University Of Miami

COOPERATIVE INSTITUTE FOR MARINE AND ATMOSPHERIC STUDIES (CIMAS)- INNOVATIVE SCIENCE, SERVICE AND STEWARDSHIP

COOPERATIVE INSTITUTE FOR MARINE AND ATMOSPHERIC STUDIES (CIMAS): ADMINISTRATIVE RENEWAL

COOPERATIVE INSTITUTE FOR MARINE AND ATMOSPHERIC STUDIES (CIMAS) REVOLUTIONARY REINVENTION

THE FLORIDA NODE ALLIANCE OF THE NATIONAL DRUG ABUSE TREATMENT CLINICAL TRIALS NETWORK

COOPERATIVE INSTITUTE OF MARINE & ATMOSPHERIC RESEARCH.

RECRUITMENT AND RETENTION FOR ALZHEIMER'S DISEASE DIVERSITY GENETIC COHORTS IN THE ADSP (READD-ADSP) - ABSTRACT THE GOAL OF THIS PROPOSAL IS TO CREATE A RESOURCE FOR STUDYING THE GENETIC ETIOLOGY OF ALZHEIMER DISEASE (AD) IN UNDERSTUDIED AND UNDERSERVED POPULATIONS. ALZHEIMER DISEASE (AD) IS THE LEADING CAUSE OF DEMENTIA IN THE ELDERLY AND OCCURS IN ALL ETHNIC AND RACIAL GROUPS. THE MAJORITY OF GENETIC STUDIES FOR AD HAVE BEEN PERFORMED IN NON-HISPANIC WHITES (NHW) OF EUROPEAN ANCESTRY. WHILE RECENT STUDIES HAVE BEGUN EXPANDING INTO OTHER POPULATIONS, THESE POPULATIONS ARE STILL UNDER-REPRESENTED IN AD GENOMICS, PARTICULARLY FOR CASES. A MAJOR BARRIER TO PARTICIPATION HAS BEEN A LACK OF COMMUNITY-SENSITIVE RECRUITMENT APPROACHES THAT OVERCOME HISTORICAL MISTRUST OF RESEARCH PARTICIPATION. GENETIC STUDIES ACROSS POPULATIONS, IN PARTICULAR AFRICAN AMERICANS (AA), HAVE SHOWN DIFFERENCES IN BOTH RISK EFFECT SIZE (E.G., APOE) AND RISK LOCI (E.G., ABCA7). FURTHER EVALUATION SUGGESTS THAT GENETIC ANCESTRY (INDEPENDENTLY OR INTERACTING WITH ENVIRONMENTAL/CULTURAL FACTORS) LIKELY UNDERLIES AT LEAST PART OF THIS HETEROGENEITY. HOWEVER, THESE EFFORTS HAVE BEEN SIGNIFICANTLY UNDERPOWERED TO FULLY CHARACTERIZE GENETIC RISK FACTORS OF AD IN US INDIVIDUALS OF AFRICAN (AF) AND HISPANIC/LATINX (HL) ANCESTRY. FULL CHARACTERIZATION REQUIRES INCLUSION OF ADDITIONAL POPULATIONS OF AFRICAN GENETIC ANCESTRY. TO ADDRESS THIS, WE PROPOSE HERE THE CREATION OF A LARGE GENOMICS RESOURCE FOR THE STUDY OF AD IN AF AND HL ANCESTRY. THIS EFFORT WILL RECRUIT, ASSESS, SAMPLE, AND GENOTYPE 13,000 INDIVIDUALS OF DIVERSE RACE/ETHNICITY, INCLUDING 5,000 FROM AFRICA, 4,000 AA, AND 4,000 HL. CLINICAL, PHENOTYPIC, AND GENETIC DATA WILL BE HARMONIZED TO OTHER EXISTING AD GENOMICS EFFORTS (SUCH AS THE ALZHEIMER DISEASE GENETICS CONSORTIUM AND THE ALZHEIMER DISEASE SEQUENCING PROJECT; ADSP). FURTHERMORE, WE INCLUDE TWO HYPOTHESIS-BASED PROJECTS TO DEMONSTRATE THE UTILITY AND VALUE OF THIS RESOURCE AND BEGIN UNDERSTANDING THE GENETIC ETIOLOGY OF AA AND HL POPULATIONS. BROADLY SPEAKING, PROJECT 1 TESTS GENOMIC AND PHENOTYPIC HYPOTHESES WITHIN COHORTS, WHILE PROJECT 2 TESTS ANCESTRY-BASED HYPOTHESES ACROSS POPULATIONS. THESE PROJECTS MAKE EXTENSIVE USE OF THE DATA GENERATED AS PART OF THIS RESOURCE, AS WELL AS TAKING ADVANTAGE OF EXISTING DATA FROM THE ADSP FOLLOW-UP STUDY (ADSP-FUS). THROUGH THE ADSP-FUS AND RELATED STUDIES WE WILL ACCESS EXISTING GENOMIC CASE AND CONTROL DATA FROM 13,100 AFRICAN ANCESTRY INDIVIDUALS, 15,900 HL INDIVIDUALS, AND AN ADDITIONAL 51,000 NON-HISPANIC WHITES. THESE STUDIES, TOGETHER WITH THE FOCUSED RESOURCE BEING GENERATED HERE, REPRESENT A POWERFUL APPROACH TO UNDERSTANDING THE TOTALITY OF AD RISK, WITH NEW LOCI AND THE MAPPING MODIFIER LOCI THAT ALTER EFFECT SIZES. THESE STUDIES WILL HELP ILLUMINATE THE PAN-POPULATION GENETIC ARCHITECTURE OF AD AND PROVIDE THE BASIS FOR IDENTIFYING DRUGGABLE TARGETS. USING ANCESTRAL POPULATIONS, SUCH THOSE FROM AFRICA, TO STUDY RISK MODIFIERS IS CENTRAL TO DISSECTING RISK NOT ONLY IN THOSE POPULATIONS BUT ALSO AMONG AA AND CARIBBEAN HISPANICS (CHI), BOTH WITH SIGNIFICANT ADMIXTURE. THIS RESOURCE WILL ENABLE IMPROVED DISEASE PREDICTION, PREVENTION, DIAGNOSIS, AND TREATMENT THROUGH PRECISION MEDICINE, NOT ONLY IN IN AA, AFRICANS, AND OTHER AFRICAN ADMIXED POPULATIONS, BUT ALL INDIVIDUALS WITH AD.

WHOLE GENOME SEQUENCING IN ETHNICALLY DIVERSE COHORTS FOR THE ADSP FOLLOW-UP STUDY (FUS)

FLORIDA NODE OF THE DRUG ABUSE CLINICAL TRIALS NETWORK

UNIVERSITY OF MIAMI DEVELOPMENTAL CENTER FOR AIDS RESEARCH (D-CFAR)

COOPERATIVE INSTITUTE FOR MARINE AND ATMOSPHERIC STUDIES (CIMAS) INNOVATIVE SCIENCE, SERVICE AND STEWARDSHIP PI: BENJAMIN PAUL KIRTMAN, UNIVERSITY OF MIAMI CIMAS PROPOSED BUDGET: $310,000,000 PROPOSED BUDGET PERIOD: OCTOBER 1, 2025 SEPTEMBER 30, 2030 THE COOPERATIVE INSTITUTE FOR MARINE AND ATMOSPHERIC STUDIES (CIMAS) IS LOCATED AT THE ROSENSTIEL SCHOOL OF MARINE AND ATMOSPHERIC SCIENCE (RSMAS). SINCE ITS ESTABLISHMENT IN 1977, CIMAS HAS SERVED AS A MECHANISM TO BRING THE RESEARCH RESOURCES OF THE UNIVERSITY OF MIAMI TOGETHER WITH THOSE OF NOAA TO FOSTER EXCELLENCE IN RESEARCH AND EDUCATION ABOUT THE EARTH'S OCEANS, ATMOSPHERE AND MARINE ECOSYSTEMS. OUR RESEARCH ON WEATHER, CLIMATE, AND MARINE ECOSYSTEMS; THE DEVELOPMENT, QUANTITATIVE ASSESSMENT AND MAINTENANCE OF OBSERVING SYSTEMS; AND MODEL DEVELOPMENT AND HYPOTHESIS TESTING IS USED FOR MANY CRITICAL APPLICATIONS. WE CREATE IMPROVED FORECASTS OF SEVERE WEATHER AND CLIMATE AND INVESTIGATE HOW WEATHER AND CLIMATE VARIABILITY AFFECT THE MANAGEMENT OF MARINE ECOSYSTEMS, FISH STOCK ASSESSMENTS AND COASTAL RESILIENCE. CIMAS RESEARCH HAS A REGIONAL AND LOCAL FOCUS IN THE CONTEXT OF GLOBAL WEATHER AND CLIMATE, INCLUDING COASTAL RESILIENCE AND THE MANAGEMENT OF NATURAL MARINE RESOURCES IN THE SOUTHEAST US, GULF OF MEXICO, CARIBBEAN AND THE SOUTH ATLANTIC. THE SCIENTIFIC AND TECHNOLOGICAL EXPERTISE PROVIDED BY THE CIMAS CONSORTIUM OF PARTNERS (CARICOOS, FAU, FIT, FIU, FSU, NOVA, UF, USF, AND UVI)1 IS A CRITICAL COMPONENT OF SCIENTIFIC AND TECHNOLOGICAL EXPERTISE FOR OUR REGIONAL/LOCAL FOCUS, AND TWO OF OUR CONSORTIUM PARTNERS (FIU AND UVI) ARE MINORITY SERVING INSTITUTIONS (MSIS). THE PROPOSED COOPERATIVE INSTITUTE (CI) WILL BUILD ON THE HIGHLY SUCCESSFUL RESEARCH AND INFRASTRUCTURE ACCOMPLISHMENTS FROM THE PREDECESSOR CI, AND WILL PROVIDE INNOVATIVE SCIENCE, SERVICE AND STEWARDSHIP ALIGNING WITH NOAAS MISSION IN SEVERAL IMPORTANT WAYS. WE HAVE FOUR RESEARCH THEMES: (I) TROPICAL WEATHER OBSERVATIONS, ANALYSIS AND PREDICTION; (II) OCEAN AND CLIMATE OBSERVATIONS, ANALYSIS AND PREDICTION; (III) ECOSYSTEM OBSERVATIONS, MODELING, FORECASTING AND MANAGEMENT; AND (IV) PROTECTION AND RESTORATION OF MARINE RESOURCES. WE WILL CONTINUE TO ACCELERATE SCIENTIFIC INNOVATION UNDER EACH OF THESE THEMES. FOR EXAMPLE, TO IMPROVE HURRICANE INTENSITY FORECASTS, WE HAVE SUCCESSFULLY IMPLEMENTED MULTIPLE MOVING HIGH-RESOLUTION NESTS SIMULTANEOUSLY CAPTURING AN ARRAY OF TROPICAL SYSTEMS IN THE UNIFIED FORECAST SYSTEM (UFS), QUANTITATIVELY ASSESSING THE UTILITY OF VARIOUS IN SITU OCEAN AND ATMOSPHERE OBSERVATIONS AND INCLUDING MACHINE LEARNING TECHNIQUES. THE PLANNED MACHINE LEARNING ACTIVITIES ARE A HIGH-PROFILE EXAMPLE OF HOW THE PROPOSED CI LEVERAGES THE NEWLY ESTABLISHED UNIVERSITY OF MIAMI INSTITUTE FOR DATA SCIENCE AND COMPUTING (IDSC) AND THE HIGH-PERFORMANCE COMPUTING CAPABILITIES HOUSED THEREIN. WE WILL CONTINUE TO INNOVATE IN OUR OCEAN OBSERVATIONS COLLABORATION WITH NOAA IN THE STEWARDSHIP OF THE GLOBAL DRIFTER PROGRAM, THE ARGO FLOATS, THE SHIP OF OPPORTUNITY PROGRAM, THE WESTERN BOUNDARY TIME SERIES OBSERVATIONS, AND PIRATA, TO NAME JUST A FEW. WE PROPOSE INNOVATIVE ANALYSES AND MODEL EXPERIMENTS TO UNDERSTAND THE ROLE OF OCEAN CIRCULATION, INCLUDING THE ATLANTIC MERIDIONAL OVERTURNING CIRCULATION, IN COASTAL FLOOD RISK FROM DAYS TO DECADES. THE PROPOSED CI WILL INNOVATE IN FISH STOCK ASSESSMENT THROUGH GENETIC TECHNOLOGY, FOR INSTANCE, IN CLOSE-KIN MARK-RECAPTURE TO STUDY THE RELATEDNESS OF ADULT AND OFFSPRINGS PRODUCTS IN FISH POPULATIONS. WE WILL CONTINUE TO DEVELOP INNOVATIVE APPROACHES TO THE QUANTIFICATION OF UNCERTAINTIES IN STOCK ASSESSMENTS. WE ARE DEVELOPING ECOSYSTEM MODELS THAT FOCUS ON ECONOMICALLY IMPORTANT FISHES AND INCORPORATE BEST AVAILABLE SCIENCE (E.G., STOCK ASSESSMENT OUTPUTS). LEVERAGING THE NEW EXPERIMENTAL REEF LABORATORY AND THE RECENTLY ESTABLISHED SOUTHEAST FLORIDA CORAL REEF RESTORATION HUB AT THE ROSENSTIEL SCHOOL, WE WILL STUDY GENOTYPIC RESILIENCE IN CORALS

THE ORIGINS OF ALZHEIMER DISEASE IN AFRICAN AMERICANS - ABSTRACT THE GOAL OF THIS PROPOSAL IS TO ADVANCE OUR UNDERSTANDING OF THE GENETIC ETIOLOGY OF ALZHEIMER DISEASE (AD) RISK IN UNDERSTUDIED AND UNDERSERVED POPULATIONS. AD IS THE LEADING CAUSE OF DEMENTIA IN THE ELDERLY AND OCCURS IN ALL ETHNIC AND RACIAL GROUPS, BUT MOST GENETIC STUDIES FOR AD HAVE BEEN PERFORMED IN NON-HISPANIC WHITES (NHW) OF EUROPEAN ANCESTRY. THIS IS PROBLEMATIC, AS MUCH SMALLER STUDIES IN AFRICAN AMERICANS (AA), WHO HAVE A HIGHER PREVALENCE OF AD COMPARED TO NHW, HAVE ALREADY REVEALED DIFFERENCES IN RISK EFFECT SIZES IN KNOWN LOCI (E.G., APOE; ABCA7), INDICATING MULTIPLE UNIQUE PATTERNS OF RISK. GENETIC ANCESTRY (INCLUDING VARIABILITY IN ALLELE RISK FREQUENCIES AND POPULATION SPECIFIC VARIANTS MODIFYING KNOWN AND NOVEL RISK LOCI), IN ADDITION TO ENVIRONMENTAL/CULTURAL FACTORS AND THEIR INTERACTIONS WITH GENETIC RISK, LIKELY UNDERLIES PART OF THIS HETEROGENEITY. WITH ONLY A SMALL NUMBER OF THE WHOLE GENOME SEQUENCES IN THE ALZHEIMER’S DISEASE SEQUENCING PROJECT (ADSP) COMING FROM AA, INCREASED SAMPLE SIZES AND MULTIPLE STUDY DESIGNS ARE NEEDED TO ELUCIDATE RISK IN DIVERSE ANCESTRAL POPULATIONS. FAMILY STUDIES PROVIDE A POWERFUL COMPLEMENTARY DESIGN TO CASE- CONTROL STUDIES THAT CAN ENHANCE RISK PREDICTION AND THE DETECTION OF NOVEL RARE RISK VARIANTS. FILLING THESE CRITICAL GAPS USING GENETIC TOOLS WILL ENHANCE OUR UNDERSTANDING OF AD RISK AND PROVIDE THE BASIS FOR IDENTIFYING PREVENTION STRATEGIES AND DRUGGABLE TARGETS. INCLUDING ANCESTRAL POPULATIONS FROM AFRICA IN PARTICULAR A UNIQUE COHORT OF MULTIPLEX AFRICAN AD FAMILIES ENABLES DISSECTING RISK NOT ONLY IN AFRICAN POPULATIONS BUT ALSO AMONG ALL POPULATIONS WITH AF ANCESTRY. OUR EFFORTS WILL ALLOW FOR IMPROVED DISEASE PREDICTION, PREVENTION, DIAGNOSIS, AND TREATMENT THROUGH PRECISION MEDICINE, IN AA, AFRICAN, AND OTHER AFRICAN ADMIXED POPULATIONS.

