Trustees Of Boston University

CARB-X

NATIONAL EMERGING INFECTIOUS DISEASES LABORATORIES OPERATIONS

BOSTON UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE

NATIONAL EMERGING INFECTIOUS DISEASES LABORATORIES OPERATIONS

BOSTON UNIVERSITY CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND - INSTITUTIONAL PORTION

NOVEL INSIGHTS INTO OSTEOARTHRITIS, PAIN AND FUNCTION: MOST4 - OVERALL ABSTRACT THE MULTICENTER OSTEOARTHRITIS (MOST) STUDY HAS BEEN A MAJOR SOURCE OF NEW KNOWLEDGE ABOUT THE COURSE OF OA AND FACTORS THAT AFFECT IT, HAVING PUBLISHED OVER 180 ARTICLES RANGING FROM STUDIES OF PAIN AND PAIN SENSITIZATION, TO INVESTIGATIONS OF BIOMECHANICS, TO INQUIRIES INTO STRUCTURAL JOINT PATHOLOGY AS VISUALIZED BY MRI, AND TO STUDIES OF DECLINE IN FUNCTION, BUCKLING AND FALLS, AMONG OTHERS. THE INITIAL COHORT ENROLLED 3026 PARTICIPANTS WITH OR AT RISK OF KNEE OA; A NEW COHORT CONSISTING OF 1525 SUBJECTS WAS RECRUITED AT THE LAST CYCLE (MOST3) WHO WERE SLIGHTLY YOUNGER AND UNLIKELY TO HAVE ADVANCED DISEASE. WE WILL RECRUIT AN ADDITIONAL 150 PARTICIPANTS FROM UNDERREPRESENTED MINORITY GROUPS FOR A TOTAL PROJECTED SAMPLE SIZE OF 2293 IN THIS NEXT CYCLE OF MOST (MOST4). IN ADDITION TO ITS SCIENTIFIC OUTPUT, THE STUDY HAS BEEN REMARKABLE IN RECRUITING AND ENCOURAGING TALENTED YOUNG INVESTIGATORS TO TAKE ON CAREER DEFINING INVESTIGATIONS WITHIN MOST, HAVING SERVED AS THE BASIS FOR 31 CAREER DEVELOPMENT AWARDS. OUR OVERALL GOAL IS TO ADVANCE OUR UNDERSTANDING OF OA AND ITS CONSEQUENCES TO OPEN DOORS TO NEW TREATMENT APPROACHES INCLUDING STRATIFIED APPROACHES TO TREATMENTS. WE WILL USE AN INTEGRATED APPROACH IN THE NEXT CYCLE OF MOST (MOST4) OVERSEEN BY AN ADMINISTRATIVE CORE, INVOLVING A CLINICAL DATA COLLECTION AND MANAGEMENT CORE, ANALYSIS CORE, AND IMAGING CORE, WITH GUIDANCE FROM AN OBSERVATIONAL SAFETY MONITORING BOARD AND INPUT FROM A COMMUNITY ADVISORY BOARD, TO EFFICIENTLY ADDRESS KEY KNOWLEDGE GAPS THROUGH THE CONDUCT OF THREE PROJECTS. OUR SPECIFIC AIMS ARE TO: 1. EVALUATE IMPAIRED EXERCISE-INDUCED HYPOALGESIA (EIH) IN KNEE OA, EVALUATE THE RELATION OF NERVOUS SYSTEM ALTERATIONS TO EIH, AND DETERMINE THE IMPACT OF EIH ON PAIN, FUNCTION, PHYSICAL ACTIVITY, AND FEAR-AVOIDANCE RELATED TO EXERCISE (PROJECT 1); 2. CARRY OUT PROTEOMICS ANALYSIS OF SYNOVIAL FLUID TO DETERMINE NETWORKS OF PROTEINS ASSOCIATED WITH GENERALIZED VS. LOCALIZED OA, PAIN AND DISEASE PROGRESSION (PROJECT 2); 3. DIFFERENTIATE TYPES OF CALCIUM CRYSTALS DEPOSITED IN THE JOINT AND, FOR EACH OF THEM, UNDERSTAND THE CLINICAL AND STRUCTURAL CONSEQUENCES OF CRYSTAL DEPOSITION (PROJECT 3); 4. TAKE ADVANTAGE OF COMPREHENSIVE LONGITUDINAL DATA ALREADY COLLECTED IN MOST TO ADDRESS A WIDE RANGE OF QUESTIONS RELATED TO OA AND ITS IMPACT ON OUTCOMES; 5. BRING A MULTIDISCIPLINARY APPROACH TO BEAR ON THIS COMPLEX DISEASE AND OFFER CAREER DEVELOPMENT OPPORTUNITIES TO INVESTIGATORS INCLUDING PILOT PROJECT GRANTS IN THIS UNDERSTUDIED CONDITION. MOST4 WILL INTRODUCE NEW APPROACHES TO UNDERSTANDING DISEASE AND WILL CONTINUE TO COMPREHENSIVELY ASSESS PAIN, STRUCTURAL, AND FUNCTIONAL OUTCOMES SO THAT THE SPECIFIC EFFECTS OF THE FACTORS PROPOSED IN THE PROJECTS AND OTHER RISK FACTORS CAN BE EXAMINED. THIS WORK WILL PRODUCE NEW ACTIONABLE INSIGHTS REGARDING PAIN, STRUCTURAL DETERIORATION AND FUNCTION LOSS IN KNEE OA.

NANOSYSTEMS ENGINEERING RESEARCH CENTER FOR DIRECTED MULTISCALE ASSEMBLY OF CELLULAR METAMATERIALS WITH NANOSCALE PRECISION: CELL-MET

PRECISION MONITORING AND ASSESSMENT IN THE FRAMINGHAM STUDY: COGNITIVE, MRI, GENETIC AND BIOMARKER PRECURSORS OF AD & DEMENTIA

BOSTON UNIVERSITY CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND - STUDENT AID

SUPERFUND BASIC RESEARCH PROGRAM AT BOSTON UNIVERSITY

DETECTION OF EARLY LUNG CANCER AMONG MILITARY PERSONNEL

PHOTONICS RESEARCH AND TECHNOLOGY

A FOLLOW-UP STUDY FOR CAUSES OF CANCER IN BLACK WOMEN

A PROPOSAL TO SUPPORT DISTRICT-LEVEL IMPLEMENTATION OF THE ZAMBIA MINISTRY OF HEA

RESILIENCE/RESISTANCE TO ALZHEIMER'S DISEASE IN CENTENARIANS AND OFFSPRING (RADCO) - PROJECT SUMMARY/ABSTRACT THE NIA FUNDED PARENT PROJECT, 1U19AG073172, “RESILIENCE/RESISTANCE TO ALZHEIMER’S DISEASE IN CENTENARIANS AND THEIR OFFSPRING (RADCO)” SEEKS TO CHARACTERIZE COGNITIVE RESILIENCE OR BRAIN RESISTANCE TO AD AND TO DISCOVER THE UNDERLYING AND HOPEFULLY TRANSLATABLE BIOLOGICAL MECHANISMS THAT ENABLE CENTENARIAN COGNITIVE SUPERAGERS TO MAINTAIN COGNITIVE FUNCTION TYPICAL OF COGNITIVELY INTACT SEPTUAGENARIANS. TO ADDRESS REVIEWERS’ CONCERNS THAT AFRICAN AMERICANS (N=88 OR 7.2%) ARE UNDERREPRESENTED IN THE RADCO SAMPLE AND THAT TOO FEW CENTENARIANS (N=75 OR 15% OF THE TOTAL NEUROIMAGED SAMPLE) UNDERGO NEUROIMAGING, THIS ADMINISTRATIVE SUPPLEMENT APPLICATION SEEKS TO FUND A FOURTH PHENOTYPING AND BIOSPECIMEN CORE AND NEUROIMAGING CORE SITE AT GEORGIA STATE UNIVERSITY (GSU). THE GSU SITE WILL ENHANCE THE DIVERSITY OF THE RADCO COHORT BY ENROLLING 234 AFRICAN AMERICANS, THUS INCREASING THE PROPORTION OF THE RADCO SAMPLE THAT IS AFRICAN AMERICAN FROM 7.2% (88/1216) TO 22.2% (322/1450). GSU IS ALSO ABLE TO BE A FOURTH NEUROIMAGING SITE FOR RADCO AS IT HAS A PRISMA MRI PLATFORM AND ROUTINELY PERFORMS THE KEY STRUCTURAL AND RESTING STATE FUNCTIONAL PULSE SEQUENCES THAT ARE IDENTICAL TO THOSE USED BY THE THREE CURRENT NEUROIMAGING CENTERS OF THE NEUROIMAGING CORE AS WELL AS THE HUMAN CONNECTOME-AGING PROJECT. WE ANTICIPATE THAT ABOUT HALF (N=103) OF THE ATLANTA-BASED PARTICIPANTS WILL UNDERGO NEUROIMAGING. OF THESE 103 ADDITIONAL NEUROIMAGED PARTICIPANTS, WE ESTIMATE 44 WILL BE CENTENARIANS. THESE 44 CENTENARIANS ADDED TO THE RADCO-WIDE SAMPLE OF 150 CENTENARIANS WILL BRING THE PROPORTION OF CENTENARIANS WHO ARE NEUROIMAGED TO 34% (194/573). DR. VONETTA DOTSON’S EXPERTISE AND DEMONSTRATED SUCCESS IN ENGAGING THE LOCAL AFRICAN AMERICAN COMMUNITY FOR ENROLLMENT IN RESEARCH STUDIES PROVIDES RADCO WITH THE OPPORTUNITY TO SUBSTANTIALLY INCREASE OUR AFRICAN AMERICAN PARTICIPANT ENROLLMENT THAT WILL PROVIDE AN ADEQUATELY POWERED SAMPLE TO DISCERN RACE-SPECIFIC DIFFERENCES AND SIMILARITIES IN DETERMINANTS OR MARKERS OF COGNITIVE SUPERAGING. THE CONDUCT OF THIS AFRICAN AMERICAN PARTICIPANT ENROLLMENT EFFORT AT GSU PROVIDES THE ADDED BENEFIT AND RARE OPPORTUNITY TO COLLABORATE WITH THE GEORGIA STATE/GEORGIA TECH CENTER FOR ADVANCED BRAIN IMAGING (CABI), LED BY VINCE CALHOUN, TO INCREASE OUR SAMPLE OF PARTICIPANTS UNDERGOING THE RIGOROUSLY STANDARDIZED NEUROIMAGING COMPONENT OF THE STUDY.

