University Of Kentucky Research Foundation

KENTUCKY CAN HEAL (COMMUNITIES AND NETWORKS HELPING END ADDICTION LONG-TERM)

KENTUCKY CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE

NUTRITION AND SUPERFUND CHEMICAL TOXICITY

UNIVERSITY OF KENTUCKY MARKEY CANCER CENTER - CANCER CENTER SUPPORT GRANT

KENTUCKY OVERDOSE DATA TO ACTION

NEXT GENERATION MATERIALS AND PROCESSING TECHNOLOGIES (NEXTGENMATPROTECH)

UNIVERSITY OF KENTUCKY CENTER FOR CANCER AND METABOLISM

SOUTHEAST CENTER FOR AGRICULTURAL HEALTH AND INJURY PREVENTION-RENEWAL

ALZHEIMER'S DISEASE CORE CENTER

RII TRACK-1: KENTUCKY ADVANCED MANUFACTURING PARTNERSHIP FOR ENHANCED ROBOTICS AND STRUCTURES

POWERING THE KENTUCKY BIOECONOMY FOR A SUSTAINABLE FUTURE

NEW AWARD DE-FE0007395 ENTITLED "APPLICATION OF A HEAT-INTEGRATED POST-COMBUSTION CARBON DIOXIDE CAPTURE SYSTEM WITH HITACHI ADVANCED SOLVENT INTO EX

STRATEGIES FOR TARGETING ASTROCYTE REACTIVITY IN ALZHEIMER'S DISEASE AND RELATED DEMENTIAS - OVERALL – ABSTRACT SUMMARY THIS P01— STRATEGIES FOR TARGETING ASTROCYTE REACTIVITY IN AD AND ADRD (STAR-ADRD) ADDRESSES THE (PATHO)PHYSIOLOGIC ROLES OF REACTIVE ASTROCYTES IN ALZHEIMER’S DISEASE (AD) AND RELATED DEMENTIAS (ADRD). THOUGH HIGHLY SIGNIFICANT TO MANY DISEASE PHENOTYPES, ASTROCYTE FUNCTIONS ARE UNDER-INVESTIGATED AND HAVE YET TO BENEFIT FROM LARGE-SCALE PROGRAMMATIC SUPPORT FROM THE NIH. TO FILL THIS VOID WE HAVE ASSEMBLED A HIGHLY ACCOMPLISHED AND COLLABORATIVE TEAM FROM THE UNIVERSITY OF KENTUCKY SANDERS-BROWN CENTER ON AGING (UK- SBCOA). THE OVERARCHING GOALS OF THIS PROJECT ARE TO: (1) USE CELL-SPECIFIC TARGETING TO MODULATE DISTINCT ASPECTS OF THE REACTIVE ASTROCYTE PHENOTYPE. (2) USE CUTTING-EDGE TECHNOLOGIES TO ASSESS THE FUNCTIONAL IMPACT OF REACTIVE ASTROCYTES IN INTACT PRECLINICAL MOUSE MODELS OF AD AND ADRD PATHOLOGIES. (3) LEVERAGE UK-SBCOA AND UK- ALZHEIMER’S DISEASE RESEARCH CENTER (ADRC) RESOURCES TO VALIDATE PRECLINICAL RESULTS IN POSTMORTEM AND LIVING HUMAN SUBJECTS. AND (4) USE AN INTEGRATED DATA PIPELINE APPROACH TO ANALYZE AND INTERPRET DATA WITHIN AND ACROSS PROJECTS. THROUGH THESE AIMS WE WILL TEST THE HYPOTHESIS THAT: INTERRELATED REACTIVE ASTROCYTE PHENOTYPES DRIVE MAJOR PATHOPHYSIOLOGIC FEATURES OF DEMENTIA INCLUDING CEREBROVASCULAR DYSFUNCTION, HYPOMETABOLISM, AND IMPAIRED NEURONAL NETWORK FUNCTION AND FIDELITY. PROJECTS ARE DESIGNED AROUND A CLEAR UNDERSTANDING THAT DEMENTIA DOES NOT EXIST AS A SINGLE PATHOLOGICAL ENTITY MOST OF THE TIME, BUT RATHER IS CHARACTERIZED BY MULTIPLE BRAIN PATHOLOGIES. PROJECT 1 (ASTROCYTIC END-FEET AND VCID) WILL USE MMP9 OVEREXPRESSION/KNOCKDOWN IN A MODEL OF CEREBRAL SMALL VESSEL DISEASE TO ADDRESS ASTROCYTE ENDFEET DEGENERATION. PROJECT 2 (ASTROCYTIC INSULIN SIGNALING AND AD) WILL OVEREXPRESS/KNOCKDOWN ASTROCYTIC INSULIN RECEPTORS (IR) IN AN ASS MODEL TO STUDY THE IMPACT OF IMPAIRED ASTROCYTIC IR SIGNALING. PROJECT 3 (ASTROCYTIC GLUTAMATE TRANSPORT IN AD AND VCID) WILL OVEREXPRESS/KNOCKDOWN THE ASTROCYTIC GLUTAMATE TRANSPORTER SLC1A2 IN A MIXED ASS-VASCULAR MODEL TO ASSESS THE ROLE OF IMPAIRED GLUTAMATE TRANSPORT IN REACTIVE ASTROCYTES. PROJECT 4 (ASTROCYTIC KATP CHANNELS IN LATE+HS) WILL OVEREXPRESS/ELIMINATE ASTROCYTIC ABCC9/SUR2 IN A MODEL OF LATE + HIPPOCAMPAL SCLEROSIS TO ASSESS THE ROLE OF KATP CHANNELS. FOUR CORES WILL SUPPORT AND FURTHER INTEGRATE OUR PROJECTS. CORE B: ANIMAL VASCULAR-METABOLIC-NEURAL NETWORK (VMN) WILL ASSESS CEREBROVASCULAR, METABOLIC, AND NEURAL NETWORK PROPERTIES IN MICE USING TWO-PHOTON MICROSCOPY, MRI/MRS, MICROELECTRODE ARRAY NEURO- CHEMISTRY, AND ELECTROPHYSIOLOGY. CORE C: HUMAN CONSULTATION-BIOSAMPLES-BIOMARKERS (CBB) WILL VALIDATE RESULTS IN MICE USING WELL CHARACTERIZED AUTOPSY TISSUE, MRI, EEG, AND FLUID BIOMARKER DATA FROM HUMANS. AND CORE D: DATA MANAGEMENT AND BIOSTATISTICS WILL ESTABLISH A DATA PIPELINE FOR EFFICIENT CATEGORIZATION, TRANSFORMATION, AND STATISTICAL ANALYSIS OF COMPLEX RELATIONSHIPS BETWEEN ASTROCYTE INTERVENTIONS AND ENDPOINT MEASURES, WITHIN AND BETWEEN PROJECTS. FINALLY, AN ADMINISTRATIVE CORE (CORE A) WILL PROVIDE LEADERSHIP, COORDINATION, INTEGRATION, AND ADMINISTRATIVE STRUCTURE, SO THAT THE P01 GOALS ARE ACHIEVED.

HEALTH CENTER CLUSTER

CENTER OF BIOMEDICAL RESEARCH EXCELLENCE IN PHARMACEUTICAL RESEARCH AND INNOVATION

OVERDOSE DATA TO ACTION - KENTUCKY CONTINUES TO BE PLAGUED BY THE DRUG OVERDOSE EPIDEMIC. IN 2021, KENTUCKY HAD AGE-ADJUSTED DRUG OVERDOSE MORTALITY RATE OF 53.6 DEATHS PER 100,000 RESIDENTS, 3RD HIGHEST STATE IN THE UNITED STATES. (CDC NCHS, 2023). SINCE 2018, KENTUCKY THE AGE-ADJUSTED DRUG OVERDOSE MORTALITY RATE HAS INCREASED 81%. (STEEL & MIRZAIAN, 2022). THE DRUG OVERDOSE MORTALITY BURDEN IS HIGH IN KENTUCKY AS IS DRUG OVERDOSE MORBIDITY. IN 2021, THE AGE-ADJUSTED RATE OF DRUG OVERDOSES TREATED IN KENTUCKY EMERGENCY DEPARTMENT (ED) WAS 308.2/100,000 RESIDENTS - 8 PERCENT INCREASE SINCE 2018. RATES OF ED VISITS FOR ANY REASON WITH A CO-OCCURRING SUBSTANCE USE DISORDER DIAGNOSIS HAS INCREASED NEARLY 5% FROM 1002.1 IN 2018 TO 1049.1/100,000 IN 2019. (KIPRC, 2022). THE BURDEN OF OVERDOSE IS FELT DISPROPORTIONATELY. BLACK KENTUCKIANS HAVE HIGHER AGE-ADJUSTED MORTALITY (58.5/100,000) AND MORBIDITY (359.2/100,000) THAN WHITE KENTUCKIANS (MORTALITY (53.5/100,000) AND MORBIDITY (324/100,000)). NINE OF THE 10 COUNTIES WITH THE HIGHEST AGE-ADJUSTED MORTALITY RATES ARE RURAL COUNTIES, AND 9 OF 10 COUNTIES WITH THE HIGHEST AGE-ADJUSTED MORBIDITY RATES ARE ALSO RURAL. TO REDUCE THESE RATES, THERE MUST BE MULTIPRONGED APPROACHES IMPLEMENTED: 1) IDENTIFICATION AND MONITORING OF SUBSTANCE USE DISORDERS (SUD) AND DRUG OVERDOSES THROUGH COMPREHENSIVE SURVEILLANCE; AND 2) ENHANCING DEVELOPMENT, IMPLEMENTATION, AND EVALUATION OF EVIDENCE-INFORMED, EVIDENCE-BASED, AND PROMISING PREVENTION PROGRAM AND POLICY STRATEGIES. THE KENTUCKY INJURY PREVENTION AND RESEARCH CENTER (KIPRC), AS A BONA FIDE AGENT FOR THE KENTUCKY DEPARTMENT OF PUBLIC HEALTH, WILL COLLABORATE WITH STATE, UNIVERSITY, AND COMMUNITY PARTNERS TO IMPLEMENT SURVEILLANCE AND PREVENTION STRATEGIES. SURVEILLANCE STRATEGIES INCLUDE ENHANCING THE SURVEILLANCE INFRASTRUCTURE; THE TIMELY ANALYSIS OF DRUG OVERDOSE ED ENCOUNTERS AND FATAL DRUG OVERDOSES USING MULTIPLE DATA SOURCES; BIO SURVEILLANCE OF DRUG INVOLVEMENT IN NON-FATAL OVERDOSES; AND DATA LINKAGES TO CRIMINAL JUSTICE DATA AT THE INDIVIDUAL LEVEL; HARM REDUCTION DATA TEMPORALLY TO OVERDOSE DATA, AND OPTIONAL STRATEGIES OF BIOSURVEILLANCE AND DATA LINKAGE. KIPRC'S PREVENTION STRATEGIES INCLUDE EDUCATING CLINICIANS ON BEST PAIN MANAGEMENT PRACTICES USING CDC PRESCRIBING GUIDELINES; TRAINING CLINICIANS ON OUD (OPIOID USE DISORDER) AND STIMULANT USE DISORDER (STUD) PATIENT STANDARDS OF CARE; SUPPORTING ED LINKAGE TO CARE WITH NAVIGATORS; EXPANDING PRESCRIPTION DRUG MONITORING PROGRAM DATA SHARING; DEVELOPING PUBLIC HEALTH (PH)/PUBLIC SAFETY (PS) PARTNERSHIPS; IMPROVING PH/PS DATA SHARING; DEVELOPING PH/PS OUD AND STUD TRAININGS; USING HARM REDUCTION (HR) NAVIGATORS TO CONNECT PEOPLE TO SERVICES; DEVELOPING A STATEWIDE HARM REDUCTION SERVICES RESOURCE LIST; HOSTING ANNUAL IN-PERSON HR SERVICES TRAINING; USING RECOVERY NAVIGATORS TO LINK VULNERABLE INDIVIDUALS TO AVAILABLE SUD TREATMENT WITH FINDHELPNOWKENTUCKY (FHNKY) AND RECOVERY HOUSING WITH FINDRECOVERYHOUSINGNOWKENTUKCKY(FRHNKY); DEVELOPING A RECOVERY MONITORING SYSTEM; DEVELOPING A RECOVERY RESIDENT MANAGEMENT SYSTEM; AND DEVELOPING A COMPREHENSIVE RESOURCES SECTION WITHIN FRHNKY. KIPRC HOPES TO REDUCE OVERDOSE MORTALITY AND MORBIDITY, IMPROVE THE STANDARD OF CARE AND LINKAGE TO CARE FOR INDIVIDUALS WITH SUD, AND INCREASE ACCESS TO RECOVERY SUPPORT THROUGH PREVENTION EFFORTS GUIDED BY ENHANCED SURVEILLANCE.

CENTRAL APPALACHIAN REGION EDUCATIONAL RESEARCH CENTER OCCUPATIONAL SAFETY CORE

UNIVERSITY OF KENTUCKY ALZHEIMER'S DISEASE RESEARCH CENTER - PROJECT SUMMARY/ABSTRACT: OVERALL THE UNIVERSITY OF KENTUCKY ALZHEIMER’S DISEASE RESEARCH CENTER (UK-ADRC) IS AN EXPERIENCED AND COLLABORATIVE CENTER THAT HAS FACILITATED PIONEERING RESEARCH IN AD AND RELATED DEMENTIAS (ADRD) SINCE ITS INCEPTION IN 1985. OUR PRINCIPAL MISSION IS TO SERVE AS THE FOCAL POINT FOR ALL AD-RELATED ACTIVITIES AT UK AND THIS REGION OF THE UNITED STATES, BY PROVIDING AN ENVIRONMENT AND CORE RESOURCES THAT CATALYZE INNOVATIVE RESEARCH, OUTREACH, EDUCATION, AND CLINICAL PROGRAMS. OUR SIGNATURE RESOURCES INCLUDE: 1) A COGNITIVELY NORMAL GROUP OF ~500 SUBJECTS FOLLOWED LONGITUDINALLY, TOGETHER WITH ~300 ADDITIONAL SUBJECTS WHO TRANSITIONED TO MCI OR DEMENTIA, AND ALL COMMITTED TO BRAIN AUTOPSY UPON DEATH; 2) A STRONG AUTOPSY PROGRAM WITH CLINICAL- NEUROPATHOLOGICAL CORRELATIONS AND SHORT POSTMORTEM INTERVAL RESEARCH MATERIAL; 3) A MATURING PROGRAM STUDYING THE EARLY PRECLINICAL BIOLOGICAL EMERGENCE OF MIXED PATHOLOGIES AND HOW THEY CONTRIBUTE TO LATE LIFE DEMENTIA STATES, WITH AN INCREASING FOCUS ON ANTEMORTEM BIOMARKER COLLECTION; 4) AN INTEGRATED CENTRALIZED DATABASE AND INNOVATIVE BIOSTATISTICAL EXPERTISE TO CHARACTERIZE CLINICAL AND BIOLOGICAL TRANSITIONS; 5) A SUCCESSFUL AND CLOSE PARTNERSHIP WITH THE AFRICAN-AMERICAN COMMUNITY AND INCREASED PARTICIPATION OF UNDERREPRESENTED INDIVIDUALS IN OUR LONGITUDINAL COHORT AND ADRC-AFFILIATED RESEARCH STUDIES AND CLINICAL TRIALS; AND 6) A RICH, INTERDISCIPLINARY TRAINING ENVIRONMENT THAT PROVIDES MULTI-FACETED EDUCATIONAL OPPORTUNITIES FOR RESEARCHERS, HEALTHCARE PROVIDERS, AND OUR COMMUNITY PARTNERS. THE OVERARCHING THEME OF THE UK-ADRC IS: TRANSITIONS FROM NORMAL TO LATE-LIFE MULTI-ETIOLOGY DEMENTIA. OUR WELL-CHARACTERIZED, LONGITUDINAL COHORT AND HISTORICALLY STRONG NEUROPATHOLOGY PROGRAM FOCUSED ON NORMAL AGING, PRECLINICAL DISEASE STATES AND EARLY COGNITIVE TRANSITIONS HAVE BEEN CENTRAL TO OUR SUCCESS IN DEFINING EARLY PATHOGENIC MECHANISMS UNDERLYING THE TRANSITIONS FROM NORMAL COGNITIVE AGING TO IMPAIRMENT. IN ADDITION, THESE EFFORTS HAVE BEEN A DRIVING FORCE IN OUR RECOGNITION OF THE HETEROGENEITY AND MULTIPLE PATHOLOGIES THAT CHARACTERIZE LATE-LIFE DEMENTIA. THE UK-ADRC WILL CONTINUE TO LEVERAGE OUR STRENGTHS TO ENHANCE OUR IMPACT AND “CENTERNESS” BY OUR FOCUS ON THIS OVERARCHING THEME, AND THE PURSUIT OF FOUR OVERALL SPECIFIC AIMS. AIM 1. FACILITATE AND ENHANCE BASIC, TRANSLATIONAL AND CLINICAL RESEARCH IN AD AND RELATED DEMENTIAS. AIM 2. PROVIDE THE NECESSARY RESOURCES AND INTERACTIVE ENVIRONMENT TO SUPPORT AND CREATE NEW OPPORTUNITIES FOR INNOVATIVE RESEARCH. AIM 3. MAINTAIN AND GROW EDUCATIONAL OPPORTUNITIES AND COMMUNITY PARTNERSHIPS TO PROMOTE AWARENESS, INCREASE PARTICIPATION IN RESEARCH, AND PROVIDE AN INNOVATIVE AND INTERDISCIPLINARY TRAINING ENVIRONMENT. AIM 4. CONTRIBUTE TO THE NATIONAL EFFORTS AND COLLABORATIVE ACTIVITIES WITH OTHER CENTERS, PROGRAMS AND GROUPS TO ADVANCE AD/ADRD RESEARCH, EDUCATION, AND CARE.