UNIVERSITY OF MIAMI APPLICATION UNDER HIGHER EDUCATION EMERGENCY RELIEF FUND FORMULA GRANTS AUTHORIZED BY SECTION 18004(A)(1) OF THE CORONAVIRUS AID, RELIEF, AND ECONOMIC SECURITY (CARES) ACT

ADDITIONAL SEQUENCING FOR THE ALZHEIMER'S DISEASE SEQUENCING PROJECT (ADSP)

THE SYLVESTER CANCER CENTER SUPPORT GRANT

ALIAS PHASE LLL TRIAL ALBUMIN IN ACUTE ISCHEMIC STROKE

ADDITIONAL SEQUENCING FOR THE ALZHEIMER DISEASE SEQUENCING PROJECT (ADSP) THE FOLLOW-UP STUDY (FUS), THE DIVERSE POPULATION INITIATIVE - ABSTRACT THE ALZHEIMER’S DISEASE SEQUENCING PROJECT (ADSP) IS A NATIONAL SEQUENCING INITIATIVE FOCUSED ON IDENTIFYING GENETIC RISK FACTORS FOR AD. THE PROJECT’S DISCOVERY PHASE INCLUDES WHOLE EXOME SEQUENCING (WES) OF 10,061 UNRELATED NON-WHITE HISPANIC INDIVIDUALS OF EUROPEAN ANCESTRY (NHW-EA) CASES (N=5,096) AND CONTROLS (N=4,965), AND WHOLE GENOME SEQUENCING (WGS) OF 584 NHW AND HISPANIC/LATINO (HL) FAMILIAL SAMPLES. THE 'DISCOVERY EXTENSION PHASE' OF THE PROJECT ADDED WGS ON ~430 ADDITIONAL FAMILIAL SAMPLES. THE ADSP FOLLOW- UP STUDY 1.0 (ADSP-FUS 1.0) PHASE FOCUSED ON EXAMINING CANDIDATE VARIANTS FROM THE DISCOVERY PHASE, AND IDENTIFICATION OF NOVEL VARIANTS THROUGH COMBINED ANALYSIS OF DIVERSE DATASETS, IS ONGOING. ITS AIM IS TO SEQUENCE EXISTING COHORTS WITH UNRELATED AD CASES THAT 'ENCOMPASS THE RICHEST POSSIBLE ETHNIC DIVERSITY' AS WELL AS HIGHLY VALUABLE SET OF AUTOPSY CONFIRMED CASES AND CONTROLS. IN TOTAL WE HAVE ALREADY INCLUDED IN FUS OVER 50,000 SAMPLES FOR SEQUENCING INCLUDING >4,700 AUTOPSY CONFIRMED CASES AND CONTROLS, >9,400 HL ANCESTRY CASES AND CONTROLS AND > 8,300 AFRICAN ANCESTRY (AA) CASES AND CONTROLS. IN THIS ADSP-FUS 2.0 APPLICATION, WHICH FOCUSES ON THE PAR-21-212 GOAL TO INCREASE DIVERSITY COHORTS IN THE ADSP WITH WGS, WE ARE PROPOSING SEQUENCING, QC AND PHENOTYPE HARMONIZATION OF AN ADDITIONAL ~16,000 INDIVIDUALS (~12,000 HL ANCESTRY, 500 AUTOPSIED NHW-EA, ~3,400 AA AND ~170 ASIAN ANCESTRY INDIVIDUALS) THAT WILL BOTH INCREASE OUR POWER TO FIND EFFECTS AND WILL ALSO ENHANCE OUR ABILITY TO FIND GENETIC EFFECTS IN UNDERSERVED GROUPS. ADDITIONALLY, THESE DATASETS WILL BECOME AN INVALUABLE RESOURCE FOR THE AD RESEARCH COMMUNITY AT-LARGE.

MARITIME SENSING RESEARCH OF THE ENVIRONMENT, FEATURES, OBJECTS AND ACTIVITIES (EFOA)

MIAMI CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE

UNIVERSITY OF MIAMI APPLICATION UNDER CARES ACT ED-GRANTS-041020-03

WOMEN HIV COHORT STUDY: HIV INFECTION AND TREATMENT AMONG WOMEN OF REPRODUCTIVE AGE

MACS/WIHS -CCS

MIAMI CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE

CLINICAL RESEARCH IN ALS & RELATED DISORDERS FOR THERAPEUTIC DEVELOPMENT (CREATE)

PURPOSE: UNIVERSITY OF MIAMI AND PARTNERS WILL IMPLEMENT AND SCALE-UP STRATEGIES TO INCREASE THE HEAT TOLERANCE OF RESTORED CORALS, BY FOCUSING ON CORALS THAT SURVIVED THE SUMMER 2023 HEATING EVENT AND CONDITIONING EARLY LIFE STAGES OF CORALS TO PREPARE THEM FOR WARMER TEMPERATURES. THE PROJECT WILL USE ITS PARTNER NETWORK TO RESTORE TENS OF THOUSANDS OF CORALS AT KEY SITES IN SOUTH FLORIDA AND THE FLORIDA KEYS, INCLUDING MISSION: ICONIC REEFS LOCATIONS. PARTNERS WILL ALSO PROVIDE BILINGUAL EDUCATION AND COMMUNITY SCIENCE OPPORTUNITIES IN SEVEN SOUTH FLORIDA COUNTIES FOCUSED ON HOW CORAL RESTORATION CONTRIBUTES TO CREATING HEALTHY REEFS THAT ARE PART OF FLORIDAS CULTURAL IDENTITY.

MARINE TECHNOLOGY AND LIFE SCIENCES SEAWATER (MTLSS) RESEARCH BUILDING

NEUROSCIENCE AND HEALTH ANNEX ON THE CORAL GABLES CAMPUS AT THE UNIVERSITY OF MIA

MULTICULTURAL COMMUNITY DEMENTIA SCREENING - ABSTRACT COMMUNITY DETECTION OF MILD COGNITIVE IMPAIRMENT (MCI) AND EARLY ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (ADRD) MAY BE LIMITED DUE TO THE LACK OF SCREENING TESTS CHARACTERIZING THE EARLIEST SIGNS OF IMPAIRMENT AND CORRESPONDENCE TO BIOMARKERS AS DEFINED BY THE AMYLOID-TAU-NEURONAL INJURY/NEURODEGENERATION (ATN) FRAMEWORK. ACCUMULATING EVIDENCE SUGGESTS THAT NEURONAL INJURY AND NEURODEGENERATION BEGINS DECADES BEFORE CLINICALLY EVIDENT COGNITIVE DECLINE. THUS, BY THE TIME ADRD IS CLINICALLY DIAGNOSED, IRREVERSIBLE NEURONAL DAMAGE HAS ALREADY OCCURRED. THIS HAS THE POTENTIAL OF LESSENING THE THERAPEUTIC BENEFITS OF DISEASE MODIFYING MEDICATIONS. IN R01AG071514, WE ARE EXAMINING NOVEL WAYS TO OVERCOME MAJOR CHALLENGES TO IMPROVE THE DETECTION OF MCI AND EARLY AD BY EMPHASIZING DEEP PHENOTYPING TO ENHANCE THE RESEARCH VALUE OF DATA AND BIOSPECIMENS CONTRIBUTED BY INDIVIDUAL PARTICIPANTS AND CROSS VALIDATE SCREENING EFFORTS LINKING PREVALENCE DATA TO BRAIN BIOMARKERS, LEVERAGING THE ATN RESEARCH FRAMEWORK TO ANCHOR THIS WORK. HOWEVER MOST CURRENT ATN BIOMARKERS ARE EXPANSIVE, INVASIVE AND NOT READILY ACCESSIBLE FOR CLINICAL CARE. TO ADDRESS THIS CRITICAL NEED, WE AIM TO DEVELOP NON-INVASIVE, EASILY ACQUIRED BIOMARKERS CONDUCIVE FOR THE EARLY DETECTION OF ADRD. THE RETINA AND BRAIN SHARE SIMILAR ANATOMIC AND PHYSIOLOGIC FEATURES, BUT, UNLIKE THE BRAIN, THE RETINA IS EASILY ACCESSIBLE FOR IMAGING. THE RETINA AND BRAIN SHARE SIMILAR ANATOMIC AND PHYSIOLOGIC FEATURES, BUT, UNLIKE THE BRAIN, THE RETINA IS EASILY ACCESSIBLE FOR IMAGING. RECENT STUDIES SHOWED THAT AMYLOID DEPOSITION OCCURS NOT ONLY IN THE BRAIN BUT ALSO IN THE RETINA, GREATER IN PATIENTS WITH AD COMPARED TO NORMAL HEALTHY CONTROLS. FOR THIS ADMINISTRATIVE SUPPLEMENT, WE TEAMED WITH DRS. JIANHUA WANG AND HONG JIANG, EXPERTS IN OPHTHALMIC IMAGING OF THE ADVANCED OPHTHALMIC IMAGING LAB AT THE BASCOM PALMER EYE INSTITUTE. CONFOCAL SCANNING LASER OPHTHALMOSCOPY (CSLO) WILL BE USED ALONG WITH OCT/OCTA TO IMAGE THE RETINA BEFORE AND AFTER ORAL CURCUMIN INTAKE. THIS PROPOSED WORK TAKES ADVANTAGE OF WELL-CHARACTERIZED AND DEEPLY PHENOTYPED COHORT FROM OUR FUNDED R01 AG071514. WE PROPOSE 3 SPECIFIC AIMS: (1) DEVELOP AND VALIDATE RETINAL AMYLOID IMAGING; (2) DETERMINE RELATIONSHIP OF RETINAL AMYLOID IMAGING TO BRAIN AMYLOID IMAGING; AND (3) TEST WHETHER BASELINE RETINAL AMYLOID IMAGING CAN PREDICT TRANSITION. AT THE CONCLUSION OF OUR STUDY, WE WILL COLLECT SUFFICIENT PRELIMINARY DATA FOR FUTURE R01 PROPOSAL AND THE COST-EFFECTIVE AND NONINVASIVE METHOD FOR IN VIVO IMAGING OF AMYLOID DEPOSITION IN THE RETINA WILL BE FULLY DEVELOPED TO BE USED FOR SCREENING AND CLINICAL TRIALS.

A PHASE 2B MULTICENTER STUDY OF THE COMPARATIVE EFFICACY AND SAFETY OF TRANSENDOCARDIAL INJECTION OF MSC IN PATIENTS WITH NONISCHEMIC DILATED CARDIOMYOPATHY

RYAN WHITE TITLE IV WOMEN, INFANTS, CHILDREN, YOUTH AND AFFECTED FAMILY MEMBERS AIDS HEALTHCARE

SLEEP IN NEUROCOGNITIVE AGING AND ALZHEIMERS RESEARCH (SANAR) - LATINOS HAVE UP TO A FOURFOLD RISK OF ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD) COMPARED TO NON- HISPANIC WHITES. FURTHER, ADRD ONSET OCCURS EARLIER IN LATINOS AND IS OFTEN ACCOMPANIED BY VASCULAR RISK FACTORS. CONSISTENT WITH THE NIA ALZHEIMER'S PREVENTION INITIATIVE, WE WILL FOCUS ON TWO VASCULAR RISK FACTORS NEVER STUDIED IN LATINO ADRD PREVENTION STUDIES: OBSTRUCTIVE SLEEP APNEA (OSA) AND NON-DIPPING OF BLOOD PRESSURE (NDBP). OVER THE LAST DECADE, OSA HAS BEEN SHOWN TO INCREASE MORTALITY, STROKE AND VASCULAR DISEASE (E.G. NDBP). OSA IS ALSO LINKED WITH A 26% INCREASE IN COGNITIVE DECLINE OR ADRD. HOWEVER, MOST STUDIES ARE LIMITED BY THE USE OF SELF-REPORTED DATA, MEASURED OSA AT A SINGLE TIME POINT OR STUDIED OLDER ADULTS, WHICH DO NOT PRECLUDE THE POSSIBILITY OF REVERSE CAUSATION. OUR PUBLISHED DATA FROM THE HISPANIC COMMUNITY HEALTH STUDY/STUDY OF LATINOS (HCHS/SOL; N˜16,000 AT VISIT-1), SHOWS THAT OSA IS ASSOCIATED WITH WORSE COGNITIVE FUNCTION, ESPECIALLY IN FEMALES<55 YEARS. OF INTEREST, OSA HAD STRONG ASSOCIATIONS WITH PREVALENT (OR 2.1) AND INCIDENT HYPERTENSION (HR 1.5). IN CLINICAL STUDIES, NDBP WAS MORE COMMON THAN CLINIC HYPERTENSION AND HAD STRONGER ASSOCIATIONS WITH STROKE AND COGNITION; YET THERE IS NO INFORMATION IN THE HIGH-RISK LATINO POPULATION. THERE IS AN IMPERATIVE TO EXAMINE WHETHER OSA IN MIDLIFE IS CAUSAL TO LATE LIFE COGNITIVE DECLINE IN LATINOS, THE LARGEST U.S. MINORITY GROUP; FINDINGS OF IMPORTANT

RYAN WHITE TITLE IV WOMEN, INFANTS, CHILDREN, YOUTH AND AFFECTED FAMILY MEMBERS AIDS HEALTHCARE

HIV TESTING AND COUNSELING IN STD CLINICS: AN ADAPTATION OF CTN 0032

STROKE INCIDENCE AND RISK FACTORS IN A TRI-ETHNIC REGION

NCMHD CENTER FOR CULTURALLY-TAILORED HISPANIC HEALTH DISPARITIES RESEARCH

MIAMI CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE - PROJECT SUMMARY LOCATED IN SOUTH FLORIDA (SOFL), THE GOALS OF UNIVERSITY OF MIAMI’S CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE (CTSI) ARE TO IMPROVE THE HEALTH OF OUR COMMUNITY, ADDRESS HEALTH DISPARITIES, AND PROMOTE HEALTH EQUITY. THE CTSI ACCOMPLISHES THESE GOALS BY CATALYZING THE DEVELOPMENT, DEMONSTRATION, AND DISSEMINATION OF SCIENTIFIC AND OPERATIONAL INNOVATIONS THAT IMPROVE THE EFFICIENCY, EFFECTIVENESS, AND QUALITY OF CLINICAL AND TRANSLATIONAL RESEARCH. THIS IS DONE THROUGH BIDIRECTIONAL ENGAGEMENT OF DIVERSE STAKEHOLDERS, INCLUDING PATIENT ADVOCATES AND COMMUNITY COLLABORATORS, TO HELP IDENTIFY GAPS, CHALLENGES, AND CHOKEPOINTS IN THE TRANSLATIONAL RESEARCH PROCESS. IN RESPONSE, THE CTSI DEVELOPS AND TEST STAKEHOLDER-DRIVEN RESOURCES, TOOLS, AND INTERVENTIONS ULTIMATELY PROMOTING THE ADOPTION AND INTEGRATION OF THOSE THAT ARE DEMONSTRATED TO BE SUCCESSFUL, THROUGH DISSEMINATION AND IMPLEMENTATION EFFORTS. THIS WORK IS SHAPED BY THREE PRIMARY FACTORS: 1) SOFL IS CHARACTERIZED BY COMPLEX AND MULTIFACETED DIVERSITY WITH RESPECT TO RACE, ETHNICITY, LANGUAGE, IMMIGRANT STATUS, SOCIOECONOMIC DISADVANTAGE, AND STIGMATIZATION. THIS COMPLEXITY ALLOWS CTSI HUB INVESTIGATORS TO EXPLORE RESEARCH QUESTIONS DIFFICULT TO CONCEPTUALIZE AND EVALUATE ELSEWHERE; 2) CTSI PRIORITIZES DIVERSITY, EQUITY, INCLUSION, AND ACCESSIBILITY (DEIA) IN ITS SCIENTIFIC WORKFORCE AND RESEARCH PARTICIPANTS; AND 3) CTSI HAS A STRONG, SUCCESSFUL AND SUSTAINED RECORD OF AUTHENTIC COMMUNITY AND STAKEHOLDER ENGAGEMENT WHICH FACILITATES MULTIDISCIPLINARY RESEARCH THAT CAN SUCCESSFULLY OVERCOME THE TRANSLATIONAL PITFALL OF REPLICATING EXISTING INEQUITIES. THE CTSI’S FOCUS, SCOPE OF ACTIVITIES AND AIMS ARE GROUNDED IN AN UNDERSTANDING OF THESE FACTORS AND THEIR COMPLEX INTERPLAY WITH ONE ANOTHER. TOGETHER WITH DIVERSE STAKEHOLDERS, THE CTSI WILL: 1) SUPPORT THE DEVELOPMENT AND DISSEMINATION OF INNOVATIVE RESOURCES AND SERVICES TO INCREASE THE QUALITY, EFFICIENCY, AND EFFECTIVENESS OF RESEARCH ACROSS THE ENTIRE TRANSLATIONAL RESEARCH SPECTRUM; 2) PROMOTE RESEARCH COLLABORATIONS AIMED AT FACILITATING AND ACCELERATING RESEARCH TO IMPROVE COMMUNITY HEALTH, ADDRESS HEALTH DISPARITIES, AND PROMOTE HEALTH EQUITY; 3) DEVELOP INNOVATIVE TRAINING PROGRAMS TO SUPPORT A TEAM SCIENCE-ORIENTED CTS WORKFORCE, FROM TRANSLATIONAL SCIENTISTS TO CLINICAL RESEARCH PROFESSIONALS AND KEY STAKEHOLDERS; AND 4) SUPPORT CTS RESEARCH RESPONSIVE TO THESE OVERARCHING GOALS. THROUGH THESE EFFORTS, THE CTSI EXPECTS TO ACHIEVE SIGNIFICANT IMPROVEMENTS IN THE QUALITY, SAFETY, EFFICIENCY, EFFECTIVENESS, AND INFORMATIVENESS OF ITS CLINICAL AND TRANSLATIONAL ENTERPRISE. THE CTSI WILL THEN BROADLY DISSEMINATE ITS ACQUIRED KNOWLEDGE REGIONALLY AND NATIONALLY TO MAXIMIZE IMPACT AND OPPORTUNITY, BOTH NOW AND IN THE FUTURE. BY DOING SO, THE CTSI ACCELERATES BRINGING THE BENEFITS OF TRANSLATIONAL SCIENCE (MORE EFFECTIVE TREATMENTS, DRUGS, DEVICES, BEHAVIORAL INTERVENTIONS, AND MEDICAL PROCEDURES) TO ALL PEOPLE, REGARDLESS OF THEIR IDENTITY OR ACCESS. PHS 398/2590 (REV. 06/09) PAGE CONTINUATION FORMAT PAGE

