this core provides critical linkages toother UK-CARES cores and has collaborative connections to relevant cooperating UK centers and theirfacilities: UKs Center for Clinical and Translational Science NCI-designated Markey Cancer Center KentuckyChildrens Hospital and the UK Center of Excellence in Rural Health which is located in the Kentucky RiverDistrict to best serve the needs of the focus communities. Participation by these four entities will facilitatepriority access by UK-CARES members to such services as study design regulatory support datamanagement and clinical informatics subject recruitment and retention specimen management and cell andanimal systems support. The central goal of the IHSFC is to enable progressive translational clinical andpopulation-based research projects that address environmental health concerns in our region. We will achievethis goal via these specific aims: 1) provide support for collaborative and team-driven efforts among basicscientists clinical researchers community engagement experts and public health researchers; 2) provide andmanage resources to facilitate the progression of environmental health sciences from basic mechanistic andtoxicological research to translational programs that improve public health and clinical practice in our affectedcommunities; 3) facilitate reverse-translational research activities by addressing community concerns orcommunity-level study findings and developing programs to stimulate preclinical research activities.

project_terms:
Address;Affect;Air;Analytical Chemistry;Animal Model;Animals;Appalachian Region;Area;Basic Science;Biological;Biological Models;Biometry;Cancer Center;Cell Culture Techniques;Cells;Clinical;Clinical Informatics;Clinical Research;Clinical Sciences;Coal;Communication;Communities;Complex;Core Facility;Development;Disadvantaged;Disease;Ecology;Elements;Environmental Health;Environmental Risk Factor;Evaluation;Exposure to;Fostering;Funding;Gases;Geology;Goals;Health;Health Sciences;Heavy Metals;High Prevalence;Infrastructure;Institution;Integrative Medicine;Interest Group;Intervention Studies;Kentucky;Life;Link;Malignant Neoplasms;Mass Spectrum Analysis;Metabolic Diseases;Mining;Modeling;Outcome;Particulate;Pediatric Hospitals;Pilot Projects;Poison;Population;Population Research;Population Sciences;Population Study;Public Health;Public Health Practice;Pulmonary Heart Disease;Radon;Research;Research Activity;Research Design;Research Personnel;Research Project Grants;Research Proposals;Resources;Rivers;Rural Health;Rural Population;Sampling;Scientist;Services;Specimen;Structure;Support System;Time;Tobacco use;Toxicology;Translational Research;United States;Universities;Work;base;career;clinical center;clinical practice;community engagement;data management;design;early life exposure;epidemiology study;flexibility;hazard;health disparity;hydraulic fracturing;improved;instrumentation;interest;laboratory equipment;lung injury;member;patient oriented;pre-clinical research;programs;recruit;research and development;success;tobacco smoke exposure;translational study


application_id: 10135066
project_number: 5P30ES026529-05
project_title: Administrative Core
administering_ic: NIEHS
award_notice_date: 2021-04-01
opportunity_number: RFA-ES-16-001
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
project_start_date: 2017-05-01
project_end_date: 2023-05-31
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 7091
contact_pi_person_id: 2107851
contact_pi: SHI, XIANGLIN
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY  Administrative CoreThe University of Kentucky Center for Appalachian Research in Environmental Sciences (UK-CARES) will beestablished as a transdisciplinary Environmental Health Sciences Core Center (EHS CC) designed to developand operationalize strategic infrastructure assets relevant to cutting-edge environmental health research andprovide leadership for scientific and programmatic activities supporting ongoing new and evolving studies inthis area. The Administrative Core is an essential component of this EHS CC providing communicationcoordination and oversight to ensure overall operations and scientific integration of all UK-CAREScomponents. In addition the Administrative Core facilitates integration of goals with community needs andconcerns through dynamic community outreach and engagement activities to enable effective translation offindings to and from the affected communities. The Administrative Core staff will closely monitor theeffectiveness of UK-CARES programs and initiatives to ensure that the Center resources enhance memberresearch productivity. Specific aims are to 1) provide scientific and programmatic leadership and coordinateand integrate the Centers components and activities as well as to facilitate communications and interactionsacross all Center components and with affected communities and community stakeholders; 2) organize andfacilitate program activities internal and external communications and research discussions among Centermembers community members and internal and external advisory board members including retreatsconsultant interactions seminars Research Interest Group meetings and media and newsletters; integratecommunity outreach and engagement activities to ensure that multi-directional translation and communicationremain at the forefront of UK-CARES efforts; 3) provide financial oversight facilitate resource support andensure regulatory compliance related to the Centers research and community activities and maintain Centerrecords and measures of success including use of UK-CARES facilities and publications pilot project awardsand new grant applications resulting from preliminary data enabled by UK-CARES; 4) coordinate the CareerDevelopment Program to promote collaboration among basic clinical and population scientists with a broadrange of skills within a rich environment for early stage investigators to develop diverse professional skills andto attract mid-level investigators and scientists in other fields through opportunities to focus on environmentallyinduced disease; and 5) evaluate the productivity effectiveness and appropriateness of UK-CARES activitiesdetermine the Center membership assess scientific opportunities and areas for collaboration among membersand citizen scientists and coordinate UK-CARES infrastructure assessments as intellectual needs change toaccommodate new opportunities for collaboration. The expected outcome is a set of seamless interactionsthroughout UK-CARES.

project_terms:
Affect;Appalachian Region;Applications Grants;Area;Award;Clinical;Collaborations;Communication;Communication Research;Communities;Community Outreach;Core Facility;Data;Decision Making;Development;Disadvantaged;Disease;Ecology;Effectiveness;Employment;Ensure;Environment;Environmental Health;Environmental Impact;Environmental Risk Factor;Event;Goals;Group Meetings;Health education;Individual;Infrastructure;Interest Group;Journals;Kentucky;Leadership;Life;Malignant Neoplasms;Measures;Medicine;Metabolic Diseases;Mission;Monitor;Newsletter;Outcome;Pilot Projects;Play;Population;Process;Productivity;Program Development;Publications;Pulmonary Heart Disease;Records;Research;Research Personnel;Resource Sharing;Resources;Role;Rural Population;Science;Scientist;Series;Socioeconomic Status;Strategic Planning;Time;Training;Translations;Universities;career;career development;citizen science;college;community engagement;design;health inequalities;innovation;interest;meetings;member;operation;programs;skills;success


