Vanderbilt University

DATA AND RESEARCH SUPPORT CENTER

AVANTE

CANCER CENTER SUPPORT GRANT

SUPPORTING SUSTAINABLE IMPLEMENTATION OF HIV AND TB SERVICES FOR EPIDEMIC CONTROL IN THE REPUBLIC OF

VANDERBILT INSTITUTE FOR CLINICAL AND TRANSLATIONAL RESEARCH (VICTR)

CRESP III NUCLEAR WASTE CLEAN UP

AVANTE ZAMBZIA: TECHNICAL ASSISTANCE TO THE MINISTRY OF HEALTH (MOH) FOR HIV SERV

COORDINATING CENTER FOR BETA CELL BIOLOGY CONSORTIUM

VANDERBILT VACCINE AND TREATMENT EVALUATION UNIT

SOUTHERN COMMUNITY COHORT STUDY

THE VANDERBILT INSTITUTE FOR CLINICAL AND TRANSLATIONAL RESEARCH (VICTR)

CCASANET: CARIBBEAN, CENTRAL AND SOUTH AMERICA NETWORK

BUNYAVIRUS AND PICORNAVIRUS PANDEMIC PATHOGEN PREPAREDNESS (BP4) CENTER - PROJECT SUMMARY PATHOGENIC PICORNAVIRUSES AND BUNYAVIRUSES HAVE AN ENORMOUS IMPACT ON PUBLIC HEALTH WORLDWIDE, AND OUR UNDERSTANDING OF MECHANISTIC CORRELATES OF IMMUNITY FOR MEMBERS OF THESE VIRUS FAMILIES IS LIMITED. BECAUSE OF THE DIVERSITY OF VIRUSES IN THESE FAMILIES, IT IS UNLIKELY MEDICAL COUNTERMEASURES (SUCH AS VACCINES AND ANTIBODIES) CAN BE DEVELOPED AHEAD OF TIME FOR EACH ONE OF THESE VIRUSES, THEREFORE A PROTOTYPE PATHOGENS APPROACH IS WARRANTED. WE HAVE ASSEMBLED A HIGHLY INTERDISCIPLINARY CONSORTIUM OF LEADING INVESTIGATORS IN THE FIELD OF PICORNAVIRUS AND BUNYAVIRUS VIROLOGY, IMMUNOLOGY, VACCINE BIOLOGY AND ANTIBODY SCIENCES TO STUDY THE MECHANISTIC CORRELATES OF IMMUNITY TO PROTOTYPE PATHOGENS FOR THESE FAMILIES, AND THEN APPLY THE PRINCIPLES WE LEARN WITH THE PROTOTYPE PATHOGENS TO DIFFERENT PATHOGENIC VIRUSES IN THOSE FAMILIES THAT ARE ANTIGENICALLY DISTINCT. ALL FIVE RESEARCH PROJECTS (RP) IN THE CENTER FOCUS ON DEVELOPING STRATEGIES EFFECTIVE AGAINST ALL PATHOGENIC MEMBERS OF A GROUP OF VIRUSES, PICORNAVIRUSES, HANTAVIRUSES, AND DIVERSE ARENAVIRUSES. RP1 FOCUSES ON INNOVATIVE VACCINE STRATEGIES FOR PICORNAVIRUSES (ENTEROVIRUS D68, ENTEROVIRUS A71, ECHOVIRUS 11 AND RHINOVIRUS C TYPES), RP2 FOCUSES ON HUMAN ANTI-PICORNAVIRUS MONOCLONAL ANTIBODIES, RP3 FOCUSES ON NOVEL VACCINE CANDIDATES FOR HANTAVIRUSES, RP4 FOCUSES ON HUMAN MABS FOR SIN NOMBRE, ANDES AND HANTAAN HANTAVIRUSES, AND RP5 PROPOSES STUDIES ON ARENAVIRUS VACCINES AND ANTIBODIES, WITH LCMV AS AN INITIAL PROTOTYPE FOR STUDY. A UNIQUE ASPECT OF THIS CENTER IS THAT IT INCLUDES FULL COMPLEMENTARY RESEARCH PROJECTS FOR BOTH VACCINE AND MABS, WHICH ARE THE TWO MOST WELL-STUDIED COUNTERMEASURES THAT PROVIDE COMPLETE PRE- OR POST-EXPOSURE PROTECTION AGAINST VIRUS INFECTIONS. THE ADVANCED LEVEL OF CERTAIN PRELIMINARY FINDINGS IN THE WORK DESCRIBED IN THE RPS IS A MAJOR STRENGTH AND ADVANTAGE OF OUR CENTER. THERE HAS RELATIVELY LITTLE SIGNIFICANT PROGRESS OVER THE LAST DECADE IN THE DEVELOPMENT OF VACCINES OR POSTEXPOSURE THERAPIES FOR PICORNAVIRUSES OR BUNYAVIRUSES. PREVENTIVE VACCINES WOULD HAVE UTILITY FOR THE PUBLIC DURING LOCAL OR LARGE-SCALE OUTBREAKS, FOR LABORATORY WORKERS, FOR FIRST RESPONDERS OR INDIVIDUALS AT HIGH-RISK EXPOSURE, AND FOR CERTAIN TRAVELERS OR MILITARY PERSONNEL. IN THE CASE OF A BIOLOGICAL ATTACK OR NATURAL OUTBREAK, HOWEVER, A PREVENTATIVE OR POSTEXPOSURE ANTIBODY TREATMENT WOULD BE THE MOST PRACTICAL APPROACH FOR RAPID DEPLOYMENT AND HAS THE ADVANTAGE THAT ANTIBODIES CAN BE USED IN ANY AGE OR HEALTH CONDITION, INCLUDING THE IMMUNOCOMPROMISED. PERFORM PIVOTAL STUDIES THAT WILL FACILITATE THE DEVELOPMENT OF PRODUCTS USED FOR THE PREVENTION AND TREATMENT OF NIPAH AND HENDRA INFECTIONS. THE COOPERATION AMONG THE PAIRED VACCINE + MAB RPS, THE ADMINISTRATIVE CORE, THE SAMPLE ACQUISITION, STRUCTURAL BIOLOGY, AND VACCINE TECHNOLOGY CORES IS BUILT INTO THE CENTER BY DESIGN, AS ALL COMPONENTS WORK TOGETHER TO PROVIDE BROADLY EFFECTIVE CANDIDATE COUNTERMEASURES. QUALITY SYSTEM DATA MANAGEMENT WILL BE EMPLOYED IN BOTH THE PREPARATION OF ADVANCED STAGE TEST ARTICLES AND IN THE CONDUCT OF ANIMAL STUDIES.

ALZHEIMER'S DISEASE SEQUENCING PROJECT PHENOTYPE HARMONIZATION CONSORTIUM - ABSTRACT IN RESPONSE TO PAR-20-099 “HARMONIZATION OF ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (AD/RD) GENETIC, EPIDEMIOLOGIC, AND CLINICAL DATA TO ENHANCE THERAPEUTIC TARGET DISCOVERY”, WE HAVE ASSEMBLED A MULTIDISCIPLINARY TEAM THAT INCLUDES EXPERTS IN NEUROIMAGING, NEUROPSYCHOLOGY, FLUID BIOMARKERS, NEUROPATHOLOGY, AND VASCULAR CONTRIBUTIONS TO ADRD TO WORK IN CLOSE PARTNERSHIP WITH THE NIH AND THE ALZHEIMER’S DISEASE SEQUENCING PROJECT (ADSP). OUR ADSP PHENOTYPE HARMONIZATION CONSORTIUM, OR “ADSP-PHC”, SEEKS TO WORK IN COORDINATION WITH EXISTING ADSP WORKGROUPS AND INITIATIVES TO (1) STREAMLINE ACCESS TO ENDOPHENOTYPE DATA, (2) PROVIDE HIGH QUALITY ENDOPHENOTYPE HARMONIZATION ACROSS MULTIPLE RESEARCH DOMAINS, AND (3) PROVIDE COMPREHENSIVE DOCUMENTATION OF BOTH DATA AVAILABILITY AND HARMONIZATION PROCEDURES. THIS PROJECT INCLUDES TWO COORDINATING CENTERS, THREE CORES, AND EIGHT DOMAIN- SPECIFIC HARMONIZATION TEAMS LED BY WORLD-RENOWNED EXPERTS IN THEIR FIELDS. WHILE OUR EFFORTS WILL FOCUS ON DATA ACCESS, DOCUMENTATION, AND HARMONIZATION, WE WILL WORK CLOSELY WITH OTHER ADSP WORKGROUPS AND OTHER LARGE-SCALE HARMONIZATION EFFORTS TO MAXIMIZE THE IMPACT AND ALIGN WITH NIH PRIORITIES. IN PARTICULAR, WE WILL FOCUS HARMONIZATION ON ADRD-RELATED ENDOPHENOTYPES, INCLUDING COGNITIVE SCORES DERIVED FROM DETAILED NEUROPSYCHOLOGICAL ASSESSMENTS, MEASURES OF NEUROPATHOLOGY MEASURED BOTH EX VIVO (NEUROPATHOLOGICAL ASSESSMENT AT AUTOPSY) AND IN VIVO (FLUID BIOMARKERS AND POSITRON EMISSION TOMOGRAPHY BIOMARKERS), CONCOMITANT PATHWAYS OF INJURY (VASCULAR RISK FACTORS AND VASCULAR BRAIN INJURY), AND MEASURES OF NEURODEGENERATION FOCUSING ON BOTH WHITE (DIFFUSION-WEIGHTED MRI) AND GREY MATTER (T1-WEIGHTED MRI). THE PROPOSED HARMONIZATION EFFORT WILL PROVIDE AN UNPRECEDENTED OPPORTUNITY TO DISENTANGLE THE GENETIC ARCHITECTURE OF INDIVIDUAL BIOLOGICAL CONTRIBUTORS TO ADRD RISK AND PROGRESSION. THE HARMONIZED DATA, PROTOCOLS, AND EDUCATIONAL TOOLS DEVELOPED BY THE ADSP-PHC WILL TRANSFORM THE ADRD LANDSCAPE, ACCELERATE DISCOVERY, AND FACILITATE THE APPLICATION OF EMERGING BIG DATA ANALYTIC APPROACHES LEVERAGING MACHINE LEARNING AND ARTIFICIAL INTELLIGENCE.

THE VANDERBILT INSTITUTE FOR CLINICAL AND TRANSLATIONAL RESEARCH (VICTR) UL1

SPORE IN BREAST CANCER

VANDERBILT RURAL MOZAMBIQUE PROJECT: PROPOSAL FOR PEPFAR-SUPPORTED CARE AND TREAT

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH IN SUPPORT OF BTO IN THE AMOUNT OF 2,524,411 ON CONTRACT HR0011-18-2-0001.

HOST AND VIRAL DETERMINANTS OF INFANT AND CHILDHOOD ALLERGY AND ASTHMA

VANDERBILT HIV CLINICAL TRIALS UNIT

GH12-1224: TECHNICAL ASSISTANCE TO THE MINISTRY OF HEALTH (MOH) FOR HIV SERVICES AND PROGRAM TRANSITION IN ZAMB

IMPROVING CLINICAL TRIAL EDUCATION, RECRUITMENT, AND ENROLLMENT AT CTSA HUBS (I-CERCH)