MID-SCALE RI-1 (M1:IP): EDUCELAB: INFRASTRUCTURE FOR NEXT-GENERATION HERITAGE SCIENCE

CENTER FOR APPALACHIAN RESEARCH IN ENVIRONMENTAL SCIENCES

TRANSFORMING KENTUCKY'S NEW ECONOMY

CENTER OF RESEARCH IN OBESITY AND CARDIOVASCULAR DISEASE (1P20 RR021954-01A1)

KENTUCKY CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE

CDART - CENTER FOR DRUG ABUSE RESEARCH TRANSLATION

VALUE-BASED MEDICAL STUDENT EDUCATION TRAINING PROGRAM

RII TRACK-1: CLIMATE RESILIENCE THROUGH MULTIDISCIPLINARY BIG DATA LEARNING, PREDICTION & BUILDING RESPONSE SYSTEMS (CLIMBS) -THE COMMONWEALTH OF KENTUCKY FACES MOUNTING THREATS FROM GLOBAL ENVIRONMENTAL CHANGE AND NATURAL HAZARDS, INCLUDING EXTREME WEATHER EVENTS, FLOODS, DROUGHTS, AND LANDSLIDES. THIS CLIMATE RESILIENCE THROUGH MULTIDISCIPLINARY BIG DATA LEARNING, PREDICTION & BUILDING RESPONSE SYSTEMS (CLIMBS) PROJECT AIMS TO ADVANCE THE FIELDS OF CLIMATE SCIENCE, GEOHAZARDS ENGINEERING, AND DISASTER MANAGEMENT TO FACILITATE IMPROVED SUSTAINABILITY, RESILIENCE, AND ADAPTATIVE ENGINEERING TO CLIMATE CHANGE. CLIMBS RESEARCH WILL TARGET UNDERSERVED COMMUNITIES IN EASTERN KENTUCKY, AN APPALACHIAN REGION THAT IS ESPECIALLY VULNERABLE TO CLIMATE CHANGE. THE RESEARCH WILL PRODUCE A HOLISTIC UNDERSTANDING OF CLIMATE CHANGE PROCESSES IN KENTUCKY ACROSS MULTIPLE SPATIAL AND TEMPORAL SCALES, DETERMINE THE INFLUENCE OF CLIMATE CHANGE ON GEOHAZARDS THAT THREATEN THE COMMONWEALTH, AND ESTABLISH AN ENHANCED TOOLS AND TECHNOLOGY FRAMEWORK FOR CLIMATE CHANGE MITIGATION AND COMMUNITY DISASTER RESPONSE. RESULTS OF THIS RESEARCH WILL BENEFIT KENTUCKY'S KEY INDUSTRIES OF MANUFACTURING, DATA ANALYTICS, ENERGY TRANSITION, AND ENGINEERING, AND HELP TRAIN A SCIENCE AND ENGINEERING WORKFORCE THAT WILL ALLOW SMALLER INDUSTRIES TO FLOURISH. CLIMBS WILL BE ADMINISTERED BY THE UNIVERSITY OF KENTUCKY IN COLLABORATION WITH SEVEN OTHER INSTITUTIONS: UNIVERSITY OF LOUISVILLE, EASTERN KENTUCKY UNIVERSITY, NORTHERN KENTUCKY UNIVERSITY, WESTERN KENTUCKY UNIVERSITY, MOREHEAD STATE UNIVERSITY, MURRAY STATE UNIVERSITY, AND THOMAS MORE COLLEGE. CLIMBS SEEKS TO ADDRESS MAJOR KNOWLEDGE GAPS THAT SURROUND: (I) CLIMATE CHANGE PROCESSES AFFECTING KENTUCKY; (II) PATTERNS IN CLIMATE CHANGE IMPACTS; (III) CONTROLS ON SEVERE WEATHER AND EXTREME EVENTS; (IV) CLIMATE TRIGGERS, THRESHOLDS, AND FEEDBACKS THAT RESULT IN FLOOD AND LANDSLIDE HAZARDS; AND (V) CLIMATE-SMART SUSTAINABLE DESIGN AND RESILIENCE ENGINEERING IN THE BUILT ENVIRONMENT. TO ADDRESS THESE ISSUES, CLIMBS WILL ACQUIRE THE CONTEMPORARY ATMOSPHERIC AND PALEOENVIRONMENTAL DATA NEEDED TO ASSESS THE CAUSES, PATTERNS, AND CHARACTERISTICS OF REGIONAL CLIMATE DYNAMICS (TO INCLUDE EXTREME WEATHER) ACROSS SPACE AND TIME, AS WELL AS FACILITATE PREDICTIONS FOR THE IMPACTS OF CLIMATE CHANGE ON KENTUCKY'S CRITICAL ZONE AND WATER RESOURCES. RESEARCHERS WILL PURSUE INTEGRATIVE, LONG-TERM ENVIRONMENTAL MONITORING EXPERIMENTS TO DEVELOP THE BIG DATA AND CYBERINFRASTRUCTURE NEEDED TO QUANTIFY THE PROCESSES, FEEDBACKS, AND THRESHOLD CONDITIONS THAT TRIGGER FLOODS AND LANDSLIDES, AND ESTABLISH INSTRUMENTED WATERSHEDS AND HILLSLOPE MONITORING SITES. INITIAL MONITORING SITES WILL BE DEPLOYED IN SOCIO-ECONOMICALLY VULNERABLE AREAS OF EASTERN KENTUCKY, TO BRIDGE WITH PROJECT ELEMENTS DESIGNED TO IMPROVE EDUCATION AND OUTREACH IN APPALACHIA. ADDITIONALLY, CLIMBS WILL ANALYZE KENTUCKY'S BUILT ENVIRONMENT AND SOCIO-BEHAVIORAL SYSTEMS, AND USE BIG DATA, ARTIFICIAL INTELLIGENCE/MACHINE LEARNING, AND COMPUTATIONAL TOOLS TO EVALUATE VULNERABILITIES TO CLIMATE CHANGE AND IMPROVE REAL-TIME DISASTER DETECTION, WARNING SYSTEMS, AND THE RESPONSE TOOLKIT. TEN NEW FACULTY HIRES ARE PLANNED IN THE FIRST THREE YEARS OF THE PROJECT. THE CORE RESEARCH PROGRAM IS WELL INTEGRATED WITH EDUCATION, WORKFORCE DEVELOPMENT, AND DIVERSITY PLANS THAT SPAN ACADEMIC, FEDERAL, COMMONWEALTH, AND PRIVATE SECTORS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

MARSOC INJURY PREVENTION AND HUMAN PERFORMANCE RESEARCH

SHIP COVID TESTING AND MITIGATION

HYPERGEN: GENETICS OF LEFT VENTRICULAR HYPERTROPHY

EXPANSION OF THE UNIVERSITY OF KENTUCKY CENTER FOR APPLIED ENERGY RESEARCH LABORATORY FACILITIES.

DEVELOPMENT OF A LONG-ACTING ENZYME THERAPY FOR TREATMENT OF COCAINE ABUSE

APPALACHIAN TOBACCO REGULATORY SCIENCE TEAM (APPALTRUST) - ABSTRACT THE OVERALL GOAL OF THE APPALACHIAN TOBACCO REGULATORY RESEARCH TEAM (APPALTRUST) IS TO INVESTIGATE THE IMPACT OF FEDERAL DRUG ADMINISTRATION CENTER FOR TOBACCO PRODUCTS (FDA CTP) REGULATORY POLICIES IN RURAL COMMUNITIES, A VULNERABLE AND UNDERSTUDIED POPULATION, THROUGH COLLABORATION, EDUCATION AND PIONEERING REGULATORY SCIENTIFIC RESEARCH. OUR MULTIDISCIPLINARY TEAM WILL INVESTIGATE THIS QUESTION WITH TWO AIMS. AIM 1. FACILITATE AND PIONEER REGULATORY SCIENCE RESEARCH IN RURAL COMMUNITIES. OUR MULTIDISCIPLINARY TEAM OF RESEARCHERS WILL EVALUATE CURRENT AND POTENTIAL REGULATORY POLICIES ACROSS PROJECTS 1-3 THAT ARE METHODOLOGICALLY COHERENT AND INTERRELATED WITH A FOCUS ON THE REGULATORY SCIENTIFIC DOMAINS OF BEHAVIOR, MARKETING, AND IMPACT ANALYSIS. P1-P3 WILL LEVERAGE THE APPALTRUST COHORT TO ADDRESS THE CRITICAL REGULATORY QUESTION OF WHETHER FDA CTP POLICY ACTIONS WILL BE BENEFICIAL, SHIFTING INDIVIDUALS TO LOWER HARM PRODUCTS OR QUITTING TOBACCO IN RURAL COMMUNITIES, OR NOT, IN A WAY THAT ASSESSES THE ASSOCIATION BETWEEN OUTCOMES AND LEVEL OF RURALITY. P1 WILL MEASURE THE FACTORS ASSOCIATED WITH TOBACCO USE BEHAVIORS OF CONVENTIONAL AND NOVEL PRODUCTS, INCLUDING INITIATION, PROGRESSION, DUAL/POLY TOBACCO USE, PRODUCT SWITCHING, AND CESSATION-RELATED BEHAVIORS ACROSS LEVELS OF RURALITY OVER TIME. P2 WILL EVALUATE HOW FDA REGULATIONS MAY AFFECT PATTERNS OF USE FOR CONVENTIONAL AND NOVEL PRODUCTS AMONG YOUNG ADULTS ACROSS LEVELS OF RURALITY. P3 WILL USE A RANDOMIZED PARALLEL GROUPS TRIAL TO ASSESS THE IMPACT OF THREE PROPOSED TOBACCO REGULATIONS USING AN EXPERIMENTAL TOBACCO MARKETPLACE TO ESTIMATE EFFECTS OF REGULATORY POLICIES ON USE BEHAVIOR ACROSS LEVELS OF RURALITY. AIM 2. SUPPORT AND CREATE NEW OPPORTUNITIES FOR INNOVATIVE TOBACCO REGULATORY SCIENCE AND CONTRIBUTE TO THE NATIONAL EFFORTS TO ADVANCE TCORS RESEARCH THROUGH EDUCATION AND COLLABORATION. THE FOLLOWING FOUR CORES WILL SUPPORT THE PROJECTS TO ENSURE CENTER COORDINATION, INTEGRATION, AND COLLABORATION: (1) AN ADMINISTRATIVE CORE TO PROVIDE EFFICIENT, COLLABORATIVE INFRASTRUCTURE TO ENHANCE SYNERGIES ACROSS THE THREE PROGRAM PROJECTS AND FOUR CORES AS WELL AS COLLABORATION WITH THE WIDER TCORS COMMUNITY; (2) A COMMUNITY OUTREACH AND PARTICIPANT ENGAGEMENT CORE TO ENGAGE RURAL AND PERI-URBAN APPALACHIAN COMMUNITIES TO SUPPORT OUR APPALTRUST COHORT; (3) A BIOSTATISTICS AND INFORMATICS CORE TO BUILD A CENTRALIZED, INTEGRATED DATA WAREHOUSE SUPPORTED BY STATISTICAL AND INFORMATICS EXPERTISE TO COLLECT, HARMONIZE, AND ANALYZE DATA AND PROVIDE STATISTICAL SUPPORT FOR PROJECTS AND CORES; AND (4) A CAREER ENHANCEMENT CORE TO CREATE A TRANSFORMATIVE ENVIRONMENT OFFERING MENTORED, MULTIDISCIPLINARY AND IMMERSIVE EXPERIENCES TO EXPAND AND SUPPORT TRS SCHOLARS, WITH EMPHASIS ON THE IMPACT OF REGULATORY POLICIES IN RURAL AREAS. IMPACT: APPALTRUST WILL PROVIDE THE SCIENTIFIC RESOURCES NEEDED TO EVALUATE THE EFFECTS OF THE INTRODUCTION OF NOVEL PRODUCTS AND POTENTIAL RESTRICTIONS ON FLAVORED AND HIGH-NICOTINE PRODUCTS IN RURAL COMMUNITIES SO THAT REGULATORY DECISIONS WILL BE MADE USING A HEALTH EQUITY LENS AND GUIDED BY A DEFINITION OF RURALITY THAT IS DIVERSE AND HETEROGENEOUS.

IMPROVEMENT OF TAFENOQUINE RADICAL CURE BY COMBINATION WITH SJ733, A NOVEL ATP4 INHIBITOR, FOR TREATMENT OF MALARIA

CENTER FOR BIOLOGIC BASIS OF ORAL/SYSTEMIC DISEASES (CB*

BETA AMYLOID AND OXIDATIVE STRESS IN ALZHEIMER'S DISEASE

LAFORA EPILEPSY - BASIC MECHANISMS TO THERAPY

INCREASING ACCESS TO HEPATITIS C TREATMENT IN OPIOID ENDEMIC RURAL AREAS: THE KENTUCKY VIRAL HEPATITIS TREATMENT (KEY TREAT) STUDY

RESOURCE CENTER FOR STABLE ISOTOPE-RESOLVED METABOLOMICS

COBRE MOLECULAR BASIS OF HUMAN DISEASE

CENTER OF BIOMEDICAL RESEARCH EXCELLENCE IN CNS METABOLISM - CENTRAL NERVOUS SYSTEM (CNS) METABOLISM AND NEURONAL EXCITABILITY ARE INTERDEPENDENT, AND SO CNS METABOLISM IS THE BIOCHEMICAL BASIS OF COGNITION, MEMORY, AND BEHAVIOR. DYSREGULATION OF CNS IS IMPLICATED IN NUMEROUS DISORDERS, INCLUDING ALZHEIMER’S DISEASE, EPILEPSY, PARKINSON’S DISEASE, AND BRAIN INJURY, BUT THE MECHANISTIC CONNECTIONS BETWEEN CNS METABOLISM AND DISEASE ARE POORLY UNDERSTOOD. THE UNIVERSITY OF KENTUCKY (UK) COLLEGE OF MEDICINE HAS MADE SIGNIFICANT INVESTMENTS OVER THE LAST FEW YEARS IN INVESTIGATORS WITH METABOLIC AND METABOLOMICS EXPERTISE AND INSTRUMENTATION TO SUPPORT THEIR RESEARCH EFFORTS, WHICH HAS ENHANCED EXISTING STRENGTHS IN NEUROSCIENCE, CANCER, CARDIOVASCULAR, AND DIABETES AND OBESITY RESEARCH. THUS, UK PROPOSES TO ESTABLISH A UNIQUE MULTIDISCIPLINARY CENTER OF BIOMEDICAL RESEARCH EXCELLENCE (COBRE) ON CNS METABOLISM (CNS-MET) AS A STRATEGICALLY DESIGNED, SUSTAINABLE FRAMEWORK THAT PROMOTES LEADING-EDGE RESEARCH FOCUSED ON THE ROLE OF METABOLIC MEDIATORS OF BRAIN FUNCTION AND DISEASE. THE PROPOSED INTERDISCIPLINARY CENTER LEVERAGES HIGHLY SPECIALIZED EXPERTISE IN GLUCOSE BIOLOGY, NEURONAL SIGNALING, MITOCHONDRIAL METABOLISM, SYSTEMS NEUROSCIENCE, AND DATA SCIENCES AS WELL AS THE PRESENCE OF ADVANCED METABOLOMICS AND IMAGING CAPABILITIES TO CREATE AN INTEGRATED RESEARCH FRAMEWORK FOCUSED ON CNS METABOLISM. THE OVERARCHING GOALS ARE TO STRENGTHEN UK’S NEUROSCIENCE RESEARCH ENTERPRISE BY PROVIDING A THEMATICALLY FOCUSED AND SUSTAINABLE MULTIDISCIPLINARY INFRASTRUCTURE DEDICATED TO DEFINING THE CONTRIBUTION OF METABOLISM TO CNS FUNCTION AND NEUROLOGICAL DISEASES AND TO USE THIS NOVEL PLATFORM TO DEVELOP PROMISING AND HIGHLY-SKILLED, EARLY-STAGE INVESTIGATORS IN AN EXCITING AND IMPACTFUL AREA OF CNS RESEARCH. TO ACCOMPLISH THESE GOALS, WE WILL MEET FOUR SPECIFIC AIMS: (1) DEVELOP A CRITICAL MASS OF FUNDED INVESTIGATORS WITH RESEARCH PROGRAMS DIRECTLY RELATED TO THE COBRE’S UNIFYING THEME; (2) PROVIDE STRONG TEAM-BASED MENTORING COMBINING BASIC AND CLINICAL EXPERTISE; (3) RECRUIT NEW INVESTIGATORS TO THE COBRE IN MULTIDISCIPLINARY AREAS OF NEUROLOGIC DYSFUNCTION THROUGH PILOT PROJECT GRANT AND RECRUITMENT OF JUNIOR RESEARCH PROJECT LEADERS; AND (4) CREATE SYNERGY AMONG RESEARCH PROJECTS VIA CRITICAL LINKS TO STRONG RESEARCH CENTERS AND CORE FACILITIES AT UK, INCLUDING EXISTING COBRES. EMERGING SYNERGIES WILL BE DEVELOPED THROUGH THREE RESEARCH PROJECTS, AN ADMINISTRATIVE CORE, A CRITICAL RESEARCH CORE IN METABOLOMICS, ALL LINKED BY STRONG BIOSTATISTICS/BIOINFORMATICS SUPPORT, ALL OF WHICH ARE CRITICAL TO THE PROPOSED STUDIES AND WILL CONTRIBUTE TO THE DEVELOPMENT OF INSTITUTIONAL RESOURCES. THE SCIENTIFIC FOCUS OF THE THREE RESEARCH PROJECTS ARE BRAIN METABOLISM INTERACTIONS WITH NEUROLOGICAL DISEASE, SPANNING BASIC AND TRANSLATIONAL PERSPECTIVES. THIS CONCENTRATION OF MULTIDISCIPLINARY EXPERTISE FOCUSED ON WIDELY RECOGNIZED YET UNDERSTUDIED METABOLIC MECHANISMS OF NEUROLOGICAL DISEASES PROMISES SIGNIFICANT NEW UNDERSTANDINGS OF CNS METABOLISM OVERALL. THE CNS-MET WILL CREATE A CRITICAL MASS OF SKILLED SCIENTISTS WHO ARE WELL EQUIPPED TO LEAD A SUSTAINABLE RESEARCH CENTER FOCUSED ON CNS METABOLISM INTO THE FUTURE.