application_id: 10135064
project_number: 5P30ES026529-05
project_title: Center for Appalachian Research in Environmental Sciences
administering_ic: NIEHS
award_notice_date: 2021-04-01
opportunity_number: RFA-ES-16-001
application_type: 5
activity_code: P30
ic: ES
serial_number: 026529
program_official: THOMPSON, CLAUDIA L
project_start_date: 2017-05-01
project_end_date: 2023-05-31
study_section: Environmental Health Sciences Review Committee[EHS(P3)-1]
contact_pi_person_id: 1906116
contact_pi: HAHN, ELLEN J
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARY  OverallThe University of Kentucky Center for Appalachian Research in Environmental Sciences (UK-CARES) willestablish an Environmental Health Sciences Core Center to enhance research capacity focused on majorenvironmental health impacts to air and water quality that have been implicated in environmentally induceddisease. This Center will provide advanced infrastructure and leading expertise dedicated career developmentand mentorship and community-engaged interactions to facilitate innovative discovery and new understandingsof environmental factors in disease initiation progression and outcomes and their community impacts. Thecentral hypothesis is that toxic environmental agents are contributors to the disproportionately high incidence ofchronic diseases e.g. cancers cardiopulmonary disease and metabolic disorders in Appalachian Kentuckyand that the impacts of early exposure are especially harmful. UK-CARES draws on a strong and diverse baseof environmental health science and community-engaged research to build environmental health researchcapacity to meet the needs of communities in three Area Development Districts in southeastern Kentucky: BigSandy Kentucky River and Cumberland Valley. Center members bring notable strengths in environmentalhealth across four Research Interest Groups: Cardiopulmonary Diseases Metabolic Disorders Cancer andChild Health and Early Life Exposures. To achieve the Centers goal UK-CARES will: 1) establish a richresearch environment and a framework for transdisciplinary leadership and integrated infrastructure to facilitatecollaboration and efficient use of resources for research expansion and development of new scientific directions;2) build research capacity in environmental health sciences by providing an outstanding intellectual environmentand advanced infrastructure to support innovation and community engagement; 3) recruit new talent andfacilitate career development of investigators whose research addresses critical issues in environmentallyinduced disease through mentorship and structured career training activities; 4) develop multi-directional andmutually beneficial communications and interactions with community residents policymakers and publichealth/healthcare professionals to identify environmental concerns of target communities as a stimulus to newresearch; and 5) bridge the gap between discovery of novel research findings and population-level awarenessand practice via community-focused science communication training. An Integrative Health Sciences FacilityCore Analytical Core and Community Outreach and Engagement Core are integral to this effort and willcatalyze multi-directional translation across the whole spectrum of research; provide advanced analyticalsupport in metabolomics computational biology analytical chemistry biospecimen management andbioinformatics; and bridge Center and community priorities. Complementary activities in career development ofscientists who are interested in tackling challenging environmental health questions and pilot project funding willsupport developing research and evolving scientific directions.

project_terms:
Address;Air;Analytical Chemistry;Appalachian Region;Area;Arsenic;Asthma;Atherosclerosis;Awareness;Bioinformatics;Chemicals;Child Health;Chromium;Chronic Disease;Chronic Obstructive Airway Disease;Clinical;Collaborations;Colorectal Cancer;Communication;Communities;Community Outreach;Complex;Computational Biology;Core Facility;Development;Diabetes Mellitus;Disease;Ecology;Environment;Environmental Health;Environmental Risk Factor;Exposure to;Fostering;Foundations;Funding;Genetic Predisposition to Disease;Goals;Health;Health Professional;Health Sciences;Healthcare;Heart;Heart Diseases;Heavy Metals;Human;Incidence;Individual;Infrastructure;Integrative Medicine;Interest Group;Kentucky;Leadership;Longevity;Malignant Neoplasms;Malignant neoplasm of lung;Medical;Medical center;Mentorship;Metabolic Diseases;Mining;National Institute of Environmental Health Sciences;Nickel;Obesity;Outcome;Particulate;Pilot Projects;Population;Positioning Attribute;Public Health;Pulmonary Heart Disease;Radon;Research;Research Personnel;Resources;Rivers;Rural;Science;Scientist;Stimulus;Structure;Talents;Toxic Environmental Substances;Toxicology;Training;Training Activity;Translations;Universities;Vision;Water;advanced analytics;base;career;career development;community engaged research;community engagement;early life exposure;health science research;hydraulic fracturing;innovation;interest;member;metabolomics;neonate;novel;population health;programs;recruit;socioeconomic disadvantage;water quality

public_health_relevance:
PROJECT NARRATIVE  OverallThe University of Kentucky Center for Appalachian Research in Environmental Sciences (UK-CARES) willenhance programmatic and scientific capacity toward the goal of facilitating innovative discovery and newunderstandings of environmental factors in disease initiation progression and outcomes and their communityimpacts. Further the Center will foster career development of environmental scientists interested in tacklingchallenging environmental health questions facing the southeastern Kentucky region. UK-CARES will achievethis goal by providing advanced infrastructure and expertise training and mentorship and community-engagedinteractions.


application_id: 10134997
project_number: 5R01AI129959-05
project_title: Enhanced diagnostic assessment in lupus using differential scanning calorimetry
administering_ic: NIAID
award_notice_date: 2021-04-22
opportunity_number: PAR-16-242
application_type: 5
activity_code: R01
ic: AI
serial_number: 129959
program_official: RICE, JEFFREY S
project_start_date: 2017-05-05
project_end_date: 2023-04-30
study_section: Bioengineering, Technology and Surgical Sciences Study Section[BTSS]
contact_pi_person_id: 11129807
contact_pi: GARBETT, NICHOLA C.
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
PROJECT SUMMARYSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease which is particularly difficult todiagnose because of highly diverse clinical manifestations. Current diagnosis is based on clinical historyphysical exam and laboratory studies including serological markers. Despite much effort the development ofimproved diagnostic approaches is still in its infancy and has yet to have a clinical impact. Therefore there is asubstantial unmet clinical need for an investment in improving the diagnostic arsenal particularly approachesthat would lead to enhanced diagnostic accuracy of SLE differentiation of SLE from other autoimmune classesand would provide information concerning disease activity and pathobiology for development of targeted andpersonalized therapies. We have recently demonstrated the use of differential scanning calorimetry (DSC) as anew diagnostic approach for the analysis of blood plasma samples for the characterization of human diseases.Our data has shown that changes in thermodynamic properties of the high abundance plasma proteomedetected by DSC correlate with disease status and therapeutic response in a number of disease settingsincluding cervical cancer lung cancer melanoma amyotrophic lateral sclerosis type 1 diabetes Lyme diseaseand SLE. We have collected preliminary data on SLE patient samples that have revealed significantdifferences in thermograms between SLE patients and controls. Comparison of results using DSC profiles (orthermograms) to standard clinical antibody tests revealed significant improvements in sensitivity and overallaccuracy with the inclusion of thermogram data. The long term goal of this proposal is to address a criticalbarrier to early diagnosis thus facilitating effective treatment of SLE patients by developing thermograms as adiagnostic technology. To this end we will determine the sensitivity of thermograms to multiple SLE clinicaland serological factors disease severity and activity as well as determine the ability of thermograms todistinguish SLE from other autoimmune and related comorbidities. In addition we will determine thecorrelation of thermograms to changes in disease activity organ involvement and therapeutic interventionduring the longitudinal assessment of SLE patients. Finally we will apply mass spectrometry approaches tointerrogate the proteome of SLE patient plasma samples to dissect the biochemical mechanisms by whichthermogram modulation occurs in SLE to reveal new biologic information for diagnostic application in SLE.The data gained from this proposal will determine the utility of thermograms for enhanced diagnosticassessment and monitoring of SLE patients and additionally could identify new biomarkers associated withSLE pathobiology which could improve our understanding of the disease process and lead to the developmentof more specific diagnostic tests.