BOSTON UNIVERSITY ALZHEIMER'S DISEASE RESEARCH CENTER - THE BOSTON UNIVERSITY ALZHEIMER'S DISEASE RESEARCH CENTER (BU ADRC) IS COMMITTED TO THE GOALS AND STRATEGIES OF NAPA INCLUDING: TO PREVENT AND EFFECTIVELY TREAT AD AND AD RELATED DEMENTIAS (ADRD) BY 2025 BY EXPANDING AD/ADRD RESEARCH; TO ACCELERATE EFFORTS TO IDENTIFY EARLY AND PRE-SYMPTOMATIC STAGES OF AD/ADRD; AND TO EDUCATE THE PUBLIC ABOUT AD/ADRD. BU ADRC RESEARCH THEMES ARE CONGRUENT WITH NIH AD/ADRD RESEARCH SUMMIT RECOMMENDATIONS INCLUDING: 1) RESEARCH ON HETEROGENEITY AND THE MULTIFACTORIAL NATURE OF AD/ADRD; 2) MOLECULAR PROFILING OF EXISTING AND NEW COHORTS; AND 3) DEVELOPING NEW PUBLIC-PRIVATE PARTNERSHIPS. WE OPERATIONALIZE OUR MISSION THROUGH 7 TIGHTLY INTEGRATED CORES: ADMINISTRATIVE, CLINICAL (CC), DATA MANAGEMENT AND STATISTICS (DMS), BIOMARKER, NEUROPATHOLOGY (NPC), OUTREACH/RECRUITMENT, ENGAGEMENT (ORE), GENETICS AND MOLECULAR PROFILING (GMP) AND A RESEARCH EDUCATION COMPONENT (REC). THE CORES ARE FOCUSED ON CUTTING EDGE RESEARCH, PROACTIVE COMMUNITY ENGAGEMENT, TRAINING THE NEXT GENERATION OF AD/ADRD CLINICIANS AND RESEARCHERS, AND SHARING KEY MATERIAL, DATA, AND EXPERTISE BOTH AMONG KEY PARTNERS AND WITH THE COMMUNITY AT LARGE. THE BU ADRC HAS MADE SIGNIFICANT CONTRIBUTIONS TO THE REMARKABLE GROWTH OF AD/ADRD RESEARCH NATIONALLY AND HAS ACTIVELY CONTRIBUTED PARTICIPANTS, BIOLOGICAL SAMPLES, CLINICAL DATA, AND SCIENTIFIC EXPERTISE TO ALL MAJOR NATIONAL AD/ADRD RESEARCH INITIATIVES. THE BU ADRC HAS BEEN THE CATALYST FOR EXCITING NEW RESEARCH ON GENETIC AND LIFESPAN ENVIRONMENTAL RISK FACTORS AND AD/ADRD, PARTICULARLY VASCULAR RISK AND EXPOSURE TO REPETITIVE HEAD IMPACTS (RHI) FROM CONTACT SPORTS, MILITARY SERVICE AND OTHER SOURCES. MAJOR BU ADRC RESEARCH THEMES INCLUDE STUDIES ON RHI FROM CONTACT SPORTS AND MILITARY SERVICE AND RISK FOR AD/ADRD, INCLUDING CHRONIC TRAUMATIC ENCEPHALOPATHY (CTE) AND DEEP PHENOTYPING AD/ADRD HETEROGENEITY WITH A RANGE OF COMPLEMENTARY INNOVATIVE APPROACHES INCLUDING DIGITAL AND EEG PHENOTYPING; NEUROPATHOLOGY; GENETICS; BIOSTATISTICAL MODELLING; BIOMARKER DISCOVERY; AND MOLECULAR PROFILING. THE BU ADRC WILL BUILD ON THIS STRONG RECORD OF ACCOMPLISHMENT TO SUPPORT NEW RESEARCH AND EDUCATE THE NEXT GENERATION OF AD/ADRD SCIENTISTS. THE BU ADRC WILL ALSO SUPPORT HIGH RISK HIGH GAIN INNOVATIVE DEVELOPMENTAL PROJECTS FOCUSED ON NAPA AND NIA STRATEGIC GOALS AND UTILIZE OUR COLLECTIVE EXPERTISE AND EXPERIENCE TO FACILITATE CAREER DEVELOPMENT OF INVESTIGATORS WITH DIVERSE BACKGROUNDS. THE BU ADRC WILL DEVELOP NEW PARTNERSHIPS AND ENHANCE CURRENT PARTNERSHIPS WITH OTHER ADRCS AND NATIONAL RESEARCH PROGRAMS, FOUNDATIONS, ADVOCACY GROUPS AND PRIVATE ORGANIZATIONS IN OUR QUEST TO PREVENT AND TREAT AD/ADRD. EXPOSURE TO RHI IS ASSOCIATED WITH CTE AND A WIDE RANGE OF OTHER AD/ADRD PATHOLOGIES. AS RECOGNIZED LEADERS IN THIS SPACE, WE ARE UNIQUELY POSITIONED TO SUPPORT RESEARCH ON GENETIC AND OTHER RISKS FACTORS AND STUDY HOW RHI AFFECTS THE CLINICAL COURSE, BIOMARKER PROFILE, AND CLINICAL-PATHOLOGICAL FEATURES OF AD/ADRD INCLUDING CTE.

BOSTON UNIVERSITY ALZHEIMER'S DISEASE CORE CENTER

CELEST: A CENTER OF EXCELLENCE FOR LEARNING IN EDUCATION SCIENCE AND TECHNOLOGY

STC: CENTER FOR INTEGRATED SPACE WEATHER MODELING

BOSTON UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE AWARD (CTSA) PROGRAM UL1

IMPROVING CAUSAL INFERENCE IN ALZHEIMER'S DISEASE PREVENTION RESEARCH ON MODIFIABLE RISK FACTORS: THE TRIANGULATION OF INNOVATIVE METHODS TO ENDAD (TIME-AD) PROJECT - OVERALL COMPONENT PROJECT SUMMARY RESEARCH ON ALZHEIMER’S DISEASE AND ALZHEIMER’S DISEASE RELATED DEMENTIAS (AD/ADRD) HAS IDENTIFIED SEVERAL PROMISING RISK FACTORS WHICH COULD GUIDE STRATEGIES TO PREVENT UP TO 40% OF AD/ADRD. NEARLY ALL PRIOR EVIDENCE RELIES ON OBSERVATIONAL DATA, WHICH IS PRONE TO BIASES FROM UNMEASURED CONFOUNDING, REVERSE CAUSATION, SELECTIVE SURVIVAL, AND MEASUREMENT ERROR. THE TRIANGULATION OF INNOVATIVE METHODS TO END AD (TIME-AD) PROGRAM ADDRESSES THESE CHALLENGES BY USING AN EVIDENCE TRIANGULATION FRAMEWORK FOR STRENGTHENING CAUSAL INFERENCE IN OBSERVATIONAL DATA. THIS FRAMEWORK SYSTEMATICALLY EVALUATES BIASES, PLANNING COMPLEMENTARY ANALYSIS APPROACHES WITH DIFFERENT DATA SOURCES AND STUDY DESIGNS TO RULE OUT ALTERNATIVE INTERPRETATIONS FOR THE ASSOCIATION OF EACH RISK FACTOR AND AD/ADRD: A) DOUBLY ROBUST OBSERVATIONAL METHODS COMBINING PROPENSITY SCORE MODELS WITH OUTCOME MODELS; B) INSTRUMENTAL VARIABLES (IV) METHODS USING GENETIC AND POLICY VARIATIONS THAT INTRODUCE RANDOM VARIATION IN EXPOSURE; AND C) QUANTITATIVE BIAS ANALYSIS TO CHARACTERIZE UNCERTAINTY. PROJECT 1 WILL ADDRESS THE EFFECTS OF ALCOHOL USE ACROSS THE LIFECOURSE ON COGNITIVE AGING AND AD/ADRD RISK. PROJECT 2 WILL EVALUATE THE EFFECTS OF DEPRESSION AND DEPRESSION TREATMENT ON AD/ADRD RISK AND POSSIBLE DIRECT AND MODIFYING ROLES OF CHRONIC PAIN. PROJECT 3 WILL ASSESS WHETHER AD/ADRD RISK MAY BE REDUCED BY PREVENTION OR TREATMENT OF VISION OR HEARING IMPAIRMENTS. PROJECT 4 WILL ASSESS THE IMPACTS OF SOCIAL ISOLATION, FOCUSING ON COMPONENTS OF SOCIAL ISOLATION THAT ARE MODIFIABLE WITH EXISTING INTERVENTIONS. EACH OF THESE EXPOSURES IS KNOWN TO BE ASSOCIATED WITH AD/ADRD OUTCOMES IN HIGHLY EDUCATED, PREDOMINANTLY WHITE POPULATIONS; THE CURRENT PROPOSALS WILL EXTEND OUR KNOWLEDGE BY FOCUSING ON CAUSATION, INCLUDING LARGE, DIVERSE SAMPLES, AND RIGOROUSLY EVALUATING HETEROGENEITY ACROSS POPULATIONS. IN ADDITION TO AN ADMINISTRATIVE CORE, PROJECTS WILL BE SUPPORTED BY A COGNITIVE OUTCOMES, EXPOSURE VARIABLES, AND COVARIATES DATA CORE, WHICH WILL HELP THE INTENSIVE DATA MANAGEMENT INVOLVED IN CONSTRUCTING ANALYTIC DATA SETS AND FOSTER HARMONIZED MEASURES AND COORDINATED ANALYSES, DRAWING ON MULTIPLE DATA SOURCES TO SUPPORT EVIDENCE TRIANGULATION. A GENETIC AND POLICY DATA CORE WILL BRING SPECIALIZED EXPERTISE ON GENETICS, POLICIES, AND IV ANALYSIS, PROVIDING CODE TO CONSTRUCT, VALIDATE, AND IMPLEMENT IV ANALYSES. AN ANALYTICS CORE WILL DEVELOP AND SHARE REUSABLE ANALYTIC CODE AND SUPPORT IMPLEMENTATION OF THE MOST UP-TO- DATE METHODOLOGY; AND AN EQUITY AND DISSEMINATION CORE WILL ENSURE AN EQUITY FOCUS IS MAINTAINED THROUGHOUT TIME-AD, MAXIMIZING THE RELEVANCE OF OUR FINDINGS TO IMPROVE OUTCOMES AMONG POPULATIONS TYPICALLY UNDERREPRESENTED IN AD/ADRD RESEARCH. THE EQUITY AND DISSEMINATION CORE WILL ENSURE THAT RESEARCH IMPLEMENTATION IS GUIDED BY POTENTIAL APPLICATIONS OF THE EVIDENCE AND THAT THE FINDINGS OF EACH STUDY ARE BROADLY DISSEMINATED TO STAKEHOLDERS WHO CAN ACT ON THE EVIDENCE. THE SYNERGIES CREATED BY SHARED CORES WITH EXPERTISE IN DATA, ANALYSIS, AND EQUITY AND DISSEMINATION ENSURE THAT TIME-AD WILL HAVE HIGH IMPACT.