KENTUCKY WOMEN'S JUSTICE COMMUNITY OPIOID INNOVATION NETWORK (WJCOIN)

CENTER OF RESEARCH IN OBESITY AND CARDIOVASCULAR DISEASE (1P20 RR021954-01A1)

KENTUCKY BIRCWH PROGRAM: TRAINING THE NEXT GENERATION OF WOMEN'S HEALTH SCHOLARS

HEALTH CENTER CLUSTER

ADVANCED MATERIALS & MANUFACTURING FOR MODERNIZATION

DEVELOPMENT AND DISTRIBUTION OF A CERTIFIED REFERENCE CIGARETTE SUITABLE FOR RESE

CIGAR REFERENCE PRODUCTS PROGRAM

UNIVERSITY OF KENTUCKY CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE ENTERPRISE DATA CENTER EXPANSION - PROJECT SUMMARY/ABSTRACT THE UNIVERSITY OF KENTUCKY (UK) PROPOSES TO SIGNIFICANTLY ADVANCE ITS SECURE RESEARCH DATA INFRASTRUCTURE CAPACITY WITHIN THE ENTERPRISE DATA CENTER (EDC), AN INTEGRAL COMPONENT OF THE KENTUCKY CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE (CCTS). THE CCTS CURRENTLY SUPPORTS MORE THAN $34.1 MILLION IN ANNUAL DIRECT COST GRANT FUNDING TO SUPPORT BIOMEDICAL AND POPULATION HEALTH PROJECTS WITH SIGNIFICANT NEEDS FOR SECURE RESEARCH DATA INFRASTRUCTURE, INCLUDING HIPAA-COMPLIANT DATA MANAGEMENT AND STORAGE. UNPRECEDENTED ADVANCES IN RESEARCH COMPUTING AND DATA CAPABILITIES ARE REVOLUTIONIZING BIOMEDICAL RESEARCH AND TRANSFORMING DISCOVERIES IN THESE RESEARCH DOMAINS. NEW COMPUTATIONALLY AND DATA-DRIVEN RESEARCH APPROACHES SUCH AS ARTIFICIAL INTELLIGENCE, MACHINE LEARNING, OMICS, DATA MINING AND ANALYTICS, AS WELL AS COMPUTATIONALLY BASED SIMULATIONS AND MODELING ARE ENABLING BOLD NEW DIRECTIONS IN BIOMEDICAL RESEARCH AND DRAWING IN ENTIRELY NEW BIOMEDICAL INVESTIGATORS WHOSE STUDIES ARE INCREASINGLY COMPUTATIONALLY BASED. CRITICAL RESEARCH DATA NEEDS AT UK RESIDE IN PROMINENT NIH-SUPPORTED CENTERS, INCLUDING THE MARKEY CANCER CENTER, THE ALZHEIMER’S DISEASE RESEARCH CENTER WITHIN THE SANDERS-BROWN CENTER ON AGING, AND THE CENTER ON DRUG AND ALCOHOL RESEARCH, AS WELL AS WITHIN A WIDE ARRAY OF INDIVIDUAL NIH-FUNDED RESEARCHERS. BURGEONING NEEDS HAVE PLACED CRITICAL DEMANDS ON THE EDC TO ACCOMMODATE INCREASED NUMBERS OF USERS, GREATER AMOUNTS OF HIGH-SPEED DATA STORAGE, AND GREATER DEMAND FOR HIGH PERFORMANCE COMPUTING INFRASTRUCTURE. THE PROPOSED FACILITIES EXPANSION WILL EXPAND THE 352 SQ. FT. EDC, UK’S ONLY HIPAA-SECURE DATA CENTER (HITRUST CERTIFICATION) BY MERGING TWO VACANT ADJACENT ROOMS TO CREATE A SECURE 1,155 SQ. FT. DATA CENTER AND ADA-COMPLIANT ENTRY CORRIDOR AND PROVIDE REQUISITE COOLING, ELECTRICAL DISTRIBUTION, AND COMMUNICATION INFRASTRUCTURE TO SUPPORT THE PURCHASE AND INSTALLATION OF 28 ADDITIONAL RACKS OF HIGH-DENSITY, HIGH-PERFORMANCE COMPUTING EQUIPMENT THROUGH UNIVERSITY RESOURCES. THE GOAL OF THE PROPOSED 1,231 SQ. FT. FACILITIES RENOVATION IS TO ADDRESS A CRITICAL SHORTAGE OF SECURE BIOMEDICAL RESEARCH DATA CENTER SPACE AT UK BY MORE THAN TRIPLING EDC CAPACITY TO ACCOMMODATE EXPONENTIALLY RISING BIOMEDICAL RESEARCH VOLUME AND ASSOCIATED DATA INFRASTRUCTURE. THE PROPOSED EXPANSION IS CONSISTENT WITH OVERARCHING UK PRIORITIES TO SUPPORT RAPID ADVANCES IN CLINICAL AND TRANSLATION DISCOVERY THROUGH ENHANCED CAPACITY FOR SECURE, HIPAA-COMPLIANT DATA INFRASTRUCTURE AND TO CONTINUE TO MEET RAPIDLY EXPANDING DEMAND PRESENTED BY NIH-FUNDED RESEARCHERS INVOLVED IN DATA-INTENSIVE BIOMEDICAL AND POPULATION HEALTH RESEARCH. THE PROPOSED FACILITIES EXPANSION PROJECT IS CLOSELY ALIGNED WITH NIH PRIORITIES FOR DATA MANAGEMENT AND SHARING AND EMBEDS CLEAR NATIONAL IMPACT BY MEETING THOSE PRIORITIES.

REC CENTERS 3012

SMOKELESS TOBACCO REFERENCE PRODUCT DEVELOPMENT, DISTRIBUTION AND RESEARCH

INSTITUTIONAL CAREER DEVELOPMENT CORE

KENTUCKY RESEARCH CONSORTIUM FOR ENERGY AND ENVIRONMENT

LIGHT-MATTER INTERACTIONS IN ARTIFICIAL SPIN LATTICES

RYAN WHITE PART C OUTPATIENT EIS PROGRAM

APPLICATION OF ENGINEERING SCALE UNIVERSITY OF KENTUCKY CARBON DIOXIDE (CO2) CAPTURE TO GLASS PRODUCTION FACILITY. THE GOAL OF THE PROPOSED WORK IS TO DEMONSTRATE THE RECIPIENT’S CARBON DIOXIDE (CO2) CAPTURE SYSTEM (CC) WITH SYNERGISTIC, TRANSFORMATIVE ELEMENTS, PROVEN AT THE BENCH AND ENGINEERING SCALES ON ELECTRICITY GENERATION POINT SOURCES USING PAST DEPARTMENT OF ENERGY (DOE) FUNDING AT A SUITABLE INDUSTRIAL HOST SITE, UTILIZING A SLIPSTREAM WITH CO2 GENERATED FROM THE OXY-FUEL COMBUSTION AND THE CARBONATED MATERIALS IN THE RAW BATCH FEED.

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PREVENTION OF ALZHEIMER'S DISEAE BY VITAMIN E AND SELENIUM

EPIDEMIOLOGIC STUDY OF THE EFFECTIVENESS OF AN ADF IN REDUCING OPIOID ABUSE

AGREEMENT ORDER FA8650-23-2-6504 IS HEREBY ESTABLISHED FOR "PERFORMANCE AND JOB TASK DEMANDS OF SPECIAL TACTICS SUPPORT AIRMEN"

LICIT & ILLICIT OPIOIDS: COMPARATIVE STUDIES IN HUMANS

APPALACHIA COMMUNITY CANCER NETWORK

SYSTEMS BIOCHEMISTRY IN LUNG CANCER: TOWARD A MECHANISTIC UNDERSTANDING OF NSCLC

PLATELET EXOCYTOSIS AND ENDOCYTOSIS IN THROMBOSIS AND IMMUNITY

DESIGN & CONSTRUCTION OF A MINI-FISCHER-TROPSCH REFINERY AT THE UNIVERSITY OF KENTUCKY CENTER FOR APPLIED ENERGY RESEARCH

CORE REDERIVATION AND BARRIER RENOVATION

KENTUCKY OCCUPATIONAL SAFETY AND HEALTH SURVEILLANCE

CANCER PREVENTION AND CONTROL PROGRAMS FOR STATE TERRITORIAL AND TRIBAL ORGANIZATIONS

REPETITIVE THOUGHT, STRESS, AND IMMUNITY IN OLDER ADULTS

KENTUCKY PRESCRIPTION DRUG OVERDOSE PREVENTION PROGRAM

RURAL HOSPITAL FLEXIBILITY PROGRAM

THE UNIVERSITY OF KENTUCKY MARKVCID BIOMARKER VALIDATION COHORT: DEVELOPMENT OF A TOOLBOX TO ADVANCE VCID INTERVENTIONAL STUDIES - ABSTRACT THE MARKVCID CONSORTIUM WAS ESTABLISHED TO DISCOVER AND CROSS-SITE VALIDATE BIOMARKERS OF CEREBRAL SMALL VESSEL DISEASE (CSVD) WITH AN ULTIMATE GOAL OF DEVELOPING A TOOLBOX OF BIOMARKERS THAT WILL HAVE DIAGNOSTIC, DISEASE STRATIFICATION, AND LONGITUDINAL TRACKING UTILITY FOR FUTURE VASCULAR CONTRIBUTIONS TO COGNITIVE IMPAIRMENT AND DEMENTIA (VCID) CLINICAL TRIALS. THE UNIVERSITY OF KENTUCKY (UK) WAS SELECTED AS ONE OF THE SEVEN MARKVCID SITES IN ITS INITIAL FUNDING PERIOD IN 2016. BEING IN THE HEART OF THE STROKE BELT, KENTUCKY IS A STATE WITH A HIGH PREVALENCE OF CARDIOVASCULAR AND CEREBROVASCULAR DISEASE, AND THE UNIVERSITY OF KENTUCKY IS A CENTER OF EXCELLENCE FOR STROKE AND DEMENTIA, WITH UK BEING A DESIGNATED COMPREHENSIVE STROKE CENTER AND HAS AN NIA ALZHEIMER'S DISEASE RESEARCH CENTER (ADRC). DURING OUR CURRENT FUNDING PERIOD, WE SUCCESSFULLY RECRUITED A COHORT OF 126 INDIVIDUALS (EXCEEDING OUR ORIGINALLY PROPOSED 120) WITH VARYING LEVELS OF CARDIOVASCULAR RISK FACTORS AND A LARGE PROPORTION OF WHOM HAVE DEFINED SUBJECTIVE MEMORY COMPLAINTS (SMCS), WITH SOME DEFINED AS MILD COGNITIVE IMPAIRMENT (MCI). ALL PARTICIPANTS UNDERWENT THE MARKVCID MRI BATTERY, BLOOD COLLECTION, AND NEUROPSYCHOLOGICAL AND CLINICAL ASSESSMENT, WHILE ONE QUARTER ALSO CONTRIBUTED CSF. IMPORTANTLY, ALL PARTICIPANTS HAVE CONSENTED TO AUTOPSY; A REQUIREMENT WE INITIATED AT THE BEGINNING OF OUR MARKVCID RECRUITMENT. UK MARKVCID HAS FULLY PARTICIPATED IN THE VALIDATION OF EVERY BIOMARKER KIT EXCEPT THE OCT-A KIT. WE HAVE ALSO LED TWO BIOMARKER KITS: THE WHITE MATTER GROWTH AND REGRESSION KIT AND THE CSF PLGF KIT. IN THIS RENEWAL CONNECTED TO UH3NS100606 UNDER RFA-NS-16-020, WE PROPOSE TO EXPAND OUR COHORT TO 200 INDIVIDUALS, WITH A PARTICULAR FOCUS ON EXPANDING RECRUITMENT OF DIVERSE POPULATIONS AND INDIVIDUALS WITH SMCS AND MCI. HAVING PARTICIPATED IN THE HARMONIZATION, INSTRUMENTAL VALIDATION, AND NOW BIOLOGICAL VALIDATION, OF ALL MRI AND FLUID BIOMARKER KITS, WE ARE POISED TO MAKE SIGNIFICANT CONTRIBUTIONS IN THE CONTINUATION OF THE CONSORTIUM. WE HAVE PROPOSED THREE SPECIFIC AIMS TO ACHIEVE THE GOALS LAID OUT IN RFA- NS-21-005: SPECIFIC AIM 1: RETAIN AND EXPAND A DIVERSE COHORT ENRICHED FOR INDIVIDUALS WITH SUBJECTIVE MEMORY COMPLAINTS AND COGNITIVE IMPAIRMENT AT HIGH RISK FOR CEREBRAL SMALL VESSEL DISEASE. SPECIFIC AIM 2: WORK WITH THE CONSORTIUM TO FACILITATE DATA, IMAGING, AND FLUID SHARING AND ACCELERATE OUR VALIDATION OF THE MARKVCID CANDIDATE BIOMARKERS IN OUR COHORT. SPECIFIC AIM 3: FULLY ENGAGE IN LEADERSHIP ROLES WITHIN THE CONSORTIUM AND SERVE IN A CONSULTING CAPACITY FOR BOTH INTERNAL AND EXTERNAL RESEARCHERS SEEKING TO EXPLORE BIOMARKERS AND OR DEVELOP NEW CLINICAL TRIALS AND INTERVENTIONAL STUDIES FOR THE TREATMENT OF VCID.

PRODUCTION AND STORAGE OF HYDROGEN FROM COAL USING C1 CHEMISTRY

OVULATION AND LUTEAL FORMATION IN RODENTS MONKEYS AND WOMEN

RURAL CANCER PREVENTION CENTER __ EARLY DETECTION OF COLORECTAL CANCER AND POLYPS

ADVANCING DRUG DEVELOPMENT FROM MEDICINAL PLANTS USING TRANSCRIPTOMICS AND METABO

HEALTHY KENTUCKY RESEARCH BUILDING FIT-UP FOR VASCULAR RESEARCH

RII TRACK-2 FEC: A MULTISCALE, MULTIPHYSICS MODELING FRAMEWORK FOR GENOME-TO PHENOME MAPPING VIA INTERMEDIATE PHENOTYPES

INFLATION REDUCTION ACT (IRA) – SO2-ROBUST CATALYTIC METHANE EMISSIONS ELIMINATION AT GAS ENGINE EXHAUST THE OVERALL GOAL IS TO DEVELOP AND COMMERCIALIZE A METHANE (CH4) EMISSION REDUCTION TECHNOLOGY AND FIELD TEST A PERMANENT INSTALLATION.