GENOMIC CHARACTERIZATION OF ALZHEIMER DISEASE RISK IN ADMIXED POPULATIONS WITH NATIVE AMERICAN AND SOUTHERN EUROPEAN GENETIC ANCESTRY - ABSTRACT ALZHEIMER DISEASE (AD) IS THE LEADING CAUSE OF DEMENTIA IN OLDER ADULTS AND OCCURS IN ALL ETHNIC AND RACIAL GROUPS. GENETIC STUDIES OF AD HAVE MOSTLY BEEN PERFORMED IN NON-HISPANIC WHITES (NHW) OF NORTHERN EUROPEAN (NE) ANCESTRY. ONLY RECENTLY HAVE EFFORTS IN AD STARTED TO EXPAND INTO OTHER POPULATIONS, SUCH AS AFRICAN-AMERICANS (AA) AND HISPANICS (HI), AND HAVE A READY DEMONSTRATED DIFFERENCES IN BOTH RISK EFFECT SIZE (E.G., APOE IN AA AND HI) AND RISK LOCI (E.G., ABCA7 IN AA). FURTHER EVALUATION DEMONSTRATES THAT GENETIC ANCESTRY (AS OPPOSED TO ENVIRONMENTAL/CULTURAL FACTORS) LIKELY UNDERLIE AT LEAST PART OF THIS HETEROGENEITY. INDIVIDUALS WITH THE AMERINDIAN (AI) ANCESTRY REMAIN ONE OF THE MOST UNDERREPRESENTED GROUPS IN AD. IMPORTANTLY, THE NHW DATASETS DID NOT DIFFERENTIATE AMONG THE EUROPEANS (EU), WHEREAS RECENT INVESTIGATIONS SHOWED THAT THESE PAN-EUROPEAN RESULTS ONLY PARTIALLY OVERLAP WITH THE FINDINGS FROM POPULATIONS FROM THE IBERIAN PENINSULA (IP) WITH SOUTHERN EUROPEAN (SE) ANCESTRY. CARIBBEAN AND SOUTH AMERICAN HISPANIC POPULATIONS ARE ADMIXED WITH BOTH AI AND SE, THUS MAKING THEIR STUDY A CRITICAL SCIENTIFIC OBJECTIVE. OUR PROPOSED STUDY ENABLES TESTING THE GENERALIZATION OF FINDINGS FROM NHW TO THESE OTHER ANCESTRIES, AS WELL AS IDENTIFY AD RISK/PROTECTIVE FACTORS CORRELATED SPECIFICALLY WITH AI AND SE ANCESTRY. OUR RESULTS WILL ALLOW FOR A BETTER AND MORE COMPLETE UNDERSTANDING OF THE GENETIC ARCHITECTURE OF AD WHICH WILL HELP IMPROVE DISEASE PREDICTION, PREVENTION, DIAGNOSIS, AND TREATMENT IN AI, ADMIXED HISPANIC POPULATIONS, AND BEYOND. TO ACCOMPLISH THESE GOALS, WE PROPOSE THREE AIMS. IN AIM 1 WE WILL CHARACTERIZE KNOWN AD LOCI IN ADMIXED POPULATIONS WITH AI AND SE ANCESTRY. THIS INCLUDES EXPANDING COLLECTIONS, GENERALIZING KNOWN AD LOCI TO AI/SE POPULATIONS, AND VARIANT DISCOVERY THROUGH ADMIXTURE MAPPING AND FINE-MAPPING. IN AIM 2 WE WILL EXTEND OUR PUERTO RICAN DATASET BY EXPANDING PR MULTIPLEX FAMILIES. THIS WILL ALLOW MORE POWERFUL LINKAGE ANALYSES, LONGITUDINAL NEUROCOGNITIVE AND BIOMARKER DATA, AND THE INITIATION OF A BRAIN DONATION PROGRAM. FINALLY, IN AIM 3 WE WILL PERFORM FUNCTIONAL FOLLOW-UP OF VARIANTS USING BIOINFORMATICS APPROACHES, ASSESSMENT OF AD BIOMARKERS, AND ASSESSMENT OF CELLULAR FUNCTION USING IPSC.

IMMUNOMODULATORY AND REGENERATIVE EFFECTS OF MESENCHYMAL STEM CELLS ON ALLOGRAFTS

YELLOW FEVER, RDNA (EP+IL-12) AND RAD35 AS VECTORS FOR AIDS VACCINE DEVELOPMENT

PRE-SYMPTOMATIC FAMILIAL ALS (PRE-FALS) STUDY: FROM PRODROME AND BIOMARKERS TO ALS/FTD PREVENTION - PROJECT SUMMARY AMYOTROPHIC LATERAL SCLEROSIS (ALS) REMAINS A FATAL NEURODEGENERATIVE DISORDER, IN PART BECAUSE DIAGNOSIS IS DELAYED AND TREATMENT IS INITIATED LATE IN DISEASE COURSE. THERAPEUTIC SUCCESS IS MOST LIKELY WHEN TREATMENT IS INITIATED EARLY, IDEALLY WHILE STILL PRE-SYMPTOMATIC. UNAFFECTED CARRIERS OF PATHOGENIC VARIANTS ASSOCIATED WITH EITHER ALS OR BOTH ALS AND FRONTOTEMPORAL DEMENTIA (FTD), HEREAFTER COLLECTIVELY REFERRED TO AS ALS/FTD ARE THE ONLY POPULATION CURRENTLY KNOWN TO BE AT SIGNIFICANTLY ELEVATED RISK FOR THESE DISORDERS, AND IN WHOM THE STUDY OF PRE-SYMPTOMATIC DISEASE IS FEASIBLE. PRE-SYMPTOMATIC FAMILIAL ALS (PRE-FALS) IS THE FIRST AND MOST LONGSTANDING NATURAL HISTORY AND BIOMARKER STUDY OF THIS POPULATION. THE OVERARCHING GOALS OF PRE-FALS ARE TO: (A) UNDERSTAND PRE-SYMPTOMATIC ALS/FTD; (B) DISCOVER THE EARLIEST MARKERS OF DISEASE; AND (C) EMPOWER ALS/FTD PREVENTION. THROUGH PRE-FALS WE HAVE DEVELOPED A CONCEPTUAL FRAMEWORK AND PROPOSED A LEXICON FOR DESCRIBING THE PRE-SYMPTOMATIC STAGES OF THESE DISEASES; IDENTIFIED NEUROFILAMENT LIGHT CHAIN AS THE FIRST RISK/SUSCEPTIBILITY BIOMARKER THAT PREDICTS PHENOCONVERSION TO CLINICALLY MANIFEST ALS; DISCOVERED AND DEVELOPED DIAGNOSTIC CRITERIA FOR MILD MOTOR IMPAIRMENT (MMI), A NOVEL CLINICAL SYNDROME AND PRODROMAL CLINICAL MARKER OF DISEASE; AND DESIGNED AND LAUNCHED, IN COLLABORATION WITH AN INDUSTRY PARTNER, THE FIRST-EVER ALS PREVENTION TRIAL (ATLAS) IN A SUBSET OF THE SOD1 POPULATION. PRE-FALS IS ALSO A UNIQUE RESOURCE FOR PRE- SYMPTOMATIC CLINICAL MARKER AND BIOMARKER DISCOVERY, GIVEN THE LONGITUDINALLY COLLECTED DEEP PHENOTYPIC DATA (MOTOR AND COGNITIVE/BEHAVIORAL) AS WELL AS BIOLOGICAL SPECIMENS, BOTH BEFORE AND AFTER PHENOCONVERSION. IN THIS RENEWAL APPLICATION, WE WILL EXPAND UPON OUR PIONEERING WORK THAT LED TO ATLAS, TO PREPARE FOR PREVENTION TRIALS IN OTHER (AND LARGER) POPULATIONS AT GENETIC RISK FOR ALS/FTD, WHICH WE BELIEVE WILL REQUIRE A MULTIMODAL APPROACH. SPECIFICALLY, WE WILL: CHARACTERIZE THE PRODROMAL STAGES OF ALS AND FTD AMONG ALS/FTD- ASSOCIATED PATHOGENIC VARIANT CARRIERS (AIM 1); CHARACTERIZE THE LONGITUDINAL TRAJECTORY (AND VARIABILITY) OF AN ARRAY OF CLINICAL MARKERS AND BIOMARKERS IN THE PRE-SYMPTOMATIC PHASE OF DISEASE, WHICH COMPRISES BOTH CLINICALLY SILENT AND PRODROMAL STAGES (AIM 2); AND IDENTIFY THE SUBGROUP OF INDIVIDUALS, BASED ON THEIR CLINICAL AND BIOMARKER PROFILE, WHO ARE AT GREATEST RISK FOR PROGRESSING TO CLINICALLY MANIFEST DISEASE (ALS OR FTD) WITHIN 5 YEARS (AIM 3). IN TURN, THE RESULTS OF THE WORK OUTLINED IN THIS PROPOSAL WILL FUEL TRANSLATION OF PRODROMAL DISEASE AND BIOMARKER DISCOVERY INTO VIABLE STRATEGIES FOR PREVENTING BOTH ALS AND FTD.

DISSECTING THE GENOMIC ETIOLOGY OF NON-MENDELIAN EARLY-ONSET ALZHEIMER DISEASE AND RELATED PHENOTYPES

ICEBERG DETECTION AND MONITORING IN SUPPORT OF NAVAL OPERATIONS

HARMONIZATION OF ADDITIONAL DATA SETS FOR THE ALZHEIMER'S DISEASE SEQUENCING PROJECT (ADSP) FOLLOW-UP STUDY (FUS)

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH SUPPORTING THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY (DARPA) BIOLOGICAL TECHNOLOGIES OFFICES (BTO) REEFENSE PROGRAM. THIS EFFORT SHALL BE CARRIED OUT GENERALLY AS SET FORTH IN EXHIBIT B, RESEARCH DESCRIPTION DOCUMENT, DATED MAY 25, 2022, AND IN THE RECIPIENTS PROPOSAL TITLED, REEF ENGINEERING TO ENHANCE FUTURE STRUCTURES (REEFS), DATED APRIL 28, 2021, COPIES OF WHICH ARE IN THE POSSESSION OF BOTH PARTIES.

OP EARLY INTERVENTION SVCS W/RESPECT TO HIV DISEASE

UNIFYING GENETICS EPIDEMIOLOGY OF MACULAR DEGENERATION

GENETICS OF PARKINSONISM

STROKE INCIDENCE AND RISK FACTORS IN A TRI-ETHNIC REGION

NATIONAL RESOURCE FOR APLYSIA

A COLLABORATIVE SEARCH FOR NEW GENES FOR NON-SYNDROMIC DEAFNESS

MIAMI CENTER FOR VISION RESEARCH

MIAMI WOMENS INTERAGENCY HIV STUDY WIHS

GENOME STUDIES IN HEREDITARY SPASTIC PARAPLEGIA

CHILD DEVELOPMENT AND MULTIDISCIPLINARY FACILITY

MIAMI HIV/AIDS CLINICAL THERAPEUTIC AND VACCINE TRIAL UNIT

BIOBEHAVIORAL BASES OF CHD RISK AND MANAGEMENT

MITOCHONDRIAL BIOGENESIS IN HEALTH AND DISEASE

HEALTHY START INITIATIVE-ELIMINATING RACIAL/ETHNIC DISPARITIES

REGULATION OF SIGNALING IN THE RETINA BY RGS PROTEINS

MOLECULAR GENETICS OF NON-SYNDROMIC DEAFNESS

CENTER FOR LATINO HEALTH RESEARCH OPPORTUNITIES-CLARO

CSTARS: A SATELLITE DATA RECEPTION AND ANALYSIS FACILITY FOR ENVIRONMENTAL MONITORING IN THE SOUTHEASTERN US, GULF OF MEXICO, CARIBBEAN BASIN AND EQ

IMPROVEMENT OF INTEGRATED HIV CLINICAL-BASED SERVICES

CHARACTERIZING THE GENETIC RISK FOR ALZHEIMER DISEASE IN AFRICAN AND ADMIXED AFRICAN-AMERICAN ANCESTRIES - ABSTRACT AD IS THE LEADING CAUSE OF DEMENTIA IN THE ELDERLY IN ALL ETHNIC AND RACIAL GROUPS, BUT MOST GENETIC STUDIES FOR AD ARE IN NON-HISPANIC WHITES (NHW) OF EUROPEAN ANCESTRY, RESULTING IN A LACK OF GENERALIZABILITY OF FINDINGS ACROSS MORE DIVERSE ANCESTRIES. THIS IS PROBLEMATIC, AS INITIAL STUDIES IN AFRICAN AMERICANS (AA), WHO HAVE A HIGHER PREVALENCE OF AD COMPARED TO NHW, HAVE ALREADY REVEALED DIFFERENCES IN RISK EFFECT SIZES IN KNOWN LOCI (E.G., APOE; ABCA7), INDICATING MULTIPLE UNIQUE PATTERNS OF RISK. THEREFORE, THE ALZHEIMER'S DISEASE SEQUENCING PROJECT (ADSP) AIMS TO ENCOMPASS THE RICHEST POSSIBLE ETHNIC DIVERSITY AND CURRENTLY INCLUDES OVER 55,000 FUNDED SAMPLES FOR WHOLE GENOME SEQUENCING (> 19,000 NHW, >14,000 HL ANCESTRY, AND > 8,000 AFRICAN ANCESTRY CASES AND CONTROLS). THUS, IN THIS ADSP-FUS 2.0 APPLICATION, WHICH FOCUSES ON THE PAR-21-212 GOAL TO INCREASE DIVERSITY COHORTS IN THE ADSP, WE ARE PROPOSING GENERATING WHOLE GENOME SEQUENCING, AD PLASMA BIOMARKERS AND CARDIOVASCULAR DISEASE BIOMARKERS IN AN ADDITIONAL ~9,000 INDIVIDUALS OF AFRICAN ANCESTRY (~5,000 AFRICAN, ~4,000 AFRICAN AMERICAN) ASCERTAINED AS PART OF THE ONGOING “RECRUITMENT AND RETENTION FOR ALZHEIMER'S DISEASE DIVERSITY GENETIC COHORTS IN THE ADSP” (READD-ADSP U19 AG074865). FURTHER, WE WILL ACQUIRE MRI DATA FROM 200 NIGERIAN PARTICIPANTS. WE WILL PERFORM LONGITUDINAL FOLLOW-UP VISITS ON MILD COGNITIVELY IMPAIRED AND COGNITIVELY UNIMPAIRED INDIVIDUALS AFTER ~4 YEARS TO FURTHER EVALUATE CLINICAL AND BIOMARKER LEVEL CHANGES LONGITUDINALLY ASSOCIATED WITH STATUS CONVERSION. THIS INCREASE IN SAMPLE SIZE ENHANCES OUR ABILITY IN THIS PROPOSAL TO DETECT AND ANALYZE RARE GENETIC VARIANTS CONTRIBUTING TO THE RISK AND PROTECTION OF AD IN INDIVIDUALS OF AFRICAN ANCESTRY AND UNDERSTAND UNDERLYING RISK CORRELATED WITH CARDIOVASCULAR DISEASE RISK AND AD PLASMA BIOMARKERS. TAKEN TOGETHER, THIS PROJECT WILL LEVERAGE THE RESOURCES COLLECTED UNDER THE READD-ADSP TO BEGIN TO UNRAVEL THE AD RISK FOR INDIVIDUALS OF AFRICAN ANCESTRY WHILE PROVIDING AN INVALUABLE RESOURCE FOR THE AD RESEARCH COMMUNITY AT-LARGE.