BIOLOGY OF THE LUNG: A MULTIDISCIPLINARY PROGRAM

TOPICS IN PARTICLE PHYSICS.

CHRONIC TRAUMATIC ENCEPHALOPATHY: DETECTION, DIAGNOSIS, COURSE, AND RISK FACTORS

CENTER FOR RESEARCH TO EVALUATE & ELIMINATE DENTAL DISPARITIES

IDENTIFYING PROTECTIVE OMICS PROFILES IN CENTENARIANS AND TRANSLATING THESE INTO PREVENTIVE AND THERAPEUTIC STRATEGIES - PROJECT ABSTRACT. CENTENARIANS (AGES >100 YRS) AND EVEN MORE-SO, SEMI-SUPERCENTENARIANS (AGES 105-109 YRS) AND SUPERCENTENARIANS (110+ YRS) ARE OUTLIERS NOT ONLY FOR THEIR EXCEPTIONALLY LONG LIFESPANS, BUT ALSO FOR THEIR LONGER FEMALE FERTILITY AND RESISTANCE TO AGING-RELATED DISABILITY AND MORBIDITIES SUCH AS ALZHEIMER’S DISEASE, HEART DISEASE, STROKE, DIABETES AND CANCER. THEIR OFFSPRING ALSO EXHIBIT DELAYED MORBIDITY AND LOWER MORTALITY COMPARED TO THEIR BIRTH COHORT. AMONG NON-HUMAN SPECIES, RODENTS INCLUDING THE NAKED MOLE RAT HAVE ALSO GAINED ATTENTION FOR THEIR VARIATION IN LIFESPAN COMPARED TO OTHER MAMMALS WITH SIMILAR BODY MASS. PROTEOMIC SIGNATURES ASSOCIATED WITH EXTREME LONGEVITY (EL) IN CENTENARIANS AND INTEGRATED TRANSCRIPTOMIC AND PROTEOMIC DATA IN NMRS SUGGEST THAT INTEGRATED ANALYSES OF MULTIPLE OMICS DATA GENERATED FROM THESE HUMAN AND ANIMAL MODELS OF SLOW AGING AND RESISTANCE TO AGING RELATED DISEASES CAN INFORM US ABOUT BIOLOGICAL MECHANISMS THAT UNDERLIE THESE SURVIVAL AND HEALTH ADVANTAGES AND, ULTIMATELY, ABOUT POTENTIAL THERAPEUTICS TO PREVENT DISEASES SUCH AS ALZHEIMER’S. TWO SPECIFIC AIMS PARALLEL THE UH2 AND UH3 PHASES OF THIS PROPOSAL. AIM 1: IN THE UH2 PHASE, THE NEW ENGLAND CENTENARIAN STUDY AND THE EINSTEIN CENTENARIAN AND OFFSPRING STUDIES WILL ESTABLISH A STANDARDIZED PHENOTYPIC DATA AND BIOLOGICAL SAMPLE COLLECTION PROTOCOL FOR IN-PERSON VISITS OF 700 SUBJECTS FROM EACH STUDY (N=1400). DETAILED COGNITIVE FUNCTION TESTING WILL DETERMINE PRESENCE OR ABSENCE OF PROBABLE ALZHEIMER’S. THE PHENOTYPING PROTOCOL WILL BE THE SAME AS THAT USED BY THE LONGEVITY CONSORTIUM’S CENTENARIAN PROJECT (N=350), SO THAT THEIR DATA CAN BE ADDED TO THIS EFFORT FOR A TOTAL SAMPLE OF 1,750. A WORLD-CLASS MULTIDISCIPLINARY TEAM WILL PLAN THE MULTI-OMICS DATA GENERATION AND ANALYTIC AND TRANSLATION EFFORTS TO BE EXECUTED IN AIM 2. THESE EFFORTS WILL BE PARALLELED BY COMPARATIVE TRANSCRIPTOMIC, PROTEOMIC AND MICROBIOMIC STUDIES OF NON-HUMAN MAMMALIAN SPECIES OF WIDELY DIFFERENT LIFE SPANS AND BY THE CREATION OF A LIBRARY OF EL-SPECIFIC IPSCS THAT WILL BE DIFFERENTIATED INTO UNLIMITED NUMBERS OF HEPATOCYTES AND NEURONS. AIM 2: IN THE UH3 PHASE, WE WILL GENERATE TRANSCRIPTOMIC, METHYLOMICS, METABOLOMICS, PROTEOMIC AND MICROBIOMIC DATA FROM CENTENARIANS AND CENTENARIAN OFFSPRING (GENERATED FROM TWO TIME POINTS IN ABOUT A THIRD OF THE SAMPLE). METHODS FOR MULTI-OMIC DATA INTEGRATION COMPILED IN AIM 1 WILL BE USED TO DISCOVER MOLECULAR PROFILES THAT ASSOCIATE WITH EL AND HEALTHY AGING PHENOTYPES INCLUDING DELAY OF OR ESCAPE FROM ALZHEIMER’S DISEASE. INTEGRATION WITH MOLECULAR PROFILES FROM FUNCTIONAL STUDIES OF RESILIENCY PERFORMED WITH IPSC-DERIVED NEURONS AND HEPATOCYTES AND WITH MOLECULAR PROFILES ASSOCIATED WITH INCREASED LIFESPAN FROM MULTIPLE SPECIES WILL POINT TO MECHANISMS AND GENERATE CANDIDATE SMALL MOLECULE AND COMPOUND THERAPEUTICS. ALL GENERATED DATA AND UNIQUE BIOLOGICAL RESOURCES, INCLUDING THE EL- IPSC DERIVED HEPATOCYTES AND NEURONS, WILL BE SHARED WITH CONSORTIA AND INDIVIDUAL INVESTIGATORS RESEARCHING ALZHEIMER’S, OTHER AGING RELATED DISEASES AND MORE GENERALLY, BASIC MECHANISMS OF AGING.