project_terms:
Address;Affect;Albumins;Amyotrophic Lateral Sclerosis;Attention;Autoantibodies;Autoimmune;Autoimmune Diseases;Biochemical;Biological;Biological Markers;Characteristics;Classification;Clinical;Clinical Trials;Cross-Sectional Studies;Data;Degenerative polyarthritis;Development;Diagnosis;Diagnostic;Diagnostic Procedure;Diagnostic tests;Differential Scanning Calorimetry;Disease;Disease remission;Early Diagnosis;Emerging Technologies;Goals;Immunologics;Insulin-Dependent Diabetes Mellitus;Investments;Laboratories;Laboratory Study;Lead;Liquid substance;Lupus;Lyme Disease;Malignant neoplasm of cervix uteri;Malignant neoplasm of lung;Mass Spectrum Analysis;Medical Technology;Molecular;Monitor;Organ;Pathology;Patient Monitoring;Patients;Performance;Plasma;Post-Translational Protein Processing;Process;Prognosis;Property;Protein Denaturation;Proteome;Recording of previous events;Rheumatoid Arthritis;Sampling;Sensitivity and Specificity;Serology;Severity of illness;Source;Structure;Systemic Lupus Erythematosus;Therapeutic Intervention;Thermodynamics;Urine;antibody test;base;comorbidity;diagnostic accuracy;diagnostic assay;diagnostic biomarker;diagnostic technologies;effective therapy;human disease;improved;infancy;melanoma;novel diagnostics;novel marker;personalized medicine;serological marker;targeted treatment;therapy development;tool;treatment response

public_health_relevance:
NARRATIVEThere is a critical need for improved diagnostic approaches to enhance diagnosis and management of SLE.Differential scanning calorimetry (DSC) is an emerging technology for medical diagnostics utilizing differencesin the thermodynamic properties of high abundance disease proteomes for the characterization of clinicalstatus. This proposal determines the utility of DSC profiles for diagnostic assessment and longitudinalmonitoring of SLE and characterizes the biochemical basis associated with DSC differences in SLE whichcould lead to the identification of new biomarkers in the SLE disease proteome.


application_id: 10134928
project_number: 5R01DC017770-03
project_title: Communities Helping the Hearing of Infants by Reaching Parents: The CHHIRP Navigator Trial
administering_ic: NIDCD
award_notice_date: 2021-03-25
opportunity_number: PA-18-385
application_type: 5
activity_code: R01
ic: DC
serial_number: 017770
program_official: KING, KELLY ANNE
project_start_date: 2019-04-01
project_end_date: 2024-03-31
study_section: Community-Level Health Promotion Study Section[CLHP]
contact_pi_person_id: 11512687
contact_pi: BUSH, MATTHEW LEE
other_pis: Not Applicable
congressional_district: 06
department: OTOLARYNGOLOGY
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 SUMMARYAs the most common neonatal sensory disorder in the United States infant hearing loss has an incidence of1.7 per 1000 births. The consequences of delayed diagnosis and failure to obtain timely intervention includesignificant communication impairment and negative socioeconomic effects. The overall lifetime medicaleducational and occupational costs due to deafness is estimated to be over $2.1 billion. Early detection ofhearing may prevent language development and learning disorders. National standards dictate that all infantsshould be screened by 1 month of age diagnosed by 3 months of age and initiate treatment by 6 months ofage (1-3-6 rule) and no more than 10% of infants should be non-adherent to diagnosis within 3 months afterbirth. In 2015 59.4% of U.S. infants failed to obtain a diagnosis within 3 months after abnormal screening.There is a need for the development and implementation of interventions that promote adherence to timelydiagnosis and treatment standards. Early infant hearing detection and intervention (EHDI) programs arecoordinated on a state level and the diagnostic process is complex and difficult for parents to navigate.Families of children with hearing loss report that they lack confidence and support in obtaining care for theirchild. Patient navigator (PN) programs have improved adherence to recommended diagnostic testing in cancercare after the detection of a screening abnormality resulting in substantial healthcare system cost savings.PNs are trained individuals who mitigate barriers to promote healthcare adherence by educating patients andimproving self-efficacy. We have recently demonstrated the PN efficacy to decrease non-adherence with infanthearing diagnostic care; however PN has yet to be tested in diverse communities or implemented into EHDIprograms and there is a gap in this field regarding effectiveness and implementation research on interventionsto reduce non-adherence. The proposed research is a community-engaged type 1 hybrid effectiveness-implementation trial of a PN intervention aimed at decreasing infant hearing diagnosis non-adherence afterfailed newborn hearing screening delivered in state-funded EHDI clinics. Guided by our community advisoryboard and partners we aim to 1) to test the effectiveness of PN to decrease non-adherence to receipt of infanthearing diagnosis within 3 months after birth using a stepped-wedge trial design 2) investigate implementationoutcomes and factors influencing implementation and 3) determine the cost-effectiveness of PN from theperspective of third party payers. This study is significant because it aims to reduce non-adherence to timelyinfant diagnostic hearing testing to prevent life-long negative consequences. This research is innovative intesting an intervention not previously assessed in hearing healthcare within a state-funded EHDI program andin integrating implementation research and cost-effectiveness methods with our effectiveness aim. Our resultswill impact the field by partnering with communities to inform the scale-up of this and other innovative patientsupportive interventions to create efficient and effective EHDI programs and maximize public health impact.

project_terms:
Address;Adherence;Adoption;Advisory Committees;Age-Months;Behavior Disorders;Birth;Caring;Characteristics;Child;Clinic;Collaborations;Communication impairment;Communities;Community Health;Complex;Congenital Disorders;Consolidated Framework for Implementation Research;Cost Savings;Cost effectiveness research;Data;Detection;Development;Diagnosis;Diagnostic;Diagnostic tests;Early Diagnosis;Early Intervention;Education;Effectiveness;Emotional;Employment;Environment;Failure;Family;Feedback;Funding;Health Services Accessibility;Healthcare;Healthcare Systems;Hearing;Hearing Tests;Impairment;Improve Access;Incidence;Individual;Infant;Intervention;Joints;Kentucky;Language Development;Learning;Learning Disorders;Life;Measures;Medical;Methods;Modality;Neonatal Screening;Newborn Infant;Occupational;Outpatients;Parents;Patient Care;Patients;Penetration;Preventive service;Process;Public Health;Randomized Controlled Trials;Recording of previous events;Reporting;Research;Research Methodology;Research Personnel;Self Efficacy;Sensory;Social Development;Speech;System;Testing;Third-Party Payer;Time;Training;Translational Research;United States;cancer care;care systems;childhood hearing loss;cognitive development;community clinic;community intervention;community setting;cost;cost effective;cost effectiveness;cost estimate;deafness;disparity reduction;early childhood;economic cost;effectiveness implementation design;effectiveness implementation study;effectiveness implementation trial;effectiveness research;effectiveness testing;effectiveness trial;falls;hearing impairment;hearing loss treatment;hearing screening;hybrid type 1 trial;implementation cost;implementation determinants;implementation intervention;implementation outcomes;implementation research;implementation strategy;improved;innovation;intervention program;navigator intervention;neonatal sensory disorder;peer support;prevent;programs;randomized trial;recruit;research to practice;scale up;screening;social;socioeconomics;standard care;standard of care;trial design

public_health_relevance:
PROJECT NARRATIVEHearing loss is the most common sensory congenital disorder and this condition is diagnosable and treatable.Infants who are born with hearing loss must undergo several hearing tests to diagnose the condition and manyfamilies are delayed in receiving this testing or never obtain the necessary testing and treatment. This studyevaluates (1) whether patient navigation in state-funded clinics throughout Kentucky increases parents' follow-through with testing (2) factors that promote or impede its delivery and (3) cost-effectiveness of this approach. !