ON-FARM BIOMASS PROCESSING: TOWARDS AN INTEGRATED HIGH SOLIDS TRANSPORTING/STORING/PROCESSING SYSTEM

HDL FUNCTION AND METABOLISM DURING INFLAMMATION

ROLE OF IMPAIRED COGNITIVE STATES & RISK FACTORS IN CONVERSION TO MIXED DEMENTIAS

GENOMEWIDE ASSOCIATION STUDY OF LIPID RESPONSE TO FENOFIBRATE AND DIETARY FAT

AMBYSTOMA GENETIC STOCK CENTER

RESEARCH RESOURCES FOR MODEL AMPHIBIANS

CENTER OF RESEARCH ON OBESITY AND CARDIOVASCULAR DISEASE

PIPP PHASE II: ENVIRONMENTAL SURVEILLANCE FOR ASSESSING PATHOGEN EMERGENCE (ESCAPE) -THE GOAL OF THE PANDEMIC ENVIRONMENTAL SURVEILLANCE CENTER FOR ASSESSING PATHOGEN EMERGENCE (PANDEMIC ESCAPE) IS THE TIMELY DETECTION OF EMERGENT PATHOGENS ACROSS A VARIETY OF SETTINGS THROUGH COST-EFFECTIVE AND EASY-TO-IMPLEMENT ENVIRONMENTAL SURVEILLANCE (ES). ES USES ENVIRONMENTAL SAMPLES, TO DISCOVER AND MONITOR PATHOGENS. PANDEMIC ESCAPE WILL ADVANCE ES TECHNOLOGY, DATA INTERPRETATION, AND ADOPTION TO PROMOTE ITS WIDESPREAD DEPLOYMENT ACROSS THE UNITED STATES. PANDEMIC ESCAPE WILL ADOPT MULTIPLE STRATEGIES TO TACKLE THIS CHALLENGE. THESE INCLUDE RESEARCH AND ENGINEERING TO DESIGN PORTABLE AND EASY-TO-USE ES DEVICES, DEVELOPMENT OF NEW METHODS FOR ES AND GENOME SEQUENCING, MODELING OF DISEASE TRANSMISSION USING ES DATA, CO-PRODUCTION OF ES KNOWLEDGE THROUGH COMMUNITY PARTNERSHIPS AND PARTICIPATORY SCIENCE, AND ENGAGEMENT THROUGH PUBLIC OUTREACH AND EDUCATION ACTIVITIES. THE CENTER WILL WORK CLOSELY WITH PUBLIC HEALTH EXPERTS AND THE PRIVATE SECTOR TO ENSURE THAT ITS SOLUTIONS ARE PRACTICAL AND CAN BE EASILY INTEGRATED INTO EXISTING INFRASTRUCTURE. THE LONG-TERM STRATEGIC GOALS OF PANDEMIC ESCAPE ARE TO 1) CREATE SIMPLIFIED TOOLS TO ADVANCE ENVIRONMENTAL SURVEILLANCE (ES) PATHOGEN MONITORING AND PREDICTION CAPABILITIES; 2) TRAIN THE NEXT GENERATION OF SCIENTISTS IN ES, EMPHASIZING PARTICIPATION OF UNDERREPRESENTED GROUPS; 3) ACCELERATE THE ADOPTION OF ES AS A PANDEMIC PREVENTION TOOL FOR EVERYONE; 4) COMMUNICATE ES DATA EFFECTIVELY, EFFICIENTLY, AND INCLUSIVELY TO SUPPORT KNOWLEDGE TO ACTION; 5) EMPOWER COMMUNITIES TO BUILD LOCAL ES CAPACITY; 6) ADVOCATE FOR PATHOGEN DETECTION AND RESPONSE STRATEGIES THAT INCLUDE ES. THROUGH COLLABORATION WITH PARTNERS IN LOW RESOURCE COMMUNITIES, THE PANDEMIC ESCAPE TEAM WILL DEVELOP THE NECESSARY TOOLS TO GROW AN EXTENSIVE ES NETWORK THAT CAN BE USED TO MONITOR FOR PATHOGENS. ACHIEVING THESE LONG-TERM GOALS WILL HAVE A TRANSFORMATIVE IMPACT ON HOW COMMUNITIES IDENTIFY, MONITOR, AND MITIGATE THE IMPACT OF EMERGING PATHOGENS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

COBRE FOR THE CENTER FOR MOLECULAR MEDICINE

THE ROLE OF PHLPP IN COLON CANCER

EPIGENETIC DETERMINANTS OF LIPID RESPONSE TO DIETARY FAT AND FENOFIBRATE

SURGICAL STUDIES OF FUNCTIONAL GENE EXPRESSION

UNIVERSITY OF KENTUCKY SURE RESOURCE CENTER - SUMMARY THE OVERARCHING GOAL OF THE UNIVERSITY OF KENTUCKY SURE RESOURCE CENTER (UK-SURE), SUPPORTED BY AN NIGMS U24 GRANT, IS TO ASSIST FACULTY AND OFFICE OF SPONSORED PROJECT (OSP) STAFF AT SURE-ELIGIBLE INSTITUTIONS (<$6 MILLION IN NIH FUNDING, >25% PELL ELIGIBLE STUDENTS) PREPARE AND SUBMIT COMPETITIVE NIH GRANTS APPLICATIONS, WITH AN EMPHASIS ON SURE AND SURE-FIRST AWARDS. TO ACCOMPLISH THIS GOAL, UK FACULTY AND RESEARCH SUPPORT STAFF WITH EXPERIENCE IN ALL ASPECTS OF NIH GRANT APPLICATIONS WILL SHARE THEIR KNOWLEDGE WITH THOSE AT SURE-ELIGIBLE INSTITUTIONS THROUGH A SERIES OF WEBINARS, WORKSHOPS, AND DIRECT CONSULTATION. THREE REGIONAL COORDINATORS WILL PROVIDE VITAL LINKS BETWEEN FACULTY AND OSP STAFF AT SURE- ELIGIBLE INSTITUTIONS AND FACULTY AND RESEARCH SUPPORT STAFF AT UK-SURE. THIS CENTER WILL ALSO COORDINATE BIENNIAL SURE CONFERENCES AND OVERSEE A COMPETITIVE SEED GRANT PROGRAM THAT WILL PROVIDE FUNDS FOR SURE-ELIGIBLE INSTITUTIONS TO ESTABLISH OR GROW OSPS. SPECIFICALLY, FOUR AIMS ARE PROPOSED: (1) ASSIST SURE- ELIGIBLE FACULTY WRITE GRANTS AND MANAGE RESEARCH PROGRAMS, WITH SUCCESS BEING MEASURED BY NUMBER OF GRANTS SUBMITTED, SCORED, AND FUNDED; NUMBER OF PUBLICATIONS, SEMINARS; AND MEETING PRESENTATIONS; AND TENURE AND PROMOTION OUTCOMES; (2) ASSIST SURE-ELIGIBLE INSTITUTIONS TO ESTABLISH AND GROW OSPS AND RESEARCH INFRASTRUCTURE, WITH SUCCESS BEING MEASURED BY GROWTH/ESTABLISHMENT OF OSPS IN SURE-ELIGIBLE INSTITUTIONS, NUMBER OF RESEARCH GRANTS RECEIVED AND OVERALL RESEARCH FUNDING AT THESE INSTITUTIONS, AND QUESTIONNAIRES FOR SURE FACULTY REGARDING THE QUALITY OF IN-HOUSE OSP SERVICES; (3) GROW THE NUMBER OF INSTITUTIONS THAT PARTICIPATE IN THE SURE PROGRAM AND ESTABLISH AN INTERACTIVE COMMUNITY OF SURE-ELIGIBLE INSTITUTIONS, WITH SUCCESS BEING MEASURED BY THE NUMBER OF INSTITUTIONS THAT PARTICIPATE IN WEBINARS, ATTEND THE BIENNIAL CONFERENCE, AND SUBMIT NIH GRANTS (WITH AN EMPHASIS ON SURE APPLICATIONS), AS WELL AS THE AMOUNT OF PEER-TO-PEER FACULTY MENTORING AND SOCIAL MEDIA ENGAGEMENT; AND (4) ENHANCE THE RESEARCH EXPERIENCE FOR STUDENTS WHO ARE WORKING IN NIH-FUNDED LABS IN SURE-ELIGIBLE INSTITUTIONS, WITH SUCCESS BEING MEASURED BY STUDENT CONFERENCE PRESENTATIONS, AUTHORSHIP ON PUBLICATIONS, DEGREES EARNED, AND POST-GRADUATE EMPLOYMENT. TAKEN TOGETHER, THESE ACTIVITIES WILL ENHANCE THE RESEARCH CAPACITY AT SURE- ELIGIBLE INSTITUTIONS AND PROMOTE HIGH-QUALITY, STUDENT-CENTRIC BIOMEDICAL RESEARCH. IN THE PROCESS, THESE OUTCOMES WILL CONTRIBUTE TO DIVERSIFYING AND STRENGTHENING THE NATION’S RESEARCH ENTERPRISE.

CENTER FOR APPLIED SEPARATION TECHNOLOGY (CAST)

DETERMINANTS OF AORTA HETEROGENEITY - ABSTRACT AORTOPATHIES, INCLUDING ANEURYSMS, DISSECTION, AND RUPTURE, REPRESENT A KEY CHALLENGE IN HLBS RESEARCH. IN THE PAST TWENTY YEARS OF OUR CONTINUOUSLY FUNDED RESEARCH ON AORTOPATHIES, WE HAVE CONTRIBUTED TO MANY MECHANISTIC INSIGHTS INTO THE AORTOPATHY RESEARCH INCLUDING A NEW CONCEPT: THERE ARE REGIONAL CHARACTERISTICS OF THE AORTA IN REGARD TO DIVERSE EMBRYONIC ORIGINS AND FUNCTIONS OF CELLS. THE OVERALL HYPOTHESIS OF THIS R35 PROGRAM IS THAT HETEROGENEITY OF CELLULAR ORIGINS IMPARTS FUNCTIONAL VARIANCES ALONG THE LENGTH OF THE AORTA, INCLUDING DIVERSITY OF EXTRACELLULAR MATRIX STABILITY, WHICH IN TURN CONTRIBUTES TO REGIONAL SPECIFICITY OF AORTOPATHIES. REGIONAL SPECIFICITY OF AORTOPATHIES IS PRESENT IN MANY MOUSE MODELS THAT WE HAVE VALIDATED AND CHARACTERIZED. OUR INITIAL SINGLE CELL TRANSCRIPTOMIC AND PROTEOMIC DATA HAVE ALSO IMPLICATED NEW POTENTIAL CONTRIBUTORS TO HETEROGENEITY OF THE NORMAL AORTIC BIOLOGY AND AORTOPATHIES. THREE MAJOR THEMES ARE PROPOSED IN THIS PROGRAM: (1) WHAT ARE THE STRUCTURAL AND MOLECULAR MECHANISMS THAT CONTRIBUTE TO BIOLOGICAL AND PATHOPHYSIOLOGICAL HETEROGENEITY ALONG THE LENGTH OF THE AORTA? (2) ARE CELLULAR AND EXTRACELLULAR HETEROGENEITY A BASIS FOR REGIONAL SPECIFICITY OF AORTOPATHIES? (3) HOW DO SIGNALING PATHWAYS, EXTRACELLULAR MATRIX, AND CROSSTALK BETWEEN RESIDENT AORTIC CELLS COORDINATE TO PROMOTE THE HETEROGENEITY OF AORTOPATHIES? WE HAVE ROBUST TOOLS INCLUDING A SPECTRUM OF REAGENTS, MULTIPLE CLASSIC AND NEW MOUSE MODELS, ULTRASONOGRAPHY, MRI, INTRAVITAL MICROSCOPY, PROTEOMICS, AND SINGLE CELL RNA SEQUENCING TECHNIQUES. IN ADDITION TO AORTOPATHY RESEARCH, THE PI HAS MORE THAN 30-YEAR EXPERTISE IN THE FIELDS OF LIPOPROTEIN METABOLISM, INFLAMMATION, AND ATHEROSCLEROSIS RESEARCH. AORTOPATHIES ARE NOT A SOLE AORTIC DISEASE, BUT IS ASSOCIATED WITH A WIDE RANGE OF DISEASES OR SYNDROMES THAT MAY AFFECT SKIN, LUNG, KIDNEY, BRAIN, BONE, AND OTHER ORGANS. THE PROPOSED RESEARCH PROGRAM WILL BENEFIT FROM THE FLEXIBILITY TO PURSUE POTENTIAL CONTRIBUTIONS OF OTHER TISSUES AND ORGANS TO AORTOPATHIES, AND VICE VERSA THE INFLUENCES OF AORTOPATHIES ON OTHER TISSUES AND ORGANS. THIS R35 MECHANISM WILL ALSO BENEFIT THE PI’S STRENGTH IN BASIC RESEARCH, ENHANCE HIS INTERACTION WITH THE TRANSLATIONAL RESEARCH IN THE CLINICAL ARENA, AND TRAIN THE NEXT GENERATION OF SCIENTISTS.

MEDICARE RURAL HOSPITAL FLEXIBILITY

CENTER FOR THE BIOLOGIC BASIS OF ORAL/SYSTEMIC DISEASES (PHASE III)

THE RURAL CANCER PREVENTION CENTER: CATEGORY 1 PROPOSAL

AGING OF FRONTAL STRUCTURE AND FUNCTION IN DOWN SYNDROME AND DEMENTIA

MECHANISMS OF ABDOMINAL AORTIC ANEURYSM FORMATION

THIS PROJECT PLANS TO CONDUCT PILOT TESTING TO OBTAIN AQUEOUS SOLUTIONS RICH IN MIXED RARE EARTH ELEMENTS AND CRITICAL MINERALS AND MATERIALS (MANGANESE, COBALT, NICKEL, AND STRONTIUM) AND A LITHIUM-CONTAINING RAFFINATE.

APPLICATION OF TRANSFORMATIONAL UNIVERSITY OF KENTUCKY 3 TONNE PER DAY CARBON DIOXIDE CAPTURE SYSTEM AT A STEEL PROCESS PLANT NEW AWARD TO UNIVERSITY OF KENTUCKY DE-FE0032133

TAS::89 0328::TAS RECOVERY ACT NEW AWARD - WORKFORCE TRAINING FOR THE ELECTRIC POWER SECTOR UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION

GENERAL SUPERVISION ENHANCEMENT GRANT

DE-FE0031827 UNIVERSITY OF KENTUCKY ''DEMONSTRATION OF SCALED-PRODUCTION OF RARE EARTH OXIDES AND CRITICAL MATERIALS FROM U.S. COAL-BASED SOURCES''

RAPID ACTIONABLE DATA FOR OPIOID RESPONSE IN KENTUCKY (RADOR-KY) - ABSTRACT OPIOID USE DISORDER (OUD) REMAINS A PERSISTENT PUBLIC HEALTH CRISIS AND EPIDEMIC. IN SPITE OF ROBUST NATIONAL, STATE, AND LOCAL PUBLIC HEALTH RESPONSES TO THE EPIDEMIC, OPIOID OVERDOSE DEATHS CONTINUE TO INCREASE; OF THE 91,799 DRUG OVERDOSE DEATHS IN 2020, REPORTED BY THE CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC), THE MAJORITY, 68,630 (75%) INVOLVED OPIOIDS, A 38% INCREASE FROM 2019. THE OPIOID OVERDOSE DEATH BURDEN IN KENTUCKY IS EVEN HIGHER, WITH A 63% INCREASE FROM 2019 (N=1,036) TO 2020 (N=1,688). IN THE CONTEXT OF THE DYNAMICALLY CHANGING OPIOID EPIDEMIC, COMPLICATED BY THE CHALLENGES PRESENTED BY THE COVID-19 PANDEMIC, AGENCIES AND ORGANIZATIONS RESPONSIBLE FOR MONITORING AND IMPROVING THE HEALTH OF THE POPULATION NEED TIMELY STATE AND LOCAL DATA TO MAKE CRITICAL DECISIONS ON RESOURCE ALLOCATION AND TARGETED RESPONSES. SUCH DECISIONS ARE TYPICALLY RELATED TO A SET OF EVIDENCE-BASED PRACTICES (EBPS) AIMED AT PREVENTING OPIOID OVERDOSE MORTALITY. WE WILL HARNESS THE INFRASTRUCTURE AND METHODOLOGICAL EXPERTISE AT THE UNIVERSITY OF KENTUCKY (UK) RESEARCH CENTERS (INCL. THE KENTUCKY INJURY PREVENTION AND RESEARCH CENTER, THE CENTER ON DRUG AND ALCOHOL RESEARCH, AND THE INSTITUTE FOR BIOMEDICAL INFORMATICS), ALONG WITH THE EXPERIENCE GAINED FROM OUR WORK ON THE HEALING COMMUNITIES STUDY SUPPORTED BY THE NATIONAL INSTITUTE ON DRUG ABUSE, AND THE OVERDOSE DATA TO ACTION PROJECT SPONSORED BY THE CDC. THE SPECIFIC AIMS OF THIS PROJECT ARE TO ESTABLISH THE RAPID ACTIONABLE DATA FOR OPIOID RESPONSE IN KENTUCKY (RADOR-KY)– AN INTEGRATED, POPULATION-BASED, NEAR-REAL TIME STATEWIDE SURVEILLANCE SYSTEM THAT WILL INGEST DATA FROM MULTIPLE STATE AGENCIES AND IMPLEMENT ADVANCED INFORMATICS ALGORITHMS FOR FAST DATA PROCESSING, DATA LINKAGE, MACHINE LEARNING AND PREDICTIVE ANALYTICS TO SHORTEN THE TIME BETWEEN DATA CAPTURE AND WHEN ANALYTICAL RESULTS ARE AVAILABLE TO SUPPORT OPIOID OVERDOSE PREVENTION AND CONTROL. RADOR-KY WILL HAVE MOBILE AND WEB-BASED APPLICATIONS TO PROVIDE IMMEDIATE DISSEMINATION AND ACCESS TO NEAR-REAL TIME COMMUNITY OR STATE LEVEL DATA, REPORTS, AND VISUAL ANALYTICS TO SHARE WITH AGENCIES AND COMMUNITY END-USERS. RADOR-KY END-USER ADVISORY GROUP, INCLUDING PARTNERS IN STATE GOVERNMENT AND LOCAL COMMUNITIES, WILL GUIDE THE DEVELOPMENT OF THE RADOR-KY REPORTING AND VISUALIZATION FUNCTIONALITY. RADOR- KY WILL ESTABLISH A LONGITUDINAL DATASET ACCESSIBLE THRU THE RADOR-KY PORTAL AND ALSO SHARED WITHIN THE HEAL DATA ECOSYSTEM. PROGRAMMING CODE FOR IMPLEMENTED ALGORITHMS AND WEB-BASED DASHBOARDS WILL BE SHARED IN A PUBLIC REPOSITORY TO ADVANCE THE EFFORTS TO MITIGATE THE OPIOID EPIDEMIC ACROSS THE U.S.