MONOCLONAL ANTIBODY-BASED MULTIPURPOSE MICROBICIDES

PRECURSORS OF STROKE INCIDENCE AND PROGNOSIS

ENDOTHELIAL REDOX STATE & PHENOTYPE IN HEALTH & DISEASE

OUR HELIOSPHERIC SHIELD

FINAL CLINICAL STUDIES FOR SUBMISSION OF A PRE-MARKET APPROVAL APPLICATION TO THE FDA FOR A BIONIC PANCREAS THAT AUTOMATES TYPE 1 DIABETES MANAGEMENT

LOCAL NEURONAL DRIVE AND NEUROMODULATORY CONTROL OF ACTIVITY IN THE PIAL NEUROVASCULAR CIRCUIT - PROJECT SUMMARY/ABSTRACT – OVERALL WE SEEK TO UNDERSTAND THE NATURE OF THE PIAL NEUROVASCULAR CIRCUIT, WHOSE DYNAMICS IS CHARACTERIZED BY ULTRALOW FREQUENCY OSCILLATIONS NEAR 0.1 HZ THAT PARCELLATE INTO SEPARATE COHERENT REGIONS ACROSS CORTEX. WE WILL USE THIS KNOWLEDGE TO FORM A MATHEMATICAL RELATION BETWEEN THE HEMODYNAMIC PATTERNS OBSERVED IN OPTICAL AND FUNCTIONAL MAGNETIC RESONANCE IMAGING EXPERIMENTS AND THE UNDERLYING BRAIN STATE. OUR PROPOSED STUDIES PROPOSE TO LEVERAGE OUR EXPERIMENTAL EXPERTISE IN IN VIVO OPTICAL MICROSCOPY IN MOUSE AND FMRI IN MOUSE AND HUMAN. THESE PRIMARY MODALITIES FOR DATA ACQUISITION ARE COMBINED WITH BEHAVIORAL TRAINING, ELECTROPHYSIOLOGY, AND DATA ANALYSIS. OUR EXPERIMENTAL EFFORT IS PARALLEL BY TWO THEORETICAL EFFORTS. ONE MIXED ANALYTICAL/COMPUTATIONAL EFFORT IS ON COUPLED OSCILLATOR DYNAMICS TO FORMULATE MODELS, AT VARYING LEVELS OF COMPLEXITY, OF THE PIAL NEUROVASCULAR CIRCUIT. A SECOND SOLELY COMPUTATIONAL EFFORT CONCERNS THE MODULATION OF THE TRANSPORT OF OXYGEN, BY REGIONAL OSCILLATIONS OF THE PIAL NEUROVASCULAR CIRCUIT. THE PIAL NEUROVASCULAR CIRCUIT IS COMPOSED OF A TWO-DIMENSIONAL NETWORK OF PIAL ARTERIOLES THAT UNDERGO RHYTHMIC OSCILLATIONS IN THE ~ 0.1 HZ VASOMOTOR BAND. EACH ELEMENT IN THIS CIRCUIT - A SEGMENT OF ARTERIOLE WHOSE DIAMETER IS MODULATED BY THE CONSTRICTION/DILATION OF SMOOTH MUSCLE, CONTAINS AN INTRINSIC RHYTHM GENERATOR, MUCH LIKE INTRINSIC BURSTING NEURONS IN CENTRAL PATTERN GENERATORS. THE PIAL ARTERIOLES INTEGRATE NEURONAL ACTIVITY FROM NEIGHBORING ARTERIOLES, UNDERLYING NEURONS, SUBCORTICAL NEURONS, AND NEUROMODULATORY CENTERS TO PRODUCE DYNAMIC PATTERNS OF COHERENT OSCILLATIONS IN ARTERIOLAR DIAMETER ACROSS THE CORTICAL MANTLE. THESE PATTERNS CONTAIN REGIONS THAT OSCILLATE AT SLIGHTLY DIFFERENT FREQUENCIES, I.E., THEY PARCELLATE INTO SEPARATE REGIONS. THE FASCINATING ISSUE IS THAT THE PARCELLATION ONLY PARTIALLY REFLECTS INPUT FROM THE DIRECTLY UNDERLYING NEURONAL INPUT. WE SEEK TO UNDERSTAND, MODEL, AND EXPLOIT THIS PARCELLATION. THE PIS HAVE COLLABORATED ON ISSUES IN NEUROSCIENCE AND NEUROVASCULAR SCIENCE FOR MANY YEARS. THIS PROPOSAL IS A RESULT OF THEIR DISCOVERIES AND CONVERGING INTEREST IN A STRUCTURED COLLABORATIVE EFFORT. PROJECT 1 WILL FORMULATE AN UNDERSTANDING OF FUNDAMENTAL PHYSIOLOGY OF THE PIAL NEUROVASCULAR CIRCUIT. THIS INCLUDES DETERMINING IF BRAIN ARTERIOLES TRULY ACT AS INTERACTING NON-LINEAR OSCILLATORS, I.E., THAT THEY ENTRAIN AND PHASE-LOCK RATHER THAN PASSIVELY FILTER. PROJECTS 1, 2, AND 4 WILL EXPLORE EXPERIMENTALLY AND THEORETICALLY HOW FOUR COMPETITIVE INTERACTIONS, VIZ, INPUT FROM NEIGHBORING ARTERIOLES, (II) INPUT FROM UNDERLYING NEURONS, (III) INPUT FROM SUBCORTICAL AREAS INVOLVED IN HOMEOSTASIS; AND (IV) INPUT FROM BRAIN NEUROMODULATORY CENTERS, LEAD TO THE OBSERVED PATTERNS OF PIAL NEUROVASCULAR ACTIVITY. PROJECTS 2 AND 4 WILL EXPLORE AND MODEL THE REGULATION OF OXYGEN IN SUBSURFACE VESSELS, WHILE PROJECT 3 WILL EXPAND THE RESOLUTION OF MR IMAGING IN HUMANS TO OBSERVE SINGLE VESSELS CBV CHANGES AND THUS MEASURE PIAL NEUROVASCULAR DYNAMICS WITH UNPARALLELED RESOLUTION. A PARTICULAR INTEREST IS TO TRANSFORM SPATIOTEMPORAL PATTERNS OF VASOMOTION INTO PREDICTIONS OF INTERNAL BRAIN STATE.

MINIMALLY VERBAL ASD: FROM BASIC MECHANISMS TO INNOVATIVE INTERVENTIONS

A FOLLOW-UP STUDY FOR CAUSES OF CANCER IN BLACK WOMEN

PREDICTING AND OPTIMIZING LANGUAGE OUTCOMES IN MINIMALLY VERBAL CHILDREN WITH AUTISM SPECTRUM DISORDER

DETERMINANTS OF CELL FATE AND DIFFERENTIATION IN THE DEVELOPING LUNG

BRAIN IMMUNE INTERACTIONS AS THE BASIS OF GULF WAR ILLNESS: GULF WAR ILLNESS CONSORTIUM (GWIC)

MULTICENTER OSTEOARTHRITIS STUDY (MOST) RENEWAL

MRI COGNITIVE GENETIC & BIOMARKER PRECURSORS OF AD & DEMENTIA IN YOUNG ADULTS

THERAPEUTIC TARGET DISCOVERY IN ADSP DATA VIA COMPREHENSIVE WHOLE-GENOME ANALYSIS INCORPORATING ETHNIC DIVERSITY AND SYSTEMS APPROACHES