PROTECT AGAINST EMERGENT ALPHAVIRUSES THROUGH COMPUTATION (PEAC) - ALPHAVIRUSES CAUSE NEUROLOGICAL AND RHEUMATIC DISEASES AND POSE SUBSTANTIAL RISKS TO HUMAN HEALTH THROUGH RECURRING NATURAL OUTBREAKS, EPIDEMICS, AND THE THREAT OF BIOTERRORISM. SOME ALPHAVIRUSES (E.G., EASTERN EQUINE ENCEPHALITIS VIRUS AND WESTERN EQUINE ENCEPHALITIS VIRUS) ARE ENDEMIC IN THE UNITED STATES, WHEREAS OTHERS HAVE ONLY RECENTLY EMERGED DOMESTICALLY. ALPHAVIRUSES ARE TRANSMITTED THROUGH MOSQUITOES, AND MULTIPLE FACTORS CONTRIBUTE TO THEIR EMERGENCE AND RE-EMERGENCE, INCLUDING CLIMATE CHANGE, URBANIZATION, AND TRAVEL. THE SINGLE APPROVED VACCINE AGAINST ALPHAVIRUSES, IXCHIQ, INDUCES ONLY SPECIES-SPECIFIC PROTECTION AGAINST CHIKUNGUNYA VIRUS. HOWEVER, MULTIPLE CROSS-REACTIVE PAN-ALPHAVIRUS ANTIBODIES THAT CAN PROTECT MICE AGAINST INFECTION BY A RANGE OF ALPHAVIRUSES HAVE BEEN IDENTIFIED BY MEMBERS OF OUR CONSORTIUM, PROVIDING TEMPLATES FOR VACCINE DESIGN. TO DEVELOP BROADLY PROTECTIVE VACCINES, WE PROPOSE CREATING HETERO-NANOPARTICLES THAT CO-PRESENT IMMUNOGENS CAPABLE OF INDUCING BROADLY PROTECTIVE ANTIBODIES AGAINST THE TWO COMPLEXES OF ALPHAVIRUSES, NAMELY ENCEPHALITIC VIRUSES AND ARTHRITOGENIC VIRUSES. DURABILITY OF THE IMMUNOGEN WILL BE ENHANCED USING AN INNOVATIVE APPROACH TO IMPROVE IN VIVO TRAFFICKING. WE WILL FURTHER COMBINE THIS B-CELL TARGETING DUAL-IMMUNOGEN WITH A BROAD T-CELL IMMUNOGEN COVERING ALL ALPHAVIRUSES. BOTH B AND T CELL IMMUNOGENS WILL BE DESIGNED USING NOVEL ARTIFICIAL INTELLIGENCE/MACHINE LEARNING (AI/ML)-BASED METHODS THAT IMPROVE UPON PREVIOUS APPROACHES IN TERMS OF THERMOSTABILIZATION, EPITOPE-FOCUSING, EPITOPE-SCAFFOLDING, GERMLINE-TARGETING, IMMUNOGENIC T CELL EPITOPE SELECTION AND T CELL EPITOPE IMMUNOGEN DESIGN. WE WILL COMBINE PREVIOUSLY PUBLISHED AI/ML TOOLS WITH OUR OWN ALGORITHMS AND TRAIN NEW NEURAL NETWORKS, WHEN NECESSARY, TO DEVELOP A ROBUST COMPUTATIONAL IMMUNOGEN DESIGN PIPELINE. WE WILL EXTENSIVELY TEST ALL IMMUNOGENS IN VITRO AND IN VIVO USING TRANSGENIC ATX-GK MICE, WHICH CARRY A FULLY HUMAN IG REPERTOIRE, THEREBY MORE CLOSELY MIMICKING THE HUMAN ANTIBODY-RESPONSE. DEEP ANALYSIS OF B-CELL RESPONSES BY SINGLE-CELL BCR SEQUENCING WILL COMPLEMENT SEROLOGICAL ASSAYS TO ITERATIVELY IMPROVE THE IMMUNOGENS. THE BEST IMMUNOGENS WILL BE VALIDATED AS PART OF IMMUNIZATION AND CHALLENGE STUDIES IN NON-HUMAN PRIMATE MODELS OF ALPHAVIRUS PATHOGENESIS. WE WILL EMPLOY THE MOST ADVANCED IN SILICO AND IN VITRO TECHNIQUES TO STRUCTURALLY CHARACTERIZE THE ALPHAVIRUS GENUS AND PROVIDE PUBLIC ACCESS TO A CURATED DATABASE FOR STRUCTURES OF VIRAL PROTEINS, RECEPTORS, ANTIBODIES AND POST-TRANSLATIONAL MODIFICATIONS. METHODS WILL INCLUDE COMPUTATIONAL PREDICTIONS (I.E., PROTEIN STRUCTURES, INTERACTIONS, AND MODIFICATIONS) AND EXPERIMENTAL VALIDATION USING EM POLYCLONAL EPITOPE MAPPING (EMPEM), HIGH-THROUGHPUT CRYO-ELECTRON MICROSCOPY, X-RAY CRYSTALLOGRAPHY AND MASS SPECTROMETRY. THIS EXTENSIVE DATASET WILL ALSO BE USED TO REFINE OUR AI/ML ALGORITHMS. THE BEST IMMUNOGEN WILL BE TESTED IN A PHASE I, FIRST-IN-HUMAN CLINICAL TRIAL BY THE VANDERBILT VACCINE RESEARCH PROGRAM, IN PARTNERSHIPS WITH MODERNA INC., KCASBIO, AND THE VANDERBILT COORDINATING CENTER. THE PROPOSED DESIGN IS A RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLINDED STUDY TO ASSESS THE SAFETY AND IMMUNOGENICITY OF THE SELECTED VACCINE CANDIDATE. THE PRIMARY OBJECTIVE OF THE PHASE I STUDY WILL BE SAFETY AND REACTOGENICITY. SECONDARY OBJECTIVES WILL ALSO INCLUDE EVALUATION OF IMMUNOGENICITY, INCLUDING THE POTENCY AND DURABILITY OF SERUM ANTIBODY RESPONSES. THE PROPOSED WORK WILL COMBINE AND IMPROVE THE MOST ADVANCED TECHNOLOGIES IN COMPUTATIONAL BIOLOGY, STRUCTURAL BIOLOGY, VACCINOLOGY, VIROLOGY AND IMMUNOLOGY TO STUDY AND UNDERSTAND ALPHAVIRUS INFECTION AND ITS INTERACTIONS WITH THE HOST IMMUNE SYSTEM. WE WILL LEVERAGE THIS INFORMATION TO DEVELOP A BROAD ALPHAVIRUS VACCINE. OUR GOAL IS TO PROTECT AGAINST EMERGENT ALPHAVIRUSES THROUGH COMPUTATION (PEAC).

VANDERBILT DIABETES RESEARCH CENTER

CRESP III NUCLEAR WASTE CLEAN-UP

H. PYLORI-INDUCED INFLAMMATION AND GASTRIC CANCER

ECHO LABORATORY CORE AT VANDERBILT FOR INTEGRATED SAMPLE BIOBANKING AND PROCESSING - SUMMARY EARLY-LIFE ENVIRONMENTAL EXPOSURES (E.G., SOCIAL-ENVIRONMENTAL, PARENTAL RISK FACTORS, NICOTINE, DIET, INFECTION) ARE INCREASINGLY IMPLICATED IN THE EARLY PATHOGENESIS OF CHILDHOOD DISEASES THAT HAVE LIFE-LONG CONSEQUENCES. MECHANISMS LINKING THESE EXPOSURES TO LONGER-TERM OUTCOMES REMAIN LIMITED. IN 2016, THE NIH ESTABLISHED THE ENVIRONMENTAL INFLUENCES ON CHILD HEALTH OUTCOMES (ECHO) PROGRAM, A COLLABORATIVE MULTI-DIMENSIONAL RESEARCH INITIATIVE TO CHARACTERIZE THE IMPACT OF EARLY-LIFE ENVIRONMENTAL FACTORS ON CHILDHOOD HEALTH (>70 COHORTS, >50K PARTICIPANTS). WHILE TARGETED ASSAYS WITHIN ECHO ARE LIKELY TO LEAD TO DISEASE-SPECIFIC INSIGHT, BROAD, COMPREHENSIVE, UNBIASED ASSESSMENT OF THE MOLECULAR SPACE FOR NOVEL DISCOVERY—A KEY MISSION OF ECHO— WILL NECESSITATE CENTRALIZATION OF BIOBANKING EFFORTS/LABORATORY MANAGEMENT WITH CAPABILITY FOR HIGH-THROUGHPUT “OMICS”/NON-“OMICS” ASSAY AS WELL AS NOVEL ASSAY DEVELOPMENT, BIOINFORMATICS, AND CLOUD ARCHITECTURE/DATA SHARING FOR COLLABORATIVE SCIENCE. IN RESPONSE TO RFA-OD-22-016, VANDERBILT WILL ADDRESS THIS NEED BY ESTABLISHING THE ECHO LABORATORY CORE AT VANDERBILT FOR INTEGRATED SAMPLE BIOBANKING AND PROCESSING (ELVIS). ELVIS FACILITATES THE COLLECTION AND PROCESSING OF BIOSPECIMENS; MANAGES THE BIOREPOSITORY; PERFORMS A WIDE RANGE OF BIOSPECIMEN ASSAYS (INCLUDING NOVEL DEVELOPMENT), AND COORDINATES METADATA AND ASSAY DATA TRANSFER TO THE COORDINATING CENTER. ELVIS IS ORGANIZED IN CORE “RESOURCES” TO PROVIDE LEADERSHIP/INTEGRATION TO MANAGE ECHO BIOBANKING, ASSAY PERFORMANCE, AND DATA DELIVERY: (1) ADMINISTRATIVE/LIMS/BIOBANKING; (2) METABOLOMICS; (3) PROTEOMICS; (4) NUCLEIC ACID ASSESSMENT; (5) METAGENOMICS; (6) BIOINFORMATICS/STUDY DESIGN. WE ARE UNIQUELY POSITIONED FOR THIS INITIATIVE, LEVERAGING VANDERBILT’S UNIQUE LONG-TERM STRATEGIC INVESTMENT IN FUNCTIONAL BIOBANKING AND ASSAY: (1) LARGE-SCALE, RELIABLE BIOREPOSITORY RECEIPT AND LABORATORY MANAGEMENT (“LIMS”) CAPABILITY (>350K PATIENTS CURRENTLY WITH BIOSPECIMENS; MANY OTHER NIH FUNDED BIOBANKS); (2) NATIONALLY RECOGNIZED SYSTEMS FOR CLINICAL METADATA CAPTURE (REDCAP, REDBRICS; USED IN NIH INITIATIVES, LIKE ALL OF US); (3) CUTTING-EDGE LABORATORY CORES WITH CAPABILITY FOR NOVEL ASSAY DEVELOPMENT/VALIDATION. WE WILL ESTABLISH HARMONIZED PROTOCOLS AND WORKFLOW FOR ECHO COHORT BIOSPECIMEN COLLECTION AND TRACKING INFRASTRUCTURE FROM THE POINT OF SAMPLE COLLECTION TO LONG-TERM STORAGE (AIM 1); PERFORM HIGH-QUALITY, WELL-POWERED MULTI-OMICS AND TARGETED ASSAYS TO IDENTIFY MOLECULAR CORRELATES OF DISEASE TRAJECTORIES IN EARLY LIFE (AIM 2), AND PROVIDE COMPREHENSIVE DATA MANAGEMENT PLATFORM TO FACILITATE INTEGRATED DATA ANALYSIS (AIM 3). ELVIS IS AN IDEAL MECHANISM FOR ECHO GIVEN (1) DEEP, FUNDED EXPERIENCE IN HANDLING THE REQUISITE SAMPLE SIZES IN BANKING AND HIGH-THROUGHPUT ASSAY, INCLUDING QUALITY ASSURANCE MEASURES; (2) PRIOR TRACK RECORD IN ECHO TO ENSURE ECHO- SPECIFIC METADATA COLLECTION, CURATION, AND HARMONIZATION; (3) SECURE METHODS FOR CLOUD INFRASTRUCTURE FOR DATA ANALYSIS PIPELINES AND DATA FLOW TO CLINICAL SITES AND DATA ANALYSIS CENTER. SUCCESSFUL COMPLETION WILL ENABLE THE SUCCESS OF ECHO’S MISSION TO DISCOVER MOLECULAR UNDERPINNINGS OF EARLY CHILDHOOD DETERMINANTS OF DISEASE.

AIDS EDUCATION AND TRAINING CENTERS PROGRAM

HDL FUNCTION IN HUMAN DISEASE

THE VANDERBILT SPECIALIZED CHEMISTRY CENTER FOR ACCELERATED PROBE DEVELOPMENT

FOGARTY INTERNATIONAL CLINICAL RESEARCH SCHOLARS SUPPORT CENTER @ VANDERBILT-AAMC

CARDIAC FUNCTION AS A MECHANISM FOR MALADAPTIVE BRAIN AGING

TENNESSEE CENTER FOR AIDS RESEARCH (TN-CFAR)

MOLECULAR AND CELLULAR BASIS FOR DIGESTIVE DISEASES

COORDINATION FOR ARDS, PNEUMONIA, AND SEPSIS SUPPORTING TRAINING, ORGANIZATION AND NETWORK EFFICIENCY (CAPSTONE) - THE ARDS, PNEUMONIA, AND SEPSIS (APS) COORDINATING CENTER WILL SUPPORT A HIGHLY FUNCTIONAL AND INTEGRATED CLINICAL AND TRANSLATIONAL RESEARCH INFRASTRUCTURE THAT WILL ENHANCE THE QUALITY AND SCIENTIFIC RIGOR OF THE RESEARCH CONDUCTED BY THE APS PHENOTYPING CONSORTIUM. WE ARE A TEAM COMPOSED OF LEADING CONTENT AND METHODS EXPERTS AT VANDERBILT, JOHNS HOPKINS, AND UNIVERSITY OF CALIFORNIA SAN FRANCISCO. WE WILL PROVIDE COORDINATION FOR ARDS, PNEUMONIA, AND SEPSIS SUPPORTING TRAINING, ORGANIZATION AND NETWORK EFFICIENCY: ‘CAPSTONE’. WE WILL SUPPORT THE CLINICAL CENTERS (CCS) IN ENROLLING AND SUSTAINING A DIVERSE COHORT; ENABLE THE EFFICIENT AND STANDARDIZED CAPTURE OF MULTI-MODAL COHORT DATA WITH REPEATED MEASUREMENTS; MODEL THE DATA TO UNDERSTAND MECHANISTIC UNDERPINNINGS OF APS, INCLUDING THE INTERPLAY OF UNDERLYING AND STATIC RISK FACTORS; AND SEGMENT THE POPULATION INTO SIMILAR PROGNOSTIC AND PREDICTIVE PHENOTYPES. THIS WILL ENABLE SCIENTIFIC PROGRESS TOWARDS A DEEPER MECHANISTIC UNDERSTANDING OF CRITICAL ILLNESS SYNDROMES AND RECOVERY. FUNCTIONALLY, WE WILL 1) IMPLEMENT THE STUDY DESIGN, DATA CAPTURE, AND STATISTICAL ANALYSIS UNIT. COORDINATE PROTOCOL DEVELOPMENT; ESTABLISH A REDCAP-BASED DATA COLLECTION, MANAGEMENT, AND SECURITY FRAMEWORK; CONDUCT AND SUPPORT ANALYSES; GENERATE REPORTS; MAKE CURATED DATA WIDELY AVAILABLE FOR RESEARCH THROUGH A FACILITATED STOREFRONT; 2) IMPLEMENT THE CLINICAL RESEARCH MANAGEMENT UNIT. MAINTAIN COHORT INTEGRITY AND ADHERENCE TO THE PROTOCOL AND MANUAL OF OPERATIONS, PERFORM ROUTINE MONITORING OF DATA QUALITY AND SITE PERFORMANCE; TRAINING OF STUDY STAFF; IMAGE AND BIOSPECIMEN MANAGEMENT. SUPPORT SITE COMMUNICATIONS; FACILITATE RECRUITMENT AND RETENTION; AND 3) IMPLEMENT THE STAKEHOLDER ENGAGEMENT AND DEVELOPMENT UNIT. ESTABLISH BIDIRECTIONAL, LONGITUDINAL ENGAGEMENT FROM DIVERSE COMMUNITIES; HELP CCS BUILD AND SUSTAIN TRUST; ENSURE STRENGTHS OF EACH CC ARE NURTURED AND SHARED; FACILITATE DISSEMINATION OF FINDINGS; SUPPORT SKILLS AND CAREER DEVELOPMENT AMONG RESEARCH TEAMS. OUR EFFORTS WILL EXPAND FOUNDATIONAL WORK ON APS PHENOTYPING, IDENTIFY GAPS, AND HELP CREATE METHODS FOR REDEFINING CRITICAL ILLNESS SYNDROMES WITH THE ULTIMATE GOAL OF IMPROVING AND PERSONALIZING MANAGEMENT STRATEGIES THAT WILL CURTAIL THE DEVASTATING MORBIDITY AND MORTALITY CAUSED BY APS.