HIPPOCAMPAL SYNAPTIC STRUCTURE--PHYSIOLOGY DURING AGING

FEDERATED DIGITAL PATHOLOGY PLATFORM FOR AD/ADRD RESEARCH AND DIAGNOSTICS - PROJECT SUMMARY/ABSTRACT WE WILL CONNECT MULTIPLE ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (AD/ADRD) RESEARCH CENTERS FOR OPTIMIZED AND STANDARDIZED WHOLE SLIDE IMAGE (WSI) ADVANCED ANALYTICS. WE PROPOSE THESE SPECIFIC AIMS: SPECIFIC AIM 1: GENERATE A FEDERATED PLATFORM FOR DATA SHARING AND ANALYSIS OF HUMAN DIGITAL NEUROPATHOLOGICAL (DNP) SLIDES. SPECIFIC AIM 1A: DEVELOP AN OPEN-SOURCE PLATFORM TO AGGREGATE DATA DISTRIBUTED ACROSS MULTIPLE REPOSITORIES INTO A CENTRAL REGISTRY PORTAL. THIS SUBAIM WILL FOLLOW FEDERATED DATA CURATION, HARMONIZATION, ANNOTATION, AND STANDARDIZATION EMPLOYING FAIR (FINDABLE, ACCESSIBLE, INTEROPERABLE, AND REUSABLE) PRINCIPLES. SPECIFIC AIM 1B: DEVELOP A FEDERATED DATA CURATION AND MANAGEMENT SYSTEM. THIS SUBAIM PROVIDES METHODS TO CURATE PHYSICAL DATA, SUCH AS DIGITAL IMAGES, ACROSS FEDERATED SITES. WSI DATA AND METADATA WILL BE SHARED WITH PRIVATE REPOSITORIES AND HIGH-PERFORMANCE CLUSTERS. SPECIFIC AIM 2: DEVELOP AND DEMONSTRATE A PLATFORM FOR FEDERATED MACHINE LEARNING/ARTIFICIAL INTELLIGENCE (ML/AI), RESULT EVALUATION, AND CENTRAL PROJECT INFORMATION, CONSTITUTING A MANAGEMENT HUB FOR AD/ADRD STUDIES. SPECIFIC AIM 2A: DEVELOP A FEDERATED DATA ANNOTATION AND AUTOMATED AI/ML PROCESSING SYSTEM. THIS SUBAIM PROVIDES METHODS FOR USERS TO PREPARE AI-READY MULTIMODAL (WSIS, METADATA, DEMOGRAPHICS, ETC.) DATASETS FROM DISTRIBUTED SOURCES AND CONDUCT MULTI-SITE DATA TRANSFER AND FEDERATED TRAINING. SERVICES AND TOOLS DEVELOPED IN AIM 1 WILL BE USED TO PROGRAMMATICALLY GENERATE AND POPULATE USER-DEFINED AI/ML PIPELINES. SPECIFIC AIM 2B: DEVELOP AN OPEN-SOURCE PLATFORM FOR THE GENERATION AND REVIEW OF DATASETS AND ASSOCIATED MODELS. THIS SUBAIM WILL PROVIDE A PROJECT EVALUATION PORTAL INTEGRATING COHORT, DATASET, AND MODEL TRAINING RESULTS IN A UNIFIED INTERFACE. A PUBLIC-FACING MODEL HUB WILL PROVIDE PROJECT, DATA, SPECIFICATIONS, AND MODEL DATA TO SUPPORT DATA SHARING AND ANALYSIS REQUIREMENTS. TO OPTIMIZE AND DEMONSTRATE THE STRENGTHS OF THE NOVEL FEDERATED NETWORK, FIVE INTEGRATED PROJECTS ARE PROPOSED. THESE WILL SPAN A DIVERSE SAMPLING OF HUMAN POPULATIONS AND DISEASES TO LEVERAGE THE UNIQUE STRENGTHS OF DNP. THE FOLLOWING SITES WILL CONTRIBUTE RESOURCES, EXPERTISE, EXPERIMENTAL STUDY DESIGN, DATA, AND ANALYSES: UNIVERSITY OF KENTUCKY (PIS NELSON AND BUMGARDNER, CO-IS CHEUNG AND FARDO). GENERATE STANDARDIZED SOPS USEFUL FOR DNP DIAGNOSES AND RESEARCH ALONG WITH ML/AI EXPERTISE FOR A FEDERATED NETWORK. NORTHWESTERN/NUN STUDY AND UTSA UNIVERSITIES (PI FLANAGAN). A FOCUS ON TDP-43 PROTEINOPATHY IN COMMUNITY-BASED COHORTS AND ETHNO-RACIALLY DIVERSE POPULATIONS. UNIVERSITYOF SÃO PAULO AND UCSF (CO-I SUEMOTO AND OSC GRINBERG). EVALUATE ADNC FROM THE BRAINS OF INDIVIDUALS WITH AFRICAN AND NON-AFRICAN ANCESTRIES. UNIVERSITY OF TORONTO (CO-I KOVACS): USE ML TO STUDY WHITE MATTER TAU PATHOLOGIC CHANGES FOR NOVEL INSIGHTS INTO MULTIPLE TAUOPATHIES. UNIVERSITY OF WASHINGTON (CO-I KEENE): STUDY TAU PATHOLOGIES ACROSS AGES AND ENVIRONMENTAL EXPOSURES WITH A FOCUS ON TRAUMATIC BRAIN INJURIES.

MECHANISMS REGULATING NEUROTENSIN SECRETION AND FUNCTION

RENAL OSTEODYSTROPHY: A FRESH APPROACH

NATIONAL PROGRAM OF CANCER REGISTRIES

SUSCEPTIBILITY PATTERNS FOR GRADE C PERIODONTITIS IN YOUNG INDIVIDUALS - THE AMERICAN ACADEMY OF PERIODONTOLOGY AND EUROPEAN FEDERATION OF PERIODONTOLOGY HAVE RECENTLY ADOPTED THE NEW TERMINOLOGY, “GRADE C PERIODONTITIS,” TO IDENTIFY INDIVIDUALS WITH A HIGH RISK FOR DISEASE PROGRESSION. THE LOCALIZED FORM OF THIS DISEASE, NOW TERMED STAGE 3-4 GRADE C, MOLAR-INCISOR PATTERN PERIODONTITIS (C/MIP), EXHIBITS A VERY WELL-DEFINED CLINICAL PRESENTATION. ALTHOUGH LESS COMMON THAN OTHER PERIODONTITIS, C/MIP HAS A SIGNIFICANT PUBLIC HEALTH IMPACT, AS IT AFFECTS SYSTEMICALLY HEALTHY, YOUNG INDIVIDUALS, OF LOW SOCIAL ECONOMIC STATUS, WHO USUALLY CANNOT AFFORD ITS EXPENSIVE AND COMPLEX TREATMENT, AS THEIR AFFECTED TEETH ARE OFTEN LOST DUE TO ITS RAPID PROGRESSION AND DELAYED DIAGNOSIS. THIS LEADS TO EARLY FUNCTION AND AESTHETICS ISSUES AND LIFE-LONG DIFFICULTIES FOR FUNCTIONAL AND AESTHETIC REHABILITATION. DUE ITS COMMON AGGREGATION IN FAMILIES, SEVERAL STUDIES HAVE SEARCHED FOR GENETIC ASSOCIATIONS WITH GRADE C DISEASE, BUT NOT IN LARGE COHORTS OF C/MIP. THUS, GENETIC CONTRIBUTIONS FOR C/MIP ARE NOT YET IDENTIFIED. THE TEAM PUT TOGETHER FOR THIS PROPOSAL HAVE CONDUCTED GROUND- BREAKING WORK IN THIS FIELD OVER THE LAST 3 DECADES, INCLUDING THE IDENTIFICATION OF CANDIDATE GENETIC SUSCEPTIBILITY VARIANTS, HYPER-INFLAMMATORY RESPONSE, AND STRONG ASSOCIATION WITH AA AND AA JP2 CLONE. HOWEVER, DIFFERENT POPULATIONS HAVE DIFFERENT GENETIC PREDISPOSITIONS, ENVIRONMENTAL EXPOSURES, AND MICROBIAL COLONIZATION, WHICH FURTHER COMPLICATES UNVEILING THE TRUE ETIOLOGY AND PATHOGENESIS OF THIS DISEASE. THUS, THERE IS A CRITICAL NEED TO EXAMINE A LARGE WELL-DEFINED COHORT OF C/MIP FAMILIES FROM DIFFERENT WORLD REGIONS TO SYSTEMATICALLY AND COMPREHENSIVELY DETERMINE THE GENETIC, HOST RESPONSE, AND MICROBIAL DETERMINANTS OF THIS DISEASE. THE GOAL OF THIS PROPOSAL IS TO CHARACTERIZE THE GENETIC, HOST, AND MICROBIAL FACTORS OF THE EARLY ONSET, WELL-DEFINED, LOCALIZED FORM OF PERIODONTITIS IN POPULATIONS WORLDWIDE. WE PROPOSE TO DO THIS BY GATHERING LARGE COHORT OF C/MIP FAMILIES IN 4 DIFFERENT CONTINENTS TO 1)IDENTIFY GENETIC SUSCEPTIBILITY VARIANTS WITHIN C/MIP FAMILIES VIA WES; 2)IDENTIFY THE INFLAMMATORY NETWORKS ASSOCIATED WITH C/MIP 2, VIA TRANSCRIPTOME AND NETWORK ANALYSIS AND INFLAMMATORY MEDIATOR PROFILE IN THE ORAL ENVIRONMENT OF THESE AFFECTED FAMILIES; AND 3) DETERMINE COMMON MICROBIOME PROFILES VIA METAGENOMIC ANALYSIS AND UNIQUE AA STRAINS IN C/MIP FAMILIES FROM DIFFERENT REGIONS OF THE WORLD ASSOCIATED WITH THIS DISEASE. OUR HYPOTHESES ARE THAT 1-C/MIP WILL BE ASSOCIATED WITH IDENTIFIABLE GENETIC VARIANTS, WHICH MAY VARY IN DIFFERENT REGIONS OF THE GLOBE, 2-A SPECIFIC TRANSCRIPTOME IS LINKED TO PRO-INFLAMMATORY PATHWAYS IN C/MIP, AND 3-GENOTYPICALLY AND PHENOTYPICALLY DIFFERENT STRAINS OF AA WILL DIFFER AMONG REGIONS OF THE GLOBE AND WILL CORRELATE WITH MICROBIOME COMMUNITIES OF DISTINCT FUNCTIONALITY AND VIRULENCE POTENTIAL. THE IMPACT OF THE PROPOSED WORK IS THE DEVELOPMENT OF AN INTEGRATIVE SERIES OF INTERACTION NETWORK AND FUNCTIONAL ANALYSES, WHICH WILL LEAD TO THE CHARACTERIZATION OF SUSCEPTIBILITY, MOLECULAR, AND MICROBIAL PHENOTYPES OF C/MIP IN DIFFERENT POPULATIONS AROUND THE WORLD, WHICH WILL PROVIDE CRITERIA FOR EARLY DISEASE DIAGNOSIS AND DEVELOPMENT OF TARGETED AND INDIVIDUALIZED THERAPIES FOR THESE HIGHLY SUSCEPTIBLE FAMILIES.

(ACCSIS) ACCELERATING COLORECTAL CANCER SCREENING THROUGH IMPLEMENTATION SCIENCE IN APPALACHIA

TYPE III EXPORTED EFFECTORS OF CHLAMYDIA TRACHOMATIS

C4WARD@SCALE: SCALED-UP COAL CONVERSION FOR CARBON FIBERS AND GRAPHITE THIS PROJECT CENTERS AROUND THE CONSTRUCTION OF A BUILDING TO FACILITATE SAFE, ROBUST AND SCALABLE PROCESSING OF COAL-DERIVED PITCHES; CARBON FIBER MANUFACTURING AND SYNTHETIC GRAPHITE MANUFACTURING.