REDUCING DISPARITIES IN DEMENTIA AND VCID OUTCOMES IN A MULTICULTURAL RURAL POPULATION

GENOMIC CHARACTERIZATION OF ALZHEIMER'S DISEASE RISK IN THE PUERTO RICAN POPULATION

RYAN WHITE TITLE IV PROGRAM

STUDY OF TREATMENT AND REPRODUCTIVE OUTCOMES - ONE-FIFTH OF THE 1.1 MILLION INDIVIDUALS LIVING WITH HIV IN THE US ARE WOMEN, AND THERE IS A DISPROPORTIONATE IMPACT ON IN THE SOUTHERN US. REPRODUCTIVE AGE WOMEN WITH HIV ARE HIGHLY AFFECTED BY WORSE HIV, REPRODUCTIVE, AND CHRONIC DISEASES OUTCOMES, LIKELY DUE TO NON-MEDICAL AND BIOLOGICAL FACTORS THAT MANIFEST DIFFERENTLY ACROSS THE REPRODUCTIVE LIFE COURSE. DESPITE EXPERIENCING POOR OUTCOMES AND FACING UNIQUE CHALLENGES, REPRODUCTIVE AGE WOMEN ARE UNDERREPRESENTED IN HIV RESEARCH. TO ADDRESS THIS GAP, STAR BECAME THE LARGEST COHORT OF REPRODUCTIVE AGE WOMEN WITH HIV AND DEMOGRAPHICALLY SIMILAR WOMEN WITHOUT HIV IN THE US SINCE ITS INAUGURAL FUNDING IN 2019, AND NOW SERVES AS A ROBUST PLATFORM TO SUPPORT HIGH IMPACT RESEARCH AND THE DEVELOPMENT OF EARLY-STAGE INVESTIGATORS. IN THIS U19 APPLICATION, WE PROPOSE TO CONTINUE AND EXPAND STAR IN THIS PROGRAM PROJECT APPLICATION TO ADDRESS THE OVERARCHING GOAL OF ADVANCING HIGH PRIORITY SCIENCE IN HIV, REPRODUCTIVE HEALTH, AND CHRONIC DISEASES FOR REPRODUCTIVE AGE WOMEN THROUGH RESEARCH, MENTORING, AND COMMUNITY ENGAGEMENT. THIS PROGRAM PROJECT WILL PROVIDE THE STRUCTURE FOR EXPANDED RECRUITMENT, PARTICIPANT RETENTION, LONGITUDINAL DATA COLLECTION, SCIENTIFIC AND COMMUNITY ENGAGEMENT, AND DEVELOPMENT OF THE NEXT GENERATION OF HIV SCIENTISTS – ALL COMPONENTS NEEDED TO OPTIMALLY ADDRESS SCIENCE FOR THIS POPULATION. THROUGH THE SCIENTIFIC ADMINISTRATIVE CORE (SAC), DATA MANAGEMENT AND ANALYSIS CORE (DMAC), AND COMMUNITY ENGAGEMENT CORE (CEC), COUPLED WITH COHORT-LINKED, SYNERGISTIC RESEARCH PROJECTS (RP1 FOCUSED ON CARDIOVASCULAR HEALTH AND RP2 FOCUSED ON SEXUAL AND REPRODUCTIVE HEALTH), WE PROPOSE TO ADDRESS THE INTERSECTING EFFECTS OF HIV, MEDICAL AND NON-MEDICAL FACTORS, AND REPRODUCTIVE TRANSITIONS ON HEALTH. WE WILL ACCOMPLISH OUR GOALS BY: (AIM 1) EXPANDING THE STAR COHORT AS A PLATFORM FOR HIV SCIENCE FOR REPRODUCTIVE AGE WOMEN; (AIM 2) LEVERAGING THE RESOURCES OF THE STAR CORES TO PROMOTE RIGOROUS PATIENT-CENTERED SCIENCE; AND (AIM 3), TESTING A UNIFYING HYPOTHESIS ON THE INTERSECTING EFFECTS OF HIV AND REPRODUCTIVE TRANSITIONS ON TWO MAJOR HEALTH CHALLENGES – COMORBIDITIES AND COINFECTIONS – VIA INTERLINKED PROJECTS THAT LEVERAGE THE STAR CORES AND UTILIZE A SHARED FRAMEWORK, MEASURES, AND OUTCOMES. THROUGH THE OUTSTANDING COLLABORATIVE TEAM ASSEMBLED DURING THE INAUGURAL FUNDING CYCLE, AND BY EXPANDING BASED ON LESSONS LEARNED, THE COHORT WILL BE RAPIDLY ESTABLISHED, EFFECTIVELY MAINTAINED, AND WILL GENERATE HIGH QUALITY LONGITUDINAL DATA WITH VALIDATED SURVEYS, SPECIMEN PROCEDURES, AND DATA MANAGEMENT TOOLS. THIS STUDY IS THEREFORE POISED TO EFFECTIVELY ENGAGE, ENABLE, AND MENTOR SCIENTISTS IN A VAST RANGE OF SCIENTIFIC AREAS ALIGNED WITH NIH/OAR/ORWH PRIORITIES, AND TO ULTIMATELY AMELIORATE THE EFFECTS OF THE EPIDEMIC ACROSS POPULATIONS. NARRATIVE: HIV SEVERELY AFFECTS WOMEN OF IN THE SOUTHERN US AND REPRODUCTIVE AGED WOMEN WITH HIV HAVE POOR HIV AND OTHER HEALTH OUTCOMES. THE OVERARCHING GOAL OF THE STUDY OF TREATMENT AND REPRODUCTIVE OUTCOMES (STAR) IS TO BUILD UPON OUR PRIOR SUCCESSES TO ADVANCE HIGH PRIORITY HIV SCIENCE FOR REPRODUCTIVE AGE WOMEN WITH AND WITHOUT HIV THROUGH RESEARCH, MENTORING, AND COMMUNITY ENGAGEMENT. IN THIS APPLICATION, WE PROPOSE THE ESTABLISHMENT OF A SCIENTIFIC ADMINISTRATIVE CORE, A DATA MANAGEMENT AND ANALYSIS CORE, AND A COMMUNITY ENGAGEMENT CORE, TO SUPPORT THE LONGITUDINAL STAR COHORT AND RESEARCH PROJECTS THAT ADDRESS THE INTERSECTING EFFECTS OF HIV, AND REPRODUCTIVE TRANSITIONS ON CARDIOVASCULAR HEALTH (RESEARCH PROJECT 1) AND REPRODUCTIVE HEALTH AND COINFECTIONS (RESEARCH PROJECT 2).

UNIVERSITY OF MIAMI FEDERATED BIOREPOSITORY FACILITY TO ADVANCE BIOMEDICAL RESEARCH

RYAN WHITE PART C OUTPATIENT EIS PROGRAM

FAMILY STUDY OF STROKE RISK AND CAROTID ATHEROSCLEROSIS

NOU LA WE ARE HERE BIOMEDICAL PREVENTION FOR PEOPLE OF HAITIAN DESCENT - PROJECT SUMMARY- NOU LA (WE’RE HERE): BIOMEDICAL PREVENTION FOR PEOPLE OF HAITIAN DESCENT ACCORDING TO THE ENDING THE HIV EPIDEMIC PLAN, MIAMI, FLORIDA IS CONSIDERED A US HIV EPICENTER.1 IN MIAMI, FLORIDA PEOPLE OF HAITIAN DESCENT HAVE BEEN DISPROPORTIONATELY AFFECTED BY HIV.2 HAITIAN-BORN PEOPLE HAD AN INCIDENCE OF 5.5% OF HIV AND 9% OF AIDS DIAGNOSES.2 THIS PLANNING PROJECT WILL DEVELOP AN IMPLEMENTATION STRATEGY “L’UNION FAIT LA FORCE OR (UNITY MAKES STRENGTH): INCREASING PREP REACH” IN WHICH WE WILL PARTNER WITH LOCAL ORGANIZATIONS ALREADY TRUSTED AND UTILIZED BY THE HAITIAN COMMUNITY TO COLLABORATE AND CREATE NEW OPPORTUNITIES FOR PREP ACCESS. THE AIMS OF THIS PROJECT ARE: AIM 1: TO CHARACTERIZE AND PRIORITIZE KNOWLEDGE AND ORGANIZATIONAL DETERMINANTS OF PREP IMPLEMENTATION AT COMMUNITY-BASED ORGANIZATIONS AND CLINICS SERVING PEOPLE OF HAITIAN DESCENT IN MIAMI. RATIONALE: TO DEVELOP A RELEVANT IMPLEMENTATION APPROACH THAT OVERCOMES THE CURRENT GAP IN PREP UPTAKE AMONG PEOPLE OF HAITIAN DESCENT WE WILL FOCUS ON THE CONTEXT OF PREP KNOWLEDGE AND DELIVERY AT SITES THAT COULD PROVIDE THE MEDICATION BUT ARE NOT CURRENTLY DOING SO AND PRIORITIZE STEPS TO ACHIEVE PREP DELIVERY. APPROACH: WE WILL PARTNER WITH THE COMMUNITY HEALTH AND EMPOWERMENT NETWORK (CHE), AND SELEST HEALTH CENTER. WE WILL CONDUCT TWO FOCUS GROUP DISCUSSIONS AT EACH SITE WITH KEY STAKEHOLDERS (PROVIDERS, LEADERS, MANAGERS, AND STAFF) AND 30 INTERVIEWS WITH CLIENTS (15 AT EACH SITE) WHICH WILL USE SEMI-STRUCTURED INTERVIEW GUIDES (DEVELOPED WITH THE HAITIAN AMERICAN PROFESSIONALS COALITION) AND WILL BE ANALYZED USING RAPID QUALITATIVE ANALYSIS. OUTCOME: FROM THIS AIM, WE WILL HAVE A BETTER UNDERSTANDING OF PREP EDUCATIONAL NEEDS AND KEY ELEMENTS FOR DELIVERY FROM THOSE OFFERING SERVICES TO MEMBERS OF THE HAITIAN COMMUNITY. AIM 2: USING A COMMUNITY ENGAGED APPROACH DESIGN AN IMPLEMENTATION STRATEGY TO INCREASE PREP UPTAKE. RATIONALE: UNDERSTANDING BARRIERS, FACILITATORS, PREP KNOWLEDGE AND THE DELIVERY NEEDS FOR IMPLEMENTATION IS ESSENTIAL TO DEVELOP CULTURALLY RELEVANT INTERVENTIONS AT COMMUNITY SITES. APPROACH: USING FINDINGS FROM THE BON SANTE STUDY AND AIM 1, WE WILL ITERATIVELY WORK THROUGH DISCUSSIONS WITH STUDY SITE PARTNERS TO DEVELOP A PRACTICAL STRATEGY THAT ADDRESSES LEADING INDIVIDUAL (CLIENT) AND SERVICE ORGANIZATION BARRIERS TO PREP UPTAKE AND DELIVERY. OUTCOME: THROUGH THIS PROCESS WE WILL DESIGN AN ACCEPTABLE AND TESTABLE IMPLEMENTATION STRATEGY. AIM 3: TEST THE ACCEPTABILITY AND FEASIBILITY OF A PREP IMPLEMENTATION STRATEGY FOR PEOPLE OF HAITIAN DESCENT. RATIONALE: IN ORDER FOR INTERVENTIONS TO BE EFFECTIVE, IT IS IMPORTANT THAT THEY ARE ACCEPTABLE. APPROACH: WE WILL CONDUCT A SURVEY AND EXIT INTERVIEWS WITH 5 PARTICIPANTS FROM EACH SITE (N =10) WHO RECEIVE PREP AND 4 KEY STAKEHOLDERS FROM EACH SITE (N= 8). WE WILL ALSO RECORD THE NUMBER OF PEOPLE GIVEN INFORMATION REGARDING OFFERED PREP AND THE NUMBER OF PEOPLE WHO INITIATE PREP. OUTCOME: THROUGH THIS PROCESS, WE WILL HAVE A MEASURE OF THE ACCEPTABILITY AND FEASIBILITY OF THE APPROACHES TO INCREASE UPTAKE OF PREP AT THE PARTNER SITES.

NATIONWIDE ONLINE RELATIONSHIP EDUCATION FOR UNDERSERVED COUPLES

SETTING THE STAGE FOR REPLACEMENT OF MITOCHONDRIAL GENES

ROLE OF RAC AND REACTIVE OXYGEN SPECIES IN KAPOSI'S SARCOMA VIRAL ONCOGENESIS

IMPLEMENTING GENOMIC MEDICINE IN CLINICAL CARE OF DEAF PATIENTS

FUNCTIONAL GENOMIC STUDIES IN DIVERSE POPULATIONS TO CHARACTERIZE RISK LOCI FOR ALZHEIMER DISEASE - PROJECT SUMMARY GENOME WIDE ASSOCIATION STUDIES (GWAS) STUDIES IN AD HAVE BEEN VERY SUCCESSFUL IN IDENTIFYING GENETIC REGIONS CONTRIBUTING TO THE DISEASE, BUT ALMOST ALL HAVE BEEN IN NON-HISPANIC WHITES (NHW). MOST OF THESE ASSOCIATED GENETIC REGIONS LIE IN NON-CODING, REGULATORY AREAS OF THE GENOME. THAT MEANS TO UNDERSTAND HOW THESE ASSOCIATED LOCI INFLUENCE THE RISK OF GETTING AD, WE MUST UNDERSTAND THE REGULATORY ARCHITECTURE OF THE GENOME IN THESE ASSOCIATED REGIONS. RECENT EFFORTS FROM OUR GROUP AND OTHERS HAVE SOUGHT TO UNDERSTAND THE GENETIC UNDERPINNING OF AD IN DIVERSE, ADMIXED POPULATIONS SUCH AS AFRICAN AMERICANS (AA) AND HISPANICS (HI). THESE STUDIES HAVE SHOWN THAT DIFFERENT ETHNIC AND RACIAL GROUPS HAVING DISTINCT GENETIC ARCHITECTURES THAT CAN LEAD TO DIFFERING GENETIC SUSCEPTIBILITY. HOWEVER, WHILE STUDIES LIKE ENCODE AND GTEX HAVE MAPPED SOME OF THE REGULATORY ARCHITECTURE OF THE HUMAN GENOME, THEY LACK INFORMATION ON DIVERSE POPULATIONS, AS THESE REGULATORY MAPPING STUDIES HAVE ALSO BEEN ALMOST EXCLUSIVELY IN NHW, AND NOT NECESSARILY IN THE ACTUAL CELL TYPES THAT ARE AFFECTED IN ALZHEIMER DISEASE (AD). THIS PROPOSAL WILL USE MULTIPLE AVENUES OF INVESTIGATION TO MAP THE REGULATORY ARCHITECTURE OF THE AFRICAN AND AMERINDIAN GENOMES, WHICH, TOGETHER WITH EUROPEAN, ARE THE COMPONENTS THAT CONTRIBUTE TO THE ADMIXED AA AND HI GENOMES. ONCE WE HAVE THIS ARCHITECTURE MAPPED, WE WILL USE IT TO UNDERSTAND THE MECHANISMS OF DISEASE ASSOCIATED WITH RARE VARIANTS AND ASSOCIATED NON-CODING LOCI IDENTIFIED IN AA AND HI ASSOCIATION STUDIES. TO ACCOMPLISH THIS, WE WILL USE INDUCIBLE PLURIPOTENT STEM CELLS FROM AA AND HI (PERUVIAN) AD CASES, CHOSEN TO MAXIMIZE EITHER AFRICAN OR AMERINDIAN GLOBAL ANCESTRIES, AS WELL AS BRAIN TISSUE FROM AA AND HI INDIVIDUALS. WITH OUR COLLABORATOR DR. FULAI JIN AT CASE WESTERN RESERVE UNIVERSITY, STATE OF THE ART HI-C TECHNIQUES WILL BE USED TO MAP INTERACTIONS IN BOTH THE DIFFERENTIATED IPSC LINES (NEURONS, OLIGODENDROCYTES, ASTROCYTES AND MICROGLIA) AS WELL AS THE FROZEN BRAIN TISSUE. WE WILL ALSO USE SINGLE NUCLEI RNASEQ AND SINGLE NUCLEI ATACSEQ TO EVALUATE THE BRAINS, BULK ATAC AND RNASEQ FOR IPSC LINES. ALL THE GENOMIC DATA WILL THEN BE COMPLIED, ALONG WITH SUPPORTING EXISTING DATA FROM EUROPEAN GENOMES (NHW), TO CREATE THE AFRICAN AND AMERINDIAN REGULATORY MAPS. WE WILL THEN TAKE THE IDENTIFIED ASSOCIATED HAPLOTYPES FROM THE OUTSIDE AA AND HI GWAS AND RARE VARIANT STUDIES AND “LAY” THEM ACROSS OUR REGULATORY LANDSCAPE TO IDENTIFY THE INTERACTING GENES AND SUBREGIONS OF THE HAPLOTYPES AFFECTING THE RISK FOR AD IN THESE POPULATIONS. NEXT WE WILL USE CRISPRA AND CRISPRI TECHNIQUES TO VERIFY THESE INTERACTIONS. FINALLY, WE WILL INCORPORATE ALL THIS DATA WITH EXISTING DATA TO HELP IDENTIFY HIGH QUALITY GENETIC TARGETS FOR THERAPEUTIC INTERVENTION FOR AD.