ANTIBODY-BASED CONTRACEPTIVE MPTS: PRECLINICAL AND CLINICAL RESEARCH

COMPLEX CHEMOTYPES: DISCOVERY, METHODOLOGY, AND LIBRARY EXPANSION

MASS SPECTROMETRY RESOURCE FOR BIOLOGY AND MEDICINE

GENETIC STUDIES OF ALZHEIMER'S DISEASE IN JEWISH AND ARAB POPULATIONS - MOST DISCOVERIES OF THE GENETIC BASIS OF ALZHEIMER DISEASE (AD) WERE MADE IN CAUCASIANS OF EUROPEAN ANCESTRY (EAS) AND REQUIRED SAMPLES BETWEEN 10,000 AND 150,000 SUBJECTS TO DETECT THEM. WE AND OTHERS HAVE DEMONSTRATED THAT DISCOVERY OF AD RISK VARIANTS CAN BE ACCOMPLISHED IN MORE GENETICALLY HOMOGENEOUS COHORTS COMPRISING SEVERAL THOUSAND OR FEWER SUBJECTS. STUDIES OF NON-EA POPULATIONS ALSO AFFORD THE OPPORTUNITY TO DISCOVER VARIANTS THAT ARE RELATIVELY RARE OR ABSENT IN EAS AND THAT DISPLAY A SMALLER EFFECT SIZE IN EAS DUE TO MODIFICATION BY OTHER GENES AND ENVIRONMENTAL FACTORS. WE WILL FOCUS ON JEWS AND ARABS CURRENTLY LIVING IN ISRAEL WHO ARE DESCENDED FROM THE MIDDLE EAST AND NORTH AFRICA (MENA). ALTHOUGH MENA JEWS ASSIMILATED TO SOME EXTENT WITH THEIR NON-JEWISH NEIGHBORS, THEY HAVE MAINTAINED A DISTINCTIVE GENETIC PROFILE THAT REFLECTS SOME ADMIXTURE WITH NON-JEWS, ANCIENT JEWISH BACKGROUND, AND A UNIQUE COMPONENT REFLECTING GENETIC DRIFT AND NEW MUTATIONS DURING THE LAST TWO MILLENNIA. OUR PREVIOUS STUDIES OF ARABS LIVING IN THE ISRAELI VILLAGE CALLED WADI ARA REVEALED A GENOME-WIDE SIGNIFICANT ASSOCIATION FOR AD WITH ACE, WERE CENTRAL TO THE ESTABLISHMENT OF SORL1 AS AN AD GENE, AND CONTRIBUTED TO A TRANS-ETHNIC GWAS LEADING TO THE DISCOVERY OF SEVERAL NOVEL AD GENES. IN THIS PROJECT, WE WILL LEVERAGE THE GENETIC ARCHITECTURE OF MENA JEWS AND ISRAELI-ARABS, AS WELL AS THEIR DISTINCTIVE ENVIRONMENTAL EXPOSURES AND LIFESTYLES, TO PROMOTE DISCOVERY OF AD-RELATED GENES AND VARIANTS. SPECIFICALLY, WE WILL RECRUIT 3,000 MENA JEWS AT THREE SITES IN ISRAEL, AS WELL AS 1,000 ISRAELI-ARABS LOCATED IN MULTIPLE VILLAGES (EQUAL NUMBERS OF AD CASES AND CONTROLS IN THE TOTAL SAMPLE). WE WILL OBTAIN FROM EACH PARTICIPANT A BLOOD SPECIMEN FOR DNA AND BIOMARKER STUDIES, AND PHENOTYPIC DATA INCLUDING CLINICAL, COGNITIVE TEST, MEDICAL HISTORY AND LIFESTYLE INFORMATION, AS WELL AS BRAIN MRI DATA FOR A PORTION OF THE SAMPLE. DNA SPECIMENS WILL BE WHOLE GENOME SEQUENCED (WGS). WGS DATA WILL BE PROCESSED USING PIPELINES ESTABLISHED BY THE ALZHEIMER DISEASE SEQUENCING PROJECT (ADSP). WE WILL CONDUCT A GWAS FOR AD USING ADMIXTURE MAPPING AND METHODS FOR SINGLE VARIANT AND GENE-BASED TESTS. TOP-FINDINGS WILL BE REPLICATED IN ASHKENAZI JEWISH AND NON-JEWISH DATASETS ASSEMBLED BY THE ALZHEIMER DISEASE GENETICS CONSORTIUM AND ADSP USING TRANS-ETHNIC ANALYSIS AND APPROACHES THAT FOCUS ON VARIANTS AFFECTING PROTEIN STRUCTURE, TRANSCRIPTION, AND GENE EXPRESSION. WE WILL ALSO CONDUCT GWAS FOR AGE AT ONSET AND AD BIOMARKERS USING SINGLE OUTCOME AND PLEIOTROPY MODELS. NEXT, WE WILL IDENTIFY GENE TARGETS OF THE TOP-RANKED SNPS BY PERFORMING EXPRESSION QUANTITATIVE TRAIT LOCUS ANALYSIS USING LOCALLY DERIVED AND PUBLICLY AVAILABLE DATA CONTAINING GENOTYPE AND GENE EXPRESSION DATA IN BRAIN AND OTHER TISSUES, AND ESTABLISH FUNCTIONAL CONNECTIONS AMONG THE TOP-RANKED SNPS AND GENES USING PATHWAY, CO- EXPRESSION NETWORK, AND MENDELIAN RANDOMIZATION ANALYSIS. FINALLY, WE WILL EVALUATE THE ASSOCIATION OF VIRUSES DETECTED IN WGS DATA WITH AD USING MACHINE LEARNING METHODS AND REGRESSION MODELS. WE EXPECT THAT THIS PROJECT WILL IDENTIFY NOVEL TARGETS FOR DEVELOPMENT OF EFFECTIVE DRUGS TO TREAT OR RETARD PROCESSES LEADING TO AD.

TRAUMATIC BRAIN INJURY AND REPETITIVE HEAD IMPACTS: CONTRIBUTIONS TO AD/ADRD AND CTE NEUROPATHOLOGY AND RESULTING CLINICAL SYNDROMES

PHOTONICS

HEALTH CARE DELIVERY SYSTEM INNOVATIONS FOR CHILDREN WITH MEDICAL COMPLEXITY

NIAMS MULTIDISCIPLINARY CLINICAL RESEARCH CENTER

COMPARING AVIATION HEALTH IMPACTS WITH OTHER SOURCE SELECTORS

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) -THE NATIONAL SCIENCE FOUNDATION (NSF) GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) IS A HIGHLY COMPETITIVE, FEDERAL FELLOWSHIP PROGRAM. GRFP HELPS ENSURE THE VITALITY AND DIVERSITY OF THE SCIENTIFIC AND ENGINEERING WORKFORCE OF THE UNITED STATES. THE PROGRAM RECOGNIZES AND SUPPORTS OUTSTANDING GRADUATE STUDENTS WHO ARE PURSUING RESEARCH-BASED MASTER'S AND DOCTORAL DEGREES IN SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) AND IN STEM EDUCATION. THE GRFP PROVIDES THREE YEARS OF FINANCIAL SUPPORT FOR THE GRADUATE EDUCATION OF INDIVIDUALS WHO HAVE DEMONSTRATED THEIR POTENTIAL FOR SIGNIFICANT RESEARCH ACHIEVEMENTS IN STEM AND STEM EDUCATION. THIS AWARD SUPPORTS THE NSF GRADUATE FELLOWS PURSUING GRADUATE EDUCATION AT THIS GRFP INSTITUTION. 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.

LIFETIME STRESSORS AND ALZHEIMER'S DISEASE GENETIC VARIANTS AND BIOMARKERS IN RELATION TO COGNITIVE DECLINE AMONG BLACK WOMEN'SHEALTH STUDY PARTICIPANTS. - ABSTRACT OLDER BLACK AMERICANS HAVE HIGHER RATES OF COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE (AD) THAN THEIR WHITE COUNTERPARTS, A DISPARITY THAT IS GREATER FOR BLACK WOMEN. GIVEN THE LACK OF EFFECTIVE THERAPIES TO SLOW DISEASE PROGRESSION AND SYMPTOMS, EFFECTIVE PREVENTION IS NEEDED. MOST KNOWLEDGE OF RISK FACTORS FOR COGNITIVE DECLINE, THE HALLMARK FEATURE OF AD, COMES FROM STUDIES OF WHITE POPULATIONS AND THE CONTRIBUTION OF RACIALLY/SOCIALLY-PATTERNED RISK FACTORS AMONG BLACK ADULTS REMAINS UNDER-STUDIED. WE PROPOSE TO STUDY 2,500 BLACK WOMEN AGES 55 AND OLDER FROM THE BLACK WOMEN’S HEALTH STUDY (BWHS), A FOLLOW-UP STUDY OF 59,000 BLACK WOMEN FROM ACROSS THE US. OUR GOAL IS TO IDENTIFY SOCIAL FACTORS THAT, TOGETHER WITH BIOMARKERS OF AD, INFLUENCE COGNITIVE DECLINE. THE BWHS PROVIDES A UNIQUE OPPORTUNITY TO ACCOMPLISH THIS GOAL. OVER 27 YEARS, THE BWHS HAS COLLECTED DATA THROUGH BIENNIAL QUESTIONNAIRES FROM PARTICIPANTS ON SOCIOECONOMIC, PSYCHOLOGICAL, AND PHYSICAL STRESSORS OCCURRING AT VARIOUS TIMES OF LIFE (E.G., LOW PARENTAL EDUCATION, CHILDHOOD SEXUAL/PHYSICAL ABUSE, INTERPERSONAL RACISM), AS WELL AS INFORMATION ON MANY POTENTIAL RISK FACTORS FOR AD AND COGNITIVE DECLINE (E.G., DEMOGRAPHICS, BODY SIZE, BEHAVIORAL FACTORS (E.G., EXERCISE, DIET, SMOKING), MEDICAL HISTORY, REPRODUCTIVE HISTORY, MEDICATION USE, HEALTH CARE). THE BWHS HAS COLLECTED AND STORED BLOOD FROM A LARGE SUBSAMPLE OF PARTICIPANTS WHO AGREED TO WIDE SHARING, SUCH AS GWAS RESULTS WITH OTHER INVESTIGATORS AND PUBLIC DATABASES. AFTER ENROLLMENT OF 2,500 SUCH PARTICIPANTS WITH ALREADY-COLLECTED BLOOD SAMPLES FROM THE BWHS, WE PROPOSE TO ADMINISTER A VALIDATED TELEPHONE COGNITIVE BATTERY ANNUALLY TO MEASURE COGNITION. WE WILL ALSO MEASURE A PANEL OF AT(N) PLASMA BIOMARKERS AND CONDUCT GWAS IN ORDER TO EXAMINE THE ASSOCIATIONS OF PLASMA BIOMARKERS AND GENETIC VARIANTS WITH COGNITIVE DECLINE. BASED ON THE COLLECTED DATA AND THE RESULTS FROM BIOMARKER ASSESSMENTS, WE WILL ASSESS THE JOINT EFFECTS OF THE STRESSORS AND BIOMARKERS ON COGNITIVE DECLINE. A FEASIBILITY STUDY DEMONSTRATED THE WILLINGNESS OF BWHS PARTICIPANTS TO COMPLETE THE COGNITIVE TEST BATTERY OVER THE TELEPHONE AND INDICATED THAT ENOUGH BWHS PARTICIPANTS WILL PARTICIPATE TO REACH A STUDY SIZE OF ~2,500 PARTICIPANTS. THE INVESTIGATORS HAVE THE EXPERIENCE AND EXPERTISE TO ENROLL PARTICIPANTS; MEASURE COGNITION WITH A VALIDATED TELEPHONE COGNITIVE BATTERY; MEASURE AT(N) BIOMARKERS IN STORED PLASMA AND CONDUCT GWAS; AND WITH THESE DATA, TO ASSESS THEIR SEPARATE AND JOINT EFFECTS ON COGNITIVE DECLINE. THE PROPOSED STUDY PROVIDES AN UNPARALLELED OPPORTUNITY TO LEVERAGE A LARGE NATIONAL SAMPLE OF OLDER BLACK WOMEN ON WHICH COMPREHENSIVE DATA ON MANY FACTORS THAT AFFECT COGNITION HAVE BEEN COLLECTED TO IDENTIFY LIFE-COURSE RISK FACTORS FOR COGNITIVE DECLINE. THE FINDINGS WILL HAVE IMPORTANT TRANSLATIONAL IMPLICATIONS FOR EFFORTS TO PREVENT COGNITIVE DECLINE IN ALL POPULATIONS, BUT ESPECIALLY IN BLACK WOMEN WHO ARE DISPROPORTIONATELY BURDENED.