PRECISION MEASUREMENTS WITH NEUTRONS

UK SPINAL CORD & BRAIN INJURY RESEARCH CENTER CORE GRANT

INVESTIGATION OF NEOCLERODANES AS NOVEL OPIOID LIGANDS

CANCER PREVENTION AND CONTROL PROGRAMS FOR STATE, TERRITORIAL, AND TRIBAL ORGANIZATIONS - THE UNIVERSITY OF KENTUCKY (UK) RESEARCH FOUNDATION SUBMITS THIS APPLICATION TO OPPORTUNITY CDC-RFA-DP22-2202: CANCER PREVENTION AND CONTROL PROGRAMS FOR STATE, TERRITORIAL, AND TRIBAL ORGANIZATIONS. OUR APPLICATION INCLUDES TWO OF KENTUCKY’S (KY) FLAGSHIP CDC-FUNDED CANCER PREVENTION AND CONTROL PROGRAMS: PROGRAM 2-NATIONAL COMPREHENSIVE CANCER CONTROL PROGRAM (NCCCP), AND PROGRAM 3-NATIONAL PROGRAM OF CANCER REGISTRIES (NPCR). BOTH PROGRAMS HAVE A LONG HISTORY OF SUCCESS AT UK SINCE THEIR INCEPTION AT CDC. THE KENTUCKY DEPARTMENT OF PUBLIC HEALTH (KDPH) DESIGNATES UK AS THE DESIGNATED BONA FIDE AGENT TO RECEIVE THE NCCCP GRANT AND STATE LAW DESIGNATES KENTUCKY CANCER REGISTRY AND RECEIVE THE NPCR GRANT. DR. PAMELA HULL SERVES AS THE PRINCIPAL INVESTIGATOR (PI) FOR THE PROGRAM 2-NCCCP, AND DR. ERIC DURBIN SERVES AS THE PI FOR PROGRAM 3-NPCR. SINCE THE TWO PROGRAMS MUST BE SUBMITTED UNDER A SINGLE COMBINED APPLICATION, DR. HULL AND DR. DURBIN COLLABORATE TOGETHER AS MULTI-PIS, AND DR. HULL IS LISTED AS THE CONTACT PI IN THE APPLICATION SYSTEM. BOTH PROGRAMS COLLABORATE CLOSELY WITH KY’S THIRD FLAGSHIP PROGRAM, KY WOMEN’S CANCER SCREENING PROGRAM (NATIONAL BREAST AND CERVICAL CANCER EARLY DETECTION PROGRAM), ADMINISTERED IN THE KY DEPARTMENT OF PUBLIC HEALTH. THE NEED FOR ALL THREE FLAGSHIP PROGRAMS IN KY IS HIGH, GIVEN THAT KY RANKS 1ST AMONG STATES FOR BOTH THE HIGHEST ALL-SITE CANCER INCIDENCE AND THE HIGHEST ALL-SITE CANCER MORTALITY, WITH SIGNIFICANT GEOGRAPHIC DISPARITIES IN APPALACHIAN AND RURAL AREAS AND SIGNIFICANT RACIAL DISPARITIES AMONG BLACK KENTUCKIANS AND HIGH POVERTY RATES. PROGRAM 2-NCCCP SUMMARY: THE PURPOSE OF THE KY COMPREHENSIVE CANCER CONTROL PROGRAM (KCCCP) IS TO DECREASE CANCER BURDEN AND DISPARITIES IN KY. KCCCP STAFF FACILITATE AND SUPPORT THE KY CANCER CONSORTIUM (KCC), A MULTI-SECTORAL COALITION COMPRISED OF 100+ ORGANIZATIONS, TO DEVELOP AND IMPLEMENT THE KY CANCER ACTION PLAN (KY CAP). IN THE KCCCP WORK PLAN, KCC PARTNERS WILL UTILIZE DATA FROM KCR AND OTHER SOURCES TO SET, IMPLEMENT, AND MONITOR PROGRESS OF KY CAP OBJECTIVES; AND THEY WILL IMPLEMENT BOTH POPULATION-WIDE AND HEALTHY EQUITY-FOCUSED/TAILORED EVIDENCE-BASED INTERVENTIONS FOCUSED ON THE PRIORITIES SELECTED BASED ON DATA AND STAKEHOLDER INPUT: 1) PRIMARY PREVENTION: TOBACCO TREATMENT, 2) EARLY DETECTION AND SCREENING: LUNG CANCER SCREENING, 3) HEALTH AND WELLBEING OF CANCER SURVIVORS, AND 4) HEALTH EQUITY: APPALACHIAN, RURAL AND BLACK POPULATIONS. THE LONG-TERM EXPECTED OUTCOMES ARE IMPROVED QUALITY OF LIFE AMONG CANCER SURVIVORS, DECREASED CANCER RISK AND CANCER INCIDENCE THROUGH PRIMARY PREVENTION, AND ULTIMATELY DECREASED MORTALITY RATES, AS WELL AS REDUCED DISPARITIES IN INCIDENCE AND MORTALITY. PROGRAM 3-NPCR SUMMARY: THE PRIMARY OBJECTIVE OF THE KENTUCKY CANCER REGISTRY (KCR) IS TO PROVIDE COMPLETE, TIMELY, AND ACCURATE POPULATION-BASED CANCER SURVEILLANCE DATA FOR THE PURPOSES OF EVIDENCE-BASED CANCER PREVENTION AND CONTROL PLANNING AND EVALUATION. SINCE 1994, KCR HAS CONSISTENTLY MET AND EXCEEDED NPCR COMPLETENESS, TIMELINESS, AND QUALITY STANDARDS. KCR IS HIGHLY INTEGRATED WITH THE KCCCP AND KWCSP. THE REGISTRY PROVIDES DATA TO KCCCP THAT ARE USED TO DEVELOP, REVISE, AND EVALUATE THE KENTUCKY CANCER ACTION PLAN. ANNUALLY KCR ALSO PROVIDES DATA TAILORED FOR EACH OF THE STATES 15 DISTRICT CANCER COUNCILS WHO USE THESE DATA TO TARGET THEIR LIMITED RESOURCES TOWARD THOSE CANCERS THAT REPRESENT THE GREATEST BURDEN. KCR ALSO PROVIDES DATA AND CONDUCTS LINKAGES WITH DATA FROM THE KWCSP TO GUIDE AND EVALUATION THEIR CANCER SCREENING ACTIVITIES. IN ORDER TO CONTINUE MEETING NPCR PROGRAM GOALS IN KENTUCKY, KCR HAS ESTABLISHED FOUR KEY STRATEGIES THROUGH ONGOING ACTIVITIES, PROCESSES, PROCEDURES, AND DOCUMENTED WORK PLANS: 1) ENHANCE NPCR DATA QUALITY, COMPLETENESS, USE, AND DISSEMINATION; 2) USE SURVEILLANCE SYSTEMS AND POPULATION-BASED SURVE

BLOOD-BRAIN BARRIER FUNCTION IN EPILEPSY: NEW TARGETS FOR THERAPY

RESEARCH TRAINING IN DRUG ABUSE BEHAVIOR

IMPACT OF CHRONIC ETHANOL CONSUMPTION ON LUNG FUNCTIONAL AND IMMUNOLOGICAL LANDSCAPE AND IMPLICATION FOR SUSCEPTIBILITY TO SARSCOV2 INFECTION

SMALL RURAL HOSPITAL IMPROVEMENT GRANT PROGRAM

LOW-COST, HIGH-STRENGTH HOLLOW CARBON FIBER FOR COMPRESSED GAS STORAGE TANKS

CHEMOENZYMATIC STUDIES OF AMINOGLYCOSIDE-RESISTANCE ENZYMES TOWARDS NEW DRUGS

KENTUCKY COMMUNITIES AND RESEARCHERS ENGAGING TO HALT THE OPIOID EPIDEMIC (CARE2HOPE)

KENTUCKY SPACE GRANT CONSORTIUM (KSGC) A DIVERSE GROUP OF 28 AFFILIATES ACROSS THE STATE USES A PORTFOLIO-OF-PROGRAMS APPROACH AND BEST PRACTICES TO SET STUDENTS AND FACULTY ON PATHWAYS OF OPPORTUNITIES TOWARDS AEROSPACE-RELATED CAREER GOALS WITH A GOAL OF CONTRIBUTING TO A SKILLED HIGH-PERFORMING AND DIVERSE WORKFORCE THAT MEETS THE EMERGING NEEDS OF NASA AND KENTUCKY. KSGC PROGRAMS ENGAGE COMPETITIVELY-SELECTED PARTICIPANTS IN STEM EDUCATION AND TRAINING PRIMARILY AT THE POST-SECONDARY LEVEL WITH COMPLEMENTARY PIPELINE PRE-COLLEGE PROGRAMS. DIVERSITY OF STUDENTS FACULTY AND INSTITUTIONAL TYPES IS ESSENTIAL AND INTEGRAL TO THIS APPROACH. PURPOSEFUL EFFORTS ARE MADE TO REACH POTENTIAL PARTICIPANTS AND INSPIRE THEM TO ENTER AND PERSIST ALONG THEIR PATHWAY OF OPPORTUNITIES. NASA MISSION DIRECTORATE (ARMD HEOMD SMD STMD) AND OSTEM ALIGNMENT IS REQUIRED FOR ALL PROGRAMS. FUNDING FOR THE 2020-2024 SPACE GRANT CYCLE WILL BE USED TO IMPLEMENT THE KSGC PROGRAMS AND THEMES DESCRIBED IN THE FOLLOWING PROPOSAL: NASA INTERNSHIPS AND FELLOWSHIPS (NIFS) INCLUDING NASA CENTER INTERNSHIPS (NCI) AND KENTUCKY INDUSTRY INTERNSHIPS (KII) ALONG WITH GRADUATE FELLOWSHIPS (GF) AND RESEARCH EXPERIENCE FOR UNDERGRADUATES (REU) OFFER A FLEXIBLE SET OF HANDS-ON NASA-ALIGNED TRAINING TO ESTABLISH INDIVIDUAL STUDENT PATHWAYS OF OPPORTUNITIES. FOR INTERNSHIPS THE INTERN'S EFFORT IS GUIDED BY A NASA OR INDUSTRY MENTOR AND SERVES TO ADVANCE THE STUDENT'S KNOWLEDGE TO PROVIDE THE EXPERIENCE OF WORKING WITH TECHNICAL PROFESSIONALS IN SUPPORT OF NASA'S MISSIONS OR WITH ESTABLISHED OR STARTUP AEROSPACE COMPANIES IN KENTUCKY. GRADUATE FELLOWSHIPS AND RESEARCH EXPERIENCE FOR UNDERGRADUATES PROJECTS PROVIDE 1-ON-1 RESEARCH-BASED TRAINING AND INTERACTION WITH AN ADVISOR INCLUDING STIPEND MATERIALS TRAVEL AND TUITION FOR GRADUATE STUDENTS. HIGHER EDUCATION FUNDING IS A PRIMARY KSGC OBJECTIVE DESIGNED TO SUPPORT COMPETITIVE AWARDS IN MULTIPLE AREAS OF RESOURCE NEEDS FOR KSGC HIGHER EDUCATION INSTITUTIONS. TEAM PROJECTS (TP) SUPPORT FACULTY-MENTORED EXPERIENCES FOCUSED ON AUTHENTIC HANDS-ON DESIGN IN SCIENCE AND ENGINEERING TO INSPIRE INNOVATION INCLUDING PARTICIPATION IN TEAM COMPETITIONS AND FLIGHT OPPORTUNITIES. ENHANCED MINI-GRANTS (EMG) SUPPORT A WIDE-ARRAY OF POSTSECONDARY PROJECTS ALIGNED WITH KENTUCKY AND NASA PRIORITIES UNDER HIGHER EDUCATION GOALS. RESEARCH INITIATION AWARDS (RIA) SUPPORT EARLY-CAREER FACULTY PROPOSING RESEARCH AND BUILDING NASA CONNECTIONS AS ONE ENTRY POINT TO THE NASA KY FACULTY PATHWAY OF OPPORTUNITY WHERE FACULTY CAN APPLY FOR INCREASINGLY-CHALLENGING RESEARCH AWARDS TO HONE THEIR PROPOSAL AND RESEARCH SKILLS AND DEVELOP STUDENT-MENTORING ABILITIES. PRE-COLLEGE EDUCATION PROGRAMS PROVIDE EDUCATIONAL OPPORTUNITIES AT SITES ACROSS KENTUCKY TO ATTRACT AND RETAIN STUDENTS AS WELL AS DEVELOP EDUCATOR CONTENT KNOWLEDGE IN NASA-RELATED STEM DISCIPLINES. MINI-GRANTS (MG) PROVIDE A WIDE VARIETY OF PRE-COLLEGE OPPORTUNITIES INCLUDING STEM CAMPS AND COMPETITIONS K-12 TEACHER TRAINING AS WELL AS MUSEUM-BASED ASTRONOMY AND AEROSPACE PROGRAMS. ENHANCED MINI-GRANTS (EMG) SUPPORT A WIDE-ARRAY OF PROJECTS ALIGNED WITH KENTUCKY AND NASA PRIORITIES UNDER PRE-COLLEGE OBJECTIVES. THREE CURRENT STRATEGIC THEMES CHOSEN BY THE CONSORTIUM ARE DATA + SCIENCE EARTH + SPACE AND AEROSPACE + INNOVATION. THESE THEMES ENABLE MULTIPLE PROGRAMS TO BE UNIFIED IN A PORTFOLIO APPROACH THAT CAN BE BALANCED TO SERVE AN ARRAY OF STATE AND NATIONAL AEROSPACE NEEDS THROUGH COMPETITIVE SELECTION AND CAREFUL MANAGEMENT OF PROJECT AWARDS. PROGRAM EVALUATION DATA IS DRAWN FROM TWO PRIMARY SOURCES: NASA KENTUCKY STUDENT INFORMATION FORMS (SIF) AND PI REPORTS OF PROJECT RESULTS INCLUDING NUMBERS OF PARTICIPANTS PUBLICATIONS AND PRESENTATIONS. PROGRAM DATA IS REPORTED TO NASA VIA OEPM AND APD. PROGRAM EVALUATION USES SMART METRICS SUCH AS DIVERSITY AND NUMBER OF AWARDS.

CENTER FOR THE BIOLOGIC BASIS OF ORAL/SYSTEMIC DISEASE (CBBOSD)

CENTER FOR BIOMEDICAL RESEARCH EXCELLENCE IN THE MOLECULAR BASIS OF HUMAN DISEASE

CONTRIBUTIONS OF HEPATIC AND INTESTINAL PATHWAYS TO CHOLESTEROL EXCRETION

NRSA TRAINING CORE

FIRST-IN-HUMAN SAD & MAD TRIALS FOR MW151, A NOVEL ALZHEIMER'S DISEASE DRUG CANDIDATE THAT ATTENUATES PROINFLAMMATORY CYTOKINE DYSREGULATION

COOPERATION OF CD8+ T CELLS AND PHAGOCYTES TO ELIMINATE TOXOPLASMA CYSTS

ACCOUNTABLE HEALTH COMMUNITIES TRACK 3 ALIGNMENT - KENTUCKY CONSORTIUM FOR ACCOUNTABLE HEALTH COMMUNITIES

PRECLINICAL DEVELOPMENT OF A SELECTIVE SUPPRESSOR OF NEUROINFLAMMATION FOR MCI/AD

RESEARCHING EQUITABLE SLEEP TIME (REST) IN APPALACHIA - INSUFFICIENT SLEEP (HABITUAL SLEEP DURATION OF =6 HOURS), IS A COSTLY, PREVALENT, PUBLIC HEALTH PROBLEM ASSOCIATED WITH NUMEROUS NEGATIVE HEALTH OUTCOMES. PRIOR RESEARCH SUGGESTS THAT INSUFFICIENT SLEEP IS MORE PREVALENT AMONG HEALTH DISPARITY POPULATIONS (E.G., RACIAL MINORITIES, ADULTS OF LOW SOCIOECONOMIC STATUS), BUT OUR UNDERSTANDING OF THE MECHANISMS AND CONSEQUENCES OF SLEEP DISPARITIES IN RURAL POPULATIONS IS LIMITED. THE PRESENT STUDY “RESEARCHING EQUITABLE SLEEP TIME IN KENTUCKY COMMUNITIES (REST-KY),” FOCUSES ON APPALACHIAN ADULTS, AN NIH-DESIGNATED HEALTH DISPARITY POPULATION, WHOSE SERIOUS HEALTH INEQUITIES INCLUDE MULTIPLE HEALTH MORBIDITIES AND PREMATURE MORTALITY. SIX OF THE COUNTIES WITH THE HIGHEST CONCENTRATION OF INSUFFICIENT SLEEP IN THE NATION ARE IN CENTRAL APPALACHIAN KENTUCKY (KY), WHERE 25-58% OF ADULTS REPORT INSUFFICIENT SLEEP 15+ NIGHTS/MONTH. THESE COUNTIES ARE SEVERELY ECONOMICALLY DISTRESSED, YET, NEARBY COUNTIES WITH COMPARABLE ECONOMIC DISTRESS, RURALITY, AND DEMOGRAPHIC HOMOGENEITY ARE NOT “HOTSPOTS” OF INSUFFICIENT SLEEP. USE OF A MIXED METHODS, LONGITUDINAL DESIGN WILL ALLOW US TO EVALUATE MECHANISMS CONTRIBUTING TO BOTH SLEEP DEFICIENCIES AND HEALTH IN THIS RURAL COMMUNITY. KNOWLEDGE GAPS INCLUDE 1) SPARSE INSIGHTS INTO SPECIFIC INDIVIDUAL-, SOCIAL-, AND SOCIETAL-LEVEL FACTORS CONTRIBUTING TO SLEEP DEFICIENCIES IN APPALACHIAN ADULTS.; 2) IT IS NOT KNOWN IF REGIONAL SLEEP AND HEALTH DISPARITIES SHARE THE SAME UNDERLYING MECHANISMS; AND 3) CRITICAL POINTS OF VARIANCE BETWEEN “HOTSPOT” AND NON-“HOTSPOT” COUNTIES HAVE NOT BEEN EXAMINED. WE WILL RECRUIT A COHORT OF 400 ADULTS FROM 6 INSUFFICIENT SLEEP “HOTSPOT” COUNTIES (N=200) IN APPALACHIAN KY, AND 6 SIMILARLY RURAL AND ECONOMICALLY DISTRESSED NON-“HOTSPOT” COUNTIES. RECRUITMENT WILL BE STRATIFIED ACROSS “HOTSPOT” AND NON-“HOTSPOT” COUNTIES BY KEY DEMOGRAPHIC FACTORS LINKED TO SLEEP DEFICIENCIES (E.G., AGE, SEX, RACE/ETHNICITY) TO PROMOTE COUNTY CLUSTER-LEVEL COMPARISONS. SPECIFIC AIMS. 1. USE MIXED METHODS TO COMPARE HOW INDIVIDUAL, SOCIAL, AND SOCIETAL FACTORS LINKED TO SLEEP DEFICIENCIES DIFFER BETWEEN INSUFFICIENT SLEEP “HOTSPOT” AND NON-“HOTSPOT” COUNTIES. 2. EVALUATE MECHANISMS DRIVING SLEEP DEFICIENCIES AND HEALTH OUTCOMES OVER TIME. BI-DIRECTIONAL MODELS OF SLEEP AND HEALTH OUTCOMES WILL BE EXAMINED. 3. QUANTIFY DAY-TO-DAY SLEEP REACTIVITY (I.E., THE DEGREE TO WHICH DAYTIME DISTRESS IMPACTS SLEEP) AND TEST IF INDIVIDUAL DIFFERENCES IN SLEEP REACTIVITY PREDICT WORSENED HEALTH OUTCOMES OVER TIME. DIFFERENCES BY SEX AND COUNTY CLUSTER (“HOTSPOT” VS. NON-“HOTSPOT”) WILL ALSO BE EXAMINED IN AIMS 2-3. OUR MULTIPLE, SOPHISTICATED OBJECTIVE AND SUBJECTIVE DATA COLLECTION METHODS, MADE POSSIBLE BY OUR INTERDISCIPLINARY TEAM’S VARIED EXPERTISE, WILL ADVANCE SCIENTIFIC KNOWLEDGE ABOUT BIOLOGICAL, BEHAVIORAL, EMOTIONAL, AND SOCIAL CONTRIBUTIONS TO SLEEP HEALTH. THIS HOLISTIC APPROACH EXPLICITLY ACKNOWLEDGES THE INSEPARABLE OVERLAP BETWEEN HEALTH FUNCTION, AND SLEEP. OUR FINDINGS WILL OFFER UNPRECEDENTED INSIGHT INTO THE BI- DIRECTIONAL RELATIONSHIPS BETWEEN SLEEP AND HEALTH IN AN UNDERSTUDIED RURAL HEALTH DISPARITY POPULATION. RESULTS WILL INFORM STRATEGIES TO REDUCE SLEEP DISPARITIES, THUS HAVING STRONG POTENTIAL FOR PUBLIC HEALTH IMPACT.