application_id: 10134746
project_number: 2R01CA180986-06A1
administering_ic: NCI
award_notice_date: 2020-12-17
opportunity_number: PA-19-056
application_type: 2
activity_code: R01
ic: CA
serial_number: 180986
suffix: A1
program_official: EMENAKER, NANCY J
project_start_date: 2014-09-01
project_end_date: 2021-08-31
study_section: Cancer Prevention Study Section[CPSS]
contact_pi_person_id: 9620088
contact_pi: LI, BING
other_pis: Not Applicable
congressional_district: 03
department: MICROBIOLOGY/IMMUN/VIROLOGY
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:
E-FABP mediates n-3 fatty acid-induced tumor prevention through epigenetic control of immune cell differentiation and function

project_abstract:
PROJECT SUMMARY/ABSTRACTDespite therapeutic advances over 600000 people in the US will die from cancer in 2019. Preventing cancereliminates the risk of mortality and/or morbidity that may occur with the development of cancer. Thus cancerprevention represents the most effective way for addressing cancer challenges. Healthy diet is considered beessential to reduce cancer risk by maintaining and improving immunity but recent VITAL trials did not showbeneficial effects of these supplements. The negative results reflect the mechanistic knowledge gap of howdietary factors modulate health. The objectives of this renewal application are to determine cellular andmolecular mechanisms by which epithelial fatty acid binding protein (E-FABP) promotes n-3 fatty acid-mediated tumor prevention by enhancing immune cell differentiation and anti-tumor activity. Data collected inthe last funding cycle have successfully established E-FABP as a new host-derived cancer prevention factor innon-obese subjects. During our studies we observed that different types of high fat diets (HFD 45% fat)including cocoa butter (rich in saturated fatty acids FAs) safflower oil (rich in 18:2 linoleic acid) fish oil (rich inn-3 FAs) all induced similar degree of obesity in mouse models. However tumor growth in these obese micewas dramatically different with the fastest growth in cocoa butter group and slowest in the fish oil group. Inanalyzing the immunophenotype of these obese mice we found an atypical population of CD8+  T cells thatwas specifically upregulated in the fish oil group. More interestingly fish oil diet-induced CD8+  Tdifferentiation and anti-tumor effects were blunted in mice lacking E-FABP suggesting a novel molecularmechanism mediated by E-FABP. Thus we hypothesized that host expression of E-FABP plays a critical rolein n-3 FA-induced immune cell differentiation and anti-tumor function. Three specific aims are proposed toaddress the central hypothesis in this renewal application. Specific Aim 1 will determine the mechanisms bywhich E-FABP promotes n-3 FA-induced immune cell differentiation. Experiments are designed to elucidatemolecular mechanisms by which consumption of dietary n-3 FAs regulate CD8+  T cell differentiation via E-FABP-dependent epigenetic reprogramming. Specific Aim 2 will delineate how E-FABP mediates n-3 FA-induced anti-tumor activity. Results of Aim 2 are expected to reveal that E-FABP promotes host anti-tumoractivity through targeting both immune cells and tumor-derived epithelial cells. Specific Aim 3 will evaluatewhether targeting E-FABP with optimized n-3 FA diets results in effective tumor prevention. In summarysuccessful completion of this proposal will offer E-FABP as a new cancer prevention target and havesignificant mechanistic and clinical implications for healthy diet-mediated cancer prevention.

project_terms:
Address;Animals;Basic Science;CD8B1 gene;Cell Differentiation process;Cell physiology;Cells;Clinical;Clinical Trials;Consumption;Custom;DNA;DNA methyltransferase inhibition;Data;Development;Diet;Dietary Factors;Dietary Fatty Acid;Epigenetic Process;Epithelial;Epithelial Cells;Exhibits;Fish Oils;Funding;Growth;Health;High Fat Diet;Human;Immune;Immunity;Immunologic Surveillance;Immunophenotyping;In Vitro;Interferons;Knockout Mice;Knowledge;Life Style;Linoleic Acids;Malignant Neoplasms;Mediating;Metabolic;Modeling;Molecular;Morbidity - disease rate;Mus;Non obese;Obese Mice;Obesity;Oleic Acids;Olive oil preparation;Omega-3 Fatty Acids;Play;Population;Prevention;Production;Reactive Oxygen Species;Role;STAT3 gene;Safflower Oil;Saturated Fatty Acids;Signal Transduction;T cell differentiation;T-Lymphocyte;Therapeutic;Toxic effect;Tumor-Derived;Tumor-infiltrating immune cells;Vitamin D;Vitamins;World Health Organization;aldehyde dehydrogenase 1;antitumor effect;cancer prevention;cancer risk;cancer therapy;cocoa butter;conditional knockout;demethylation;design;dietary;dietary supplements;dosage;experimental study;fatty acid-binding proteins;good diet;improved;in vivo;insight;mortality risk;mouse model;neoplastic cell;novel;preclinical study;prevent;protein expression;response;sensor;tumor;tumor growth; T cells

public_health_relevance:
PROJECT NARRATIVEData from this study are expected to establish E-FABP as a novel molecular sensor mediating n-3 FA-inducedanti-tumor effects. This proposal will not only have basic science ramifications for understanding molecularmechanisms by which n-3 FAs epigenetically enhance immune cell differentiation but will also have significanttranslational implications for the role of healthy diets in cancer prevention.


application_id: 10133701
project_number: 5R03HD097075-02
project_title: MicroRNAs as Mediators of Birth Defects
administering_ic: NICHD
award_notice_date: 2021-03-29
opportunity_number: PA-18-481
application_type: 5
activity_code: R03
ic: HD
serial_number: 097075
program_official: TOYAMA, REIKO
project_start_date: 2020-04-01
project_end_date: 2022-12-31
study_section: Developmental Biology Study Section[CHHD-C]
contact_pi_person_id: 1861667
contact_pi: GREENE, ROBERT M
other_pis: PISANO, M. MICHELE
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/Abstract: Orofacial clefts are amongst the most prevalent birth defects occurring in ~1/800 live births worldwide.Despite progress identifying genetic and environmental risk factors for orofacial clefting causes of the majorityof isolated cleft cases  particularly clefts of the palate  continue to elude our complete comprehension. Agreater depth of understanding of the molecular underpinnings of orofacial development is therefore essentialfor the development of diagnostic preventative and therapeutic strategies. The discovery of vast conserved stretches in the human genome of non-coding regulatory RNAs suchas microRNAs (miRNAs) has revealed a previously unrecognized layer of genomic information of significanceto human health and disease. Studies proposed in the current application enter this new and challengingscientific arena to examine the function of miRNAs in orchestrating the complex morphogenetic mechanismsand gene expression programs underlying formation of the mammalian secondary palate. These studies which are a logical extensions of our published comprehensive profile of miRNAsexpressed in the developing facial processes and palate will investigate the functions of carefully selectedmiRNAs in mammalian palatal ontogenesis. Loss/gain of function strategies and in situ hybridization will beemployed to systematically determine the biological functions and spatio-temporal expression patterns duringdevelopment of the secondary palate. Results from these studies will elucidate miRNA functionality in specificaspects of mammalian palatal morphogenesis growth and cellular differentiation. The immediate impact of theproposed research will be delineation of miRNA candidate genes that can be interrogated for human variantsassociated with an increased risk of human isolated cleft palate.