MIAMI-ECHO: A DIVERSE COHORT OF MOTHERS, CHILDREN AND FATHERS IN MIAMI-DADE COUNTY - PROJECT SUMMARY/ABSTRACT DISPARITIES IN MATERNAL-CHILD HEALTH INCREASE GENERATIONALLY BECAUSE STRESS EXPERIENCED BY MOTHERS CAN BE TRANSFERRED TO THEIR CHILDREN, WITH BOTH BIOLOGICAL AND PSYCHOLOGICAL CONSEQUENCES. WITHOUT CLEAR UNDERSTANDING OF FACTORS DRIVING THESE DISPARATE OUTCOMES AND WITHOUT LONGITUDINAL ASSESSMENTS ACROSS RACIAL AND ETHNIC GROUPS, INEQUITIES WILL PERSIST. THE ENVIRONMENTAL INFLUENCES ON CHILD HEALTH OUTCOMES (ECHO) PROGRAM AIMS TO UNDERSTAND THE EFFECTS OF EARLY ENVIRONMENTAL FACTORS ON CHILD HEALTH AND DEVELOPMENT, AND THEREFORE NEEDS A DIVERSE COHORT OF CHILDREN AND THEIR PARENTS WHO REPRESENT THE VARIETY OF U.S. POPULATIONS, ESPECIALLY RACIAL AND ETHNIC MINORITY POPULATIONS WHO OFTEN ARE AT THE INTERSECTION OF SOCIOECONOMIC ADVERSITY AND SOCIAL STRESSORS RELATED TO RACE/ETHNICITY. WE PROPOSE TO ESTABLISH THE MIAMI-ECHO COHORT OF RACIALLY AND ETHNICALLY DIVERSE MOTHERS, CHILDREN, AND FATHERS. WE WILL RECRUIT AND RETAIN A RACIALLY AND ETHNICALLY DIVERSE COHORT OF PREGNANT WOMEN (N=1,250), THEIR OFFSPRING, AND THE CONCEIVING FATHER FROM MIAMI-DADE COUNTY (MDC), FLORIDA. IN ADDITION, WE WILL RECRUIT AND RETAIN 60-80% OF THE COHORT MOTHERS INTO THE ECHO PRECONCEPTION PILOT PROTOCOL. MDC IS A MINORITY-MAJORITY COUNTY WITH A POPULATION OF 69.4% HISPANIC/LATINOS (INCLUDING AFRO-CARIBBEANS), 17.7% AFRICAN AMERICANS, 12.9% NON-HISPANIC WHITES, 3% ASIANS, AND 1.3% MULTI-RACIAL INDIVIDUALS.TO ONE OF THE MOST ETHNICALLY AND CULTURALLY DIVERSE U.S. POPULATIONS. MDC, HOWEVER, IS NOT YET REPRESENTED IN THE ECHO PROGRAM. OUR DIVERSE, MULTI-DISCIPLINARY TEAM HAS ACCESS TO THE LARGEST POPULATIONS OF PREGNANT WOMEN AND THOSE GIVING BIRTH IN MDC, AND TO COMMUNITY-BASED INFRASTRUCTURES CARING FOR THE MOST VULNERABLE WOMEN IN THE REGION FOR OVER 40 YEARS. FURTHERMORE, TO ADVANCE ECHO SCIENCE, WE WILL ADDRESS THESE AIMS: A) EXAMINE SOCIAL ENVIRONMENT AND PLACENTAL GENOME INFLUENCES ON CHILDREN'S NEURODEVELOPMENT AND GLOBAL HEALTH. WE WILL DETERMINE WHETHER THE PLACENTAL GENOME MEDIATES THE RELATIONSHIP BETWEEN PRE- AND PERINATAL SOCIAL ENVIRONMENT AND CHILDREN'S NEURODEVELOPMENT AND GLOBAL HEALTH DURING EARLY AND MIDDLE CHILDHOOD; AND IDENTIFY THE INTERACTIVE (GENE X EPIGENE X SOCIAL ENVIRONMENT) EFFECTS ON CHILDREN'S NEURODEVELOPMENT AND GLOBAL HEALTH DURING EARLY AND MIDDLE CHILDHOOD. B) IDENTIFY FACTORS THAT PROTECT AGAINST THE EFFECTS OF DISCRIMINATION ON CHILDREN'S NEURODEVELOPMENT AND GLOBAL HEALTH. WE WILL DISTINGUISH THE EFFECTS OF MATERNAL AND PATERNAL DISCRIMINATION – SEPARATELY AND IN COMBINATION – ON CHILDREN'S NEURODEVELOPMENT AND GLOBAL HEALTH FROM EARLY TO MIDDLE CHILDHOOD; AND DETERMINE THE DEGREE TO WHICH THE SOCIAL ENVIRONMENT, SOCIAL IDENTITY (RACE, ETHNICITY, SKIN COLOR, NATIVITY), AND SOCIAL SUPPORT MEDIATE THE EFFECTS OF DISCRIMINATION ON CHILDREN'S NEURODEVELOPMENT AND GLOBAL HEALTH. C) IDENTIFY THE EFFECTS OF MODIFIABLE SOCIAL DETERMINANTS OF HEALTH AND ACCESS TO FAMILY PLANNING DURING THE PRE-CONCEPTION PERIOD ON SUBSEQUENT PREGNANCY MORBIDITY AND BIRTH OUTCOMES.

THE FUNCTIONAL SIGNIFICANCE OF CTL ESCAPE

CLASI: THE COASTAL LAND AIR-SEA INTERACTION EXPERIMENT

IMMUNOGLOBULINS DELIVERED BY AAV VECTOR FOR THE PREVENTION OF SIV INFECTION

UNIVERSITY OF MIAMI DEVELOPMENTAL HIV/AIDS MENTAL HEALTH RESEARCH CENTER (D-ARC)

HEALTHY START INITIATIVE-ELIMINATING RACIAL/ETHNIC DISPARITIES

COOPERATIVE INSTITUTE FOR MARINE AND ATMOSPHERIC STUDIES PARALLEL AWARD

AIR-SEA INTERACTION STUDIES OF THE INDIAN AND PACIFIC OCEANS (TASK 1: NASCAR; TASK 2: PALAU; TASK 3: PHILIPPINES

MIAMI-ECHO: A COHORT OF MOTHERS, CHILDREN AND FATHERS IN MIAMI-DADE COUNTY - VARIABILITY IN MATERNAL AND CHILD HEALTH OUTCOMES CAN EMERGE ACROSS GENERATIONS, AS STRESS EXPERIENCED BY MOTHERS MAY INFLUENCE THEIR CHILDREN’S DEVELOPMENT THROUGH BOTH BIOLOGICAL AND PSYCHOLOGICAL PATHWAYS. WITHOUT A CLEAR UNDERSTANDING OF THE FACTORS CONTRIBUTING TO THESE OUTCOME PATTERNS—AND WITHOUT LONGITUDINAL ASSESSMENT ACROSS LARGE POPULATIONS—IMPORTANT GAPS IN KNOWLEDGE WILL REMAIN. THE ENVIRONMENTAL INFLUENCES ON CHILD HEALTH OUTCOMES (ECHO) PROGRAM SEEKS TO ADVANCE UNDERSTANDING OF HOW EARLY LIFE FACTORS SHAPE CHILD HEALTH AND DEVELOPMENT. TO DO THIS EFFECTIVELY, THE PROGRAM REQUIRES A LARGE DEMOGRAPHICALLY REPRESENTATIVE COHORT OF CHILDREN AND THEIR PARENTS. WE PROPOSE TO ESTABLISH THE MIAMI-ECHO COHORT SITE, COMPOSED OF MOTHERS, CHILDREN, AND FATHERS FROM MIAMI-DADE COUNTY (MDC), FLORIDA. WE WILL RECRUIT AND RETAIN A LARGE COHORT OF PREGNANT WOMEN (N=1,250), THEIR OFFSPRING, AND THE CONCEIVING FATHER. IN ADDITION, WE WILL ENROLL MOTHERS WHO HAVE A SECOND PREGNANCY INTO THE ECHO PRECONCEPTION PROTOCOL. MIAMI-DADE COUNTY (MDC) INCLUDES ONE OF THE LARGEST URBAN POPULATION IN THE NATION. YET, THIS REGION IS NOT CURRENTLY REPRESENTED IN THE ECHO PROGRAM. OUR TEAM HAS LONGSTANDING ACCESS TO THE REGION’S LARGEST HEALTH CARE SETTINGS AND HAS COLLABORATED WITH ORGANIZATIONS THAT HAVE SERVED FAMILIES IN MDC FOR OVER 40 YEARS. TO ADVANCE THE GOALS OF ECHO SCIENCE, WE PROPOSE TO ADDRESS THE FOLLOWING AIMS: A) EXAMINE SOCIAL ENVIRONMENT AND PLACENTAL GENOME INFLUENCES IN CHILDREN’S NEURODEVELOPMENT AND POSITIVE HEALTH (E.G., GLOBAL HEALTH) OUTCOMES. WE WILL DETERMINE WHETHER THE PLACENTAL GENOME MEDIATES THE RELATIONSHIP BETWEEN PRE- AND PERINATAL FACTORS AND CHILDREN'S NEURODEVELOPMENT AND GLOBAL HEALTH DURING EARLY AND MIDDLE CHILDHOOD; AND IDENTIFY THE INTERACTIVE (GENE X EPIGENE X ENVIRONMENT) EFFECTS ON CHILDREN'S NEURODEVELOPMENT AND GLOBAL HEALTH DURING EARLY AND MIDDLE CHILDHOOD. B) IDENTIFY FACTORS THAT PROTECT AGAINST THE EFFECTS OF STRESSORS ON CHILDREN’S NEURODEVELOPMENT AND POSITIVE HEALTH (E.G., GLOBAL HEALTH) OUTCOMES. WE WILL DISTINGUISH THE EFFECTS OF STRESSORS – SEPARATELY AND IN COMBINATION – ON CHILDREN'S NEURODEVELOPMENT AND GLOBAL HEALTH FROM EARLY TO MIDDLE CHILDHOOD; AND DETERMINE THE DEGREE TO WHICH THE EARLY LIFE FACTORS AND SOCIAL SUPPORT MEDIATE THE EFFECTS OF STRESS ON CHILDREN'S NEURODEVELOPMENT AND GLOBAL HEALTH. C) ESTABLISH THE MIAMI ECHO COHORT SITE OF MOTHERS, CHILDREN, AND FATHERS. AND D) IDENTIFY THE EFFECTS OF MODIFIABLE STRESSORS AND PRECONCEPTION HEALTH ON PREGNANCY MORBIDITY AND BIRTH OUTCOMES. THESE AIMS WILL CONTRIBUTE TO BETTER UNDERSTANDING CHILD HEALTH DEVELOPMENTAL OUTCOMES IN OUR NATION.

TAT, AMYLOID BETA AND BRAIN ENDOTHELIAL BARRIER FUNCTION

ENSEMBLE KALMAN FILTERS AND OSEES IN HURRICANE MODELS

SUPPORTING EDUCATOR'S ACADEMIC LITERACIES AND ENHANCED DISCOURSE (SEALED)

MECHANISMS OF RECOVERY FOLLOWING TRAUMATIC BRAIN INJURY

ORPHAN RECEPTORS IN REGULATION OF NEURONAL G PROTEIN SIGNALING

DISRUPTION OF TRANSCRIPTION NETWORKS IN ESOPHAGEAL ADENOCARCINOMA TUMORIGENESIS - SUMMARY/ABSTRACT: THE INCIDENCE OF ESOPHAGEAL ADENOCARCINOMA (EAC) HAS INCREASED MORE THAN SIX-FOLD OVER THE PAST THREE DECADES. EAC PATIENTS' 5-YEAR SURVIVAL RATE IS LESS THAN 15%, UNDERSCORING THE NEED TO UNDERSTAND THE UNDERLYING BIOLOGY TO IDENTIFY NEW THERAPEUTIC APPROACHES. CHRONIC GASTROESOPHAGEAL REFLUX DISEASE (GERD), WHERE ACIDIC BILE SALTS (ABS) ABNORMALLY REFLUXATE INTO THE ESOPHAGUS, AFFECTS MORE THAN 20% OF THE US POPULATION. IN THIS PROGRAM PROJECT, WE HYPOTHESIZE THAT INTERACTIONS BETWEEN APE1 REDOX FUNCTIONS AND ISOLEVUGLANDINS (ISOLGS) PROTEIN ADDUCTS PROMOTE ACTIVATION AND STABILITY OF CRITICAL ONCOGENIC TRANSCRIPTION NETWORKS TO MEDIATE CELL SURVIVAL AND EXPANSION IN ESOPHAGEAL TUMORIGENESIS. THIS PROGRAM PROJECT LEVERAGES UNIQUE EXPERTISE OF THE PRINCIPAL INVESTIGATORS AND TAKES ADVANTAGE OF ADVANCED GENETIC AND SURGICAL ANIMAL MODELS, 3-DIMENSIONAL IN VITRO MODELS, HUMAN TISSUES, PATIENT-DERIVED XENOGRAFTS (PDXS), AND INNOVATIVE TECHNOLOGIES. PROJECT 1 INVESTIGATES MECHANISMS BY WHICH APE1-REDOX FUNCTION PROMOTES ACTIVATION OF SOX9 TRANSCRIPTION FACTOR IN EACS UNDER REFLUX CONDITIONS. MECHANISTIC AND FUNCTIONAL STUDIES WILL EXPLORE THE ROLE OF APE1 REDOX FUNCTION AND ISOLGS ADDUCTS IN REGULATING SOX9 TO PROMOTE CANCER CELL SURVIVAL AND EXPANSION. TRANSLATIONAL STUDIES WILL DETERMINE THE EFFICACY APE1 REDOX INHIBITORS USING IN VIVO MOUSE MODELS. PROJECT 2 INVESTIGATES NOVEL MECHANISMS OF STAT3 BY ISOLG PROTEIN ADDUCTS, AS A CELLULAR RESPONSE TO OXIDATIVE STRESS INDUCED BY REFLUX CONDITIONS. THE TRANSLATIONAL EXPERIMENTS INCLUDE THE USE OF ISOLG INHIBITORS TO SUPPRESS FORMATION OF ONCOGENIC PROTEIN ADDUCTS AND PROGRESSION TO EAC IN ANIMAL MODELS OF BARRETT’S TUMORIGENESIS. PROJECT 3 INVESTIGATES THE ROLE SOX4 IN EAC DEVELOPMENT. THE TRANSLATION STUDIES IN PROJECT 3 INCLUDE TESTING FDA-APPROVED DRUGS THAT INHIBIT SOX4, AS A PROOF OF CONCEPT TO DEVELOP A NOVEL STRATEGY TO TREAT EACS. THE INTEGRATED DATA EXCHANGE IN THIS PROGRAM PROJECT WILL ENABLE US TO COLLECTIVELY INVESTIGATE THE ROLE OF APE1 REDOX FUNCTIONS AND ISOLG PROTEIN ADDUCTS IN ESOPHAGEAL TUMORIGENESIS. THE THREE PROPOSED CORES DELIVER KEY SERVICES FOR ALL THE PROJECTS. THE ADMINISTRATIVE CORE (CORE A) WILL MANAGE ALL SCIENTIFIC AND FISCAL ISSUES AND FACILITATE RESEARCH INTERACTIONS. THE MOLECULAR PATHOLOGY CORE (CORE B) WILL PROVIDE HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY SERVICES FOR ANIMAL AND HUMAN TISSUES. THE BIOSTATISTICS AND BIOINFORMATICS CORE (CORE C) WILL PLAY A CENTRAL ROLE IN PROVIDING COMPUTATIONAL, STATISTICAL, AND BIOINFORMATICS SERVICES. VIA THESE PROJECT AND CORE INTERACTIONS WE WILL IDENTIFY BIOLOGY-RELEVANT ONCOGENIC MOLECULAR VULNERABILITIES THAT CAN BE THERAPEUTICALLY TARGETED TO BENEFIT EAC PATIENTS

PRECLINICAL DEVELOPMENT OF HIV-1 VIF ANTAGONISTS

GENOMIC CONVERGENCE IN ALZHEIMER DISEASE

CELLULAR CHOLESTEROL AND PODOCYTE FUNCTION IN DIABETIC KIDNEY DISEASE

CARDIOPROTECTIVE EFFECT OF GROWTH HORMONE RELEASING HORMONE

SHIP OPERATIONS FOR THE R/V F.G. WALTON SMITH

COLLABORATIVE RESEARCH: GLOBAL OCEAN REPEAT HYDROGRAPHY, CARBON & TRACER MEASUREMENTS 2015-2020

COLLABORATIVE RESEARCH: GLOBAL OCEAN REPEAT HYDROGRAPHY, CARBON, AND TRACER MEASUREMENTS, 2009-2014

CHILD DEVELOPMENT AND MULTIDISCIPLINARY FACILITY

PROGRAM TO INCREASE DIVERSITY IN FACULTY ENGAGED IN BEHAVIORAL AND SLEEP MEDICINE

PRETARGETED RADIOIMMUNOTHERAPY OF CD20+ LYMPHOMAS

POST DPP FOLLOW-UP STUDY

MIAMI HIV/AIDS CLINICAL THERAPEUTIC AND VACCINE TRIAL UNIT

SPECIFICITY OF CD8 CELLS IN ISLETS FROM TYPE 1 DIABETES PATIENTS

PARTNERSHIP FOR MR SPECTROSCOPIC IMAGING DATA PROCESSING

MORPHIC DATA RESOURCE AND ADMINISTRATIVE COORDINATING CENTER - PROJECT SUMMARY SINCE THE SUCCESSFUL CONCLUSION OF THE HUMAN GENOME PROJECT (HGP), SIGNIFICANT PROGRESS HAS BEEN MADE TOWARDS THE NHGRI STRATEGIC VISION TO CHARACTERIZE THE BIOLOGICAL FUNCTION(S) OF EVERY HUMAN GENE. A SYSTEMATIC CATALOGUE OF MOLECULAR AND CELLULAR PHENOTYPIC EFFECTS OF GENE KNOCKOUTS FOR ALL HUMAN GENES IN COMPLEX CELL- BASED MODEL SYSTEMS WOULD FILL A CURRENT GAP BETWEEN DIRECT MOLECULAR READOUTS SUCH AS GENE EXPRESSION AND WHOLE MODEL ORGANISM PHENOTYPES. IT WOULD PROVIDE ANOTHER CRITICAL TOOL TO CHARACTERIZE THE BIOLOGICAL FUNCTIONS OF ALL GENES TOWARDS THE STRATEGIC VISION. THE PILOT PHASE OF THE MOLECULAR AND CELLULAR PHENOTYPES OF NULL ALLELES IN CELLS (MORPHIC) PROGRAM WILL STUDY THE FEASIBILITY, SCALABILITY, REQUIRED SCOPE, AND UTILITY OF SUCH A CATALOGUE TO CHARACTERIZE PHENOTYPES ASSOCIATED WITH GENES IN TISSUE- AND DISEASE-RELEVANT HUMAN CELLULAR MODEL SYSTEMS. THE PROPOSED MORPHIC DATA RESOURCE AND ADMINISTRATIVE COORDINATING CENTER (DRACC) WILL ENABLE AND SUPPORT THE MORPHIC RESEARCH CONSORTIUM BY PROVIDING THE HIGHEST QUALITY FAIR (FINDABLE, ACCESSIBLE, INTEROPERABLE, REUSABLE) MORPHIC DATA RESOURCE, ANALYZING, ANNOTATING, AND DISSEMINATING MORPHIC DATA, INTEGRATING EXTERNAL DATA/INFORMATION, AND SERVING AS AN ADMINISTRATIVE AND COORDINATION CENTER. THESE FUNCTIONS WILL BE FULFILLED IN CLOSE COOPERATION AND COLLABORATING WITH THE DATA PRODUCTION RESEARCH AND DEVELOPMENT CENTERS (DPCS) AND THE DATA ANALYSIS AND VALIDATION CENTERS (DAVS) TO SUPPORT RIGOROUS DATA STANDARDS, RICH METADATA ANNOTATIONS, THE HIGHEST DATA AND SOFTWARE QUALITY, AND REPRODUCIBILITY AND PORTABILITY OF DATA PROCESSING AND -ANALYSIS TOOLS. MEMBERS OF OUR TEAM HAVE PREVIOUSLY SERVED IN LEADERSHIP POSITIONS OF SEVERAL NATIONAL AND INTERNATIONAL RESEARCH CONSORTIA, INCLUDING THE HUMAN CELL ATLAS (HCA), KNOCKOUT MOUSE PROGRAM (KOMP), GENOME-WIDE ASSOCIATION STUDIES (GWAS) CATALOG, LIBRARY OF INTEGRATED NETWORK-BASED CELLULAR SIGNATURES (LINCS), ILLUMINATING THE DRUGGABLE GENOME (IDG), BIG DATA TO KNOWLEDGE (BD2K), AND MONARCH INITIATIVE. OUR TEAM HAS THE TECHNOLOGICAL, SCIENTIFIC, AND ADMINISTRATIVE EXPERTISE TO SUCCESSFULLY OPERATE THE CENTER AND COMPLETE THE CENTER AND CONSORTIUM CRITICAL FUNCTIONS AND DELIVERABLES VIA SPECIFIC AIMS TO 1) ESTABLISH AND OPERATE THE CENTER, 2) DEPLOY A STATE-OF-THE-ART INFRASTRUCTURE TO MANAGE DATA ACROSS THE ENTIRE LIFE CYCLE, 3) COLLATE, CONVERGE, AND DEPLOY CLOUD-ENABLED ANALYSIS TECHNIQUES, MODELS AND DATA PROCESSING PROTOCOLS, 4) CREATE AND DEPLOY THE MORPHIC WEB PORTAL TO PROVIDE GLOBAL ACCESS TO MORPHIC DATA, 5) MAP AND INTEGRATE EXTERNAL DATA SOURCES, AND 6) ADMINISTER AND COORDINATE THE CONSORTIUM. SUCCESSFUL COMPLETION OF THESE AIMS WILL ENABLE THE ASSESSMENT OF FEASIBILITY, SCALABILITY, REQUIRED SCOPE, AND UTILITY OF A MORPHIC CATALOGUE WITH THE PROSPECT TO MASSIVELY SCALE THE FUNCTIONAL CHARACTERIZATION OF EVERY HUMAN GENE VIA PHENOTYPE MAPPING IN RELEVANT HUMAN MODEL SYSTEMS.