RISK AND RESILIENCE, CLINICAL PRESENTATION, AND BIOMARKER PROFILES OF CHRONIC TRAUMATIC ENCEPHALOPATHY AND RELATED DEMENTIAS: THE DIAGNOSE CTE RESEARCH PROJECT II - CHRONIC TRAUMATIC ENCEPHALOPATHY (CTE) IS A NEURODEGENERATIVE DISEASE DIAGNOSED POSTMORTEM IN PEOPLE EXPOSED TO REPETITIVE HEAD IMPACTS (RHI) FROM FOOTBALL AND OTHER CONTACT SPORTS. NINDS CONSENSUS RESEARCH DIAGNOSTIC CRITERIA FOR THE CLINICAL SYNDROME OF CTE, KNOWN AS TRAUMATIC ENCEPHALOPATHY SYNDROME (TES), WERE PUBLISHED IN 2021. HOWEVER, WE CANNOT DIAGNOSE CTE IN LIFE DUE TO THE FOLLOWING KNOWLEDGE GAPS: 1) TES CRITERIA DO NOT INCLUDE BIOMARKERS, LIMITING DISEASE SPECIFICITY; (2) LONGITUDINAL STUDIES ARE LACKING; (3) BIOMARKERS AND CLINICAL FEATURES THAT DISTINGUISH CTE FROM OTHER AD/ADRDS ARE UNKNOWN; AND (4) RISK/RESILIENCE FACTORS OF TES ARE UNCLEAR, PARTICULARLY SOCIAL DETERMINANTS OF HEALTH (SDOH). IN 2015, WE WERE AWARDED A NINDS FUNDED 7- YEAR U01 KNOWN AS THE DIAGNOSE CTE RESEARCH PROJECT (DIAGNOSE), DESIGNED IN PART TO DEVELOP BIOMARKERS OF CTE. IT ENROLLED 180 FORMER FOOTBALL PLAYERS (120 PROFESSIONAL, 60 COLLEGE) AND 60 NON-RHI CONTROLS, ALL MALES AGES 45-74. BASELINE CLINICAL EXAMS, MRI, TAU (FLORTAUCIPIR) AND AMYLOID PET, AND BLOOD DRAWS WERE COMPLETED IN 2020. FOUR-YEAR REMOTE FOLLOW-UPS, INCLUDING IN-HOME BLOOD DRAWS, WERE FINISHED IN NOV. 2023. WE HAD A 90% RETENTION RATE. THE GOALS OF THIS R01 ARE TO RETAIN AND GROWN DIAGNOSE AND EXAMINE THE CLINICAL AND BIOMARKER COURSE AND PROFILES OF TES (AIM 1); INVESTIGATE RISK/RESILIENCE FACTORS OF TES (AIM 2); AND COMPARE BIOMARKERS OF AMYLOID (AΒ), P-TAU, NEURODEGENERATION, NEUROINFLAMMATION, AND WHITE MATTER INJURY BETWEEN TES AND AD SYNDROMES (AIMS 3-4). OUR HYPOTHESES ARE THAT TES HAS UNIQUE CLINICAL AND BIOMARKER PROFILES, AND RHI AND NON-RHI RISK FACTORS INFLUENCE THE DEVELOPMENT OF TES. THERE WILL BE 3 GROUPS: (1) RETENTION, 150 FORMER FOOTBALL PLAYERS AND 50 CONTROLS RETAINED FROM DIAGNOSE; (2) EXPANSION, WE WILL GROW DIAGNOSE BY NEWLY RECRUITING 75 FORMER COLLEGE AND PROFESSIONAL FOOTBALL PLAYERS AND 25 CONTROLS; (3) AD, 50 AΒ+ PARTICIPANTS WITH COGNITIVE IMPAIRMENT. IN TOTAL, WE WILL STUDY 225 FORMER FOOTBALL PLAYERS, 75 CONTROLS, AND 50 AD. GROUPS WILL BE SIMILAR IN AGE (50+), SEX (MALES), AND RACE (40% BLACK). PARTICIPANTS WILL COMPLETE A SINGLE VISIT, INCLUDING CLINICAL EXAMS, SDOH MEASURES, MRI, BLOOD DRAW, AND TAU PET, AT 1 OF 5 P30 AD RESEARCH CENTERS: BU, UCSF, ARIZONA, 1FLORIDA, OR SOUTH TEXAS. RETENTION COHORT WILL HAVE FLORTAUCIPIR PET TO STUDY ITS LONGITUDINAL VALUE. EXPANSION COHORT WILL HAVE MK-6240 PET TO BUILD ON OUR R21. A SUBSET OF RETENTION (N=20) WILL HAVE FLORTAUCIPIR AND MK- 6240 FOR TRACER COMPARISON. BLOOD WILL BE ANALYZED FOR 6 P-TAU EPITOPES, AΒ40/42, NEUROINFLAMMATION, AND WHITE MATTER INJURY. RETENTION COHORT WILL HAVE LEGACY DATA FOR LONGITUDINAL STUDY OF OUTCOMES (2-3 TIMEPOINTS OVER 6-8 YEARS). EXPANSION WILL CONTRIBUTE TO POOLED CROSS-SECTIONAL ANALYSES. DIAGNOSE PARTICIPANTS WERE ASKED FOR BRAIN DONATION; 8 HAVE DONATED. THIS R01 WILL PERMIT CONTINUED BRAIN DONATION AND CLINICAL-PATHOLOGICAL VALIDATION STUDIES. THIS R01 WILL RETAIN AND GROW A UNIQUE, DEEPLY PHENOTYPED, LONGITUDINAL COHORT OF PEOPLE AT RISK FOR CTE. RESULTS WILL HELP REFINE THE TES CRITERIA AND DIFFERENTIATE IT FROM OTHER AD/ADRDS. THIS R01 WILL PROVIDE INSIGHT INTO THE DETECTION, DIAGNOSIS, AND PROGNOSIS FOR PEOPLE LIVING WITH CTE, PAVING THE WAY FOR TREATMENT TRIALS.

MODELING AFFINITY MATURATION AT MOLECULAR RESOLUTION

CAF?: A RESEARCH COORDINATING CENTER TO CONVENE, ACCELERATE, FOSTER, AND EXPAND THE CLIMATE CHANGE AND HEALTH COMMUNITY OF PRACTICE - PROJECT SUMMARY / ABSTRACT RESEARCH IN CLIMATE AND HEALTH IS CURRENTLY HAMPERED BECAUSE: (1) THE COMMUNITY OF PRACTICE (COP) IN THIS SPACE IS FRACTURED, FREQUENTLY SILOED WITHIN DISCIPLINES, AND CONCENTRATED IN A FEW WELL-RESOURCED INSTITUTIONS AND COUNTRIES; (2) CUTTING-EDGE DATA ASSETS EXIST, BUT ARE OFTEN HARD TO FIND, INCONSISTENTLY DOCUMENTED, AND CHALLENGING TO MANAGE AND LINK TO OTHER DATA RESOURCES; (3) MANY RESEARCHERS, ESPECIALLY EARLY-STAGE INVESTIGATORS (ESIS), DO NOT HAVE ACCESS TO COMPLIANT, COMPUTATIONALLY EFFICIENT, AND SECURE COMPUTING ENVIRONMENTS; AND (4) WE LACK A CENTRALIZED PLATFORM THAT CAN SUPPORT THE DOMESTIC AND GLOBAL CAPACITY-BUILDING INITIATIVES NEEDED TO EXPAND PATHWAYS FOR CCH RESEARCHERS, INCLUDING PROVIDING EDUCATIONAL RESOURCES, MENTORING, AND FUNDING FOR PILOT AND TIME-SENSITIVE PROJECTS. WE PROPOSE TO CREATE THE BUSPH-HSPH-CAFÉ, A RESEARCH COORDINATING CENTER (RCC) LEVERAGING THE ECOSYSTEM OF STATE-OF-THE-ART RESEARCH, EDUCATION, AND POLICY TRANSLATION IN CLIMATE CHANGE AND HEALTH (CCH) AT THE BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH AND THE HARVARD T.H. CHAN SCHOOL OF PUBLIC HEALTH TO: (1) CONVENE THE COMMUNITY OF PRACTICE (COP) VIA THE ADMINISTRATIVE FUNCTION; (2) ACCELERATE RESEARCH VIA THE DATA MANAGEMENT FUNCTION; (3) FOSTER COLLABORATIONS ACROSS THE COP VIA THE RESOURCE FUNCTION; AND (4) EXPAND THE CCH- COP VIA THE CAPACITY BUILDING FUNCTION. DR. GREGORY WELLENIUS, DR. FRANCESCA DOMINICI, AND DR. AMRUTA NORI-SARMA ARE THE IDEAL MULTIPLE-PI TEAM FOR THE CAFÉ BASED ON: (1) THEIR LARGE AND DIVERSE NETWORK OF COLLABORATORS, INCLUDING TOP EXPERTS IN THE FIELDS OF CLIMATE CHANGE, ADVERSE HEALTH OUTCOMES, ENVIRONMENTAL EPIDEMIOLOGY, DATA SCIENCES, AND STATISTICS, (2) THEIR PRIOR EXPERIENCE LEADING HIGH-IMPACT RESEARCH RELEVANT TO CCH; AND (3) THEIR COMMITMENT TO CAPACITY BUILDING THROUGH MENTORSHIP AND SUPPORT, PARTICULARLY IN SUPPORT OF DIVERSITY AND INCLUSION. BY ENGAGING OUR PARTNERS IN NGOS, GOVERNMENT, INDUSTRY, AND COMMUNITY-BASED GROUPS, AND BY LEVERAGING THE EXPERTISE OF THE PIS, THE CAFÉ WILL ENABLE THE COP TO MORE RAPIDLY AND EFFECTIVELY ADVANCE OUR UNDERSTANDING – AND MINIMIZE THE CONSEQUENCES – OF THE HEALTH CONSEQUENCES OF CONTINUED CLIMATE CHANGE RESEARCH ADVANCES OF THE COP WILL BE TIMELY, POLICY-RELEVANT, AND CATALYTIC, WITH FAR-REACHING APPLICATIONS FOR IMPROVED LOCAL, NATIONAL, AND GLOBAL CLIMATE RESILIENCE.