SOUTHERN COMMUNITY COHORT STUDY

HORMONAL, METABOLIC AND SIGNALING INTERACTIONS IN PAH

MECHANISMS OF FAMILIAL PULMONARY FIBROSIS

CATALYZING AND HARMONIZING OPERATIONAL INNOVATION FOR RECRUITMENT (CHOIR) - WHILE RECRUITMENT INTO CLINICAL RESEARCH HAS BEEN A LONGSTANDING CHALLENGE FOR NIH FUNDED MULTI-SITE STUDIES, IT HAS BECOME CLEAR THAT THERE IS SUBSTANTIAL VARIABILITY IN RECRUITMENT SUCCESS ACROSS THE NATIONAL PORTFOLIO CAUSED BY MANY FACTORS: ELIGIBILITY PARAMETERS, REQUIRED PROCEDURES, COMPENSATION LEVELS, ENGAGEMENT PRACTICES, RECRUITMENT RESOURCES, SKILL AND AWARENESS OF RECRUITMENT TEAMS, GEOGRAPHIC CONSTRAINTS, TRUST, AND PERCEIVED BENEFIT/RISK. STUDIES THAT DO NOT INTEGRATE THESE FACTORS INTO RECRUITMENT AND RETENTION OFTEN CLOSE FOR POOR ACCRUAL. IN ADDITION, THERE ARE NOW MORE EQUITABLE DEFINITIONS OF WHAT CONSTITUTES “RECRUITMENT SUCCESS” BEYOND AN ABSOLUTE TARGET, INCLUDING: DIVERSITY, REPRESENTATIVENESS OF THE ACTUAL POPULATION, COSTS OF ENROLLMENT, RETENTION, AND TIME REQUIRED. THESE COMPLEX DYNAMICS SUGGEST THERE IS NO ‘ONE SIZE FITS ALL’ SOLUTION, AND CAREFUL ATTENTION AND CONSIDERATION MUST BE A PART OF THE RECRUITMENT PLAN. OUR TEAM HAS BEEN FORMING EFFECTIVE RECRUITMENT COLLABORATIONS FOR THE PAST 6 YEARS -- CONSIDERING THE STUDY SPECIFICS, CAPABILITIES OF THE STUDY TEAM, AND NEEDS AND VALUES OF THE PARTICIPANT POPULATION -- TO TOGETHER CRAFT FEASIBLE, EFFECTIVE PLANS. IN THE NEXT CYCLE, WE WILL CATALYZE AND HARMONIZE OPERATIONAL INNOVATION FOR RECRUITMENT (CHOIR) AND WILL CONTINUE TO BE LED BY A LONG-STANDING SYNERGISTIC PARTNERSHIP BETWEEN PAUL HARRIS, PHD, AS PI RESPONSIBLE FOR INFORMATICS DEVELOPMENT, AND CONSUELO WILKINS, MD, MSCI, AS PI OF COMMUNITY AND STAKEHOLDER ENGAGEMENT. FORMAL PARTNERSHIPS WITH 10 OTHER CTSAS PROVIDE BROAD UNDERSTANDING OF HUB NEEDS, ALONG WITH KEY AREAS OF EXPERTISE. WE WILL EXTEND AND BUILD UPON EXISTING RECRUITMENT-RELATED ASSETS AND DATA TOOLS AND RESOURCES ALREADY IN USE BY OUR TEAM AND OTHERS (FASTERTOGETHER, RESEARCHMATCH, REDCAP TRIALSTODAY, FHIR CLINICAL DATA-BASED RECRUITMENT INFRASTRUCTURE). THESE INNOVATIONS ACKNOWLEDGE RECRUITMENT IS NOT A ONE-TIME ACTIVITY BUT IS A CONTINUUM. WE WILL PROVIDE A NATIONAL, DISEASE AGNOSTIC HOME FOR SHARING RECRUITMENT TOOLS, TRAINING, MATERIALS, AND BEST PRACTICES FOR DIVERSE POPULATIONS. SPECIFIC AIMS ARE: 1) PARTNER WITH STUDY TEAMS TO CREATE STUDY-SPECIFIC RECRUITMENT PLANS, AND SUPPORT ONGOING SKILLS DEVELOPMENT. 2) EVALUATE CLINICAL TRIAL RECRUITMENT AND RETENTION METHODS AND MAKE CONTINUAL IMPROVEMENTS. 3) ENHANCE NATIONAL CLINICAL TRIAL AWARENESS THROUGH ENGAGEMENT AND EDUCATION; FACILITATE PARTICIPANT IDENTIFICATION OF STUDIES WITH ONLINE TOOLS. AND, 4) DEVELOP AND DISSEMINATE TECHNICAL AND PROCEDURAL APPROACHES TO CATALYZE ENROLLMENT IN CLINICAL TRIALS ACROSS ALL CTSAS.

ENGAGING COOPERATIVE SITES FOR TRIAL ACCELERATION, TRUST, INNOVATION, AND CAPABILITY (ECSTATIC) - CLINICAL RESEARCH COMES IN MANY DIFFERENT SHAPES AND SIZES, AND A ROBUST NETWORK MUST ACCOMMODATE ALL TRIAL TYPES. NO SINGLE ORGANIZATION CAN DO THIS WORK ALONE. WE HAVE A DEEP COMMITMENT TO BOTH TRIAL INNOVATION AND COLLECTIVE NETWORK CAPACITY WITHIN AND BEYOND THE CTSA CONSORTIUM AND HAVE A LENGTHY HISTORY OF SUPPORTING THIS APPROACH. WE HAVE DEMONSTRATED AN EXCEPTIONAL ABILITY TO COLLABORATIVELY INNOVATE AND SHARE TOOLS SUPPORTING CLINICAL RESEARCH COORDINATION, INCLUDING: GLOBAL DATA MANAGEMENT, MOBILE DATA COLLECTION, RECRUITMENT, ELECTRONIC HEALTH RECORD (EHR) RESEARCH, SINGLE IRB COORDINATION, CONTRACTING, COMMUNITY ENGAGEMENT, RETURNING VALUE TO PARTICIPANTS, ECONSENT, VIRTUAL/REMOTE PARTICIPATION IN STUDIES, AND EHR INTEGRATION WITH REDCAP. WE WILL LEVERAGE AND EXPAND UPON THESE PROGRAMS AS WE ARE ENGAGING COOPERATIVE SITES FOR TRIAL ACCELERATION, TRUST, INNOVATION, AND CAPABILITY (ECSTATIC). WE WILL ESTABLISH A DISTRIBUTED ALLIANCE OF 6 CTSA-ALIGNED COORDINATING CENTERS TO ADD ELASTIC CAPACITY AND BROADEN EXPERTISE TO THE TIN’S CCC/DCC INFRASTRUCTURE. OUR ALLIANCE HAS 14 EXPERT TRIALISTS THAT CAN INFORM THE USE OF INTEGRATED APPROACHES FOR MORE EFFICIENT CLINICAL RESEARCH. ADDITIONALLY, WE WILL PARTNER WITH THE WELL-ESTABLISHED BIOSTATISTICS, EPIDEMIOLOGY, AND RESEARCH DESIGN (BERD) GROUP AND HEALTH EQUITY EXPERTS TO ENSURE EVERY STUDY HAS ACCESS TO NEEDED EXPERTISE STARTING FROM STUDY DESIGN THROUGH ANALYSIS. WE WILL BROADEN THE TYPES OF ORGANIZATIONS THAT CAN READILY PARTICIPATE IN CLINICAL RESEARCH ACROSS THE U.S., INCLUDING HISTORICALLY BLACK COLLEGES AND UNIVERSITIES (HBCUS), TO REACH THE POPULATIONS MOST IN NEED OF SUPPORT. BASED ON OUR NOVEL STRUCTURE, MERGING TEAMS FROM SIX DIFFERENT COORDINATING CENTER GROUPS, OUR TIC’S CAPACITY IS BOTH SCALABLE AND MATCHED BY EXPERTISE TO INTENTIONALLY ACCOMMODATE ALL STUDY DESIGN TYPES. LED BY GORDON BERNARD, MD, WESLEY SELF, MD, AND CHRISTOPHER LINDSELL, PHD, EACH SEASONED IN LEADING AND COLLABORATING WITH MULTISITE CLINICAL TRIAL NETWORKS, ECSTATIC WILL EMBRACE AND DRAW ON DIVERSE EXPERTISE TO BUILD, TEST, AND SHARE NEW RESOURCES THAT WILL ENHANCE AND ACCELERATE RIGOROUS, REPRODUCIBLE RESEARCH FOR ALL CTSAS, TO MORE RAPIDLY IMPROVE HUMAN HEALTH. OUR SPECIFIC AIMS ARE TO: 1) DEMONSTRATE AND DISSEMINATE NOVEL INTEGRATED APPROACHES FOR MORE EFFICIENT CLINICAL RESEARCH INCLUDING EHR-EMBEDDED, REMOTE NO-TOUCH, AND PLATFORM TRIALS, ALIGNING WITH STUDY NEEDS; 2) EXPAND AND ENRICH CLINICAL TRIAL CAPABILITY BY INCREASING POTENTIAL PARTICIPATING SITE EXPRESSION OF INTEREST (EOI) REACH AND READINESS SUPPORT (HBCUS AND RURAL PRACTICE-BASED RESEARCH NETWORKS), BETTER PROCESS INTEGRATION WITH CTSAS, PREPARING STUDY TEAMS, AND BROADER EXPERT ENGAGEMENT; 3) INNOVATE CLINICAL TRIAL METHODOLOGY BY CREATING, EVALUATING, AND DISSEMINATING NEW METHODS FOR RISK MONITORING, AE REPORTING, DIRECT EHR TO REDCAP DATA CAPTURE, AND DATA STANDARDS TO ALL CTSAS; AND 4) PROVIDE A DISTRIBUTED ALLIANCE OF CLINICAL AND DATA COORDINATING CENTERS WITH EXTENSIVE AND DIVERSE EXPERTISE TO OFFER SUPPORT TAILORED FOR TRIAL DESIGN, POPULATION, AND CONDITION.

SPORE IN GL CANCER

MMC, VICC & TSU: PARTNERS IN ELIMINATING CANCER DISPARITIES ( 2 OF 3)

EDUCATION RESEARCH AND DEVELOPMENT CENTERS

TRANSFORMING CLINICAL PRACTICE INITIATIVE (TCPI), PRACTICE TRANSFORMATION NETWORKS (PTN)

MODIFICATION TO PROVIDE INCREMENTAL FUNDING IN THE AMOUNT OF $311,610.

REVERSE-LONG COVID: A MULTICENTER RANDOMIZED, PLACEBO-CONTROLLED CLINICAL TRIAL OF IMMUNOMODULATION (WITH BARICITINIB) FOR LONG COVID RELATED ADRD - PROJECT SUMMARY/ABSTRACT COGNITIVE IMPAIRMENT, INCLUDING ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (ADRD), AND CARDIOPULMONARY DYSFUNCTION FOLLOWING COVID-19, ARE COMPONENTS OF THE CHRONIC SYNDROME KNOWN AS LONG COVID (LC). LC IS AN UNPRECEDENTED PUBLIC HEALTH CRISIS LEADING TO COGNITIVE, MENTAL HEALTH, AND FUNCTIONAL DISABILITIES FOR MILLIONS OF PEOPLE LIVING IN THE UNITED STATES AND AROUND THE WORLD. LARGE EPIDEMIOLOGIC STUDIES HAVE DEMONSTRATED THAT THE RISK OF ADRD INCREASES MULTIFOLD IN MANY OLD AND YOUNG PATIENTS FOLLOWING EVEN MILD SARS-COV-2 INFECTION. PATIENTS WITH LC ALSO FREQUENTLY EXPERIENCE PROFOUND LIMITATIONS IN PHYSICAL FUNCTION AND EXERCISE INTOLERANCE THAT, WHEN PAIRED WITH ADRD, ARE LIFE ALTERING AND RESULT IN INABILITY TO WORK AND LEAD A FAMILY. RAPIDLY GROWING EVIDENCE LINKS THE CLINICAL MANIFESTATIONS OF LC TO PATHOPHYSIOLOGIC MECHANISMS OF ABNORMAL INFLAMMATION AND IMMUNE DYSREGULATION. THERE IS A DRIVING, UNMET NEED FOR ROBUST CLINICAL TRIALS DIRECTLY TARGETING IMMUNE DYSREGULATION TO REDUCE ADRD AND CARDIOPULMONARY INJURY RELATED TO LC. OUR CENTRAL HYPOTHESIS IS THAT IMMUNOMODULATORS MAY BE THE MOST EFFECTIVE TREATMENT FOR THESE SEQUELAE OF LC. BARICITINIB IS AN IMMUNOMODULATOR (JAK1/2 INHIBITOR) THAT IS FDA-APPROVED TO TREAT ACUTE COVID-19 INFECTION AS WELL AS CERTAIN AUTOIMMUNE CHRONIC DISEASES LIKE RHEUMATOID ARTHRITIS. JAK1/2 SIGNALING IS A CARDINAL DRIVER OF BOTH SYSTEMIC AND NEUROINFLAMMATION. OUR STUDY, THE RANDOMIZED TRIAL EVALUATING BARICITINIB ON PERSISTENT NEUROLOGIC AND CARDIOPULMONARY SYMPTOMS OF LONG COVID (REVERSE-LC), WILL ENROLL 500 PATIENTS WITH LC AND COGNITIVE IMPAIRMENT AT HIGH RISK FOR LONG-TERM ADRD ACROSS 4 SITES TO TEST THE HYPOTHESIS THAT 6 MONTHS OF BARICITINIB VERSUS MATCHED PLACEBO WILL IMPROVE NEUROCOGNITIVE AND PHYSICAL FUNCTION IN LC. AIM 1 WILL MEASURE THE TRAJECTORY OF NEUROCOGNITIVE FUNCTION AT ENROLLMENT, 6- AND 12-MONTHS IN BARICITINIB VERSUS PLACEBO PATIENTS USING AN OBJECTIVE NEUROPSYCHOLOGICAL BATTERY AS WELL AS PATIENT-REPORTED COGNITIVE FUNCTION. AIM 2 WILL MEASURE PHYSICAL FUNCTION USING CARDIOPULMONARY EXERCISE TESTING AND OTHER FUNCTIONAL MEASURES IN ADDITION TO PATIENT-REPORTED PHYSICAL SYMPTOMS IN PATIENTS TREATED WITH BARICITINIB VERSUS PLACEBO. AIM 3 WILL EVALUATE THE EFFECT OF BARICITINIB VERSUS PLACEBO ON PLASMA, CEREBROSPINAL FLUID, AND NEUROIMAGING INFLAMMATORY MARKERS AT ENROLLMENT, AS WELL AS 6- AND 12-MONTH FOLLOW-UP STUDY VISITS IN PATIENTS WITH LC TO IDENTIFY INFLAMMATORY MEDIATORS OF NEUROPSYCHOLOGICAL (ADRD) OUTCOMES. THE REVERSE-LC TRIAL IS NOVEL IN TARGETING IMMUNE DYSREGULATION AND INFLAMMATION FOR PATIENTS WITH LC AND IS BASED ON OUR GROWING UNDERSTANDING OF THE MECHANISM OF THIS EMERGING, POST-INFECTIOUS CAUSE OF RAPIDLY-ACQUIRED ADRD RISK. REGARDLESS OF THE OUTCOME OF REVERSE-LC, THIS STUDY WILL PROVIDE CRUCIAL INSIGHTS INTO TREATMENT OF ADRD, SEQUELAE OF COVID, AND DISEASE PATHOGENESIS. THIS INVESTIGATION WILL ALSO ESTABLISH AN INNOVATIVE TRIAL PLATFORM BY WHICH TO TEST FUTURE INTERVENTIONS FOR RAPIDLY-ACQUIRED NEUROCOGNITIVE DYSFUNCTION, CARDIOPULMONARY DISEASE, LC, AND OTHER AGE- RELATED COMORBIDITIES LEADING TO ADRD. IT WILL ADVANCE THE SCIENCE OF AGING BRAIN DISEASE AND DISABILITY.