AVANZANDO CAMINOS (LEADING PATHWAYS): THE HISPANIC/LATINO CANCER SURVIVORSHIP COHORT STUDY.” - PROJECT SUMMARY CANCER IS THE LEADING CAUSE OF DEATH AMONG HISPANICS/LATINOS (H/LS) IN THE US. H/LS ACCOUNT FOR 57.5 MILLION AMERICANS (18%), NOW THE LARGEST MINORITY EXPECTED TO DOUBLE OVER THE NEXT FOUR DECADES. H/LS HAVE VARIABLE SES, NATIVITY, GEOGRAPHIC DISTRIBUTION, GENETIC ADMIXTURE, AND SOCIAL, PSYCHOSOCIAL AND BEHAVIORAL DETERMINANTS OF HEALTH. SIGNIFICANT DISPARITIES EXIST IN PREVALENCE, INVASIVENESS AND MORTALITY IN SPECIFIC CANCERS (E.G., CERVIX, LIVER, STOMACH) AND ACROSS MULTIPLE PATIENT REPORTED OUTCOMES (PROS) REGARDLESS OF DISEASE SITE. H/LS ARE MORE LIKELY TO PRESENT WITH ADVANCED DISEASE, GREATER COMORBIDITIES AND REPORT GREATER SYMPTOM BURDEN AND POORER HEALTH-RELATED QUALITY OF LIFE (HRQOL). SURVIVORSHIP IN H/LS IS FURTHER COMPROMISED BY LOW SES, EDUCATION AND INSURANCE COVERAGE, LANGUAGE BARRIERS AND LIMITED ACCESS TO CARE. SURVIVORSHIP STUDIES IN H/LS HAVE BEEN LIMITED DUE TO: (A) SMALL SAMPLES WITH SHORT FOLLOW-UPS; (B) FOCUS ON COMMON CANCER (E.G., BREAST OR PROSTATE), LIMITING ATTENTION TO HIGH-PREVALENCE/MORTALITY SITES; RESTRICTED H/L ORIGIN AND SES REPRESENTATION; AND (D) LACK OF GUIDING MODELS CONSIDERING MULTIPLE DETERMINANTS (E.G., SOCIOCULTURAL, MEDICAL, STRESS, PSYCHOSOCIAL, LIFESTYLE, BIOLOGICAL) OF SURVIVORS’ OUTCOMES. AVANZANDO CAMINOS (LEADING PATHWAYS): THE HISPANIC/LATINO CANCER SURVIVORSHIP COHORT STUDY WILL INVOLVE RECRUITMENT, ASSESSMENT AND FOLLOW-UP OF ~3,000 H/LS WHO COMPLETED PRIMARY CANCER TREATMENT WITHIN THE PAST 2 YEARS AND ARE DIVERSE IN H/L BACKGROUND, URBAN VS. RURAL RESIDENCE AND CANCER SITE ACROSS TWO MAJOR US METROPOLITAN AREAS—MIAMI AND SAN ANTONIO. BOTH AREAS HAVE MAJORITY H/L POPULATIONS (~65% OF MIAMI; ~64% OF SAN ANTONIO), ARE DIVERSE REGARDING H/L ORIGIN AND SES AND ARE SERVED BY NCI-DESIGNATED CANCER CENTERS. WE WILL RECRUIT A SAMPLE THAT APPROXIMATES THE DIVERSITY OF THE H/L POPULATION IN THE US (~ 50% MEXICAN & ~50% OTHER H/L ORIGIN). THE FLORIDA CANCER DATA SYSTEM AND THE TEXAS CANCER REGISTRY WILL SUPPLEMENT RECRUITMENT (~30% OF COHORT) AND SERVE TO ESTABLISH REPRESENTATIVENESS. OUR PRIMARY OUTCOMES ARE SYMPTOM BURDEN (E.G., PAIN, FATIGUE, DEPRESSION, COGNITION), HRQOL AND DISEASE ACTIVITY (E.G., PROGRESSION, RECURRENCE, CANCER & ALL-CAUSE MORTALITY). OUR TRANSDISCIPLINARY TEAM HAS A STRONG AND SUCCESSFUL RECORD OF ACADEMIC PRODUCTIVITY AND COLLABORATION ACROSS THE FIVE TARGETED DOMAINS THAT WILL BE EVALUATED AS DETERMINANTS OF OUR OUTCOMES: (1) SOCIOCULTURAL (E.G., SES, ACCULTURATION, CULTURAL VALUES); (2) STRESS AND ADVERSITY (E.G., CHRONIC AND TRAUMATIC STRESS, ETHNIC-STRESS); (3) PSYCHOSOCIAL (E.G., SOCIAL SUPPORT, COPING, FAMILY COHESION/CONFLICT); (4) LIFESTYLE AND BEHAVIORAL (E.G., PHYSICAL ACTIVITY, NUTRITION, HEALTH INFORMATION SEEKING); AND (5) BIOLOGICAL (E.G., INFLAMMATORY/PRO-METASTATIC GENE EXPRESSION SIGNALING, CARDIOMETABOLIC MARKERS, GENETIC ADMIXTURE). PARTICIPANTS WILL BE ASSESSED AT BASELINE, 6-MONTHS, 12-MONTHS AND ANNUALLY THEREAFTER. METHODS IN MULTILEVEL LATENT LONGITUDINAL MODELING, CANCER GENOMICS AND COMPUTATIONAL BIOLOGY WILL BE USED TO TEST OUR HYPOTHESES. DURING THE UG3 PHASE, WE WILL HIRE AND TRAIN STAFF, ESTABLISH AND FINALIZE STUDY PROTOCOLS, RECRUIT ~18% OF THE SAMPLE AND CONDUCT PRELIMINARY ANALYSES. DURING THE UH3 PHASE WE WILL COMPLETE RECRUITMENT, CONDUCT ALL REMAINING ASSESSMENTS, ANALYZE DATA AND DISSEMINATE FINDINGS TO GUIDE AND IMPLEMENT SECONDARY AND TERTIARY PREVENTION IN H/L SURVIVORS.

RNASES AND RNA METABOLISM IN BACTERIA

HOST DEFENSE REGULATION AND VIRAL ONCOGENESIS

INNOVATIVE DEEP PHENOTYPING OF AFRICAN AMERICANS AT RISK FOR ALZHEIMERS DISEASE - PROJECT SUMMARY A CRITICAL GAP IN ALZHEIMER’S DISEASE (AD) AND ALZHEIMER’S DISEASE RELATED DISORDERS (ADRD) CLINICAL RESEARCH IS THE VAST UNDER-UNDER-REPRESENTATION OF BLACK/AFRICAN AMERICAN (AA) OLDER ADULTS. IT IS WELL-DOCUMENTED THAT AD+ADRD IS MORE PREVALENT IN AA INDIVIDUALS RELATIVE TO WHITE INDIVIDUALS OF EUROPEAN ANCESTRY. EARLY DETECTION OF AD+ADRD IS CRITICAL FOR CLINICAL TRIALS AIMING TO DEVELOP OPTIMAL THERAPEUTICS. WITHOUT ADEQUATE REPRESENTATION OF AA IN COGNITIVE AND BIOMARKER STUDIES EXAMINING THE EARLIEST CHANGES IN AD+ADRD, THE DIAGNOSTIC, PROGNOSTIC, AND CLINICAL UTILITY OF PROMISING BIOMARKERS AND THEIR EFFECTS ON COGNITION CANNOT BE ESTABLISHED. THEREFORE, THERE IS A PRESSING NEED TO INCLUDE AND DEEPLY PHENOTYPE AAS USING NOVEL COGNITIVE AND BIOMARKER ASSESSMENTS THAT CONSIDER THE MULTIPLE CO-MORBIDITIES IDENTIFIED IN THIS POPULATION. STUDY LOCATION HAS BEEN IDENTIFIED AS ONE OF THE MOST PREVALENT ENROLLMENT BARRIERS FOR AA OLDER ADULTS. THIS CURRENT RESEARCH PROPOSAL LEVERAGES OUR VAST EXPERTISE IN CONDUCTING HOME-BASED ASSESSMENT TO EVALUATE CLINICAL AND NEUROPSYCHOLOGICAL STATUS WITH EQUIPMENT THAT WE PLACE WITHIN THE HOME. IMPORTANTLY, WE WILL PROVIDE DOOR-TO-DOOR TRANSPORTATION FOR MRI AND AMYLOID PET IMAGING STUDIES THAT WE HAVE SUCCESSFULLY EMPLOYED TO RECRUIT AND RETAIN CULTURALLY DIVERSE OLDER ADULTS INCLUDING AA, WITH AND WITHOUT COGNITIVE IMPAIRMENT INTO BIOMARKER STUDIES. THIS WILL FACILITATE A USER-FRIENDLY AND EFFECTIVE APPROACH THAT SUPPORTS THE ENGAGEMENT OF AA OLDER ADULTS. OTHER IMPORTANT AND INNOVATIVE ASPECTS OF OUR PROPOSED STUDY INCLUDE: A) THE USE OF OUR NOVEL COGNITIVE CHALLENGE TESTS (CCTS) THAT EMPLOY SENSITIVE AND SPECIFIC COGNITIVE ASSESSMENT PARADIGMS THAT HAVE BEEN ASSOCIATED TO BIOMARKERS OF AD AND NEURODEGENERATION, AND HAVE BEEN VALIDATED FOR USE IN AA OLDER ADULTS WITH AND WITHOUT MILD COGNITIVE IMPAIRMENT (MCI); B) USE OF STATE-OF-THE-SCIENCE PLASMA-BASED MARKERS OF AD AND NEURODEGENERATION THAT LEVERAGE EXTREMELY SENSITIVE SIMOA TECHNOLOGY; C) WE WILL UNIQUELY RELATE OUR NOVEL CCTS AT BASELINE AND LONGITUDINALLY TO CHANGES OVER TIME IN SERIALLY COLLECTED PLASMA BIOMARKERS (E.G., P-TAU181, P-TAU217, NFL, GFAP), D) COMPARISON OF PLASMA MARKERS OF AD AND NEURODEGENERATION WITH AMYLOID PET IMAGING AND EXTRA-CELLULAR FREE WATER DIFFUSION AS WELL AS NEURODEGENERATIVE CHANGES ON MRI; E) ACCOUNTING FOR THE COMORBIDITY OF COMMON CHRONIC CONDITIONS IN THE AA POPULATION, WE WILL OBTAIN SENSITIVE MEASURES OF CEREBROVASCULAR DISEASE, INFLAMMATION, DIABETES AND METABOLIC RISK, AS WELL AS CHRONIC KIDNEY DISEASE; F) STRUCTURAL AND SOCIAL DETERMINANTS OF HEALTH WILL ALSO BE ASSESSED. THE DEEP PHENOTYPING OF 270 NON-HISPANIC AA OLDER ADULTS IN THE PROPOSED RESEARCH STUDY AND OUR RESOURCE SHARING PLAN WILL ACCELERATE EFFORTS TO GAIN CRITICALLY NEEDED KNOWLEDGE OF AD+ADRD IN A SERIOUSLY UNDERREPRESENTED AA GROUP. THE DATA OBTAINED WILL PROMOTE THE REPRODUCIBILITY OF THIS WORK IN EXTANT DATABASES THAT INCLUDE AA AND CAN FACILITATE COMPARISON OF FINDINGS WITH NON-AA SAMPLES. THIS IMPORTANT COHORT WILL CONTINUE TO BE FOLLOWED THROUGHOUT THE FUNDING PERIOD AND BEYOND.

INNOVATIVE APPROACH TO TRAUMA COMBAT EDUCATION

ENHANCER RNA THERAPY

ROLE OF FIBROBLASTS IN AXON REGENERATION AFTER SCI

INNOVATIVE APPROACHES TO COMBAT EDUCATION

DEVELOPMENT AND PROOF-OF-CONCEPT IMPLEMENTATION OF THE SOUTH FLORIDA MIAMI RADX-RAD SARS-COV-2 WASTEWATER-BASED SURVEILLANCE INFRASTRUCTURE - PROJECT SUMMARY THE UNIVERSITY OF MIAMI (UM), WITH THREE PRIMARY CAMPUSES IN MIAMI, FLORIDA, IS GEOGRAPHICALLY SPREAD WITHIN ONE OF THE WORST CURRENT COVID-19 HOTBEDS. UM HAS DEPLOYED AN ELABORATE HUMAN SURVEILLANCE TESTING, TRACKING AND TRACING (3T) SYSTEM TO MONITOR THE STUDENT BODY, FACULTY, AND STAFF. THIS 3T SYSTEM INCLUDES A MAJOR HOSPITAL THAT IS PART OF UM AND THAT TREATS COVID-19 PATIENTS. TO AUGMENT THIS COVID-19 MONITORING SYSTEM, UM HAS DEPLOYED A PILOT WASTEWATER SURVEILLANCE PROGRAM FOR DETECTING SARS-COV-2 FROM CLUSTERS OF BUILDINGS ON CAMPUS. WEILL CORNELL MEDICINE (WCM) IS LOCATED IN NEW YORK CITY, NY, AN AREA THAT UNTIL RECENTLY HAD ONE OF THE WORST OUTBREAKS OF COVID-19. WCM HAS ESTABLISHED AN INTERNATIONAL CONSORTIUM FOR SARS-COV-2 ENVIRONMENTAL SURVEILLANCE, INCLUDING IN NYC AND GLOBALLY WITH THE METASUB CONSORTIUM, WHICH IS CREATING METAGENOMIC AND METATRANSCRIPTOMIC MAPS OF THE WORLD’S SEWAGE. BASED ON THIS WORK AT BOTH UM AND WCM, THIS PROPOSAL AIMS TO DEVELOP, IMPLEMENT, AND DEMONSTRATE EFFECTIVE AND PREDICTIVE WASTEWATER SURVEILLANCE BY OPTIMIZING SAMPLING, CONCENTRATION, AND DETECTION STRATEGIES. WORKING CLOSELY WITH THE RADX-RAD DATA COORDINATION CENTER (DCC), THIS APPLICATION (SF-RAD) WILL DEVELOP AND IMPLEMENT DATA STANDARDS AND INFORMATICS INFRASTRUCTURE AND PERFORM INTEGRATIVE ANALYSES TO MAKE ALL DATA, RESULTS, AND MODELS AVAILABLE TO THE COMMUNITY, THUS PROVIDING A CRITICAL CONTRIBUTION TO THE NATIONAL SARS-COV-2 RADX-RAD WASTEWATER DETECTION CONSORTIUM. OUR OBJECTIVES WILL BE ADDRESSED THROUGH THREE AIMS. AIM 1: DATA STANDARDIZATION, FOCUSES ON DEVELOPING AND IMPLEMENTING DATA STANDARDS AND QUALITY METRICS, AND ESTABLISHING THE OPERATIONAL INFRASTRUCTURE TO MANAGE SARS-COV-2 WASTEWATER-BASED SURVEILLANCE DATASETS AND METADATA. AIM 2: WASTEWATER CHARACTERIZATION, FOCUSES ON OPTIMIZING WASTEWATER SURVEILLANCE PROTOCOLS AND PARAMETERS FOR WASTEWATER SAMPLING, SAMPLE CONCENTRATION, AND VIRAL DETECTION TECHNOLOGIES. AIM 3: INTEGRATION WITH HUMAN HEALTH SURVEILLANCE, FOCUSES ON METATRANSCRIPTOMIC ANALYSES AND ON THE INTEGRATION OF WASTEWATER QUANTIFICATION DATA WITH COMMUNITY AND HOSPITAL COVID-19 PREVALENCE, TO DEVELOP PREDICTIVE MODELS TO DETECT LOCAL AND COMMUNITY LEVEL SPREAD OF COVID-19. ALL DATA WILL BE MADE FINDABLE, ACCESSIBLE, INTEROPERABLE AND REUSABLE (FAIR) IN CLOSE COLLABORATION WITH THE DCC, AND WILL BE COLLECTED AND MANAGED WITH ATTENTION TO ETHICAL ISSUES IN SURVEILLANCE AND DATA MANAGEMENT, INCLUDING EFFORTS TO ENSURE RESEARCH RIGOR AND REPRODUCIBILITY. THE RESULTS FROM THIS PROPOSAL WILL DEVELOP AND DEPLOY EXPERIMENTAL AND INFORMATICS INFRASTRUCTURE AND OPERATIONS AS PART OF THE NATIONAL RADX-RAD SARS-COV-2 WASTEWATER SURVEILLANCE NETWORK AND WILL PROVIDE A PROOF-OF-CONCEPT IMPLEMENTATION TO USE WASTEWATER FOR INFECTIOUS DISEASE SURVEILLANCE FOR EARLY DETECTION OF LOCALIZED COVID-19 OUTBREAKS.