CENTER FOR INNOVATION IN POINT OF CARE TECHNOLOGIES FOR THE FUTURE OF CANCER CARE

ION CHANNEL MODULATION BY THE PRION PROTEIN: A NOVEL TOXIC MECHANISM

EPIDEMIOLOGY OF DEMENTIA IN THE FRAMINGHAM STUDY

PREFRONTAL AND MEDIAL-TEMPORAL INTERACTIONS IN MEMORY

A FOLLOW-UP STUDY FOR CAUSES OF ILLNESS IN BLACK WOMEN

DEVELOPING PLURIPOTENT STEM CELLS TO MODEL AND TREAT LUNG DISEASE - SUMMARY: OVERALL PROGRAM THE GOAL OF THIS PROGRAM PROJECT GRANT (PPG) IS ADVANCING THE LATEST DISCOVERIES IN STEM CELL BIOLOGY, HUMAN ORGANOID MODELS, AND GENE EDITING TO UNDERSTAND AND TREAT GENETIC LUNG DISEASES. AFTER A CENTURY OF BASIC SCIENCES ADVANCES, CULMINATING IN RECENT NOBEL PRIZE-WINNING DISCOVERIES, SUCH AS NUCLEAR REPROGRAMMING AND GENE EDITING, BIOMEDICAL RESEARCH NOW FACES AN INFLECTION POINT, POISED FOR CLINICAL TRANSLATION OF BASIC SCIENCE SUCCESSES. WHILE IT IS HARD TO ENVISION A MORE OPTIMISTIC TIME IN HEALTH-RELATED RESEARCH, TREATMENTS FOR MANY DEVASTATING LUNG DISEASES HAVE NOT YET BEEN REALIZED, AND CLINICAL THERAPIES IN MOST CASES STILL LARGELY FOCUS ON TREATING SYMPTOMS OR MAINTAINING LIFE SUPPORT TO ALLOW ENDOGENOUS LUNG TISSUE STEM CELLS ENOUGH TIME TO REPAIR, WITHOUT AVAILABLE THERAPIES ABLE TO INTERRUPT DISEASE-INITIATING MECHANISMS OR AUGMENT THE LUNG’S CAPACITY TO REGENERATE. HERE WE ADDRESS THESE CHALLENGES BY PROPOSING AN INTEGRATED, MULTI-INVESTIGATOR PPG TO TRANSLATE LUNG STEM CELL RESEARCH FROM BASIC DISCOVERY TO FUTURE CLINICAL APPLICATIONS. AN INITIAL FOCUS ON AMELIORATING GENETIC LUNG DISEASES OF THE AIRWAY AND ALVEOLI IS PURSUED, GIVEN THAT THEIR PROXIMAL DISEASE-DRIVING GENE MUTATIONS ARE WELL DESCRIBED. THE USE INDUCED PLURIPOTENT STEM CELLS (IPSCS) CARRYING THESE MUTATIONS OR THEIR GENE-EDITED PROGENY IS A SHARED TECHNOLOGY HARNESSED BY ALL PROJECTS TOGETHER WITH A PROPOSED GENE EDITING CORE, AND COORDINATED BY AN ADMINISTRATIVE CORE. OUR 4 PROJECT LEADERS HAVE WORKED TOGETHER EXTENSIVELY TO DEVELOP PROTOCOLS TO DIFFERENTIATE IPSCS INTO A BROAD DIVERSITY OF LUNG EPITHELIAL LINEAGES, RECENTLY OPTIMIZING METHODS TO PRODUCE THE TWO STEM CELL POPULATIONS THAT MAINTAIN ALL AIRWAY AND ALVEOLAR EPITHELIA, BASAL CELLS AND ALVEOLAR TYPE 2 CELLS (AT2S), RESPECTIVELY. HAVING ESTABLISHED THESE STEM CELL BANKS AND PROTOCOLS, WE TURN OUR FOCUS HERE ON APPLYING THESE RESOURCES TO ADVANCE OUR MECHANISTIC UNDERSTANDING OF HOW GENE MUTATIONS INITIATE AIRWAY AND ALVEOLAR EPITHELIAL DYSFUNCTION RESULTING IN DISEASE, AND WE SEEK TO THERAPEUTICALLY INTERVENE WITH NOVEL PRECISION THERAPEUTICS OR REGENERATIVE CELL THERAPIES. TOWARDS THESE GOALS, WE HERE PROPOSE 4 PROJECTS AND 2 CORES, ALL INTERACTING TO COMPLETE SHARED AIMS, AND SYNERGISTIC CROSS-PROJECT EXPERIMENTS. AIM 1 WILL PROMOTE COLLABORATIVE, INTEGRATED CROSS-PROJECT APPROACHES THAT PRODUCE NEW HUMAN MODELS OF GENETIC AIRWAY AND ALVEOLAR DISEASES, AND WILL APPLY THESE IN VITRO IPSC AND ORGANOID-BASED MODELS TO UNDERSTAND BASIC PATHOGENIC MECHANISMS THAT LEAD FROM EPITHELIAL DYSFUNCTION TO LUNG DISEASE. AIM 2 WILL IDENTIFY POTENTIAL THERAPEUTIC STRATEGIES ABLE TO REVERSE OR AMELIORATE ABERRANT PATHWAYS RESPONSIBLE FOR THE ALVEOLAR DYSFUNCTION PRESENT IN GENETIC DISEASES THAT AFFECT THE DISTAL LUNG, INCLUDING PROTEOSTASIS, MITOCHONDRIAL DYSFUNCTION, AND METABOLIC CHANGES THAT WE HYPOTHESIZE LEAD TO REVERSIBLE EPITHELIAL TOXIC GAIN-OF-FUNCTION PHENOTYPES. AIM 3 WILL DEVELOP A FUTURE APPROACH FOR TREATING GENETIC LUNG DISEASES BASED ON THE IN VIVO RECONSTITUTION OF AIRWAY AND ALVEOLAR STEM CELL COMPARTMENTS VIA INTRA-AIRWAY TRANSPLANTATION OF PLURIPOTENT STEM CELL-DERIVED AIRWAY BASAL OR DISTAL ALVEOLAR EPITHELIAL CELLS.

NEURAL SUBSTRATES OF COGNITIVE DECLINE IN AGING MONKEYS

ALZHEIMER DISEASE GENETIC ARCHITECTURE IN AFRICAN AMERICANS

SEQUENCING AND INITIATION IN SPEECH PRODUCTION

GLOBIN GENE EXPRESSION IN SICKLE CELL GENOTYPE-SPECIFIC IPS CELLS

CHEMICAL SYNTHESIS OF COMPLEX NATURAL PRODUCTS FOR TRANSLATIONAL SCIENCE

BOSTON UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE AWARD (CTSA) PROGRAM UL1

IDENTIFYING PROTECTIVE OMICS PROFILES IN CENTENARIANS AND TRANSLATING THESE INTO PREVENTIVE AND THERAPEUTIC STRATEGIES

COMPREHENSIVE METABOLIC PROFILING OF EXERCISE TO PREDICT CARDIOMETABOLIC RISK

NEURO-AUTONOMY: NEUROSCIENCE-INSPIRED PERCEPTION, NAVIGATION, AND SPATIAL AWARENESS FOR AUTONOMOUS ROBOTS (BOSTON UNIVERSITY)