CENTER OF BIOMEDICAL RESEARCH EXCELLENCE- WOMEN'S HEALTH

RURAL HEALTH RESEARCH GRANT PROGRAM COOPERATIVE AGREEMENT

MUSCULOSKELETAL HEALTH CONSIDERATIONS TO IMPROVE RESILIENCY AND LETHALITY IN FEMALE MARINES

IN VITRO GLYCORANDOMIZATION OF NATURAL PRODUCTS

RII TRACK-2 FEC: DATA-ENABLED DISCOVERY AND DESIGN TO TRANSFORM LIQUID-BASED ENERGY STORAGE (D3TALES)

TRANSLATING SHIP1 GENETICS TO GENERATE A NOVEL ALZHEIMER'S PHARMACOLOGIC AGENT

DEVELOPMENT OF A PARACORPOREAL PUMP-INTEGRATED ARTIFICIAL LUNG FOR TRANSPORT OF WARFIGHTERS WITH ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)

SPECIAL EDUCATION-TECHNICAL ASSISTANCE AND DISSEMINATION TO IMPROVE SERVICES AND RESULTS FOR CHILDREN WITH DISABILITIES - REGIONAL RESOURCE CENTER

REGULATION OF INTESTINAL STEM CELL ACTIVATION IN COLITIS

CORONAVIRUS STATE HOSPITAL IMPROVEMENT PROGRAM

CALPAIN AS A THERAPEUTIC TARGET FOR TBI (P01)

RESTORATION AND MAINTENANCE OF PHYSICAL AND NEUROSENSORY PERFORMANCE (RAMP) IN NAVAL AND MARINE CORPS AVIATION

CERAMIDE AND ACUTE PHASE PROTEIN ELEVATION DURING AGING

SLEEP FRAGMENTATION AND ALZHEIMER?S DISEASE

THE AMYLIN DYSHOMEOSTASIS HYPOTHESIS OF VASCULAR CONTRIBUTIONS TO COGNITIVE IMPAIRMENT AND DEMENTIA (VCID)

KENTUCKY NETWORK FOR INNOVATION & COMMERCIALIZATION (?KYNETIC?)

DEVELOPMENT OF LONG-ACTING COCAINE HYDROLASE AS A TREATMENT FOR COCAINE ABUSE

POLICY & ENVIRONMENTAL APPROACHES & COMMUNITY-CLINICAL LINKAGES IN CANCER PROGRAM

SMALL RURAL HOSPITAL IMPROVEMENT GRANT PROGRAM

IMPLEMENTING AN EVIDENCE-BASED MHEALTH DIET AND ACTIVITY INTERVENTION: MAKE BETTER CHOICES 2 FOR RURAL APPALACHIANS

CENTRAL STATES CRIMINAL JUSTICE DRUG ABUSE CENTER

RADON ON THE RADAR

SEX DIFFERENCES IN ANGIOTENSIN-INDUCED VASCULAR DISEASES

SCHOLARSHIPS FOR DISADVANTAGED STUDENTS

EFFECTS OF ANTI-MIR-33 ON ATHEROSCLEROSIS REGRESSION AND RCT IN NONHUMAN PRIMATES

TO SUPPORT NASA'S MISSION AND SERVE KENTUCKY'S NEEDS, NASA KENTUCKY SPACE GRANT CONSORTIUM, A DIVERSE GROUP OF 25 AFFILIATES ACROSS THE STATE, PROPOS

"EARLY ICU STANDARDIZE REHABILITATION THERAPY FOR THE CRITICALLY INJURED BURN PATIENT"

MOLECULAR MECHANISMS OF PLATELET EXOCYTOSIS

REGIONAL RESOURCE CENTER

SAFETY AND MODULATION OF ABCC9 PATHWAYS BY NICORANDIL FOR THE TREATMENT OF HIPPOCAMPAL SCLEROSIS OF AGING (SMART???HS)

REGULATION SIGNALING AND DYNAMICS OF GLUCAN PHOSPHATASES.

CERAMIDE-INDUCED CELL DEATH IN NEURODEGENERATION

KENTUCKY CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE

ALBUMIN-AFP GENE FAMILY REGULATION IN FETAL AND ADULT LIVER

A SOLVENT/MEMBRANE HYBRID POST-COMBUSTION CO2 CAPTURE PROCESS FOR EXISTING COAL-FIRED POWER PLANTS

MOLECULAR ANALYSIS OF JUVENILE HORMONE ACTION

NEURAL CIRCUITRY IN THE DORSAL VAGAL COMPLEX

UNIVERSITY OF KENTUCKY, 2707-1555 NEW AWARD DE-FOA-0002707(MINER) PROJECT TITLE: DEVELOPMENT OF A CARBON-NEGATIVE PROCESS FOR COMMINUTION ENERGY REDUCTION AND ENERGY-RELEVANT MINERAL EXTRACTION THROUGH CARBON MINERALIZATION AND BIOLOGICAL CARBON FIXATION UNIVERSITY OF KENTUCKY TO REDUCE COMMINUTION ENERGY BY ALTERING THE ENERGY-RELEVANT MINERAL PROPERTY USING SUPERCRITICAL CO2 AND AQUEOUS CO2 ASSISTED GRINDING AND DEVELOP AN INNOVATIVE PROCESS TO IMPROVE MINERAL RECOVERY UTILIZING HYDROFLOAT TO RECOVER LOW DEGREE LIBERATION MINERALS AND ENHANCED BIOLEACHING WITH CARBON FIXATION.

LOUIS STOKES STEM PATHWAYS AND RESEARCH ALLIANCE: KY-WV LSAMP

** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** DIVERSIFIED FRUIT AND VEGETABLE GROWERS ARE A HALLMARK OF THE ORGANIC AGRICULTURE INDUSTRY AND MOVEMENT. DIVERSIFICATION OPENS MARKET OPPORTUNITIES, HEDGES RISKS, CONSERVES BIODIVERSITY, AND GROWS HEALTHY COMMUNITIES AND LOCAL ECONOMIES. AT THE SAME TIME, DIVERSIFIED ORGANIC GROWERS MUST MASTER THE PRODUCTION OF MANY SPECIALTY CROPS WITH A LIMITED SET OF TOOLS TO COMBAT PESTS, DISEASES, WEEDS, AND A CHANGING CLIMATE. SOME OF THESE TOOLS, LIKE OMRI (ORGANIC MATERIALS REVIEW INSTITUTE)-LISTED PESTICIDES PERFORM SUB-OPTIMALLY AND FAIL TO REDUCE DAMAGE FROM PESTS AND DISEASES. MOUNTING EVIDENCE SUGGESTS MESOTUNNEL PROTECTION SYSTEMS LIMIT PESTS, DISEASES, AND SOME EXTREME WEATHER CONDITIONS. HOWEVER, WHILE MESOTUNNELS REDUCE THE USE OF OMRI-LISTED PESTICIDES, CONSUMER CONCERNS OVER PLASTIC USE IN AGRICULTURE MAY PRESENT NEW SOCIAL CHALLENGES TO THE ADOPTION OF THESE PLASTIC-BASED SYSTEMS. THE OVERALL GOAL OF THIS FOUR-YEAR PROJECT IS TO EXPAND THE ORGANIC TOOL KIT TO OVERCOME BIOTIC AND ABIOTIC CHALLENGES TO SPECIALTY CROPS IN THE SOUTHEAST, MIDWEST, AND NORTHEAST. FIELD EXPERIMENTS AND ON-FARM TRIALS WITH BRASSICA (GREENS, BROCCOLI), CUCURBIT (MELONS AND SQUASH), AND SOLANACEOUS CROPS (EGGPLANT) WILL OPTIMIZE THE USE OF MESOTUNNEL PROTECTION SYSTEMS TO CONTROL BIOTIC AND ABIOTIC STRESSORS (OBJECTIVE 1). INNOVATIVE STRATEGIES TO INCORPORATE MESOTUNNELS INTO DIVERSIFIED ORGANIC FRUIT AND VEGETABLE ROTATIONS WILL AIM TO MAXIMIZE THE BENEFITS TO GROWERS IN EACH REGION. DATA GENERATED FROM EXPERIMENTS WILL BE USED TO DETERMINE WHICH MESOTUNNEL-CROP COMBINATIONS MAXIMIZE GROWER PROFITS (OBJECTIVE 2). TO UNDERSTAND MARKETING, POLICY, AND ADOPTION BARRIERS, WE WILL ASSESS GROWER AND CONSUMER ACCEPTABILITY OF MESOTUNNELS THROUGH SURVEYS, INTERVIEWS, AND CONSUMER PREFERENCE EXPERIMENTS (OBJECTIVE 3). GROWERS AND INDUSTRY STAKEHOLDERS WILL PROVIDE CONTINUOUS INPUT TO GUIDE THE PROJECT THROUGH AN ADVISORY PANEL, SURVEYS, LISTENING SESSIONS, AND ON-FARM TRIALS. FINALLY, A COORDINATED REGIONAL AND NATIONAL OUTREACH PROGRAM WILL REACH THOUSANDS OF GROWERS AND MILLIONS OF CONSUMERS TO HIGHLIGHT THE MOST PROMISING PROTECTION SYSTEMS (OBJECTIVE 4). TOGETHER, THESE OBJECTIVES ADDRESS FIVE OREI GOALS AND WILL HELP THE ORGANIC SPECIALTY CROP INDUSTRY TO GROW RESILIENT TO CHANGING CLIMATES AND CONSUMER DEMANDS TO INSURE THE SUSTAINABILITY OF THE ORGANIC INDUSTRY.

MECHANISMS OF INCREASED SUSCEPTIBILITY TO PULMONARY NONTUBERCULOUS MYCOBACTERIAL DISEASE IN THE ELDERLY

PSYCHOSOCIAL STRESS INTERACTIONS WITH ELECTROPHYSIOLOGY AND BRAIN AGING

DYSREGULATION OF MATERNAL IMMUNITY DURING PREGNANCY BY PREGRAVID OBESITY

SMALL VESSEL DISEASE BIOMARKERS IN A LONGITUDINALLY-FOLLOWED "STROKE-BELT" COHORT

METABOLIC SYNDROME AND HIPPOCAMPAL CA2+ DYSREGULATION IN AGING-RELATED MEMORY DEC

ANGIOTENSIN: A LINK BETWEEN OBESITY AND HYPERTENSION

LONG-LASTING COCAINE-METABOLIZING ENZYME FOR COCAINE ADDICTION TREATMENT

INTEGRATED CHEMOSELECTIVE AND INFORMATIC PLATFORM FOR LARGE-SCALE METABOLOMICS

COMMUNITY-BASED WORKFORCE TO INCREASE COVID-19 VACCINATIONS IN UNDERSERVED COMMUNITIES

WASTEWATER ASSESSMENT FOR CORONAVIRUS IN KENTUCKY: IMPLEMENTING ENHANCED SURVEILLANCE TECHNOLOGY - WASTEWATER ASSESSMENT FOR CORONAVIRUS IN KENTUCKY – IMPLEMENTING ENHANCED SURVEILLANCE TECHNOLOGY SURVEILLANCE FOR SARS-COV-2 IS HINDERED BY THE AVAILABILITY OF TESTING, PARTICULARLY IN REMOTE AND RURAL AREAS. SCREENING OF WASTEWATER FOR SARS-COV-2 VIRAL BIOMARKERS OFFERS A VIABLE ALTERNATIVE TO INDIVIDUAL TESTING AND IT CAN IDENTIFY COMMUNITIES AND FACILITIES THAT ARE AT RISK OF BECOMING HOTSPOTS.WASTEWATER SURVEILLANCE OVERCOMES SEVERAL LIMITATIONS OF CLINICAL SURVEILLANCE, SUCH AS THE NEED FOR ROBUST HEALTHCARE AND LABORATORY INFRASTRUCTURE AND THE LACK OF REPRESENTATIVE AND COMPREHENSIVE TESTING WITHIN COMMUNITIES. CONVENTIONAL WASTEWATER SURVEILLANCE TAKES SAMPLES FROM SEWER SYSTEMS OR WASTEWATER TREATMENT FACILITIES AND USES A SERIES OF EXTRACTION STEPS PRIOR TO ADVANCED PCR TECHNOLOGY TO QUANTITATE THE VIRAL BIOMARKER (RNA). THIS APPROACH IS TIME AND RESOURCE-INTENSIVE, WHICH LIMITS ITS WIDE-SCALE APPLICATION. DEVELOPING NEXT GENERATION TECHNOLOGY TO SIMPLIFY WASTEWATER RNA EXTRACTION AND QUANTITATION WILL MAKE IT FEASIBLE TO USE MORE BROADLY AT FACILITIES AND IN RURAL COMMUNITIES. THE LIMITED CLINICAL TESTING FOR COVID-19 IN RURAL SOUTHEASTERN KENTUCKY HAMPERS DISEASE SURVEILLANCE AND PREVENTS INFORMED PUBLIC ACTION TO MITIGATE AND CONTAIN THE SPREAD OF DISEASE. WASTEWATER TESTING FOR SARS-COV- 2 IN THESE COMMUNITIES USING FIELD-FRIENDLY TECHNOLOGY WILL PROVIDE IMPORTANT INFORMATION TO LOCAL AUTHORITIES AND CITIZENS ABOUT THE SPREAD AND TREND OF SARS-COV-2 INFECTION IN THEIR COMMUNITIES. OUR PROJECT WILL ACCOMPLISH TWO AIMS: 1) DEVELOP NEXT GENERATION WASTEWATER ASSESSMENT TECHNOLOGY AND 2) IMPLEMENT AND EVALUATE THE NEXT GENERATION WASTEWATER ASSAY. FOR AIM 1 WE ADAPT TECHNOLOGY INVENTED BY OUR TEAM TERMED EXCLUSION-BASED SAMPLE PREPARATION (ESP) TO SIMPLIFY AND IMPROVE RNA EXTRACTION FROM WASTEWATER. WE WILL PAIR ESP WITH LOOP-MEDIATED ISOTHERMAL AMPLIFICATION (LAMP) TECHNOLOGY FOR RNA DETECTION TO CREATE A SENSITIVE, ROBUST, AND FIELD-FRIENDLY PLATFORM FOR TESTING WASTEWATER FOR SARS- COV-2 RNA. WE WILL COMPARE THE NEXT GENERATION ASSAY WITH ESTABLISHED TECHNIQUES ON METRICS OF SENSITIVITY, SPECIFICITY, AND USABILITY (E.G., ASSAY TIME, NUMBER OF ASSAY STEPS). FOR AIM 2 WE WILL FIRST VALIDATE THE NEXT GENERATION ASSAY IN THE FIELD AT CONGREGATE LIVING FACILITIES IN A SIDE-BY-SIDE COMPARISON WITH CONVENTIONAL WASTEWATER SURVEILLANCE. NEXT, BUILDING ON EXISTING RELATIONSHIPS IN APPALACHIAN KENTUCKY, WE WILL RECRUIT AND TRAIN A PURPOSIVE GROUP OF WASTEWATER TREATMENT PLANT OPERATORS, WATERSHED WATCH CITIZEN SCIENTISTS, AND SCHOOL SCIENCE TEACHERS TO TEST WASTEWATER IN THEIR COMMUNITIES AND SCHOOLS USING THE FIELD-FRIENDLY NEXT GENERATION WASTEWATER ASSAY. FIELD RESULTS WILL BE VALIDATED IN THE LAB. A ROBUST MIXED METHODS EVALUATION USING THE RE-AIM FRAMEWORK WILL ASSESS COMMUNITY PERCEPTIONS OF FEASIBILITY, ACCEPTABILITY, AND UTILITY OF WASTEWATER SURVEILLANCE FOR SARS-COV-2 AND IDENTIFY COMMUNITY MEASURES TAKEN IN RESPONSE TO TEST RESULTS.