BRAIN-2 COVID-19 ADMINISTRATIVE SUPPLEMENT

CHEMICAL THREAT ASSESSMENT BY RAPID MOLECULAR PHENOTYPING

SPECIAL EDUCATION-PERSONNEL PREPARATION TO IMPROVE SERVICES AND RESULTS FOR CHILDREN WITH DISABILITIES - NATIONAL IHE FACULTY ENCHANCEMENT CENTER

MEDICAL SCIENTIST TRAINING PROGRAM

PHARMACOGENOMICS OF ARRHYTHMIA THERAPY

IMAGING MASS SPECTROMETRY RESEARCH RESOURCE AT VANDERBILT UNIVERSITY

AUTONOMIC CARDIOVASCULAR REGULATION

REGIONAL AIDS EDUCATION AND TRAINING CENTERS PROGRAM - VANDERBILT UNIVERSITY MEDICAL CENTER (VUMC) PROPOSES TO LEAD THE SOUTHEAST AIDS EDUCATION AND TRAINING CENTER (SE AETC). THE SOUTHEAST (SE) HAS A POPULATION OF OVER 67 MILLION PEOPLE LIVING IN EIGHT STATES INCLUDING ALABAMA, FLORIDA, GEORGIA, KENTUCKY, MISSISSIPPI, NORTH CAROLINA, SOUTH CAROLINA, AND TENNESSEE. ACCORDING TO THE CDC, AN ESTIMATED 323,100 PEOPLE IN THE SE LIVE WITH HIV (BOTH DIAGNOSED AND UNDIAGNOSED), AND THE AVERAGE RATE OF NEW DIAGNOSES IN 2021 WAS 16.8 PER 100,000 POPULATION. VUMC WILL BUILD UPON SUCCESSFUL INTERVENTIONS AND INTRODUCE INNOVATIVE PROGRAMS, ORGANIZED AS FOUNDATIONS OF HIV (FH), CAPABILITY AND EXPERTISE EXPANSION (CEE), PRACTICE TRANSFORMATION (PT), HIV INTERPROFESSIONAL EDUCATION (IPE), MINORITY AIDS INITIATIVE (MAI), AND ENDING THE HIV EPIDEMIC (EHE) IN THE US INITIATIVES. VUMC WILL BUILD UPON RELATIONSHIPS ESTABLISHED OVER THE PAST NINE YEARS AS THE SE AETC CENTRAL OFFICE (CO). VUMC HAS A GROWING REACH INCLUDING 81,970 TRAINEES REPRESENTING PRIORITY POPULATIONS IN DIVERSE ORGANIZATIONS. THIS NETWORK PROVIDES OPPORTUNITIES FOR STRATEGIC PARTNERSHIP WITH ORGANIZATIONS SUCH AS HEALTH DEPARTMENTS, PRIMARY CARE ASSOCIATIONS (PCAS), RYAN WHITE HIV/AIDS PROGRAM (RWHAP)-FUNDED ENTITIES, EHE-FUNDED JURISDICTIONS, FEDERALLY QUALIFIED HEALTH CENTERS (FQHCS), MINORITY SERVING INSTITUTIONS (MSIS), HEALTH PROFESSIONAL PROGRAMS (HPPS), AND OTHER HEALTH RESOURCES AND SERVICES ADMINISTRATION (HRSA)-FUNDED GROUPS. FOR EXAMPLE, AN EXISTING PARTNERSHIP WITH THE UNITED SOUTHERN AND EASTERN TRIBES (USET) WILL CONTINUE TO BE VITAL TO REACH AND SUPPORT TRIBAL HEALTH CLINICS. ACTIVITIES WILL BE DIRECTED AT PRIORITY PROVIDERS THROUGHOUT THE SE THROUGH INTERACTIVE CASE-BASED SESSIONS, SMALL GROUP WORKSHOPS, ONLINE SELF-PACED LEARNING, AND OTHER INNOVATIVE ADULT LEARNING APPROACHES FOR BUSY PROVIDERS (E.G., THE TEXT/EMAIL-BASED MICROLEARNING TOOL QUIZTIME). VUMC WILL INCREASE HIV WORKFORCE TRAINING THROUGH CLINICAL SKILLS DEVELOPMENT VI A IN-PERSON CONFERENCES AND WORKSHOPS, CLINICAL CONSULTATIONS, PRECEPTORSHIPS, AND INTENSIVE HIV FELLOWSHIPS AND ACADEMIES. AN INNOVATIVE STRUCTURE WILL BE USED TO ORGANIZE CONTENT EXPERTISE AND TRAINING PARTNERS INTO DISTINCT COMMUNITIES OF PRACTICE (COP) FOCUSED ON ACHIEVING MAJOR PROGRAM GOALS AND ACTIVITIES. EVALUATION STRATEGIES TO MEASURE TRAINING ACCEPTABILITY AND OUTCOMES WILL BE APPLIED THROUGH VARIOUS METHODS, BASED ON QUANTITATIVE AND QUALITATIVE DATA, AND ADAPTIVE TO HRSA REQUIREMENTS AND REQUESTS. USE OF THE EVENT REGISTRATION AND EVALUATION DATABASE DEVELOPED BY VUMC (MEASURING OUTCOMES ACROSS THE SOUTHEAST [MOXSE]) ALLOWS REAL-TIME DATA TRACKING AND MARKETING OF TRAINING EVENTS TO HEALTH PROFESSIONALS FROM A VARIETY OF BACKGROUNDS. LOCAL PARTNERS (LPS) WILL COLLABORATE WITH THE CO IN ASSESSING NEED, PROVIDING TRAINING, COLLECTING EVALUATION DATA, AND FACILITATING COLLABORATION WITH STATE AND REGIONAL PUBLIC HEALTH INITIATIVES. LPS WILL EXECUTE LOCAL WORKPLANS AND COLLABORATE WITH PERTINENT ORGANIZATIONS (E.G., THEIR STATES RWHAP FUNDED ENTITIES). THE UNIVERSITY OF ALABAMA AT BIRMINGHAM, UNIVERSITY OF MIAMI, UNIVERSITY OF FLORIDA, MOREHOUSE SCHOOL OF MEDICINE, UNIVERSITY OF KENTUCKY, UNIVERSITY OF MISSISSIPPI MEDICAL CENTER, UNIVERSITY OF NORTH CAROLINA, DUKE UNIVERSITY (MAI), AND UNIVERSITY OF SOUTH CAROLINA WILL SERVE AS LPS TO EXPAND REACH AND PARTNERSHIP TO INCLUDE BOTH URBAN AND RURAL AREAS OF EACH STATE. VUMC WILL SERVE AS BOTH THE CO AND THE LP FOR TN. SPECIFIC INITIATIVES WILL BE SUPPORTED BY LPS BASED ON EXPERTISE AND OPPORTUNITIES; FOR EXAMPLE, MOREHOUSE SCHOOL OF MEDICINE AND DUKE UNIVERSITY WILL LEAD MAI EFFORTS AND WORK WITH MSIS TO INTEGRATE HIV EDUCATION INTO HPP CURRICULA. IN SUMMARY, VUMC SEEKS TO LEAD THE SE AETC TO CONTINUE TO INNOVATE HIV TRAINING AND TECHNICAL ASSISTANCE ACROSS AN ESSENTIAL US REGION WITH STRONG PARTNERSHIPS AND COLLABORATIONS.

THE ELECTRONIC MEDICAL RECORDS AND GENOMICS (EMERGE) NETWORK PHASE III - COORDINATING CENTER (U01)

AIDS EDUCATION AND TRAINING CENTERS PROGRAM

DECRYPTING VARIANTS OF UNCERTAIN SIGNIFICANCE IN LONG-QT SYNDROME

SOUTHEAST COLLABORATIVE FOR INNOVATIVE AND EQUITABLE SOLUTIONS TO CHRONIC DISEASE DISPARITIES - THE BURDEN OF RACIAL AND ETHNIC HEALTH DISPARITIES IS MOST EVIDENT IN THE SOUTHEASTERN UNITED STATES, WHERE BLACK AND LATINO POPULATIONS SUFFER THE HIGHEST RATES OF CARDIOVASCULAR DISEASE, DIABETES, OBESITY, HYPERTENSION, CANCER, AND ASTHMA. THESE CHRONIC CONDITIONS ARE A PRIMARY CAUSE OF POOR HEALTH, REDUCED QUALITY OF LIFE, AND PREMATURE DEATH, AND ACCOUNT FOR MORE THAN 50% OF HEALTH CARE EXPENDITURES. DESPITE SUBSTANTIAL REDUCTION OF SOME CHRONIC DISEASES AND RISK FACTORS OVER THE LAST FEW DECADES, THE SOUTHEAST CONTINUES TO HAVE THE HIGHEST NUMBER OF POTENTIALLY PREVENTABLE DEATHS FOR EACH OF THE FIVE LEADING CAUSES OF DEATH. RACIAL AND ETHNIC MINORITIES COMPRISE 39% OF THE POPULATION OF THE SOUTHEAST (HHS REGION IV), WHICH INCLUDES NEARLY 15 MILLION AFRICAN AMERICANS AND 9 MILLION LATINOS. MINORITIES IN THE SOUTHEAST FARE WORSE ON MANY HEALTH INDICATORS COMPARED TO OTHER REGIONS, IN LARGE PART DUE TO POOR SOCIOECONOMIC STATUS, WITH MORE THAN 22% OF SOUTHEASTERN RESIDENTS LIVING IN POVERTY. EFFECTIVELY ADDRESSING PERVASIVE CHRONIC DISEASE DISPARITIES WILL REQUIRE INTERVENTIONS THAT CONSIDER THE NEEDS, PRIORITIES, AND LIVED EXPERIENCES OF THOSE DISPROPORTIONATELY IMPACTED. RESEARCH TEAMS WITH EXPERTISE IN SOCIAL, ENVIRONMENTAL, BEHAVIORAL, AND BIOLOGICAL DISCIPLINES MUST COLLABORATE TO DEVELOP AND TEST MULTICOMPONENT STRATEGIES AIMED AT THE MULTILEVEL DETERMINANTS THAT DRIVE DISPARITIES. VIA A NEW CENTER - THE SOUTHEAST COLLABORATIVE FOR INNOVATIVE AND EQUITABLE SOLUTIONS TO CHRONIC DISEASE DISPARITIES, WE WILL BRING TOGETHER VANDERBILT UNIVERSITY MEDICAL CENTER, UNIVERSITY OF MIAMI, AND MEHARRY MEDICAL COLLEGE TO ADDRESS TO REDUCE RISK FACTORS FOR AND DISPARITIES IN DIABETES, CARDIOVASCULAR DISEASE, OBESITY, AND RELATED CONDITIONS AMONG AFRICAN AMERICAN AND LATINO POPULATIONS IN THE SOUTHEAST. WE AIM TO: SPECIFIC AIM 1: ESTABLISH THE HUMAN AND TECHNICAL INFRASTRUCTURE TO FOSTER HIGHLY COLLABORATIVE, TRANSDISCIPLINARY RESEARCH COLLABORATIONS FOCUSED ON USING TECHNOLOGY AND DATA SCIENCE TO REDUCE CHRONIC DISEASE DISPARITIES AMONG AFRICAN AMERICAN AND LATINO POPULATIONS IN THE SOUTHEASTERN UNITED STATES. SPECIFIC AIM 2: FACILITATE A REGIONAL, CROSS-INSTITUTIONAL PILOT AWARDS PROGRAM FOCUSED ON CHRONIC DISEASE DISPARITIES THAT NURTURES AND SUPPORTS CAREER DEVELOPMENT, ADVANCES USE OF DATA SCIENCE, TECHNOLOGY, AND BIOINFORMATICS TO ADDRESS THE COMPLEX DRIVERS OF HEALTH DISPARITIES, AND PROMOTES INCLUSIVE EXCELLENCE. SPECIFIC AIM 3: PROPEL NOVEL HEALTH DISPARITIES RESEARCH LEVERAGING TECHNOLOGY, INDIVIDUAL-LEVEL AND COMMUNITY- LEVEL SOCIAL DETERMINANTS OF HEALTH DATA, AND GENOMIC AND PHENOTYPIC DATA TO PREVENT, TREAT, AND MANAGE DIABETES, CARDIOVASCULAR DISEASE, OBESITY AND RELATED CONDITIONS IN AFRICAN AMERICAN AND LATINO POPULATIONS. SPECIFIC AIM 4: PARTNER WITH AFRICAN AMERICAN AND LATINO COMMUNITIES IN THE SOUTHEAST INTEGRATE THEIR PRIORITIES INTO THE CENTER’S INFRASTRUCTURE, AND COLLABORATIVELY DEVELOP, ADAPT, AND TEST SOCIALLY AND CULTURALLY APPROPRIATE INTERVENTIONS TO SECURE THE EARLIEST IMPACT ON ELIMINATING CHRONIC DISEASE DISPARITIES.