REPLICATION AND EXTENSION OF ADSP DISCOVERIES IN AFRICAN-AMERICANS

IMMUNE MECHANISMS IN OCULAR GRAFT VERSUS HOST DISEASE

ELUCIDATION OF INTEGRATOR'S FUNCTION

LEBER HEREDITARY OPTIC NEUROPATHY: GENE THERAPY TRIAL

ADOLESCENT TRIALS NETWORK FOR HIV/AIDS INTERVENTIONS (A*

POLYUNSATURATED FATTY ACIDS AS ANTI-ARRHYTHMIC AGENTS

SEX AND GENDER INFLUENCES ON ADDICTION AND HEALTH: A DEVELOPMENTAL PERSPECTIVE

SATELLITE SAR EXPLOITATION AND IMAGING AND MEASUREMENT OF OCEANIC PHENOMENA

RELATIVE CONTRIBUTION OF TRYPSIN & INFLAMMATION IN ACUTE & CHRONIC PANCREATITIS

PRECLINICAL DEVELOPMENT OF HIV-1 VIF ANTAGONISTS

REGULATION OF ANTI-TUMOR IMMUNITY

BEHAVIORAL MEDICINE RESEARCH IN CARDIOVASCULAR DISEASE

TYPE 1 DIABETES TRIALNET CLINICAL CENTER: EFFECTS OF ALEFACEPT IN NEW ONSET T1D

TARGETING CELL-TYPE SPECIFIC DISEASE PHENOTYPES TO PROMOTE CNS REPAIR - PROJECT SUMMARY/ABSTRACT DESPITE DECADES OF INTENSIVE RESEARCH, THERE ARE CURRENTLY NO DISEASE-MODIFYING THERAPIES TO TREAT SPINAL CORD INJURY (SCI). ONE MAJOR REASON FOR THIS DIRE UNMET NEED IS THE SPATIOTEMPORAL HETEROGENEITY OF THE CELLS THAT COMPRISE THE INJURY SITE. THERAPEUTIC MOLECULES (E.G., SMALL MOLECULES, RNAS, PROTEINS) THAT TARGET ONE CELL TYPE MAY BE CONTRAINDICATED FOR ANOTHER CELL TYPE, THEREBY MASKING ANY POTENTIAL BENEFICIAL EFFECTS. IN THIS PROPOSAL, WE WILL ADDRESS THIS ISSUE BY UTILIZING SINGLE-CELL TRANSCRIPTOMICS AND PROTEOMICS DATA OF THE SPINAL CORD INJURY SITE TO BIOINFORMATICALLY IDENTIFY COMPOUNDS THAT ARE PREDICTED TO REVERSE THE DISEASE PHENOTYPE IN A CELL-TYPE AND CELL-STATE-SPECIFIC MANNER. OUR RESEARCH TEAM HAS RECENTLY DEVELOPED A NOVEL DRUG DISCOVERY PLATFORM THAT INTEGRATES SINGLE-CELL GENE EXPRESSION DATA WITH PERTURBATION-RESPONSE DATA DERIVED FROM THE NIH LIBRARY OF INTEGRATED NETWORK-BASED CELLULAR SIGNATURES (LINCS) L1000 DATASET TO IDENTIFY COMPOUNDS THAT TARGET SPECIFIC CELL-TYPES IN TISSUES WITH DIVERSE CELLULAR HETEROGENEITY. ANOTHER CHALLENGE THAT WILL BE ADDRESSED IN THIS PROPOSAL IS THAT OF CELL-TYPE SPECIFIC DRUG DELIVERY. WE WILL DEVELOP AN ADVANCED DRUG DELIVERY SYSTEM CAPABLE OF HIGHLY EFFICIENT CELL-TYPE TARGETED DELIVERY WITH STIMULI-RESPONSIVE DRUG RELEASE AT THE SPINAL CORD INJURY SITE. THESE NOVEL TECHNOLOGIES WILL BE USED TO TARGET MACROPHAGES AND FIBROBLASTS THAT COMPRISE THE FIBROTIC SCAR AT THE SPINAL CORD INJURY SITE, WHICH IS A MAJOR BARRIER TO THE REGENERATION OF AXONS AND OLIGODENDROCYTES.

WEB-BASED MARRIAGE PREPARATION, ENRICHMENT, AND DIVORCE PREVENTION FOR LOW-INCOME COUPLES

INCREASING AVAILABILITY AND ACCEPTABILITY OF CIRCUMCISION IN ZAMBIA

ELUCIDATING A NOVEL MOLECULAR BIOMARKER FOR CASTRATION-RESISTANT PROSTATE CANCER

DETERMINANTS OF INSUFFICIENT SLEEP AMONG BLACKS AND EFFECTS ON DISPARITIES IN HEALTH OUTCOMES

MOLECULAR AND GENETIC EPIDEMIOLOGY OF AUTISM

STABILIZING THE TRIPARTITE SYNAPTIC COMPLEX FOLLOWING TBI

NOVEL RESUSCITATION STRATEGIES

TARGETING P300 AND LYSINE ACETYLATION IN AML

ISCHEMIC PRECONDITIONING: MECHANISMS OF NEUROPROTECTION

IMMUNE DYSFUNCTION IN HIV+ OPIOID USERS

MOLECULAR BASIS OF PHOTORECEPTOR WIRING

LEBER'S HEREDITARY OPTIC NEUROPATHY: GENE THERAPY CLINICAL TRIAL

REPP-CONNECTIVITY-PULLEY RIDGE: POPULATION CONNECTIVITY OF THE PULLEY RIDGE - SOUTH FLORIDA CORAL REEF ECOSYSTEM: PROCESSES TO DECISION-SUPPORT TOOLS

MOBILE SOLUTIONS FOR DISASTER AND MASS CASUALTY EVENTS

MOLECULAR PREDICTIVE TESTING IN OCULAR MELANOMA

SOUTHEAST ENROLLMENT CENTER (SEEC)

UNIVERSITY OF MIAMI PEDIATRIC PERINATAL HIV/AIDS CLINICAL TRAILS UNIT

SOUTH FLORIDA CENTER FOR REDUCING CANCER DISPARITIES

IDENTIFYING PROTECTIVE GENETIC VARIANTS FOR APOE4

UM CALABRESI CLINICAL ONCOLOGY RESEARCH CAREER DEVELOPMENT AWARD

CELL BASED THERAPY FOR NON-ISCHEMIC DILATED CARDIOMYOPATHY

NOVEL GENE TARGETS FOR CNS AXONAL REGENERATION

P53 FAMILY IN GASTRIC CANCER DEVELOPMENT

THE INHIBITION OF HSP70 INDUCES APOPTOSIS IN PANCREATIC CANCER CELLS

ONCOGENIC MECHANISMS, MOLECULAR STRATIFICATION AND THERAPEUTIC TARGETS OF BRAIN TUMORS - ABSTRACT THE WORK TO BE PURSUED IN THIS APPLICATION WILL CONTINUE AND EXPAND THE PROGRAM PIONEERED BY DR. IAVARONE TO COMBINE INNOVATIVE COMPUTATIONAL TOOLS AND STATE-OF-THE-ART EXPERIMENTAL CANCER MODELS IN VITRO AND IN VIVO TO IDENTIFY HOMOGENEOUS SUBGROUPS OF CANCER PATIENTS IN ORDER TO DISSECT THE PATHOGENESIS OF CANCER AND DESIGN TAILORED AND FULLY VALIDATED PERSONALIZED THERAPEUTIC APPROACHES. THE APPLICATION IS FOCUSED ON GLIOBLASTOMA MULTIFORME, ONE OF THE MOST LETHAL FORMS OF HUMAN CANCER. THE INVESTIGATION OF GLIOBLASTOMA HAS REPRESENTED A LONG-STANDING EFFORT OF DR. IAVARONE’S LABORATORY, WHICH IN RECENT WORK HAS PRODUCED NOVEL TARGETED THERAPEUTIC OPPORTUNITIES CURRENTLY BEING TESTED IN CLINICAL STUDIES. THE PROPOSAL WILL ALSO BENEFIT FROM THE ORGANIZATIONAL CONTEXTS RECENTLY SET IN MOTION BY THE LARGE NETWORK OPERATIONS COORDINATED BY THE PI. THE RESEARCH PLAN IS ARTICULATED AROUND THE DEVELOPMENT OF A NOVEL AND INTEGRATED COMPUTATIONAL-EXPERIMENTAL FRAMEWORK FOR: I) THE IDENTIFICATION OF HOMOGENEOUS GROUPS OF TUMORS SHARING ACTIVATION OF THE SAME BIOLOGICAL PATHWAYS; II) THE STUDY OF CANCER HETEROGENEITY AT THE SINGLE CELL LEVEL TO ACCURATELY INFORM TUMOR CLASSIFICATIONS; III) THE THERAPEUTIC PREDICTION EMERGING FROM THE IDENTIFICATION OF DRIVER MODULES AND SYNTHETIC LETHAL RELATIONSHIPS OF MALIGNANT GLIOMA. WE WILL DEVELOP AND APPLY NOVEL TECHNOLOGIES FOR HIGH-THROUGHPUT TRANSCRIPTOMIC AND PROTEOMIC ANALYSIS OF INDIVIDUAL CELLS WITHIN MALIGNANT GLIOMA TISSUES. THESE APPROACHES, WHICH WE HAVE PIONEERED IN OUR LABORATORY AT COLUMBIA UNIVERSITY DURING THE LAST FEW YEARS, WILL SERVE AS THE BASIS FOR THE MULTIFACETED COMPUTATIONAL ANALYSIS THAT WILL EXTRACT GENES AND PROTEINS RESPONSIBLE FOR THE PHENOTYPIC STATE OF INDIVIDUAL CELLS. EXPERIMENTAL VALIDATIONS WILL BE SELECTIVELY APPLIED TO THE NOVEL AND MOST EXCITING MOLECULAR PATHWAYS AND WILL BE PERFORMED BY OUR LABORATORY THAT HAS AN ARRAY OF EXPERIMENTAL TOOLS AND SEQUENCE-ANNOTATED PATIENT-DERIVED MODELS TO PURSUE EACH INDIVIDUAL QUESTION. AS FOR THE SELECTION OF ONCOGENE-DEPENDENT AND INDEPENDENT VULNERABILITIES IDENTIFIED BY OUR PREVIOUS WORK, THE ABILITY OF OUR STUDIES TO IDENTIFY NOVEL DRIVER PHENOTYPES AND MASTER REGULATORS OF INDIVIDUAL TUMOR CELLS WILL BE GEARED TOWARDS ROUTING THE NEW MECHANISMS INTO PATHWAY-BASED SYNTHETIC LETHALITY THAT WILL INFORM SPECIFIC DRUG SENSITIVITIES. THE SUCCESSFUL OUTCOME OF THIS PROPOSAL IS AN INTEGRATED COMPUTATIONAL-EXPERIMENTAL PIPELINE THAT WILL BE ABLE TO MECHANISTICALLY IDENTIFY THE DETERMINANTS OF TUMOR GENOMES AND PHENOTYPES OF SOLID TUMORS. THIS INFORMATION WILL BE OF INVALUABLE SIGNIFICANCE TO DECIPHER EVOLVING TUMOR DEPENDENCIES AND PROVIDE THE MOST ACCURATE THERAPEUTIC PREDICTIONS.

CULTURALLY ADAPTED COGNITIVE BEHAVIORAL STRESS AND SELF-MANAGEMENT (C-CBSM) INTERVENTION FOR PC

HISPANIC STROKE PREVENTION INTERVENTION RESEARCH PROGRAM

REPRESSION VIA FACULTATIVE HETEROCHOMATIN

HEAT SHOCK PROTEINS AND PANCREATITIS

FUNCTIONAL ROLE OF O-GLYCOSYLATION OF HIV-1

PH REGULATION OF CELL SURFACE RECEPTORS

OPTOMECHANICAL CHARACTERISTICS OF LENS ACCOMMODATION

SOUTH FLORIDA'S COASTAL AND MARINE ECOSYSTEMS PROVIDE CRITICAL ECOSYSTEM SERVICES TO THE NATION, GENERATING BILLIONS OF DOLLARS FOR THE ECONOMY AND TENS OF THOUSANDS OF JOBS ANNUALLY. THE WELL-BEING OF OVER SIX MILLION PEOPLE IN COASTAL COUNTIES DEPEND ON THESE ECOSYSTEMS, WHICH ARE BESET BY MULTIPLE STRESSORS AND GLOBAL CLIMATE CHANGE. THIS PROJECT ADDRESSES THESE MULTIPLE INTERACTING STRESSORS (I.E., OCEAN ACIDIFICATION, HYPOXIA, HARMFUL ALGAL BLOOMS, INCREASING WATER TEMPERATURES, AND EUTROPHICATION) AND THEIR VARYING CONCENTRATIONS ACROSS SOUTH FLORIDA'S ECOSYSTEMS FROM THE WEST FLORIDA SHELF TO THE FLORIDA KEYS NATIONAL MARINE SANCTUARY. IT INVESTIGATES HOW THEY ARE IMPACTING/WILL IMPACT ECOSYSTEMS UNDER PRESENT AND FUTURE CLIMATE CHANGE SCENARIOS, AND DIFFERENT MANAGEMENT/RESTORATION STRATEGIES UNDER MISSION: ICONIC REEFS AND THE COMPREHENSIVE EVERGLADES RESTORATION PLAN.