IMPROVING CHEMOTHERAPY OF CASTRATION-RESISTANT PROSTATE CANCER

THE ROLE OF SATELLITE CELLS IN ADULT SKELETAL MUSCLE GROWTH AND MAINTENANCE

ELUCIDATING THE ROLE OF PLACENTAL GROWTH FACTOR IN DIFFUSE WHITE MATTER DISEASE

REMOTE ALCOHOL MONITORING TO FACILITATE ABSTINENCE REINFORCEMENT WITH AN UNDERSERVED POPULATION

MECHANISMS FOR ACTIVATION OF BEIGE ADIPOSE TISSUE IN HUMANS - WE HAVE BEEN STUDYING SUBCUTANEOUS WHITE ADIPOSE TISSUE (SC WAT) BEIGING IN RESPONSE TO MIRABEGRON, WHICH IS A SS3 ADRENERGIC RECEPTOR (SS3AR) AGONIST. SS3ARS ARE FOUND IN ADIPOCYTES AND SMOOTH MUSCLE, AND MIRABEGRON IS AN FDA APPROVED DRUG FOR OVERACTIVE BLADDER. TREATMENT OF OBESE, INSULIN RESISTANT HUMANS FOR TWELVE WEEKS WITH MIRABEGRON CONSISTENTLY INDUCED SC WAT BEIGING AND THIS LED TO IMPROVED ORAL GLUCOSE TOLERANCE AND A LOWER HBA1C. THE MECHANISM FOR IMPROVED GLUCOSE HOMEOSTASIS INVOLVED BOTH A SMALL IMPROVEMENT IN INSULIN SENSITIVITY AND A SIGNIFICANT IMPROVEMENT IN SS-CELL FUNCTION (INSULIN SECRETION) ALONG WITH AN INCREASE IN MUSCLE OXIDATIVE TYPE 1 FIBERS; HOWEVER, THERE WAS NO WEIGHT LOSS OR INDUCTION OF BROWN FAT. SINCE PANCREATIC SS-CELLS AND MUSCLE DO NOT EXPRESS THE SS3AR, THE BENEFICIAL EFFECTS OF MIRABEGRON IN THESE CELLS LIKELY OCCURRED BY AN INDIRECT MECHANISM. THE PHYSIOLOGICAL EFFECTS OF MIRABEGRON ARE LIKELY MEDIATED IN PART BY THE INDUCTION OF BEIGE ADIPOSE, WHICH REPRESENTS A METABOLIC SINK FOR GLUCOSE AND LIPIDS AND WHICH MAY ALTER ADIPOSE REMODELING. IN ADDITION, THE CHANGES IN ADIPOSE TISSUE AND OTHER ORGANS MAY RESULT IN SECONDARY EFFECTS THAT TARGET OTHER TISSUES. SPECIFIC AIM 1. TO EXAMINE THE EFFECTS OF THE SS3 AGONIST MIRABEGRON ON GLUCOSE METABOLISM, WE WILL COMPREHENSIVELY ANALYZE GLUCOSE TOLERANCE, INSULIN SENSITIVITY, AND SS-CELL FUNCTION IN PREDIABETIC SUBJECTS IN A 4-MONTH, PLACEBO-CONTROLLED, RANDOMIZED TRIAL. WE WILL ASSESS CHANGES IN ADIPOSE TISSUE INCLUDING BEIGING, INFLAMMATION, FIBROSIS, AND INSULIN-STIMULATED GLUCOSE UPTAKE BY ADIPOCYTES. WE WILL ALSO FULLY CHARACTERIZE GENE EXPRESSION IN SC WAT BY RNA-SEQ TO IDENTIFY POTENTIAL MECHANISMS SUCH AS ALTERED ADIPOKINE PROFILES. SPECIFIC AIM 2. WE HYPOTHESIZE THAT MIRABEGRON CAUSES CELLS THAT EXPRESS THE SS3AR TO CHANGE THE LEVELS OF SECRETED FACTORS THAT AFFECT PERIPHERAL CELL TYPES SUCH AS SS-CELLS AND MUSCLE. WE WILL USE BIOCHEMICAL AND PHARMACOLOGICAL APPROACHES TO IDENTIFY THE MECHANISM BY WHICH CONDITIONED MEDIUM FROM MIRABEGRON-TREATED ADIPOCYTES INCREASES PGC1A EXPRESSION IN MUSCLE IN VITRO. WE WILL UTILIZE UNBIASED APPROACHES TO IDENTIFY CHANGES IN LIPIDS, METABOLITES, AND EXOSOME MIRNA COMPOSITION IN THE ADIPOCYTE CONDITIONED MEDIA. WE WILL USE THESE APPROACHES TO IDENTIFY MOLECULES ALTERED IN PLASMA BY MIRABEGRON TREATMENT THAT ARE RESPONSIBLE FOR THE IMPROVEMENT IN SS-CELL AND MUSCLE FUNCTION. CLINICAL RELEVANCE: MIRABEGRON TREATMENT HAS POSITIVE EFFECTS ON GLUCOSE TOLERANCE DUE TO IMPROVEMENTS IN INSULIN SENSITIVITY AND SS-CELL FUNCTION. THIS MAY BE EXPLOITED TO PREVENT CONVERSION OF PREDIABETES TO DIABETES OR USED AS A THERAPEUTIC IN DIABETICS. THIS APPLICATION WILL ALSO INCREASE OUR UNDERSTANDING OF THE MECHANISM(S) BY WHICH MIRABEGRON ACTS, WHICH MAY REVEAL NEW THERAPEUTIC TARGETS

TARGETING TRANSLATION DEPENDENCE IN COLORECTAL CANCER PROGRESSION

NANOSCALE MATERIALS AND ARCHITECTURES FOR ENERGY CONVERSION

NEUROTENSIN: A NOVEL MEDIATOR OF OVULATION

APPALACHIAN CAREER TRAINING IN ONCOLOGY (ACTION) PROGRAM

CONTRIBUTIONS OF ASTROCYTE RELA SIGNALING IN AGING-RELATED NEURODEGENERATIVE SEQUELAE FOLLOWING TBI - ABSTRACT TRAUMATIC BRAIN INJURY (TBI) IS SIGNIFICANTLY CORRELATED WITH INCREASED RISK FOR DEVELOPING SEVERAL NEURODEGENERATIVE DISORDERS, INCLUDING ALZHEIMER’S DISEASE (AD) AND AD-RELATED DEMENTIA (ADRD), REPRESENTING ONE OF THE MOST POWERFUL ENVIRONMENTAL RISK FACTORS FOR AD/ADRD. COMPOUNDING THESE CORRELATES IS THAT AGING IS A SUBSTANTIAL FACTOR IN THE INCIDENCE AND VULNERABILITY TO TBI. OWING TO THE COMPLEXITIES SURROUNDING TBI AS A PROGRESSIVE NEURODEGENERATIVE DISORDER LEADING TO AD/ADRD, THE CELLULAR MECHANISMS POTENTIALLY UNDERLYING THE AGING BRAIN’S SUSCEPTIBILITY TO ACQUIRE DEGENERATIVE RESPONSES REMAINS ELUSIVE. TO DATE, THE BULK OF PUBLISHED FINDINGS RELATED TO TBI-RELATED ALZHEIMER’S-LIKE IMPAIRMENTS HAVE BEEN EXAMINED USING YOUNG ADULT AND PREDOMINANTLY MALE RODENTS, WHICH DOES NOT ACCURATELY MODEL THE GREATEST AT-RISK POPULATION IN HUMANS. HOWEVER, OUR AGING TBI MODEL RECAPITULATES SEVERAL CORRELATES OF ALZHEIMER’S LIKE IMPAIRMENTS INCLUDING CHRONIC MEMORY IMPAIRMENT, EXACERBATED NEUROINFLAMMATION, GLIOSIS, PHOSPHORYLATED TAU, AS WELL AS MICROGLIAL PHENOTYPES PREVIOUSLY DOCUMENTED IN BOTH HUMAN’S AND MOUSE MODELS OF ALZHEIMER’S DISEASE. GUIDED BY PRELIMINARY FINDINGS, OUR OVERARCHING HYPOTHESIS IS THAT IN THE AGING BRAIN FOLLOWING TBI, RELA DRIVES EXACERBATED ASTROCYTE RESPONSES, UNDERLYING THE AGING BRAIN’S SUSCEPTIBILITY FOR PERSISTENT DECREMENTAL OUTCOMES RELATED TO HOMEOSTATIC ASTROCYTE SUSCEPTIBILITY, NEUROINFLAMMATION, AND NEURAL NETWORK DYSFUNCTION. WE BELIEVE THESE ALTERED RESPONSES, INITIATED BY TBI IN THE AGING BRAIN ULTIMATELY MANIFEST IN CORRELATES CHARACTERISTIC OF PROGRESSIVE NEURODEGENERATION ASSOCIATED WITH AD/ADRD. WE WILL PURSUE THREE AIMS TO TEST THIS HYPOTHESIS USING NOVEL GENETIC MODELS FOR TARGETING ASTROCYTES IN YOUNG AND AGED MICE TO DETERMINE 1.) THE SUSCEPTIBILITY OF AGED ASTROCYTES TO LOSE CRITICAL HOMEOSTATIC FEATURES FOLLOWING TBI, 2.) THE ABILITY OF ASTROCYTES TO REGULATE THE CONVERSION OF MICROGLIA TOWARDS DECREMENTAL AD-ASSOCIATED INFLAMMATORY PHENOTYPES FOLLOWING TBI, AND 3.) THE ROLE OF ASTROCYTES IN THE VULNERABILITY OF SYNAPTIC CIRCUITRY AND IMPAIRED MEMORY, A CRITICAL HALLMARK ASSOCIATED WITH TBI/ADRD. CUMULATIVELY, THESE STUDIES WILL HELP TO ELUCIDATE BOTH THE CELLULAR AND MOLECULAR SUBSTRATES THROUGH WHICH THE AGING BRAIN’S RESPONSE TO TBI FACILITATES PROGRESSIVE NEURODEGENERATIVE SEQUELAE THAT CAN EVENTUALLY LEAD TO AD/ADRD. OUR SALIENT FINDINGS WILL ULTIMATELY DETERMINE THE EXTENT TO WHICH RELA IS A CRITICAL MEDIATOR IN THESE AD-ASSOCIATED SEQUELAE WITH THE POTENTIAL TO ELUCIDATE NEW THERAPEUTIC TARGETS TOWARD THEIR PREVENTION.

BIOSYNTHESIS OF NUCLEOSIDE ANTIBIOTICS TARGETING BACTERIAL TRANSLOCASE

NON-OPIATE TREATMENT AFTER PRENATAL OPIATE EXPOSURE TO PREVENT POSTNATAL INJURY TO THE YOUNG BRAIN (NO-POPPY)

THE ROLE OF MC1R IN MELANOCYTIC UV-INDUCED DNA DAMAGE AND REPAIR RESPONSES

FUNDAMENTAL STUDIES OF THE NEUTRON AT JEFFERSON LAB AND THE SNS

HEDGEHOG SIGNALING IN DEVELOPMENT AND METABOLISM

CIRCADIAN REGULATION OF METABOLIC RISK IN MICE AND WOMEN: ROLE OF ESTROGEN AND TIME-RESTRICTED FEEDING - ABSTRACT TEXT PROJECT SUMMARY MEN AND WOMEN DIFFER IN THEIR SUSCEPTIBILITY TO OBESITY-RELATED DISORDERS AND ESTROGEN IS A PRIMARY PROTECTIVE FACTOR IN WOMEN. PREMENOPAUSAL WOMEN HAVE A LOWER INCIDENCE OF CARDIOMETABOLIC DISEASE COMPARED TO AGE- MATCHED MEN. AFTER MENOPAUSE, WHEN CIRCULATING ESTROGENS DECLINE, A WOMAN’S RISK FOR METABOLIC SYNDROME AND HEART DISEASE INCREASES DRAMATICALLY. THE CIRCADIAN SYSTEM IS ALSO A CRITICAL REGULATOR OF METABOLISM AND OBESITY. CIRCADIAN RHYTHMS ARE ~24-HOUR CYCLES OF BEHAVIOR AND PHYSIOLOGY THAT ARE GENERATED BY A NETWORK OF MOLECULAR CLOCKS LOCATED IN NEARLY EVERY TISSUE IN THE BODY. THESE CLOCKS ARE ENTRAINED BY CUES SUCH AS FOOD AND LIGHT AND ARE TYPICALLY SYNCHRONIZED WITH ENVIRONMENTAL LIGHT-DARK CYCLES. STUDIES OF SHIFT WORKERS, WHO HAVE DISORDERED EXPOSURE TO FOOD AND LIGHT, SHOW THAT DISRUPTION OF THE CIRCADIAN SYSTEM INCREASES RISK OF OBESITY, HEART DISEASE, METABOLIC SYNDROME, AND TYPE 2 DIABETES. OUR OVERALL OBJECTIVES ARE TO ELUCIDATE THE ESTROGEN-RELATED CIRCADIAN MECHANISMS THAT REGULATE METABOLISM AND TO TEST INTERVENTIONS THAT TARGET THE CIRCADIAN SYSTEM AND BENEFIT WOMEN WHO ARE ESTROGEN DEFICIENT. MOST STUDIES TO DATE HAVE INVESTIGATED CIRCADIAN REGULATION OF OBESITY AND DIABETES IN MALES. HIGH-FAT DIET FEEDING IN MALE MICE PROFOUNDLY DISRUPTS DAILY RHYTHMS AND THIS CIRCADIAN DISRUPTION REGULATES DIET-INDUCED OBESITY. IN CONTRAST, VERY LITTLE IS KNOWN ABOUT THE INTERPLAY BETWEEN CIRCADIAN RHYTHMS AND METABOLISM IN FEMALES. THE OBJECTIVE OF THIS PROPOSAL IS TO INVESTIGATE THE INTERACTION BETWEEN ESTROGEN SIGNALING, TIME-RESTRICTED FEEDING, AND CIRCADIAN RHYTHMS IN REGULATING OBESITY AND ITS COMORBIDITIES IN MICE AND WOMEN. WE WILL TEST THE CENTRAL HYPOTHESIS THAT DAILY METABOLIC RHYTHMS ARE REGULATED BY ESTROGEN SIGNALING AND ARE THERAPEUTIC TARGETS TO TREAT OBESITY AND PREDIABETES IN POSTMENOPAUSAL WOMEN. IN AIM 1, EXPERIMENTS WILL ELUCIDATE THE MOLECULAR MECHANISMS BY WHICH ESTRADIOL PROTECTS DAILY METABOLIC RHYTHMS FROM DISRUPTION BY HIGH-FAT FEEDING IN FEMALE MICE. THESE MECHANISMS WILL BE STUDIED USING GLOBAL ESTROGEN RECEPTOR (ER) KNOCKOUT MICE AND BY TARGETING ER EXPRESSION IN HEPATOCYTES. THEN WE WILL DETERMINE WHETHER TIME-RESTRICTED FEEDING INHIBITS DIET-INDUCED OBESITY, INSULIN RESISTANCE, AND GLUCOSE INTOLERANCE IN FEMALE ER KNOCKOUT MICE. IN AIM 2, EXPERIMENTS WILL TEST THE HYPOTHESIS THAT TIME-RESTRICTED FEEDING IMPROVES METABOLIC RISK FACTORS IN POSTMENOPAUSAL WOMEN. USING A TWO-ARM RANDOMIZED CONTROLLED CLINICAL TRIAL DESIGN, METABOLICALLY-UNHEALTHY POSTMENOPAUSAL WOMEN WILL BE RANDOMIZED TO EITHER A 16-WEEK TIME-RESTRICTED FEEDING INTERVENTION OR NO INTERVENTION CONTROL AND WE WILL MEASURE METABOLIC AND ANTHROPOMETRIC OUTCOMES AND CIRCADIAN REST-ACTIVITY PATTERNS BY ACTIGRAPHY, WITH CHANGE IN INSULIN SENSITIVITY AND BODY WEIGHT AS PRIMARY OUTCOMES. TOGETHER, THESE EXPERIMENTS WILL ELUCIDATE THE INTERPLAY BETWEEN ESTROGENS, DAILY RHYTHMS, AND INTERVENTIONS THAT TARGET CIRCADIAN RHYTHMS TO ALLEVIATE METABOLIC DYSFUNCTION.