HEALTH CARE INNOVATION CHALLENGE

VANDERBILT-INGRAM CANCER CENTER SPORE IN GASTROINTESTINAL CANCER

NSF I-CORPS HUB (TRACK 1): MID-SOUTH REGION -THE BROADER IMPACT/COMMERCIAL POTENTIAL OF THIS NSF I-CORPS HUBS PROJECT IS THE DEVELOPMENT OF A SUSTAINABLE, INCLUSIVE, INNOVATION ECOSYSTEM THAT WILL IMPART SHARED ECONOMIC PROSPERITY ACROSS THE US MID-SOUTH REGION. THE MID-SOUTH HUB?S FORMATIVE, EVIDENCE-DRIVEN APPROACH MAY INFORM HOW INCLUSIVE INNOVATION ECOSYSTEMS CAN BE ESTABLISHED IN REGIONS WITH NASCENT ECONOMIC ACTIVITY. THIS KNOWLEDGE WILL AUGMENT TEAM PREPARATION, MAXIMIZING THE VALUE EXTRACTED FROM I-CORPS TRAINING. THE HUB WILL FURTHER AMPLIFY THE DOWNSTREAM SUCCESSES AND SUSTAINABILITY OF DEEP TECHNOLOGY VENTURES, INCLUDING GRANT ACQUISITION, FUNDRAISING, SUSTAINABLE REVENUES, AND NET-POSITIVE LIQUIDITY EVENTS. SUCCESS WILL BE LEVERAGED TO INFLUENCE INNOVATION CULTURE AT REGIONAL INSTITUTIONS, LEADING TO THE INCENTIVIZATION OF ENTERPRISING FACULTY, STUDENTS, AND STAFF. THE DIVERSE LEADERSHIP TEAM AND INCLUSIVE BENCH OF INSTRUCTORS WILL INCREASE THE HUB?S ABILITY TO CONNECT TO INNOVATORS AND MENTORS OF ALL BACKGROUNDS, INCLUDING THOSE WHO ARE DISADVANTAGED OR UNDERREPRESENTED. THESE EFFORTS WILL INCLUDE BUILDING COMMERCIALIZATION CAPACITY AT UNDERREPRESENTED INSTITUTIONS. EVIDENCE FROM THE DELIBERATE IMPLEMENTATION OF A DEMOCRATIZED ORGANIZATIONAL STRUCTURE WILL BE EVALUATED FOR ITS CAPABILITY TO ENCOURAGE AND PRESERVE THE COGNITIVE PROXIMITY OF ECOSYSTEM MEMBERS. THIS KNOWLEDGE WILL BE DISSEMINATED VIA THE NATIONAL INNOVATION NETWORK TO DRIVE TRANSLATIONAL IMPACTS AND ECONOMIC DEVELOPMENT, SHAPING THE FUTURE OF AMERICAN INNOVATION. THIS I-CORPS HUBS PROJECT IS BASED ON THE DEVELOPMENT OF A USE-INSPIRED INCUBATOR THAT USES DATA-DRIVEN APPROACHES TO DEVELOP BEST PRACTICES, INFLUENCE ECONOMIC POLICY, INSPIRE ADOPTION OF INCLUSIVE APPROACHES TO INNOVATION, AND INSTRUCT FUTURE PROGRAMMATIC INVESTMENTS. CURRENTLY, A GAP EXISTS IN UNDERSTANDING HOW REGIONAL INNOVATION CLUSTERS CAN UNIFY TO DRIVE THE DEVELOPMENT OF A PROLIFIC INNOVATION ECOSYSTEM. ADDRESSING THIS GAP WILL ENABLE POLICYMAKERS AND GOVERNMENT AGENCIES TO IMPLEMENT EVIDENCE-BASED APPROACHES TO INFORM PROGRAMMATIC INVESTMENTS AND MAXIMIZE TECHNOLOGY COMMERCIALIZATION, ECONOMIC DEVELOPMENT, AND OVERALL NATIONAL INNOVATION READINESS. THIS CONSORTIUM OF DIVERSE, DEEP TECHNOLOGY-PRODUCING INSTITUTIONS FROM DISPARATE LOCATIONS WITHIN THE MID-SOUTH REGION WILL LEVERAGE THE I-CORPS PROGRAM TO CATALYZE TECHNOLOGICAL COMMERCIALIZATION, SPUR ECONOMIC DEVELOPMENT, AND INFORM THE FUTURE OF INCLUSIVE AMERICAN INNOVATION. THE HUB WILL PRIORITIZE A FORMATIVE, LONGITUDINAL ASSESSMENT TO ITERATIVELY OPTIMIZE KEY ACTIVITIES, INCLUDING TEAM RECRUITMENT, REGIONAL AND NATIONAL I-CORPS TRAINING, UPSTREAM CHANGES IN UNIVERSITY INNOVATION CULTURE, DOWNSTREAM IMPACTS ON SUCCESSFUL COMMERCIALIZATION, AND AN INCLUSIVE INNOVATION CORRIDOR ACROSS THE MID-SOUTH. THIS EFFORT WILL ADVANCE TECHNOLOGY TRANSFER FROM ACADEMIC INSTITUTIONS INTO ENTREPRENEURIAL VENTURES THAT SEED EMERGENT, REGIONAL ECOSYSTEMS. THE DATA-DRIVEN, PERFORMANCE IMPROVEMENT APPROACH WILL ENSURE BEST PRACTICES ARE EVIDENCE-BASED AND CREATE A MODEL FOR OTHER REGIONS SEEKING TO INDUCE INCLUSIVE INNOVATION CLUSTER DEVELOPMENT. 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.

VANDERBILT BIOMEDICAL INFORMATICS TRAINING PROGRAM

CODA:?COVID AND?DIABETES?ASSESSMENT - PROJECT SUMMARY SEVERAL STUDIES HAVE FOUND THAT INFECTION WITH SARS-COV-2 AND COVID-19 DIAGNOSIS ARE ASSOCIATED WITH THE DEVELOPMENT AND PROGRESSION OF BOTH TYPE 1 (T1D) AND TYPE 2 DIABETES (T2D), POSSIBLY THROUGH INFECTION OF BETA CELLS, INCREASED INSULIN RESISTANCE, INCREASED INFLAMMATION AND FIBROSIS, AND OTHER BIOLOGICAL PROCESSES. THE PROPOSED STUDY WILL TAKE ADVANTAGE OF ROBUST EXISTING INFRASTRUCTURE TO RAPIDLY IDENTIFY, RECRUIT, AND RETAIN DIVERSE COHORTS OF ENGLISH AND SPANISH SPEAKING PEDIATRIC AND ADULT PATIENTS WITH RECENTLY DIAGNOSED T1D OR T2D. THE STUDY WILL INCLUDE 1600 STUDY PARTICIPANTS DIAGNOSED WITH DIABETES IN THE LAST 3 MONTHS, WHO HAVE HAD A KNOWN COVID-19 INFECTION IN THE PAST 90 DAYS AND THOSE WITH RECENT DIAGNOSIS OF DIABETES AND NO KNOWN COVID-19 INFECTION IN THE PAST YEAR. THE STUDY WILL LEVERAGE PCORNET, A UNIQUE NATIONAL NETWORK OF OVER 60 HEALTH SYSTEMS WITH ELECTRONIC HEALTH RECORD (EHR) DATA ON OVER 80 MILLION PATIENTS AND A TRACK RECORD FOR SUCCESSFUL STUDY RECRUITMENT. WE WILL QUERY EHR RECORDS TO SWIFTLY IDENTIFY POTENTIAL STUDY SUBJECTS WITH RECENT DIAGNOSIS OF DIABETES AND CONTACT THEM VIA PATIENT PORTALS, TELEPHONE, FACE-TO-FACE ENCOUNTERS, AND OTHER APPROACHES. WE WILL ALSO LEVERAGE THE T1D EXCHANGE (T1DX), A NATIONAL NETWORK OF 54 DIABETES CENTERS AND AN ONLINE PATIENT REGISTRY OF 17,000 INDIVIDUALS WITH T1D. CONSENTED PARTICIPANTS WILL PARTAKE IN REGULAR WEB/MOBILE OR TELEPHONE SURVEYS LEVERAGING A PREVIOUSLY DEVELOPED REDCAP/TWILIO PLATFORM. PARTICIPANTS WILL ALSO COME TO SITES FOR REGULAR SEROLOGICAL TESTING, AND A SUBSAMPLE WILL PARTICIPATE IN MORE ROBUST TESTING OF GLUCOSE TOLERANCE, BIOMARKERS, AND VASCULAR FUNCTION. THIS DATA WILL BE SUPPLEMENTED BY LONGITUDINAL EHR DATA FROM PARTICIPATING SITES AND ACROSS PCORNET. PARTICIPANTS WILL BE FOLLOWED FOR 2 YEARS. AIM 1 WILL EXAMINE IF PATIENTS WITH RECENT T2D WHO HAVE RECENT COVID-19 ARE MORE LIKELY TO HAVE WORSE GLYCEMIC CONTROL, INCREASED INFLAMMATION AND INCREASED INSULIN RESISTANCE THAN PATIENTS WITHOUT RECENT COVID-19. AIM 2 WILL EXAMINE IF PATIENTS WITH RECENT T1D WHO HAVE RECENT COVID-19 ARE MORE LIKELY TO HAVE WORSE GLYCEMIC CONTROL, INCREASED INFLAMMATION AND MORE RAPID REDUCTION IN BETA CELL FUNCTION THAN PATIENTS WITHOUT RECENT COVID-19. AIM 3 WILL EVALUATE A SUBSET OF PATIENTS WITH DIABETES TO EXAMINE IF COVID-19 IS ASSOCIATED WITH WORSE VASCULAR FUNCTION, INCREASED INFLAMMATION AND HYPERCOAGULABILITY. AIM 4 WILL EXPLORE THE ROLE OF GENOMIC/SOCIAL/ENVIRONMENTAL FACTORS ON INFLAMMATION AND METABOLIC FUNCTION. AIM 5 WILL LEVERAGE EHR DATA TO EXPLORE THE ROLE OF COVID-19 AND COVID-19 TREATMENTS ON DIABETES DEVELOPMENT AND DIABETES-RELATED OUTCOMES ACROSS THE PANDEMIC. THE STUDY WILL BE LED BY A TEAM WITH SIGNIFICANT EXPERIENCE RELATED TO COVID-19, POST-ACUTE SEQUELAE OF COVID-19 (PASC), OBESITY AND DIABETES IN CHILDREN AND ADULTS, EPIDEMIOLOGICAL RESEARCH, INFORMATICS, HEALTH SERVICES RESEARCH, GENOMICS, METABOLOMICS, PHYSIOLOGY, PATIENT AND FAMILY ENGAGEMENT AND OTHER AREAS. THE PROPOSED WORK WILL PROVIDE A DEEPER UNDERSTANDING OF THE RELATIONSHIP BETWEEN COVID-19 AND DIABETES, THAT CAN SUPPORT FUTURE INTERVENTIONS AND PUBLIC HEALTH APPROACHES TO IMPROVE HEALTH.

CORE GRANT IN VISION RESEARCH

NOVEL TARGETS IN CANCER CHEMOTHERAPY: CHEMICAL BIOLOGY OF GUANINE ALKYLATION

VANDERBILT PROTEOME CHARACTERIZATION CENTER

CLINICAL AND TRANSLATIONAL SCIENCE COORDINATING CENTER

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

NATIENS: A PHASE III RANDOMIZED DOUBLE BLINDED STUDY TO DETERMINE THE MECHANISMS AND OPTIMAL MANAGEMENT OF STEVENS-JOHNSON SYNDROME AND TOXIC EPIDERMAL NECROLYSIS

BREAST CANCER GENETIC STUDY IN AFRICAN-ANCESTRY POPULATIONS

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

VANDERBILT CLINICAL ONCOLOGY RESEARCH CAREER DEVELOPMENT PROGRAM

IMPROVING PREDICTION OF DRUG ACTION

EMERGENCY FINANCIAL AID GRANTS TO STUDENTS UNDER THE CORONAVIRUS AID, RELIEF, AND ECONOMIC SECURITY (CARES) ACT

VALIDATION OF BIOMARKERS OF RISK FOR THE EARLY DETECTION OF LUNG CANCER

VANDERBILT CENTER FOR UNDIAGNOSED DISEASES (VCUD)

TENNESSEE VALLEY COOPERATIVE HUMAN TISSUE NETWORK

HARMONIST: A SCALABLE TOOLKIT FOR STANDARDIZING AND COORDINATING DATA SHARING ACROSS INTERNATIONAL RESEARCH NETWORKS

LONG-TERM NICOTINE TREATMENT OF MCI PA-14-077

STUDIES ON THE STRUCTURE OF BASEMENT MEMBRANES

THE ROLE OF INFLAMMATION IN CARDIOVASCULAR DISEASE

PHARMACOGENOMICS OF HIV THERAPY

INTEGRATIVE SINGLE-CELL ATLAS OF HOST AND MICROENVIRONMENT IN COLORECTAL NEOPLASTIC TRANSFORMATION

STRUCTURE BASED DESIGN OF ANTIBODIES AND VACCINES

CENTER OF EXCELLENCE IN PRECISION MEDICINE AND POPULATION HEALTH

GROWING RIGHT ONTO WELLNESS (GROW): CHANGING EARLY CHILDHOOD BMI TRAJECTORIES

EXPANDING AND SCALING THE PYRAMID MODEL IN PRE-KINDERGARTEN AND KINDERGARTEN CLASSROOMS IN DISTRICTS ACROSS THE U.S.