MECHANISMS OF NEUROPROTECTION AGAINST CARDIAC ARREST

REVEALING HIV-1 PERSISTENCE IN MYELOID CELL RESERVOIRS

ANTIBODY RESPONSES IN AGING SIV INFECTED MONKEYS

IN VITRO MODELS FOR BIODEFENSE

GAMMA-2 HERPESVIRUSES AS VACCINE VECTORS FOR AIDS

GENETIC EPIDEMIOLOGY OF EARLY-ONSET ALZHEIMERS DISEASE IN CARIBBEAN HISPANICS AND NON-HISPANIC WHITES

AKT/MTOR SIGNALING AND REGULATION OF CELL CYCLE IN BETA CELLS

PATIENT-SPECIFIC SIMULATIONS TO GUIDE CORONARY BIFURCATION STENTING

MOLECULAR BASIS OF TASTE CELL SIGNALING

HOST DEFENSE AND THE REGULATION OF INTERFERON PRODUCTION

BIOBEHAVIORAL PREDICTORS OF ILLNESS PROGRESSION IN ADOLESCENT DEPRESSION

EVALUATING THE EFFECTIVENESS OF AN EHEALTH EBI FOR LATINO YOUTH IN PRIMARY CARE

FAMILIAS UNIDAS STAGE III STUDY: PREVENTING SUBSTANCE ABUSE IN HISPANIC YOUTH

CONFORMAL ISLET ENCAPSULATION FOR TRANSPLANTATION AT VASCULARIZED SITES TO ALLOW PHYSIOLOGICAL INSULIN SECRETION

MEDICAL SCIENTIST TRAINING PROGRAM - PROJECT SUMMARY THE GOAL OF THE MEDICAL SCIENTIST TRAINING PROGRAM (MSTP) AT THE UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE (UMMSM) IS TO PROVIDE A RICH, SUPPORTIVE AND INCLUSIVE TRAINING ENVIRONMENT THAT FOSTERS THE DEVELOPMENT OF DIVERSE, HIGHLY MOTIVATED AND GOAL-ORIENTED PHYSICIAN SCIENTISTS WHO WILL PURSUE CAREERS MATCHING STATE OF THE ART RESEARCH WITH EVIDENCE-BASED MEDICINE. THE MILLER SCHOOL IS FULLY POSITIONED TO ENSURE THE SUCCESS OF THE MSTP. THE CONTINUOUS EXPANSION OF BASIC AND CLINICAL FUNDED RESEARCH, THE ESTABLISHMENT OF SEVERAL NEW NIH FUNDED CENTERS AND TRAINING GRANTS, THE INSTITUTIONAL INVESTMENT IN NEW INFRASTRUCTURE AND CORE FACILITIES OVER THE LAST 10 YEARS, AS WELL AS MIAMI’S DIVERSE POPULATION AND ACCESS TO LATIN AMERICA & THE CARIBBEAN, MAKE UMMSM AN OUTSTANDING PLACE FOR MSTP TRAINING. STUDENTS ARE RECRUITED FROM COLLEGES AND UNIVERSITIES THROUGHOUT THE US AND ARE SELECTED THROUGH A HOLISTIC REVIEW PROCESS THAT FOCUSES ON RESEARCH EXPERIENCE, CHARACTER, AND PASSION FOR A DUAL RESEARCH AND MEDICINE CAREER. SOUTH FLORIDA’S UNIQUE DEMOGRAPHICS HAS BEEN A KEY ELEMENT IN THE RECRUITMENT OF A DIVERSE MSTP STUDENT BODY, WHICH HAS 36% OF TRAINEES UNDERREPRESENTED IN MEDICINE (26% UNDERREPRESENTED MINORITIES). THE AWARD OF A MSTP T32 IN 2017 HAS INCREASED THE NUMBER AND QUALITY OF OUR APPLICATIONS AND HAS ALSO FACILITATED STRONGER INSTITUTIONAL AND PROGRAMMATIC LEADERSHIP SUPPORT, RESULTING IN A 30% INCREASE IN THE PROGRAM SIZE IN 5 YEARS. THE PROGRAM IS WELL INTEGRATED WITH THE NEWLY ESTABLISHED UMMSM NEXTGENMD CURRICULUM THAT HIGHLY VALUES SCHOLARLY ACTIVITIES. THIS CURRICULUM ALLOWS MSTP STUDENTS TO COMPLETE THEIR DUAL DEGREE IN 7-8 YEARS, AND EFFECTIVELY INCORPORATES PHD TRAINING AFTER EXPOSURE TO BOTH PRECLINICAL COURSEWORK (14 MONTHS) AND CLINICAL CLERKSHIPS (1ST 6 MONTHS). STUDENTS ARE ABLE TO SELECT AMONG PHD TRAINING PROGRAMS IN EIGHT INTERDISCIPLINARY PROGRAMS IN BIOMEDICAL SCIENCES, AS WELL AS PROGRAMS IN PUBLIC HEALTH SCIENCES AND BIOMEDICAL ENGINEERING. GRADUATE TRAINING THAT CONFERS THE DEVELOPMENT OF COMPETENCIES NEEDED TO CARRY OUT RIGOROUS AND ETHICAL RESEARCH AND MSTP SUPPORT OF FORMAL TRAINING TO ENHANCE PRODUCTIVE MENTOR-MENTEE RELATIONSHIPS ARE COMPLEMENTED BY A SERIES OF OTHER MSTP ACTIVITIES ENHANCING SKILLS NECESSARY TO BUILD A SOLID PHYSICIAN SCIENTIST UNIQUE IDENTITY. THESE INCLUDE A JOURNAL CLUB FOR MSTP STUDENTS IN THEIR EARLY YEARS OF MEDICAL SCHOOL, LONGITUDINAL CLINICAL EXPERIENCES DURING GRADUATE TRAINING WHICH INCLUDES EXPOSURE TO CLINICAL RESEARCH RELATED ACTIVITIES, AND STUDENT-LED ACTIVITIES THAT BRING TOGETHER ALL MSTP STUDENTS, SUCH AS MONTHLY SCIENTIFIC & PROFESSIONAL DEVELOPMENT WORKSHOPS, MONTHLY CLINICAL CASE REVIEWS, ANNUAL MSTP STUDENT RESEARCH SYMPOSIUM, ANNUAL RETREAT AND OTHER CAREER DEVELOPMENT AND SOCIAL ACTIVITIES. MEASURABLE OUTCOMES OF THE PROGRAM INCLUDE, AMONG OTHERS, STRONG PUBLICATION RECORDS, HIGH SUCCESS RATES OF NRSA FELLOWSHIP APPLICATIONS, AND EXCELLENT RESIDENCY MATCHES. OVERALL THE MSTP PROVIDES AN INTEGRATED TRAINING EXPERIENCE THAT FOSTERS A TRUE CULTURE AND PASSION FOR LEARNING HOW TO GENERATE AND TRANSLATE INNOVATIVE RESEARCH TO MEDICINE.

CELLULAR AND MOLECULAR CONSEQUENCES OF RESPIRATORY CHAIN DEFECTS IN NEURONS

MEASURING INTERANNUAL VARIABILITY OF THE AMOC AND MERIDIONAL OCEAN HEAT TRANSPORT AT 26.5N: THE RAPID-MOCHA ARRAY

REVERSING HIV T CELL DYSFUNCTION BY APTAMER TARGETING OF THERAPEUTIC SIRNAS

SATELLITE-BASED MONITORING OF THE ARCTIC POLAR REGIONS

THE HUMAN BRAINOME III: EQTL REGULATION BY NATURAL ANTISENSE RNA IN ALZHEIMER S DISEASE

INTEGRATIVE GENOMIC APPROACHES FOR UNDERSTANDING SEX DIFFERENCES IN ALZHEIMER'S DISEASE

NOVEL ROLE OF OCCLUDIN AND PERICYTES IN ISCHEMIC STROKE IN HIV INFECTION

IDENTIFYING THE GENETIC ETIOLOGY OF NEUROPATHOLOGY FOR ALZHEIMER DISEASE AND RELATED DEMENTIAS

RANDOMIZED PHASE II TRIAL OF PROLONGED OVERNIGHT FASTING AND/OR EXERCISE ON FATIGUE AND OTHER PATIENT REPORTED OUTCOMES IN WOMEN WITH HORMONE RECEPTOR POSITIVE ADVANCED BREAST CANCER (FASTER) - ABSTRACT MORE THAN 40,000 WOMEN DIE EACH YEAR OF METASTATIC BREAST CANCER. THE MAJORITY OF THESE TUMORS ARE HORMONE RECEPTOR POSITIVE (HR+) THAT ARE TREATED WITH A CYCLIN DEPENDENT KINASE 4/6 (CDK4/6) INHIBITOR IN COMBINATION WITH AN AROMATASE INHIBITOR OR FULVESTRANT. WITH THESE TREATMENTS, WOMEN WITH ADVANCED BREAST CANCER ARE LIVING LONGER, BUT TREATMENT RELATED TOXICITIES INEVITABLY OCCUR, AND QUALITY OF LIFE IS LIMITED BY SIDE EFFECTS OF CANCER TREATMENT WHICH MAY RESULT IN DOSE REDUCTIONS AND DELAYS. FATIGUE IS THE MOST COMMONLY CITED ADVERSE SIDE EFFECT REPORTED FOR WOMEN TAKING CDK4/6 INHIBITORS AND MECHANISTICALLY MAY BE ASSOCIATED WITH INFLAMMATION. WHEN UNMANAGED, FATIGUE IS DEBILITATING DIRECTLY IMPACTING BOTH PSYCHOLOGICAL AND PHYSICAL QUALITY OF LIFE AND A KEY DRIVER IN DISCONTINUATION OF THERAPY. LIFESTYLE INTERVENTIONS TARGETING DIET AND EXERCISE HAVE EVIDENCE FOR IMPROVING FATIGUE IN EARLY STAGE BREAST CANCER, HOWEVER WHETHER THESE STRATEGIES ARE EFFICACIOUS FOR IMPROVING OUTCOMES IN WOMEN WITH ADVANCED BREAST CANCER REMAINS UNKNOWN, WITH EVEN LESS INFORMATION FOR WOMEN FROM UNDERREPRESENTED BACKGROUNDS, WHO SUFFER DISPROPORTIONATELY FROM BREAST CANCER AND ITS TREATMENT. RESEARCH REGARDING THE IMPACT OF THESE STRATEGIES ON HIGH GRADE FATIGUE INDUCED BY CDK4/6 INHIBITORS IN ADVANCED DISEASE FROM A DIVERSE PATIENT POPULATION ARE NEEDED. THE PROLONGED OVERNIGHT FASTING AND/OR EXERCISE ON FATIGUE AND OTHER PATIENT REPORTED OUTCOMES IN WOMEN WITH HORMONE RECEPTOR POSITIVE ADVANCED BREAST CANCER (FASTER) STUDY, WILL EVALUATE A PHASE II, 2 X 2 RANDOMIZED CONTROLLED TRIAL TESTING THE EFFECTS OF A PROLONGED OVERNIGHT FASTING (POF) INTERVENTION ALONE, MODERATE-INTENSITY EXERCISE ALONE, OR IN COMBINATION, ON FATIGUE IN 260 WOMEN WITH ADVANCED BREAST CANCER INITIATING TREATMENT WITH HORMONAL THERAPY IN COMBINATION WITH A CDK4/6 INHIBITOR. PARTICIPANTS WOULD UNDERGO ASSESSMENT OF FATIGUE AND ASSOCIATED INFLAMMATORY BIOMARKERS, AS WELL AS ASSESSMENT OF PHYSICAL ACTIVITY, DIET, PHYSICAL FUNCTION, BODY COMPOSITION AND PATIENT REPORTED OUTCOMES AT BASELINE (PRIOR TO THE INITIATION OF CDK4/6 INHIBITOR) AND 12 WEEKS (POST-INTERVENTION), 6 AND 12 MONTHS AFTER STUDY ENROLLMENT. THE PRIMARY OUTCOME OF THE STUDY IS TO EVALUATE THE IMPACT OF THE INTERVENTIONS (VS CONTROL) ON FATIGUE IN WOMEN AT 12 WEEKS. SECONDARY OUTCOMES INCLUDE INFLAMMATORY BIOMARKERS, PATIENT-REPORTED OUTCOMES, PHYSICAL FUNCTION AND BODY COMPOSITION. THE FASTER STUDY WILL ALSO EXPLORE THE IMPACT OF THE INTERVENTION ON CIRCADIAN RHYTHMS, FATIGUE, SLEEP, DEPRESSION, ANXIETY, QUALITY OF LIFE, PHYSICAL FUNCTION AND BODY COMPOSITION. THE OVERARCHING GOAL OF THE FASTER STUDY IS TO DETERMINE WHETHER PROLONGED OVERNIGHT FASTING OR MODERATE- INTENSITY EXERCISE ALONE OR IN COMBINATION CAN MITIGATE THE ADVERSE CONSEQUENCES OF TREATMENT AND IMPROVE FATIGUE AND OTHER OUTCOMES, IN WOMEN WITH ADVANCED BREAST CANCER TREATED WITH CDK4/6 INHIBITORS TO ULTIMATELY IMPROVE BOTH QUANTITY AND QUALITY OF LIFE FOR THIS GROWING POPULATION OF WOMEN.

BASCOM PALMER EYE INSTITUTE CENTER FOR OPHTHALMIC INNOVATION

TH17 CELLS AS A NEW THERAPEUTIC TARGET FOR DEPRESSION

POISON CONTROL STABILIZATION AND ENHANCEMENT PROGRAM

DORMIR: DETERMINANTS, OUTCOMES, RESPONSES AND MARKERS OF INSUFFICIENT SLEEP IN RURAL-URBAN SETTINGS

REHABILITATION STRATEGIES FOR MEMORY DYSFUNCTION AFTER TRAUMATIC BRAIN INJURY

CYCLIC NUCLEOTIDE REGULATION IN TRAUMATIC BRAIN INJURY

MECHANISMS OF SLEEP DEFICIENCY AND EFFECTS ON BRAIN INJURY AND NEUROCOGNITIVE FUNCTIONS AMONG OLDER BLACKS

AN OBSERVING SYSTEM FOR THE MERIDIONAL OVERTURNING CIRCULATION AND OCEAN HEAT TRANSPORT IN THE SUBTROPICAL NORTH ATLANTIC: EXTENSION OF THE RAPID-MOC

NATIVE ALZHEIMER'S DISEASE RESOURCE CENTER FOR MINORITY AGING RESEARCH (NAD-RCMAR)

EVALUATION OF LIFE-STEPS TO ENHANCE ADHERENCE AND ENGAGEMENT IN PREP CARE

MHC-BOUND, SIV-DERIVED, CTL & HTL EPITOPES

INTEGRATED NAVIGATION SERVICES FOR TREATMENT ADHERENCE, COUNSELING, AND RESEARCH (INSTACARE) - PROJECT SUMMARY: THE PRIMARY AIM OF THIS APPLICATION IS TO EXAMINE THE EFFECTS OF A CLINIC-INTEGRATED COMMUNITY HEALTH WORKER (CHW) INTERVENTION ON HIV OUTCOMES AMONG BLACK PEOPLE WITH POORLY MANAGED HIV. MIAMI-DADE COUNTY, FLORIDA, IS AN HIV EPICENTER WHERE BLACK ADULTS ACCOUNT FOR 17% OF THE POPULATION AND 64% OF AIDS- RELATED DEATHS. THESE HEALTH DISPARITIES ARISE FROM THE SOCIAL DETERMINANTS OF HEALTH (SDOH), THE MODIFIABLE CIRCUMSTANCES IN WHICH PEOPLE GROW, LIVE, WORK, AND AGE. AMONG BLACK PEOPLE, NEGATIVE SDOH LIMIT HEALTHCARE ACCESS AND FOSTER RACIAL INEQUITIES. IN MIAMI-DADE, BLACK PEOPLE ACCOUNT FOR ~60% OF THE HOMELESS, ARE MORE THAN TWICE AS LIKELY TO LIVE BELOW THE FEDERAL POVERTY LEVEL, AND THREE TIMES MORE LIKELY TO BE UNEMPLOYED COMPARED TO THE NON-BLACK POPULATION. THESE DISPARITIES HIGHLIGHT THE CRITICAL NEED FOR MULTI-LEVEL INTERVENTIONS THAT AMELIORATE THE IMPACT OF THE SDOH ON THIS POPULATION. ACCORDINGLY, THIS APPLICATION AIMS TO EXAMINE THE EFFECTS OF THE CHW INTERVENTION ON THE IMPACT OF THE SDOH AND SYSTEM-LEVEL FACTORS ON HIV OUTCOMES. FOR OVER 15 YEARS, THE UNIVERSITY OF MIAMI HAS SUPPORTED RESEARCH ON CHW INTERVENTIONS TO REDUCE HIV DISPARITIES. OUR EARLIER WORK FOUND BLACK PLH RANDOMIZED TO RECEIVE COMMUNITY BASED CHW SUPPORT FOR 12 MONTHS IMPROVED RATES OF VIRAL SUPPRESSION VS. THOSE RECEIVING STANDARD HIV CARE. FURTHER RESEARCH FOUND CLINIC BASED CHW SUPPORT ALSO LED TO IMPROVED HIV OUTCOMES AMONG BLACK PLH. EXPANDING THIS WORK, THIS APPLICATION PROPOSES TO BROADEN CHW SUPPORT TO BOTH COMMUNITY AND CLINICAL SETTINGS BY INTEGRATING CHWS INTO HIV CLINICAL TEAMS WITHIN MIAMI-DADE’S LARGEST PUBLIC HEALTH SYSTEM. FEASIBILITY RESEARCH (1R56NR019755-01) ELICITED STAKEHOLDER INPUT ON CHW CLINIC INTEGRATION AND DATA WAS USED TO DEVELOP A CLINIC-BASED CHW INTERVENTION THAT EXTENDS CARE TO COMMUNITY SETTINGS. AS THIS WORK OCCURRED DURING THE PANDEMIC, STAKEHOLDERS WERE ALSO QUERIED ON PERCEPTIONS OF EMERGING HEALTHCARE CHALLENGES AND POTENTIALLY RESPONSIVE CHW SUPPORT STRATEGIES. INTEGRATED NAVIGATION SERVICES FOR TREATMENT ADHERENCE, COUNSELING, AND RESEARCH (INSTACARE) WILL EMBED CHWS TRAINED IN MOTIVATIONAL INTERVIEWING INTO HIV CLINICAL CARE TEAMS TO ADDRESS SDOH, SYSTEM-LEVEL FACTORS, AND INDIVIDUAL SELF-CARE BEHAVIORS AMONG 300 BLACK PLH. USING A RANDOMIZED CONTROLLED TRIAL DESIGN, PARTICIPANTS WILL RECEIVE A 12-MONTH CHW INTERVENTION OR USUAL HIV CARE. AS 1 IN 3 LOCAL BLACK PERSONS EMIGRATED FROM THE CARIBBEAN, CHWS WILL RECEIVE ROBUST TRAINING TO UTILIZE MI STRATEGIES WITH BLACK CARIBBEAN SUBPOPULATIONS. INTERVENTION EFFECTS ON VIRAL LOAD, MEDICATION ADHERENCE, HOSPITALIZATIONS, AND SELF-EFFICACY IN TREATMENT ADHERENCE AT 12 MONTHS WILL BE DETERMINED FROM MEDICAL RECORDS, PARTICIPANT TRACKING DATA AND PRE AND POST ASSESSMENTS. SUBGROUP ANALYSES WILL COMPARE OUTCOMES BETWEEN AFRICAN AMERICAN, CARIBBEAN- BLACKS, AND LGBTQ PARTICIPANTS. RESULTS WILL CONTRIBUTE TO KNOWLEDGE ON THE UTILITY OF CLINIC- AND COMMUNITY- BASED CHWS TO IMPROVE HIV OUTCOMES AMONG BLACK PLH. IF SUCCESSFUL IN OPTIMIZING HIV HEALTH OUTCOMES, THIS RESEARCH COULD MAKE A SUBSTANTIVE CONTRIBUTION TOWARDS REDUCING OTHER HEALTH DISPARITIES IN THIS POPULATION.

TFH DYSFUNCTION IN HIV AND AGING

GENETIC BASIS OF AGE-AT-ONSET OF ALZHEIMER DISEASE