project_terms:
Affect;Animal Model;Apoptosis;Biological Process;Breathing;Candidate Disease Gene;Cell Culture Techniques;Cell Proliferation;Cell physiology;Cells;Chondrogenesis;Cleaved cell;Cleft Palate;Complex;Comprehension;Congenital Abnormality;DNA;DNA Sequence;Data;Development;Developmental Process;Diagnostic;Disease;Elements;Embryonic Development;Embryonic Palate;Environmental Risk Factor;Enzymes;Epigenetic Process;Epithelial;Etiology;Extracellular Matrix;Face;FaceBase;Failure;Family;Fetus;Future;Gene Activation;Gene Expression;Gene Silencing;Genetic;Genetic Determinism;Genetic Risk;Genome;Genomics;Growth;Health;Hearing;Heritability;Histones;Human;Human Genome;In Situ Hybridization;Individual;Instruction;Investigation;Link;Live Birth;MSX1 gene;Medial;Mediator of activation protein;Mesenchymal;Mesenchymal Differentiation;MicroRNAs;Molecular;Morphogenesis;Mus;Mutant Strains Mice;Nasal cavity;Oral cavity;Organ Culture Techniques;Palate;Pattern;Phenotype;Play;Pregnancy;Primordium;Process;Production;Publishing;RNA;Regulator Genes;Research;Risk;Role;Secondary Palate;Signal Transduction;Signaling Molecule;Speech;Stretching;Syndrome;System;Therapeutic;Time;Tissues;Transforming Growth Factor beta;Ubiquitin;Untranslated RNA;Variant;base;cell motility;craniofacial;epigenome;feeding;gain of function;genetic association;homologous recombination;loss of function;methyl group;orofacial;orofacial cleft;orofacial development;programs;repository;spatiotemporal;success

public_health_relevance:
Project Narrative:Orofacial clefting represents one of the most common of birth defects. Failure of the palate (roof of themouth) to develop properly during gestation results in continuity between the oral and nasal cavitiescausing problems in feeding breathing speech and hearing in affected individuals. Causes of cleftpalate are poorly understood. This research proposes to investigate recently discovered elements in thehuman epigenome  microRNAs  that may play critical roles in palate development and clefting.


application_id: 10133666
project_number: 5P42ES007380-23
project_title: Fate and Transport of Contaminants in Aging Piping Systems
administering_ic: NIEHS
award_notice_date: 2021-01-28
opportunity_number: RFA-ES-18-002
application_type: 5
activity_code: P42
ic: ES
serial_number: 007380
project_start_date: 1997-04-07
project_end_date: 2025-01-31
study_section: ZES1-JAB-D
subproject_number: 5743
contact_pi_person_id: 8776790
contact_pi: PENNELL, KELLY G
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_terms:
Address;Aging;Air;Analytical Chemistry;Biological Monitoring;Biomedical Research;California;Communication;Communities;Computer Models;Coupled;Data;Data Analyses;Deterioration;Ecology;Ensure;Environment;Environmental Engineering technology;Environmental Exposure;Environmental Hazards;Environmental Health;Environmental Pollution;Equation;Ethylenes;Evidence based practice;Foundations;Fracture;Gases;Goals;Hazardous Waste;Health;Human;Individual;Indoor Air Quality;Industry;Infrastructure;Inhalation Exposure;Interview;Joints;Kentucky;Knowledge;Measurement;Measures;Membrane;Modeling;North Carolina;Outcome;Outcome Study;Pathway interactions;Policies;Polymers;Public Health;Regulation;Reporting;Research;Research Project Grants;Risk;Risk Reduction;Route;Sampling;Science;Services;Site;Superfund;Surveys;System;Techniques;Temperature;Testing;Tetrachloroethylene;Time;Toxic effect;Transcend;Translational Research;Transport Process;Trichloroethylene;Uncertainty;United States;Volatilization;Water;Water Supply;aged;base;community engagement;contaminant transport;data interoperability;data management;data modeling;drinking water;engineering design;epidemiology study;field study;ground water;health literacy;hookah;informant;mass flux;novel;nutrition;predictive modeling;pressure;prevent;research facility;sensor;sensor technology;stakeholder perspectives;superfund chemical;superfund site;tool;vapor intrusion;ventilation;water quality


application_id: 10133665
project_number: 5P42ES007380-23
project_title: Responsive Membranes and Advanced Materials for Sensing and Remediation of Halo-organics
administering_ic: NIEHS
award_notice_date: 2021-01-28
opportunity_number: RFA-ES-18-002
application_type: 5
activity_code: P42
ic: ES
serial_number: 007380
project_start_date: 1997-04-07
project_end_date: 2025-01-31
study_section: ZES1-JAB-D
subproject_number: 5742
contact_pi_person_id: 8534525
contact_pi: BHATTACHARYYA, DIBAKAR
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_terms:
Adsorption;Advanced Development;Aftercare;Area;Attention;Biomedical Research;Carbon;Carbon Tetrachloride;Catalysis;Catalytic Domain;Chemicals;Chloroform;Collaborations;Consumption;Detection;Development;Drug Metabolic Detoxication;Engineering;Environment;Environmental Health;Fiber;Funding;Gel;Goals;Hazardous Waste Sites;Health;Heating;Human;Hydrogels;Individual;Industrialization;International;Iron;Kentucky;Lead;Magnetism;Membrane;Metals;Methods;Nanostructures;Natural regeneration;Nutritional Science;Oxidants;Oxides;Polychlorinated Biphenyls;Polymers;Property;Public Health;Research;Risk;Science;Site;Soil;Solvents;Source;Sulfate;Superfund;Surface;System;Techniques;Technology;Temperature;Tetrachloroethylene;Toxic effect;Toxicant exposure;Trichloroethylene;Water;base;contaminated water;cost;cost effective;design;drinking water;food science;global environment;graphene;ground water;magnetic field;magnetite ferrosoferric oxide;materials science;microbial;nanocomposite;nanoparticle;nanoscale;nanosized;novel;nutrition;particle;pollutant;prevent;reaction rate;remediation;sensor;superfund chemical;superfund site;water sampling


application_id: 10133664
project_number: 5P42ES007380-23
project_title: Postnatal Complications and Interventions against Halogenated Organics during Pregnancy
administering_ic: NIEHS
award_notice_date: 2021-01-28
opportunity_number: RFA-ES-18-002
application_type: 5
activity_code: P42
ic: ES
serial_number: 007380
project_start_date: 1997-04-07
project_end_date: 2025-01-31
study_section: ZES1-JAB-D
subproject_number: 5741
contact_pi_person_id: 10180341
contact_pi: PEARSON, KEVIN JOSEPH
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_terms:
Acids;Address;Adipocytes;Adolescent;Adult;Agonist;Aryl Hydrocarbon Receptor;Behavior Therapy;Biochemical;Body Composition;Breast;Cells;Child;Collaborations;Development;Diabetes Mellitus;Discipline of Nursing;Endocrine Disruptors;Environmental Exposure;Environmental Impact;Environmental Pollution;Epidemic;Erythroid;Evaluation;Exercise;Exposure to;Fatty acid glycerol esters;Female;Funding;Future;Gender;Glucose Clamp;Glucose Intolerance;Goals;Gold;Hazardous Substances;Health;Home;Human;Human Development;Impairment;Infant;Insulin Resistance;Intervention;Kentucky;Knockout Mice;Life Style;Liver;Measures;Mesenchymal Stem Cells;Metabolic;Methods;Modeling;Molecular;Mus;Muscle Cells;Neonatal;Nuclear;Obesity;Outcome;Oxidative Stress;Pathway interactions;Perinatal;Perinatal Exposure;Phenotype;Play;Polychlorinated Biphenyls;Predisposition;Pregnancy;Process;Research;Risk;Role;Running;Sampling;Serum;Superfund;Testing;Thinness;Time;Tissues;Toxic effect;Umbilical cord structure;Universities;Work;adipocyte differentiation;base;biological adaptation to stress;blood glucose regulation;cohort;cost effective;dechlorination;detection method;diabetes risk;diphenyl;disorder risk;exercise intervention;fetal;glucose uptake;impaired glucose tolerance;improved;in utero;in vivo;innovation;insight;insulin sensitivity;insulin signaling;lipid biosynthesis;male;mouse model;neonate;nutrition;obesity development;obesity in children;obesity risk;obesogen;offspring;offspring obesity;perfluorooctanoic acid;perinatal development;pollutant;postnatal;prenatal exposure;preventive intervention;programs;sedentary;specific biomarkers;superfund chemical;transcription factor;trend