THROUGH DIMS3, THE US AGENCY FOR INTERNATIONAL DEVELOPMENT, BUREAU OF LATIN AMERICA AND THE CARIBBEAN, OFFICE OF REGIONAL SUSTAINABLE DEVELOPMENT, DEMOCRACY, HUMAN RIGHTS, AND GOVERNANCE TEAM (USAID/LAC/RSD/DRG) AIMS TO SUPPORT CITIZEN-RESPONSIVE GOVERNANCE AND DEMOCRATIC DEVELOPMENT WITH RIGOROUS PUBLIC OPINION RESEARCH ON DEMOCRATIC NORMS, ATTITUDES, AND EXPERIENCES IN THE LATIN AMERICA AND CARIBBEAN (LAC) REGION. THIS WILL BE ACHIEVED THROUGH FOUR PRIMARY WORK STREAMS: 1) COLLABORATIVE, PERIODIC, INNOVATIVE PUBLIC OPINION SURVEYS AND RESEARCH ON DEMOCRATIC VALUES, BEHAVIORS, AND PERCEPTIONS IN LAC; 2) DISSEMINATION OF DATA, ANALYSIS, AND RESEARCH ABOUT DEMOCRATIC NORMS AND ATTITUDES IN LAC; 3) SUPPORT AND DEVELOPMENT OF INNOVATIVE TOPICS AND METHODOLOGIES IN PUBLIC OPINION RESEARCH AND ANALYSIS; AND 4) BUILDING THE LOCAL CAPACITY OF RESEARCHERS AND INSTITUTIONS ON SURVEY DESIGN, DATA COLLECTION, DATA ANALYSIS AND REPORTING, AND EVIDENCE BASED POLICY MAKING. THE FOUNDATION OF THESE EFFORTS IS LONGITUDINAL, COUNTRY, AND COMPARATIVE CROSS-NATIONAL TREND ANALYSIS ON TOPICS RELEVANT TO THE DEMOCRACY SECTOR IN LAC, SUCH AS DEMOCRATIC NORMS AND VALUES, PERCEPTIONS OF INSTITUTIONS, AND EXPERIENCES WITH CORRUPTION, CRIME VICTIMIZATION, AND MIGRATION.

"IMPLEMENTATION OF PROGRAMS FOR PREVENTION, CARE AND TREATMENT OF HIV/AIDS IN THE

MULITIDISCIPLINARY TRAINING IN MOLECULAR ENDOCINOLOGY

GLUCONEOGENESIS AND GLYCOGENOLYSIS - ROLE AND REGULATION

AUTONOMIC RARE DISEASES CLINICAL RESEARCH CONSORTIUM

VANDERBILT UNIVERSITY - INSTITUTIONAL PORTION OF THE HIGHER EDUCATION EMERGENCY RELIEF FUND

TRAINING PROGRAM IN ENVIRONMENTAL TOXICOLOGY

ETIOLOGICAL STUDIES OF GASTRIC CARCINOMA

ENHANCED SURVEILLANCE FOR NEW VACCINE PREVENTABLE DISEASES

RELATIVISTIC HEAVY ION EXPERIMENTAL PHYSICS

EXRNA IN COLORECTAL CARCINOMA: BIOGENESIS AND FUNCTION

ACCELERATING THE ACADEMIC ACHIEVEMENT OF STUDENTS WITH DISABILITIES RESEARCH INITIATIVE

TAS::89 0222::TAS; NEW; MEETING THE COMPUTING NEEDS OF THE CMS-HI RESEARCH PROGRAM IN THE U.S.; PI - CHARLES MAGUIRE

ENDURING EFFECTS OF EARLY-LIFE SEROTONIN SIGNALING

6/6 HBCD PRENATAL EXPERIENCES AND LONGITUDINAL DEVELOPMENT (PRELUDE) CONSORTIUM VANDERBILT - PROJECT SUMMARY/ABSTRACT BRAIN DEVELOPMENT OCCURS AT A RAPID PACE PRENATALLY AND THROUGHOUT CHILDHOOD, IMPACTED BY DYNAMIC GENETIC AND ENVIRONMENTAL INFLUENCES. STUDIES USING ADVANCED NEUROIMAGING HAVE PROVIDED SIGNIFICANT INSIGHTS INTO BRAIN DEVELOPMENT BUT HAVE BEEN LIMITED BY SMALL SAMPLE SIZE, ESPECIALLY FOR HIGH-RISK POPULATIONS. SUBSTANCE- EXPOSED INFANTS ARE AT PARTICULARLY HIGH RISK FOR ADVERSE OUTCOMES; HOWEVER, FINDINGS ARE INCONSISTENT, MAKING IT DIFFICULT TO DISENTANGLE PRENATAL EXPOSURE EFFECTS FROM OTHER ADVERSE INFLUENCES. THE OBJECTIVES OF OUR HEALTHY BRAIN AND CHILD DEVELOPMENT (HBCD) PRENATAL EXPERIENCES AND LONGITUDINAL DEVELOPMENT (PRELUDE) CONSORTIUM ARE TO CHARACTERIZE TYPICAL TRAJECTORIES OF BRAIN DEVELOPMENT FROM BIRTH THROUGH CHILDHOOD, MEASURING THE INFLUENCE OF KEY BIOLOGIC AND ENVIRONMENTAL FACTORS AND THEIR INTERACTIONS ON CHILD SOCIAL, COGNITIVE, AND EMOTIONAL DEVELOPMENT. WE WILL ASSESS HOW CHILDREN PRENATALLY EXPOSED TO OPIOIDS AND OTHER SUBSTANCES, AS WELL AS ENVIRONMENTAL ADVERSITY, DIFFER IN THOSE BRAIN TRAJECTORIES AND OUTCOMES. OUR CONSORTIUM CONSISTS OF SIX CENTERS (ARKANSAS CHILDREN’S RESEARCH INSTITUTE, CASE WESTERN RESERVE UNIVERSITY, CINCINNATI CHILDREN’S HOSPITAL, CHILDREN’S NATIONAL MEDICAL CENTER, UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL, AND VANDERBILT UNIVERSITY) WHICH HAVE COLLABORATED PREVIOUSLY AND HAVE COMPLEMENTARY EXPERTISE IN NEUROIMAGING, NEUROPHYSIOLOGY, LONGITUDINAL CLINICAL RESEARCH, CHILD DEVELOPMENT, SUBSTANCE EXPOSURE AND ADDICTION, ETHICAL/LEGAL ISSUES, AND CLINICAL CARE OF HIGH-RISK INFANTS/CHILDREN. THE PRELUDE CONSORTIUM WILL RECRUIT 680 PREGNANT WOMEN WITH SUBSTANCE USE, 680 AT-RISK PREGNANT WOMEN WITHOUT SUBSTANCE USE, AND 1360 COMPARISON PREGNANT WOMEN REPRESENTATIVE OF THE GENERAL POPULATION TO CONTRIBUTE TO THE OVERALL HBCD STUDY. WE WILL WORK CLOSELY WITH THE OTHER SITES, THE HBCD CONSORTIUM ADMINISTRATIVE CORE, AND THE HBCD DATA COORDINATING CENTER TO DEVELOP A COMPREHENSIVE STUDY PROTOCOL AND ENSURE COMPLIANCE OF STUDY WORKFLOW AND DATA TRANSFER. OUR CONSORTIUM HAS AN OPTIMIZED RESEARCH PROTOCOL AND 4 SPECIFIC AIMS: 1) EMPLOY ETHICAL AND EVIDENCE-BASED BEST PRACTICES TO ENROLL AND RETAIN A DIVERSE COHORT OF PREGNANT WOMEN INTO A LONGITUDINAL STUDY OF INFANT/CHILD BRAIN DEVELOPMENT, OVERSAMPLING MOTHERS FROM HIGH-RISK BACKGROUNDS AND THOSE USING SUBSTANCES DURING PREGNANCY; 2) ENGAGE A COMPREHENSIVE ARRAY OF MATERNAL- AND CHILD-ORIENTED COMMUNITY STAKEHOLDERS TO IDENTIFY COMMUNITY CONCERNS AND PRIORITIES REGARDING THIS RESEARCH, MINIMIZE RISKS, AND PROMOTE LONG-TERM ENGAGEMENT OF THE RECRUITED CHILD-MOTHER DYADS; 3) COLLECT RICH DATA TO EXAMINE HOW MATERNAL HEALTH CONTEXT AND BROADER ENVIRONMENTAL FACTORS MAY AFFECT THE MATERNAL-FETAL DYAD AND NEURODEVELOPMENT OF CHILDREN; 4) CAPTURE KEY DEVELOPMENTAL WINDOWS DURING WHICH MATERNAL AND ENVIRONMENTAL FACTORS MAY INTERACT WITH BRAIN AND BEHAVIORAL DEVELOPMENT OF CHILDREN. THE INSIGHTS FROM THESE DATA WILL PROVIDE GREATER UNDERSTANDING OF FACTORS AFFECTING EARLY CHILDHOOD BRAIN DEVELOPMENT, ALLOWING TARGETED INTERVENTIONS AND IMPROVED OUTCOMES FOR MOTHER-CHILD DYADS.

ROLE OF ICOSANIODS IN RENAL FUNCTION

MOLECULAR CONTROL OF VASCULAR FUNCTION BY OXIDANT STRESS

VANDERBILT ALZHEIMER'S DISEASE RESEARCH CENTER - VANDERBILT ALZHEIMER’S DISEASE RESEARCH CENTER – OVERALL PROJECT SUMMARY WE AIM TO ESTABLISH THE VANDERBILT ALZHEIMER’S DISEASE RESEARCH CENTER (VADRC) AS A WORLD-CLASS INTERDISCIPLINARY CENTER IN NASHVILLE, TENNESSEE. WITH HIGH REGIONAL BURDEN OF ALZHEIMER’S DISEASE (AD) AND RELATED DEMENTIAS (ADRD) AS WELL AS VASCULAR RISK FACTORS, THERE IS A PRESSING NEED TO UNDERSTAND THE COMPLEXITIES UNDERLYING THE INTERSECTION BETWEEN VASCULAR RISK AND ADRD. VASCULAR RISK FACTORS, THE MAJORITY OF WHICH ARE MODIFIABLE, ARE LINKED TO ADRD RISK AND HIGHLY PREVALENT IN OUR REGION, ESPECIALLY WITHIN THE BLACK AND AFRICAN AMERICAN COMMUNITY. THE VADRC’S MISSION IS TO CHARACTERIZE HOW VASCULAR BURDEN INTERSECTS WITH ADRD PATHOGENESIS, MANIFESTATION, PREVENTION, AND TREATMENT AT THE CELLULAR, SYSTEMS BIOLOGICAL, AND POPULATION LEVELS. THIS EFFORT WILL CAPITALIZE ON THE SCIENTIFIC STRENGTHS OF OUR CAMPUS-WIDE INVESTIGATORS, EXPANSIVE AND COLLABORATIVE INSTITUTIONAL RESOURCES, AND FOUNDATIONAL WORK COMPLETED OVER THE LAST SEVERAL YEARS. THE ADMINISTRATIVE CORE WILL SERVE AS THE HUB FOR ALL LOCAL ADRD RESEARCH ACTIVITIES AND COORDINATE AND INTEGRATE ALL CENTER INTERACTIONS AND COLLABORATIONS. THE OUTREACH, RECRUITMENT, AND ENGAGEMENT CORE WILL BUILD UPON EXISTING COMMUNITY PARTNERSHIPS TO BRING AWARENESS OF ADRD AND RELEVANT VASCULAR RISK FACTORS TO THE COMMUNITY. THE OUTREACH, RECRUITMENT, AND ENGAGEMENT CORE TEAM WILL RECRUIT PARTICIPANTS WITH A VASCULAR RISK PROFILE REFLECTIVE OF OUR LOCAL COMMUNITY INTO OUR CLINICAL CORE ALONGSIDE A SPECIFIC FOCUS ON OUTREACH IN THE BLACK AND AFRICAN AMERICAN COMMUNITY. THE CLINICAL CORE WILL ENROLL, DEEPLY PHENOTYPE, AND ANNUALLY FOLLOW 400 PARTICIPANTS, CAPTURING CLINICAL, NEUROPSYCHOLOGICAL, CARDIAC IMAGING, NEUROIMAGING, AND BIOFLUID DATA IN COLLABORATION WITH THE BIOMARKER CORE. THE NEUROPATHOLOGY CORE WILL OBTAIN POST-MORTEM BRAINS AND BIOFLUIDS FROM PARTICIPANTS, ALLOWING FOR COMPLETE POST-MORTEM CHARACTERIZATION OF ADRD AND VASCULAR PATHOLOGIES. OUR DATA MANAGEMENT AND STATISTICAL CORE WILL ENSURE ALL DATA COLLECTED IS PROPERLY STORED IN AN INTEGRATED INFORMATICS INFRASTRUCTURE, IS SHARED WITH NATIONAL REPOSITORIES, AND IS READILY ACCESSIBLE TO OTHER INVESTIGATORS VIA OUR WEB-BASED DATA SHARING PLATFORM. FINALLY, THE VADRC WILL FOSTER PROFESSIONAL DEVELOPMENT FOR THE NEXT GENERATION OF ADRD CLINICIANS, SCIENTISTS, AND LEADERS, WITH A PARTICULAR FOCUS ON SUPPORTING EARLY CAREER FACULTY SCHOLARS THROUGH THE RESEARCH EDUCATION COMPONENT. THE VADRC IS EXCEPTIONALLY WELL POSITIONED TO BECOME THE FIRST CENTER OF ITS KIND IN TENNESSEE AND SERVE A GROWING POPULATION SUFFERING FROM ADRD.