MODERNIZATION OF HIGH AND MAXIMUM CONTAINMENT RESEARCH FACILITIES AT THE NATIONAL EMERGING INFECTIOUS DISEASES LABORATORIES (NEIDL) TO MEET CURRENT AND FUTURE NATIONAL RESEARCH PRIORITIES - PROJECT SUMMARY/ABSTRACT THE NATIONAL EMERGING INFECTIOUS DISEASES LABORATORIES (NEIDL) AT BOSTON UNIVERSITY (BU) WAS ESTABLISHED TO GENERATE ESSENTIAL INFORMATION ABOUT NEW AND REEMERGING INFECTIOUS PATHOGENS AND THE DISEASES THEY CAUSE, TO FACILITATE DEVELOPMENT OF VACCINES, THERAPEUTICS, AND DIAGNOSTICS, AND TO TRAIN FUTURE GENERATIONS OF SCIENTISTS TO SAFELY STUDY PATHOGENS WITH PANDEMIC POTENTIAL. IT IS ONE OF TWO NATIONAL LABORATORIES HOUSING BOTH HIGH (BIOSAFETY LEVEL 3) AND MAXIMUM (BIOSAFETY LEVEL 4) CONTAINMENT LABS ESTABLISHED BY THE NATIONAL INSTITUTE OF HEALTH (NIH) AT ACADEMIC MEDICAL CENTERS AS PART OF THE BIODEFENCE RESEARCH PROGRAM. INCREASING FREQUENCY OF NEW AND REEMERGING HIGH CONSEQUENCE PATHOGENS CAUSING HUMAN (AND ANIMAL) DISEASES AND THE LIMITED AVAILABILITY OF PROVEN SAFE AND EFFECTIVE MEDICAL COUNTERMEASURES HIGHLIGHT THE NEED TO IMPROVE OPERATIONAL EFFICIENCY FOR RESEARCH ON RISK GROUP 3 PATHOGENS. NEIDL WAS DESIGNED IN 2003, COMPLETED IN 2008, AND APPROVED FOR CONTAINMENT RESEARCH IN 2018. SHORTLY AFTER RESEARCH OPERATIONS HAD BEGUN, NEIDL INVESTIGATORS WERE FACED WITH THE NEED TO URGENTLY PIVOT TO WORK ON THE NEW PANDEMIC PATHOGEN, SARS-COV-2. THIS EFFORT REVEALED INFRASTRUCTURE DEFICIENCIES IN THE FACILITY THAT IMPEDED RESEARCH FLEXIBILITY, REDUCED OPERATIONAL EFFICIENCY AND TURNAROUND TIME BETWEEN STUDIES, LIMITED THE NUMBER OF PATHOGENS AND ARTHROPOD VECTORS THAT COULD BE INVESTIGATED CONCURRENTLY, AND SLOWED SCIENTIFIC PRODUCTIVITY AND THE DEVELOPMENT OF ESSENTIAL MEDICAL COUNTERMEASURES AND DIAGNOSTICS. THE FOLLOWING THREE MODERNIZATION GOALS IDENTIFIED WILL SIGNIFICANTLY IMPROVE OUR ABILITY TO MANAGE THE FACILITY AND BETTER MEET THESE FUTURE RESEARCH NEEDS: GOAL 1. MODIFY BIOSAFETY LEVEL (BSL)-3 AND ANIMAL BIOSAFETY LEVEL (ABSL)-3 SPACES TO FACILITATE INDIVIDUAL ROOM ISOLATION FOR DECONTAMINATION AND ESSENTIAL MAINTENANCE, ALLOWING UNINTERRUPTED WORK IN OTHER BSL-3/ABSL-3 AREAS. UPDATING THE ORIGINAL ROOM AIR PRESSURE CONTROL SYSTEMS WILL PRECLUDE INADVERTENT POSITIVE PRESSURIZATION OF ADJACENT SPACES, WHILE THE INSTALLATION OF ADDITIONAL IN-PARALLEL HIGH EFFICIENCY PARTICULATE AIR (HEPA) FILTER HOUSINGS WILL INCREASE CAPACITY FOR EXTENDED OR PHASED RISK GROUP 3 STUDIES IN ANIMALS AND ROOM BY ROOM ANNUAL MAINTENANCE AND CERTIFICATION. GOAL 2. RENOVATE ARTHROPOD CONTAINMENT (HIGH) LEVEL SPACE TO ADD CAPACITY FOR TICK RESEARCH AND PERMIT CONCURRENT MOSQUITO VECTOR STUDIES, FACILITATE DIRECT VECTOR-TO-HOST TRANSMISSION STUDIES IN ANIMAL MODELS OF HUMAN DISEASE, AND IMPROVE VECTOR BIOSECURITY WHEN DOORS ARE OPENED AND CLOSED. GOAL 3. MODERNIZE AND CONVERT THE BSL-4 AIR LOCKS TO MICROCHEM AS AN OPTION TO GASEOUS PHASE DECONTAMINATION TO REDUCE THE REQUIRED PROCESS TIME FROM DAYS TO MINUTES AND EXPEDITE TURNAROUND TIME FOR STUDIES TO RESUME.

DERIVATION OF TRANSPLANTABLE LUNG EPITHELIAL PROGENITORS FROM IPS CELLS

PUBLIC HEALTH TRAINING CENTERS

NEUROBEHAVIORAL RESEARCH ON INFANTS AT RISK FOR SLI AND AUTISM

UTILIZING SYNTHETIC BIOLOGY TO CREATE PROGRAMMABLE MICRO-BIO-ROBOTS

NATIONAL CENTER ON IMPROVING LITERACY

ENVIRONMENTAL EPIDEMIOLOGY IN COMMUNITY SETTINGS

BOSTON ALCOHOL RESEARCH COLLABORATION ON HIV/AIDS - COMORBIDITY CENTER (BOSTON ARCH CC) - PROJECT SUMMARY/ABSTRACT EFFECTIVE ANTIRETROVIRAL THERAPY HAS INCREASED THE LIFESPAN OF PEOPLE LIVING WITH HIV (PLWH). ALCOHOL USE, COMMON AMONG PLWH, PLAYS AN INCREASINGLY IMPORTANT ROLE IN THE RISK FOR AND MANAGEMENT OF HIV-ASSOCIATED COMORBIDITIES. UNHEALTHY DRINKING CAN EXACERBATE TWO HIGHLY PREVALENT HIV-RELATED COMORBIDITIES/CO-OCCURRING CONDITIONS, CHRONIC PAIN AND PHYSICAL INACTIVITY, WHICH IN TURN, CAN INTENSIFY ALCOHOL USE AND AFFECT PHYSICAL AND MENTAL FUNCTION IN PLWH. WE PROPOSE THE BOSTON ALCOHOL RESEARCH COLLABORATION ON HIV/AIDS – COMORBIDITY CENTER (BOSTON ARCH CC) AS AN EXTENSION OF OUR BOSTON ALCOHOL RESEARCH COLLABORATION ON HIV/AIDS (ARCH) COHORT LAUNCHED IN 2011 AND RENEWED IN 2016 WITH FUNDING FROM NIAAA. IN BOSTON ARCH CC WE TARGET IN RANDOMIZED TRIALS THESE TWO MODIFIABLE CONDITIONS, PAIN AND PHYSICAL INACTIVITY, THAT HAVE A CRITICAL IMPACT ON A VARIETY OF OTHER HIV-RELATED COMORBIDITIES. BOSTON ARCH CC CONTAINS 4 INTEGRATED COMPONENTS THAT MAKE UNIQUE CONTRIBUTIONS TO OUR INTERDISCIPLINARY APPROACH: TWO RANDOMIZED TRIALS (RESEARCH PROJECT COMPONENTS), AN ADMINISTRATIVE CORE (AC) THAT COORDINATES THE P01, AND A BIOSTATISTICS AND DATA MANAGEMENT (BDM) CORE THAT SUPPORTS THE TRIALS METHODOLOGICALLY AND PROVIDES DATA MANAGEMENT AND BIOSTATISTICAL EXPERTISE TO THEM, AND CONTINUES SECONDARY ANALYSES USING EXTANT BOSTON ARCH DATA. IN OBJECTIVE 1 WE WILL CONDUCT STATE-OF-THE-ART E-HEALTH CLINICAL TRIALS RESEARCH ON SCALABLE APPROACHES TO ADDRESS THE HIV-ASSOCIATED CONDITIONS CHRONIC PAIN AND PHYSICAL INACTIVITY IN PLWH WITH UNHEALTHY ALCOHOL USE. BY RECRUITING, ASSESSING, AND INTERVENING WITH PARTICIPANTS OUTSIDE OF STANDARD MEDICAL VISITS, THROUGH ENTIRELY ONLINE E-HEALTH PROCEDURES, OUR TRIALS ADDRESS UNHEALTHY DRINKING IN THE CARE OF COMPLEX HIV PATIENTS. IN OBJECTIVE 2 WE WILL SUPPORT SECONDARY ANALYSES OF THE EXISTING BOSTON ARCH COHORT, AND PROVIDE SUPPORT AND MENTORING TO TRAINEES AND INVESTIGATORS ACCESSING THE COHORT DATA. THE NEARLY TEN- YEAR PROSPECTIVE BOSTON ARCH COHORT ENROLLED PLWH WITH CURRENT OR PAST SUBSTANCE USE, AND PROVIDES THE BASIS FOR CREATING A PROGRAM FOR EARLY STAGE ALCOHOL-HIV INVESTIGATORS INTERESTED IN SCIENTIFIC QUESTIONS RELATED TO PAIN, PHYSICAL INACTIVITY, AND PHYSICAL AND MENTAL FUNCTIONING. TO ACHIEVE THE GOAL OF ADDRESSING THESE TWO CO-OCCURRING CONDITIONS, WE BRING TOGETHER MULTIDISCIPLINARY EXPERTS IN FIELDS INCLUDING ALCOHOL AND HIV, PUBLIC HEALTH, ADDICTION MEDICINE, CLINICAL TRIALS, PSYCHOLOGY, PAIN, PHYSICAL ACTIVITY, ECOLOGICAL MOMENTARY ASSESSMENT, FUNCTIONAL STATUS MEASUREMENT, AND RESEARCH METHODS AND SERVICES (BIOSTATISTICS AND DATA MANAGEMENT). THE INTEGRATION ACROSS THESE FIELDS PROVIDES A COHESIVE PROGRAM WHERE THE WHOLE IS BIGGER THAN THE SUM OF THE PARTS, SUPPORTING INVESTIGATORS WHOSE WORK CAN BE RAPIDLY TRANSLATED TO COMMUNITY-BASED POPULATION IMPACT.