application_id: 10133662
project_number: 5P42ES007380-23
project_title: Superfund Chemicals Nutrition and Multi-Organ Cardiovascular Risk
administering_ic: NIEHS
award_notice_date: 2021-01-28
opportunity_number: RFA-ES-18-002
application_type: 5
activity_code: P42
ic: ES
serial_number: 007380
project_start_date: 1997-04-07
project_end_date: 2025-01-31
study_section: ZES1-JAB-D
subproject_number: 5740
contact_pi_person_id: 1897514
contact_pi: HENNIG, BERNHARD
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_terms:
Acute;Address;Animal Model;Antibiotics;Atherosclerosis;Binding;Biological;Biological Markers;Blood Vessels;Cardiometabolic Disease;Cardiovascular Diseases;Cause of Death;Ceramides;Chemicals;Chronic;Data;Data Set;Development;Diet;Dietary Fiber;Dietary Intervention;Dioxins;Disease;Down-Regulation;Ecology;Endothelium;Environment;Environmental Engineering technology;Environmental Exposure;Enzymes;Epigallocatechin Gallate;Event;Exposure to;Fiber;Functional disorder;Future;Gene Expression;Genes;Goals;Green tea;Hazardous Waste Sites;Health;Hepatic;Hepatocyte;Human;In Vitro;Inflammation;Inflammatory;Insulin Resistance;Inulin;Link;Lipids;Liver;Liver Dysfunction;Low Density Lipoprotein Receptor;Mediating;Metabolic;Metabolic dysfunction;Metabolism;Methionine;Modeling;Molecular;Mus;NF-kappa B;Nutrient;Outcome;Oxidation-Reduction;Pathology;Peripheral;Permeability;Plants;Plasma;Poison;Polychlorinated Biphenyls;Population;Pre-Clinical Model;Process;Production;Public Health;Reporting;Research;Resistance development;Risk;Sampling;Signal Pathway;Signal Transduction;Sphingolipids;Stains;Superfund;Technology;Testing;Toxic effect;United States;Vascular Endothelial Cell;Volatile Fatty Acids;animal data;atherosclerosis risk;base;biobank;body system;cardiovascular disorder risk;cardiovascular risk factor;chemical stability;choline deficient diet;chronic inflammatory disease;disorder risk;experimental study;exposed human population;gut bacteria;gut microbiota;in vivo;lipid metabolism;liver injury;macrophage;metabolic profile;metabolomics;nutrition;oxidation;persistent organic pollutants;pollutant;polyphenol;prebiotics;prevent;programs;response;stable isotope;superfund chemical;systemic inflammatory response;toxicant;transcriptomics;trimethyloxamine;vascular inflammation


application_id: 10133660
project_number: 5P42ES007380-23
project_title: Research Experience and Training Coordination Core
administering_ic: NIEHS
award_notice_date: 2021-01-28
opportunity_number: RFA-ES-18-002
application_type: 5
activity_code: P42
ic: ES
serial_number: 007380
project_start_date: 1997-04-07
project_end_date: 2025-01-31
study_section: ZES1-JAB-D
subproject_number: 5739
contact_pi_person_id: 8239234
contact_pi: HILT, JAMES ZACH
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_terms:
Address;Affect;Bioinformatics;Clinical;Clinical Sciences;Collaborations;Communities;Complex;Data Analyses;Data Collection;Data Science;Development;Discipline;Doctor of Philosophy;Ecology;Education;Educational workshop;Environmental Engineering technology;Environmental Health;Exposure to;Funding;Goals;Government;Grant;Health;Individual;Industrialization;Industry;Interdisciplinary Study;Kentucky;Knowledge;Laboratory Research;Leadership;Life Style;Location;Medical Ethics;Mentors;Methods;Mind;Modeling;Modernization;Outcome;Policies;Positioning Attribute;Postdoctoral Fellow;Problem Solving;Productivity;Public Health;Recording of previous events;Reporting;Research;Research Project Grants;Resources;STEM field;Science Technology Engineering and Mathematics;Scientist;Series;Signal Recognition Particle;Social Impacts;Source;Students;Superfund;Technology;Thinking;Toxic effect;Toxicology;Training;Training Activity;Training Programs;Training and Education;Translational Research;Universities;Water;Writing;base;career;career development;clinical center;community engagement;data management;data sharing;design;experience;flexibility;innovation;interdisciplinary approach;interest;laboratory experience;meetings;multidisciplinary;next generation;novel;nutrition;outreach;pollutant;programs;recruit;remediation;responsible research conduct;skills;skills training;student training;success;superfund chemical;superfund site;training opportunity;webinar


application_id: 10133658
project_number: 5P42ES007380-23
project_title: Community Engagement Core
administering_ic: NIEHS
award_notice_date: 2021-01-28
opportunity_number: RFA-ES-18-002
application_type: 5
activity_code: P42
ic: ES
serial_number: 007380
project_start_date: 1997-04-07
project_end_date: 2025-01-31
study_section: ZES1-JAB-D
subproject_number: 5738
contact_pi_person_id: 12559398
contact_pi: BREWER, DAWN
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_terms:
Address;Adopted;Affect;Age;Air Pollution;Area;Back;Behavior;Biological;Chemicals;Chronic Disease;Coal Mining;Collaborations;Communication;Communities;Consumption;Country;County;Development;Drug Metabolic Detoxication;Education;Elderly;Environmental Hazards;Environmental Health;Environmental Pollutants;Environmental Pollution;Evaluation;Exposure to;Family;Focus Groups;Fostering;Goals;Hazardous Substances;Health;Health Benefit;Health behavior;Health behavior change;Home;Individual;Intervention;Interview;Journals;Kentucky;Kidney;Knowledge;Lead;Life Style;Liver;Longevity;Methods;Modeling;Needs Assessment;Outcome;Peer Review;Physical activity;Physiological;Plants;Policies;Polychlorinated Biphenyls;Population;Population Growth;Populations at Risk;Prevention;Public Health;Recommendation;Reporting;Research;Research Activity;Research Project Summaries;Resources;Risk;Science;Scientist;Services;Site;Solvents;Superfund;Surveys;System;Toxic effect;Translating;United States;Universities;Water Pollution;Work;Youth;behavior change;community center;community engagement;community organizations;design;environmental change;evidence base;experience;farmers markets;good diet;health knowledge;health literacy;healthy lifestyle;improved;innovation;meetings;novel;nutrition;pollutant;prevent;preventive intervention;programs;rapid growth;social;superfund chemical;superfund site;symposium;tool;tool development;walking program