POST-DOCTORAL RESEARCH FELLOWSHIPS

SCCOR IN HEMOSTATIC AND THROMBOTIC DISEASES

CLINICAL PHARMACOLOGY TRAINING PROGRAM

DIABETES RESEARCH AND TRAINING CENTER

MULTISCALE MATHEMATICAL MODELING OF CANCER INVASION

RESEARCH CENTER FOR PHARMACOLOGY & DRUG TOXICOLOGY

STRUCTURE-FUNCTION STUDIES OF VISUAL ARRESTIN

EVALUATION OF STATE AND DISTRICT EDUCATION PROGRAMS AND POLICIES

EFFECT OF EARLY WEIGHT BEARING ON REHABILITATION OUTCOMES IN PATIENTS WITH UNICONDYLAR PROXIMAL TIBIA FRACTURES AND BIMALLEOLAR ANKLE FRACTURES

VANDERBILT NCDDDG FOR DISCOVERY OF NOVEL TREATMENTS FOR SCHIZOPHRENIA

INSTITUTIONAL CAREER DEVELOPMENT CORE

SPORE IN LUNG CANCER

KINASE MODULATION OF NA+-DEPENDENT CI-COUPLED TRANSPORTERS IN MOUSE KIDNEY

EPIDEMIOLOGIC ARCHITECTURE FOR GENES LINKED TO ENVIRONMENT (EAGLE)

REGULATION OF SIGNALING BY MGLUR5

VANTAGE:CONSOLIDATION TO CREATE THE VANDERBILT TECHNOLOGIES FOR ADVANCED GENOMICS

PROJECT TITLE: PATH-TN PARTNERSHIP FOR AI-DRIVEN MULTIMODAL TRANSPORTATION SERVICES INTEGRATION IN TENNESSEE CITIES :::: PROJECT DESCRIPTION: PATH-TN PARTNERSHIP FOR AI-DRIVEN MULTIMODAL TRANSPORTATION SERVICES INTEGRATION IN TENNESSEE CITIES

MUSCARINIC RECEPTOR ACTIVATORS AS NOVEL ANTIPSYCHOTIC AGENTS

MOLECULAR BASIS FOR LENS TRANSPARENCY

GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST TREATMENT IN ADULT, OBESITY-RELATED, SYMPTOMATIC ASTHMA - PROJECT SUMMARY OBESITY IS CLEARLY DETRIMENTAL IN ASTHMA, YET WE LACK TOOLS TO TREAT THE UNIQUE OBESE ASTHMA PHENOTYPE. COMORBID OBESITY IMPACTS >40% OF ADULT ASTHMATICS1 AND INCREASES ASTHMA SEVERITY, SYMPTOMS AND EXACERBATIONS WHILE SIMULTANEOUSLY REDUCING THE EFFICACY OF CONVENTIONAL THERAPIES.2-5 OUR LONG-TERM GOAL IS TO DEVELOP NOVEL TREATMENTS FOR AIRWAY INFLAMMATION IN THE OBESE ASTHMA PHENOTYPE. OUR OVERALL OBJECTIVE, WHICH IS THE NEXT STEP IN TRANSLATING OUR PRECLINICAL AND PRELIMINARY CLINICAL FINDINGS, IS TO DETERMINE THE IMPACT OF GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS (GLP-1RA) ON ASTHMA CONTROL AND AIRWAY AND ADIPOSE INFLAMMATION IN ADULTS WITH OBESE ASTHMA. OUR CENTRAL HYPOTHESIS IS THAT GLP-1RA IMPROVE ASTHMA CONTROL AND REDUCE AIRWAY INFLAMMATION DUE TO DIRECT EFFECTS ON THE RESPIRATORY TRACT IN OBESE ASTHMA. TO GENERATE THE PROOF-OF- CONCEPT DATA TO SUPPORT DEFINITIVE PHASE 3 CLINICAL TRIALS OF GLP-1RA IN THE OBESE ASTHMA PHENOTYPE AND TEST OUR CENTRAL HYPOTHESIS, WE PROPOSE THE FOLLOWING SPECIFIC AIMS: 1) DETERMINE THE EFFICACY OF GLP-1RA ON ASTHMA CONTROL AND ASSESS TOLERABILITY IN OBESE ASTHMA AND 2) DETERMINE THE TISSUE-SPECIFIC IMPACT OF GLP- 1RA ON INFLAMMATION IN THE AIRWAY AND ADIPOSE IN OBESE ASTHMA. IN A 12-WEEK DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF ORAL SEMAGLUTIDE 7 MG ONCE DAILY IN ADULT SUBJECTS WITH OBESITY-RELATED, SYMPTOMATIC ASTHMA WITHOUT DMII, WE WILL TEST THE HYPOTHESES THAT SEMAGLUTIDE IMPROVES ASTHMA CONTROL (AIM 1A), IS TOLERATED (AIM 1B) AND REDUCES TYPE-2 AND NON-TYPE 2 AIRWAY INFLAMMATION INDEPENDENT OF WEIGHT LOSS (AIM 2). THE PRIMARY CLINICAL OUTCOME WILL BE CHANGE FROM BASELINE IN ACQ-7. THE PRIMARY MECHANISTIC OUTCOME WILL BE CHANGE FROM BASELINE IN SERUM PERIOSTIN. BECAUSE INSULIN RESISTANCE IS VARIABLE IN OBESITY AND BASELINE BLOOD EOSINOPHIL COUNTS ARE OFTEN PREDICTIVE OF RESPONSE TO ASTHMA THERAPEUTICS, THESE MARKERS WILL BE USED FOR PRESPECIFIED SUBGROUP ANALYSES. SUBCUTANEOUS ABDOMINAL ADIPOSE AND RESPIRATORY TRACT SAMPLES AT BASELINE AND 5 AND 12 WEEKS OF THERAPY WILL BE COMPARED USING RNA SEQUENCING TO TEST THE HYPOTHESIS THAT GLP-1RA REDUCE INFLAMMATION TO RESTORE HOMEOSTASIS IN THE RESPIRATORY TRACT OPPOSITE TO CHANGES IN ADIPOSE TISSUE IN OBESE ASTHMA. THIS PROPOSAL FACILITATES THE COLLECTION OF THE NECESSARY CLINICAL, MECHANISTIC, AND TOLERABILITY DATA TO INFORM THE DESIGN OF A DEFINITIVE PHASE III CLINICAL TRIAL OF A GLP-1RA IN ASTHMA. IT THEREBY SUPPORTS THE RAPID DEVELOPMENT OF A NOVEL THERAPEUTIC CLASS FOR ASTHMA AND REPRESENTS A PARADIGM SHIFT IN THE APPROACH TO THERAPEUTIC INTERVENTION IN ASTHMA THROUGH THE TARGETING OF A METABOLIC PATHWAY WHICH REGULATES UPSTREAM INFLAMMATION ACROSS MULTIPLE ORGAN SYSTEMS, MAY BE DISEASE MODIFYING, AND ULTIMATELY GLUCOCORTICOID SPARING.

CENTER IN MOLECULAR TOXICOLOGY

MICROBIOME, METABOLITES, AND ALCOHOL IN HIV TO REDUCE CVD (META HIV CVD) - THE OVERARCHING THEME FOR THIS PROGRAM PROJECT GRANT (PPG) IS THAT ALCOHOL ASSOCIATED GUT DYSBIOSIS AND GUT DYSBIOTIC METABOLITES ARE CARDIOVASCULAR DISEASE (CVD) RISK FACTORS AMONG PEOPLE LIVING WITH HIV INFECTION (PLWH) WHO ARE HEAVY DRINKERS. THE GOALS OF THIS RESEARCH ARE (1) TO DETERMINE IF A TAILORED PROBIOTIC (I.E., CONTAINS BACTERIA SUPPORTING BUTYRATE SYNTHESIS) CAN MITIGATE ALCOHOL ASSOCIATED GUT DYSBIOSIS AND LOWER LEVELS OF MICROBIAL TRANSLOCATION, INFLAMMATION, AND IMPROVE HARMFUL DYSBIOTIC METABOLITE PROFILES (E.G. TRIMETHYLAMINE N OXIDE, TMAO) AND (2) TO DETERMINE IF THESE METABOLITES ARE ASSOCIATED WITH INCIDENT CVD AND DEATH AMONG PLWH. WE HYPOTHESIZE THAT, AMONG PLWH, A PROBIOTIC VS. PLACEBO CAN MITIGATE ALCOHOL ASSOCIATED GUT DYSBIOSIS AND LOWER LEVELS OF MICROBIAL TRANSLOCATION, INFLAMMATION, AND IMPROVE METABOLITE PROFILES (PROJECT 1 RCT, N=250); AND THAT HARMFUL ALTERATIONS OF THESE METABOLITES WILL BE ASSOCIATED WITH HIGHER RISK OF INCIDENT CVD AND DEATH (PROJECT 2 COHORT, N=2,900). PROJECT 1 WILL BE CONDUCTED AT PAVLOV STATE MEDICAL UNIVERSITY IN ST. PETERSBURG, RUSSIA, THE SAME SITE AS OUR GUT MICROBIOME AND METABOLITE STUDIES (ACME HIV AND TMAO HIV). PROJECT 2 WILL LEVERAGE THE VETERANS AGING COHORT STUDY, AN OBSERVATIONAL COHORT OF VETERANS LIVING WITH AND WITHOUT HIV. THE PROJECTS WILL BE SUPPORTED BY OUR ADMINISTRATIVE CORE AT VANDERBILT UNIVERSITY MEDICAL CENTER AND THE INTEGRATED METAGENOMICS AND METABOLOMICS CORE AT THE UNIVERSITY OF LOUISVILLE'S ALCOHOL RESEARCH CENTER (ULARC). THE LATTER IS THE CORE FOR ACME HIV AND WILL GENERATE THE METAGENOMICS AND METABOLOMICS FOR THIS PPG. THE FORMER WILL COORDINATE ALL STUDY PROJECTS/CORES AND INTEGRATE THE VANDERBILT SCHOLARS IN HIV AND HEART, LUNG, BLOOD, AND SLEEP RESEARCH NIH K12 TRAINING PROGRAM INTO THE PPG. OUR PRELIMINARY DATA: (1) HIV INFECTION IS A CVD RISK FACTOR; (2) INFLAMMATION IS ASSOCIATED WITH INCREASED RISK OF CVD AMONG PLWH; (3) AMONG PLWH, HEAVY DRINKING IS ASSOCIATED WITH INCREASED CVD RISK AND CORRELATED WITH MEASURES OF GUT DYSBIOSIS, CHARACTERIZED BY LOSS OF BUTYRATE PRODUCING BACTERIA; (4) GUT DYSBIOSIS AMONG PLWH WHO ARE HEAVY DRINKERS IS CORRELATED WITH HIGHER LEVELS OF INFLAMMATION, TMAO, AND ADVERSE BILE ACID METABOLITE PROFILES; AND (5) ULARC DATA IN MURINE MODELS SHOW HEAVY DRINKING CAUSES DYSBIOSIS, THAT DYSBIOSIS LEADS TO INCREASED BIOMARKER LEVELS OF INFLAMMATION, AND THAT PROBIOTIC ADMINISTRATION TARGETING ALCOHOL-ASSOCIATED GUT DYSBIOSIS ATTENUATES THE RISE IN THESE INFLAMMATORY BIOMARKERS EVEN IN THE PRESENCE OF ALCOHOL CONSUMPTION. CROSS PROJECT VALIDATION: BIOSPECIMENS FROM PROJECT 1 WILL BE USED TO VALIDATE SIGNIFICANT FINDINGS IN PROJECT 2. METABOLITES SIGNIFICANTLY ASSOCIATED WITH ALCOHOL AND CVD IN PROJECT 2, WILL BE EXPLORED IN PROJECT 1 TO SEE IF PROBIOTICS FAVORABLY IMPACT THE LEVELS OF THOSE METABOLITES. THE MICROBIOME, METABOLITES, AND ALCOHOL IN HIV TO REDUCE CVD (META HIV CVD) PPG WILL INFORM PROBIOTICS' ROLE AS STANDARD ADJUNCTIVE THERAPY COMPLEMENTING ALCOHOL INTERVENTIONS AMONG PLWH WHO ARE HEAVY DRINKERS AND ADVANCE THE UNDERSTANDING OF HOW ALCOHOL ASSOCIATED GUT DYSBIOSIS AND ITS METABOLITES CONTRIBUTE TO CVD AND DEATH.

ROLE OF MT-MMPS IN RENAL DEVELOPMENT

THIS PROJECT AIMS TO CREATE A FULL SET OF MODULAR TOOLS FOR AUTONOMOUS ROBOTIC SURGERY AS WELL AS THE PERCEPTUAL CAPABILITIES AND LOGICAL FRAMEWORK TO INTEGRATE THEM INTO FULL PROCEDURES. THE TEAM HAS DIVIDED SURGICAL PROCEDURES INTO SEVEN CORE TASKS RETRACTION RESECTION HEMOSTASIS PROPRIOCEPTION DEBRIDEMENT PALPATION AND SUTURING. THE TEAM THEN CREATES A LOGICAL FRAMEWORK THAT DEFINES PROCEDURES IN TERMS OF THESE SEVEN BASIC TASKS AND ALLOWS THE ROBOT TO PROGRESS FROM ONE TASK TO ANOTHER. AS THE ROBOT CARRIES OUT A PROCEDURE IT NOT ONLY ASSESSES COMPLETENESS OF THE SUBTASK BUT ALSO ITS OWN UNCERTAINTY ALLOWING IT TO REQUEST HUMAN SURGEON INTERVENTION WHEN UNCERTAINTY IS HIGH. THE PROGRAM CULMINATES WITH TWO DEMONSTRATIONS OF AUTONOMOUS ROBOTIC SURGERY.

JOHN F. KENNEDY CENTER FOR MENTAL RETARDATION

PHENOTYPE HETEROGENEITY AND DYNAMICS IN SCLC

INTEGRATED PROGRAM FOR HUMAN PANCREAS PROCUREMENT AND ANALYSIS

INTEGRATED APPROACH TO STUDY EARLY AND LATE EVENTS IN COLONIC NEOPLASIA: MOUSE TO MAN

MOLECULAR MECHANISMS OF HUMAN AND MURINE BETA CELL PROLIFERATION AND REGENERATION

OVERALL: EUNICE KENNEDY SHRIVER INTELLECTUAL AND DEVELOPMENTAL DISABILITIES RESEARCH CENTER AT VANDERBILT

THE CONSORTIUM FOR RISK EVALUATION WITH STAKEHOLDER PARTICIPATION (CRESP IV) COOPERATIVE AGREEMENT WILL ADVANCE COST-EFFECTIVE, RISK-INFORMED CLEANUP OF THE NATION'S NUCLEAR WEAPONS PRODUCTION FACILITY WASTE SITES AND COST-EFFECTIVE, RISK-INFORMED MANAGEMENT OF LEGACY DEFENSE AND ENERGY NUCLEAR WASTES AND POTENTIAL FUTURE NUCLEAR SITES AND WASTES. THIS MISSION WILL BE ACCOMPLISHED BY SEEKING TO IMPROVE THE SCIENTIFIC AND TECHNICAL BASIS FOR ENVIRONMENTAL MANAGEMENT DECISIONS TO BE MADE BY THE DOE AND BY FOSTERING PUBLIC PARTICIPATION IN THAT SEARCH.