application_id: 10133657
project_number: 5P42ES007380-23
project_title: Data Management and Analysis Core
administering_ic: NIEHS
award_notice_date: 2021-01-28
opportunity_number: RFA-ES-18-002
application_type: 5
activity_code: P42
ic: ES
serial_number: 007380
project_start_date: 1997-04-07
project_end_date: 2025-01-31
study_section: ZES1-JAB-D
subproject_number: 5737
contact_pi_person_id: 8776790
contact_pi: PENNELL, KELLY G
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_terms:
Academy;Address;Adverse effects;Animals;Awareness;Basic Science;Biometry;Chemicals;Collaborations;Common Data Element;Communities;Complex;Computational Science;Consensus;Data;Data Analyses;Data Science;Data Scientist;Data Set;Deposition;Development;Discipline;Documentation;E-learning;Ecology;Educational workshop;Ensure;Environment;Environmental Health;Formulation;Fostering;Gap Junctions;Goals;Government Agencies;Grant;Hazardous Chemicals;Hazardous Substances;Information Resources;Infrastructure;Interdisciplinary Study;Investigator-Initiated Research;Kentucky;Knowledge;Knowledge Discovery;Life Cycle Stages;Metadata;Methods;National Institute of Environmental Health Sciences;Online Systems;Ontology;Outcome;Planet Earth;Population;Problem Solving;Process;Protocols documentation;Public Health;Quality Control;Registries;Reproducibility;Research;Research Personnel;Research Project Grants;Research Support;Resource Sharing;Resources;Risk;Science;Scientist;Secure;Series;Site;Superfund;Technology;Terminology;Testing;Toxic effect;Training;Translational Research;Universities;Validation;Work;application programming interface;base;biomedical informatics;community engagement;dashboard;data archive;data dictionary;data ecosystem;data integration;data management;data quality;data resource;data sharing;data standards;data tools;design;experience;experimental study;improved;innovation;interoperability;meetings;member;nutrition;programs;quality assurance;remediation;repository;superfund chemical;symposium;tool;training opportunity;training project;webinar


application_id: 10133655
project_number: 5P42ES007380-23
project_title: Biomonitoring and Environmental Analytical Chemistry Core
administering_ic: NIEHS
award_notice_date: 2021-01-28
opportunity_number: RFA-ES-18-002
application_type: 5
activity_code: P42
ic: ES
serial_number: 007380
project_start_date: 1997-04-07
project_end_date: 2025-01-31
study_section: ZES1-JAB-D
subproject_number: 5736
contact_pi_person_id: 1879477
contact_pi: MORRIS, ANDREW J
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_terms:
Address;Amendment;Analytical Chemistry;Basic Science;Biological;Biological Markers;Biological Monitoring;Biological Process;Businesses;Cardiovascular Diseases;Chemicals;Clinical;Clinical Management;Cohort Studies;Collaborations;Communities;Consent;Coupled;Data Analyses;Data Analytics;Data Reporting;Data Science;Data Storage and Retrieval;Detection;Development;Diet and Nutrition;Disease;Doctor of Philosophy;Ecology;Ensure;Environmental Engineering technology;Environmental Exposure;Environmental Health;Environmental Pollutants;Equipment;Evaluation;Exercise;Exposure to;Funding;Gas Chromatography;Gas-Liquid Chromatography;Goals;Grant;Health;High Pressure Liquid Chromatography;Human;Human Resources;In Vitro;Institutional Review Boards;Intervention;Investigation;Laboratories;Lead;Life Style;Link;Liquid Chromatography;Literature;Malignant Neoplasms;Management Information Systems;Mass Spectrum Analysis;Measurement;Medical center;Methods;National Institute of Environmental Health Sciences;Outcome;Pre-Clinical Model;Preparation;Procedures;Protocols documentation;Publications;Quality Control;Reaction;Reporting;Research;Research Design;Research Personnel;Research Project Grants;Research Support;Resolution;Risk;Role;Sampling;Schedule;Service provision;Services;Soil;Source;Superfund;Support System;System;Technology;Testing;Toxic Environmental Substances;Toxic effect;United States Department of Veterans Affairs;United States National Institutes of Health;Veterans Health Administration;Vulnerable Populations;Water;Work;analytical method;base;cardiovascular disorder risk;clinical translation;computerized data processing;data management;disorder risk;environmental chemical;environmental chemical exposure;environmental intervention;experience;human disease;improved;instrument;instrumentation;interest;laboratory facility;lipidomics;mass spectrometer;metabolomics;nutrition;offspring;operation;pollutant;population health;preclinical study;programs;quality assurance;ranpirnase;remediation;stressor;superfund chemical;water sampling


application_id: 10133654
project_number: 5P42ES007380-23
project_title: Administration Core
administering_ic: NIEHS
award_notice_date: 2021-01-28
opportunity_number: RFA-ES-18-002
application_type: 5
activity_code: P42
ic: ES
serial_number: 007380
project_start_date: 1997-04-07
project_end_date: 2025-01-31
study_section: ZES1-JAB-D
subproject_number: 5735
contact_pi_person_id: 1897514
contact_pi: HENNIG, BERNHARD
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_terms:
Academia;Address;Advisory Committees;Analytical Chemistry;Animal Model;Animals;Appalachian Region;Biological Monitoring;Biomedical Research;Chemicals;Clinical Sciences;Communication;Communities;Community of Practice;Complex;Coupled;Data;Data Analyses;Databases;Detection;Development;Ecology;Educational workshop;Engineering;Ensure;Environment;Environmental Engineering technology;Environmental Exposure;Environmental Health;Evaluation;Event;Exercise;Exposure to;Funding;General Population;Goals;Government Agencies;Grant;Health;Human;Human Resources;Individual;Industry;Information Dissemination;Infrastructure;Institutes;Internships;Intervention;Investigator-Initiated Research;Kentucky;Leadership;Life Style;Link;Longevity;Maintenance;Mentorship;National Institute of Environmental Health Sciences;Physical activity;Polychlorinated Biphenyls;Positioning Attribute;Prevention;Process;Productivity;Reporting;Research;Research Activity;Research Personnel;Research Project Grants;Resources;Risk;Role;Science;Scientist;Structure;Superfund;Targeted Research;Technology;Technology Transfer;Testing;Toxic effect;Toxicity Tests;Training;Training Activity;Translating;Translational Research;Translations;United States National Institutes of Health;Universities;Water;arm;base;clinical center;community engagement;crosslink;data management;design;disorder risk;experience;healthy lifestyle;innovation;materials science;meetings;member;multidisciplinary;novel;nutrition;pollutant;prevent;programs;ranpirnase;remediation;superfund chemical;technology development;webinar


application_id: 10133653
project_number: 5P42ES007380-23
project_title: Nutrition and Superfund Chemical Toxicity
administering_ic: NIEHS
award_notice_date: 2021-01-28
opportunity_number: RFA-ES-18-002
application_type: 5
activity_code: P42
ic: ES
serial_number: 007380
program_official: HENRY, HEATHER F
project_start_date: 1997-04-07
project_end_date: 2025-01-31
study_section: ZES1-JAB-D(SF)
contact_pi_person_id: 8776790
contact_pi: PENNELL, KELLY G
other_pis: Not Applicable
congressional_district: 06
department: VETERINARY 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: EARTH SCIENCES/RESOURCES
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_terms:
Address;Aging;Appalachian Region;Awareness;Binding;Biochemical;Biological;Biological Markers;Biological Models;Biological Monitoring;Biomedical Engineering;Biomedical Research;Biomimetics;Chemicals;Communication Research;Communities;Complex;Consumption;Data;Data Analyses;Diet and Nutrition;Diffusion;Disease;Disease Outcome;Ecology;Economically Deprived Population;Engineering;Environment;Environmental Engineering technology;Environmental Health;Environmental Pollutants;Environmental Pollution;Evaluation;Exercise;Exposure to;Fiber;Fostering;Funding;Future;Goals;Hazardous Substances;Health;Human;Industry;Intake;Interdisciplinary Study;Intervention;Iron;Kentucky;Life;Life Style;Link;Membrane;Metabolic;Metals;Methods;Molecular;Nanostructures;National Institute of Environmental Health Sciences;Nutrient;Outcome;Oxides;Pathway interactions;Physical activity;Physiological;Plants;Policies;Policy Maker;Polychlorinated Biphenyls;Predisposition;Pregnancy;Prevention;Prevention strategy;Primary Prevention;Problem Sets;Recommendation;Research;Research Project Grants;Research Training;Resources;Risk;Risk Assessment;Risk Management;Science;Scientist;Services;Site;Superfund;System;Techniques;Technology;Tetrachloroethylene;Toxic effect;Toxicant exposure;Training;Translational Research;Trichloroethylene;Universities;Vulnerable Populations;base;chemical stability;chronic inflammatory disease;community engaged research;community engagement;community intervention;community involvement;data management;detection method;dietary;disadvantaged population;disorder prevention;disorder risk;environmental chemical;environmental chemistry;experience;exposure pathway;graphene;healthy lifestyle;human old age (65+);improved;innovation;insight;interdisciplinary approach;lifestyle intervention;lipidomics;metabolomics;next generation;novel;nutrition;organic contaminant;pollutant;polyphenol;prevent;programs;remediation;social;superfund chemical;superfund site;tool


application_id: 10133172
project_number: 5R01NS116058-02
administering_ic: NINDS
award_notice_date: 2021-03-22
opportunity_number: PA-19-056
application_type: 5
activity_code: R01
ic: NS
serial_number: 116058
program_official: CORRIVEAU, RODERICK A
project_start_date: 2020-04-01
project_end_date: 2025-03-31
study_section: Brain Injury and Neurovascular Pathologies Study Section[BINP]
contact_pi_person_id: 9696701
contact_pi: DESPA, FLORIN
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2021-04-01
project_terms:
Acids;Adherence;Adhesions;Aging;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimers disease biomarker;Amyloid;Amyloid beta-42;Amyloid beta-Protein;Arteries;Axon;Behavioral;Biopsy;Blood;Blood Vessels;Blood capillaries;Brain;Cardiovascular system;Carrying Capacities;Cerebral small vessel disease;Cerebrospinal Fluid;Cerebrovascular Circulation;Cerebrovascular system;Cerebrum;Clinical;Clinical Data;Data;Dementia;Deposition;Development;Diabetes Mellitus;Disease;Disease Marker;Elderly;Endocrine;Enrollment;Enzymes;Epoxide hydrolase;Erythrocytes;Genetic;Gliosis;Glucose;Hemoglobin;Hormone Antagonists;Hormones;Human;Hypersensitivity skin testing;Hypoxia;Hypoxic-Ischemic Brain Injury;Impaired cognition;Impairment;Individual;Insulin;Isomerism;Laboratories;Lead;Link;Magnetic Resonance Imaging;Measures;Mediating;Mediator of activation protein;Metabolic dysfunction;Microspheres;Modeling;National Institute of Neurological Disorders and Stroke;Neurologic;Neurologic Deficit;Non-Insulin-Dependent Diabetes Mellitus;Outcome;Pancreas;Participant;Pathologic;Pathologic Processes;Pathology;Pathway interactions;Patients;Pharmacology;Phenotype;Prevention;Prevention strategy;Proteins;Rattus;Regulation;Reporting;Research Project Grants;Sampling;Satiation;Senile Plaques;Signal Pathway;Skin;Techniques;Testing;Therapeutic Intervention;Vascular Cognitive Impairment;Vascular Endothelial Cell;axonal degeneration;beta amyloid pathology;brain cell;cerebral capillary;cerebrovascular;cohort;comorbidity;effective therapy;hypoxic ischemic injury;in vivo;inhibitor/antagonist;innovation;islet amyloid polypeptide;mild cognitive impairment;neuroinflammation;novel therapeutic intervention;tau Proteins;tool;translational study;vascular cognitive impairment and dementia


application_id: 10132997
project_number: 5R25CA203637-05
project_title: Training in Interprofessional Education for Palliative Care in Oncology
administering_ic: NCI
award_notice_date: 2021-07-12
opportunity_number: PAR-15-151
application_type: 5
activity_code: R25
ic: CA
serial_number: 203637
program_official: RADAEV, SERGEY
project_start_date: 2017-03-14
project_end_date: 2024-06-30
study_section: Institutional Training and Education Study Section (F)[NCI-F]
contact_pi_person_id: 8126973
contact_pi: PFEIFER, MARK P
other_pis: SCHAPMIRE, TARA J
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
Project Summary/Abstract Excellent oncology care requires the close collaboration of numerous professionals. Extending andenhancing interdisciplinary care will require interprofessional education (IPE)for students which develops theirunderstanding of the strengths capabilities skills roles and cultures of other professionals and teaches thecommunication and collaboration skills essential for effective teamwork. Integration of palliative care is nowrecommended at the time of a cancer diagnosisregardless of prognosisand palliative care by its verynature requires interdisciplinary patient-centered care to meet the complex needs of oncology patients. Thisproject will develop a critical mass of competent equipped oncology educators skilled in the development andimplementation of IPE for palliative oncology care. Through faculty development webinars and materials atrain-the-trainer workshop ongoing educational activities and mentoring by experienced interprofessionaleducators 160 health science educators (representing the fields of medicine nursing social work andchaplaincy) from 35-50 institutions will develop the skills knowledge and resources to overcome barriers toIPE and teach oncology palliative care and teamwork to students of multiple disciplines. Guided by thisprojects faculty the trainees will work in interprofessional faculty teams to develop a plan for implementing anIPE curriculum in palliative oncology at their site. Trainee and institutional outcomes will be evaluated usingvalidated instruments and a pre/post-test design. A national summit on interdisciplinary palliative oncologyeducation will be held at the completion of the project; sites will share their experiences and other interestededucators will be invited to attend and present their own initiatives.

project_terms:
Accreditation;Address;Cancer Patient;Caring;Collaborations;Communication;Complex;Crowding;Development;Diagnosis;Discipline;Discipline of Nursing;Education;Educational Activities;Educational Curriculum;Educational workshop;Faculty;Future;Goals;Health Sciences;Infrastructure;Institution;Knowledge;Lead;Learning Skill;Length;Logistics;Malignant Neoplasms;Medicine;Mentors;Modeling;Nature;Nurses;Oncology;Outcome;Palliative Care;Patient Care;Patient-Centered Care;Patients;Physicians;Pre-Post Tests;Prognosis;Program Sustainability;Quality of life;Resources;Role;Site;Social Work;Social Workers;Students;Teacher Professional Development;Time;Trainers Training;Training;Training Programs;Work;base;cancer care;cancer diagnosis;cancer education;cancer palliative treatment;design;experience;health care service utilization;improved;instrument;interest;method development;palliative;patient oriented;pedagogy;practice setting;programs;science teacher;skills;student training;success;symposium;webinar

public_health_relevance:
Project Narrative (Relevance)Excellent care of patients diagnosed with cancer requires the integration of palliative care and the closecollaboration of professionals from many disciplines including physicians nurses chaplains and socialworkers. Through faculty development webinars online modules and a train-the- trainer program this projectwill train 160 health science educators to provide interprofessional education in oncology palliative care at 35-50 institutions across the nation. As a result students of the health sciences at these institutions will learn theskills and knowledge essential for providing effective team-based patient-centered palliative oncology care.