HOST-MEDIATED ZINC SEQUESTRATION DURING ACINETOBACTER BAUMANNII INFECTION

SYSTEMATICALLY MAPPING VARIANT EFFECTS FOR CARDIOVASCULAR GENES - CARDIOVASCULAR DISEASES ARE LEADING GLOBAL CAUSES OF DEATH AND DISABILITY, PRESENTING AS INTERRELATED PHENOTYPES OF ATHEROSCLEROTIC VASCULAR DISEASE, HEART FAILURE, AND ARRHYTHMIAS. THEY ARISE FROM INTERACTIONS BETWEEN ENVIRONMENTAL FACTORS AND COMMON AND RARE GENETIC VARIANTS, INCLUDING RELATIVELY COMMON MENDELIAN LIPID DISORDERS, CARDIOMYOPATHIES, AND ARRHYTHMIAS THAT COLLECTIVELY OCCUR IN AT LEAST 1/100 INDIVIDUALS. THE AVAILABILITY OF GENETIC SEQUENCING IS ALTERING CLINICAL MANAGEMENT, BUT A MAJOR BARRIER TO THE WIDESPREAD APPLICATION OF THIS PRACTICE IS THAT THE FUNCTION OF THE VAST MAJORITY OF VARIANTS IN KEY CARDIOVASCULAR DISEASE GENES IS UNKNOWN. VARIANT EFFECT MAPS THAT DEFINE FUNCTION FOR NEARLY ALL MISSENSE VARIANTS IN A TARGET SEQUENCE OFFER A WAY FORWARD. THIS PROJECT BRINGS TOGETHER SCIENTISTS AT THE FOREFRONT OF VARIANT EFFECT MAPPING IN DIVERSE CELLULAR SYSTEMS, ILLUMINATING UNDERLYING CARDIOVASCULAR BIOLOGY, ESTABLISHING RELATIONSHIPS BETWEEN VARIANT FUNCTION AND HUMAN PHENOTYPES, AND WORKING WITH OTHERS IN MULTI-INSTITUTIONAL COLLABORATIONS. OUR CARDIOVAR TEAM WILL GENERATE A COMPREHENSIVE ATLAS OF VARIANT EFFECT MAPS FOR KEY CARDIOVASCULAR DISEASE GENES. IN AIM 1, WE WILL DEVELOP, OPTIMIZE, AND VALIDATE A RANGE OF HIGH-THROUGHPUT CELLULAR ASSAYS. WE WILL USE A RANGE OF GENERALIZABLE (E.G. SURFACE ABUNDANCE) AND BESPOKE (E.G. ELECTROPHYSIOLOGICAL, LIPOPROTEIN UPTAKE) ASSAYS TO DIRECTLY MEASURE VARIANT FUNCTION IN DISEASE-RELEVANT CONTEXT. ASSAYS WILL BE ASSESSED BY THEIR ABILITY TO DISCRIMINATE PATHOGENIC FROM BENIGN VARIANTS. IN AIM 2, WE WILL USE IN SITU TARGETED MUTAGENESIS OR INSERTION OF VARIANT CONSTRUCTS AT A SAFE HARBOR SITE TO GENERATE POOLS OF CELLS CAPTURING ALL SINGLE-NUCLEOTIDE CHANGES IN TARGET GENES. WE WILL THEN DEPLOY EXISTING VALIDATED ASSAYS AND THOSE EMERGING FROM AIM 1 TO GENERATE AND VALIDATE VARIANT EFFECT MAPS AT SCALE. FUNCTIONAL SCORES AND UNCERTAINTY ESTIMATES WILL BE DERIVED AND EVALUATED, BOTH BY PERFORMANCE ON PATHOGENIC AND BENIGN VARIANTS AND ON CORRELATION WITH DISCRETE AND QUANTITATIVE PHENOTYPES IN CLINICAL COHORTS. IN AIM 3, WE WILL DERIVE BIOLOGICAL AND CLINICAL INSIGHTS FROM VARIANT EFFECT MAPS. DISCORDANT CASES, WHERE VARIANT SCORES DIVERGE FROM CLINICAL ANNOTATION, WILL BE FURTHER INVESTIGATED IN ZEBRAFISH, IPSC-CARDIOMYOCYTES, AND AUTOMATED PATCH CLAMPING SYSTEMS. THROUGH A COMBINATION OF HYPOTHESIS-DRIVEN ANALYSIS AND MACHINE LEARNING MODELS, WE WILL REVEAL RELATIONSHIPS AMONG VARIANT EFFECTS, PROTEIN STRUCTURE, PROTEIN FUNCTION, AND HUMAN PHENOTYPES. TO OPTIMIZE USE OF THE ATLAS, WE WILL PROVIDE A PORTAL SERVING AS A VARIANT-CENTRIC DECISION SUPPORT SYSTEM FOR EVALUATING FUNCTIONAL EVIDENCE OF PATHOGENICITY. WE WILL RELEASE VARIANT EFFECT MAP DATA PRE- PUBLICATION VIA MAVEDB (THAT WE CO-DEVELOPED) AND SHARE ALL RENEWABLE VARIANT ASSAY REAGENTS. THE CARDIOVAR ATLAS OF MISSENSE VARIANT EFFECTS, COVERING KEY CARDIOVASCULAR DISEASE GENES, WILL BE AN ESSENTIAL AND INTERPRETABLE COMMUNITY RESOURCE FOR CLINICAL AND MECHANISTIC STUDIES OF CARDIOVASCULAR DISEASE.

GENETIC PRIVACY AND IDENTITY IN COMMUNITY SETTINGS - GETPRECISE

ANTIDEPRESSANTS AND INTRACELLULAR SIGNALING LINKED TO BDNF

INTEGRATED, INDIVIDUALIZED, AND INTELLIGENT PRESCRIBING (I3P) CLINICAL TRIAL NETWORK

H. PYLORI RELATIONSHIP TO DIGESTIVE DISEASES AND CANCER

OPTIMIZING CARDIOVASCULAR STEM CELLS FOR CARDIAC REPAIR AND REGENERATION

VANDERBILT-COORDINATED HUMAN VIROME COLLABORATIVE CENTER (V2C2) - VIRUSES ARE RESPONSIBLE FOR SIGNIFICANT MORBIDITY/MORTALITY AT THE HEART OF MOST OF GLOBAL PANDEMICS OF THE 21ST CENTURY. RECENT DEVELOPMENTS IN TECHNICAL AND BIOINFORMATIC CAPABILITIES TO ADDRESS VIRAL SEQUENCE DIVERSITY IN A HIGH-THROUGHPUT CONTEXT ALONGSIDE INTEGRATED HOST RESPONSES HAVE USHERED IN THE POTENTIAL FOR INVESTIGATING VIRAL PRESENCE AND CONSEQUENCES AT EPIDEMIOLOGIC SCALE. HERE, WE ESTABLISH THE VANDERBILT-COORDINATED VIRUS CHARACTERIZATION CENTER (V2C2) TO RESPOND TO RFA-RM-23-019 TO ADDRESS THE CENTRAL CALL OF THE HUMAN VIROME PROGRAM (HVP)—TO PROVIDE A COMPREHENSIVE, ANNOTATED, HOST-CONTEXTUALIZED VIROME. THE CENTRAL THEME/HYPOTHESIS OF V2C2 IS THAT UNRECOGNIZED EUKARYOTIC/PROKARYOTIC VIRUSES IN HUMAN ECOLOGY (1) EXHIBIT IMPORTANT INTERACTIONS WITH HOST BIOLOGY AND FLORA, WITH PREVALENCE OF VIRAL PERSISTENCE OR INTEGRATION RELATED TO VARIATION IN BIOLOGICALLY RELEVANT PHENOTYPES IN HEALTHY INDIVIDUALS (E.G., OBESITY, INFLAMMATION). TO ADDRESS THIS HYPOTHESIS, WE WILL STUDY (1) ≈2250 HISPANIC/LATINX INDIVIDUALS AT THE US-MEXICO BORDER (AGES 8-90; 1750 WITH 2 SERIAL SAMPLES ALREADY COLLECTED WITH UP TO ≈20 YEARS FOLLOW-UP; 500 WITH 3 SERIAL SAMPLES TO BE PROSPECTIVELY COLLECTED OVER ≈4 YEARS); (2) ≈200 CHILDREN (AGES 0-5, CANOE-VU) WITH SERIAL SAMPLES (SOME ALREADY COLLECTED). WE PROPOSE A BROAD SAMPLING SCHEME FOR PROSPECTIVE SAMPLES, SPANNING OCULAR, NASAL, OROPHARYNGEAL, PLASMA, BLOOD (EXTRACELLULAR VESICLES, PBMCS, PLATELETS), URINE, AND STOOL SAMPLES, AND ACCOMPANYING PLACENTAL AND BREAST MILK SAMPLES (PEDIATRIC COHORT), AND WILL PRIORITIZE PLASMA (ALL SAMPLES) AND 3 ADDITIONAL SAMPLE TYPES (PROSPECTIVE ONLY) BASED ON CONSORTIUM DISCUSSION. OUR HOST-CONTEXTUALIZED VIRAL CHARACTERIZATION APPROACH (AIM 1) WILL INCLUDE VIRAL WHOLE METAGENOMIC/METATRANSCRIPTOMIC SEQUENCING (TO ASSESS VIRAL PRESENCE, FUNCTION) WITH TARGETED CAPTURE-BASED CONFIRMATION. WITH OTHER HVP MEMBERS (E.G., FUNCTIONAL INTERACTION AWARDEES), WE WILL STUDY HOST-VIRAL INTERACTIONS (AIM 2) VIA (1) HOST GENOMICS (FOR INTEGRATION); (2) VIRAL TROPISM STUDIES (USING SINGLE CELL AND IN VITRO INFECTION STUDIES); (3) HOST RESPONSE CHARACTERIZATION (AT THE CELLULAR AND ORGANISM-WIDE LEVEL WITH PROTEOMICS/TRANSCRIPTOMICS). IN AIM 3, WE WILL ESTABLISH A REPOSITORY OF HARMONIZED METADATA AND MOLECULAR INFORMATION FOR DATA SHARING IN AN ETHICALLY RESPONSIBLE MANNER TO ALLOW MULTI-OMIC CONNECTIONS BETWEEN LONGITUDINAL PHENOTYPES AND HOST-VIRAL CHARACTERISTICS. WE WILL EXECUTE THIS VISION COLLABORATIVELY WITHIN THE HVP VIA (1) A CORE STRUCTURE (LED BY ADMINISTRATIVE) THAT ADDRESSES BIOSPECIMEN COLLECTION, ASSAY, DATA ANALYSIS/SUBMISSION, AND ETHICAL/LEGAL/SOCIAL IMPLICATIONS THAT (2) FOLLOW A PRE-DETERMINED SERIES OF MILESTONES (PREDICATED ON ESTABLISHING CONSORTIUM-WIDE PROTOCOLS IN THE INITIAL 6 MONTH PLANNING PHASE). V2C2 LEADERSHIP HAS (1) PUBLISHED EXPERTISE IN LARGE SAMPLE VIRAL CHARACTERIZATION/BIOLOGICAL DISCOVERY, WITH EXTENSIVE PRELIMINARY DATA BEARING DIRECTLY ON HVP; (2) COHORT EPIDEMIOLOGY; (3) EXTENSIVE CONSORTIUM EXPERIENCE IN NIH, CDC, AND COMMON FUND INITIATIVES. THE EFFECTIVENESS OF V2C2 IS AUGMENTED BY STRONG COMMUNITY ENGAGEMENT (CCHC), INSTITUTIONAL SUPPORT, AND PROGRAM MANAGEMENT STAFF WITH EXPERIENCE AT THE SCALE OF HVP.

DEVELOPING THE VUMC MICRO FACILITY TO ADVANCE INNOVATIVE BSL3 RESEARCH - PROJECT ABSTRACT IN RESPONSE TO THE GLOBAL INCREASE AND SPREAD OF INFECTIOUS DISEASE AND ITS IMPACT ON HUMAN HEALTH, VANDERBILT UNIVERSITY MEDICAL CENTER (VUMC) HAS ESTABLISHED A TRANS-INSTITUTIONAL STRATEGIC FRAMEWORK FOR INFECTION AND IMMUNOLOGY RESEARCH, INCLUDING SIGNIFICANT INVESTMENTS IN RESEARCH FOCUSED ON HIGHLY VIRULENT PATHOGENS. VANDERBILT INVESTIGATORS ARE RAPIDLY ADVANCING DISCOVERY IN THE FIELDS OF MICROBIAL PATHOGENESIS, THERAPEUTIC DEVELOPMENT, AND VACCINE DESIGN INCLUDING CRITICAL RESEARCH COMBATTING COVID-19. VANDERBILT’S GROWING LEADERSHIP IN MICROBIAL PATHOGENESIS MAKES RESEARCH AT BIOSAFETY LEVEL 3 (BSL3) CRITICAL TO ENABLING BREAKTHROUGHS. HOWEVER, VANDERBILT’S TWO SMALL BSL3 LABORATORIES SERVE INDIVIDUAL INVESTIGATORS AND OPERATE AT CAPACITY. MOST VANDERBILT RESEARCHERS THEREFORE HAVE NO ACCESS TO BSL3 FACILITIES. THE PROPOSED MICROBIAL INFECTIOUS DISEASE CORE RESOURCE (MICRO) WILL BE A MODERN, COMPREHENSIVE BSL3 SHARED RESEARCH FACILITY THAT SIGNIFICANTLY EXPANDS CAPACITY FOR BSL3 RESEARCH AT VANDERBILT. REGIONAL PARTNERSHIPS WITH INSTITUTIONS SUCH AS THE UNIVERSITY OF TENNESSEE AND MEHARRY MEDICAL COLLEGE WILL ADVANCE BSL3 WORK ACROSS THE SOUTHEASTERN UNITED STATES TO MAXIMIZE THE MICRO’S BENEFIT AND IMPACT. KEY PROJECT GOALS WILL BE ACCOMPLISHED THROUGH THE RENOVATION OF 3,587 NET SQUARE FEET (NSF) OF SPACE IN THE HEART OF VANDERBILT’S BIOMEDICAL RESEARCH ZONE. THE MICRO WILL BE FLEXIBLY CONFIGURED TO MEET STRINGENT ISOLATION REQUIREMENTS FOR BSL3 AND SELECT AGENT PATHOGENS AND CAN BE RAPIDLY MODIFIED AS RESEARCH AND PUBLIC HEALTH NEEDS EVOLVE. THE MICRO WILL CONTAIN THREE BSL3 SUITES WITH A TOTAL OF SEVEN PROCEDURE ROOMS AND WILL BE SERVED BY NEW AND/OR REROUTED MECHANICAL AND PLUMBING SYSTEMS THAT COMPLETELY ISOLATE THE BSL3 SPACE. A 1,038 NSF BSL3-DEDICATED SPACE WILL BE CONSTRUCTED TO ENCLOSE NEW MECHANICAL EQUIPMENT, INCLUDING DEDICATED AIR HANDLING UNITS AND AN EXHAUST FILTRATION SYSTEM. THE PROJECT WILL BE DESIGNED TO MEET LEED SILVER STANDARDS AS WELL AS NATIONAL INSTITUTES OF HEALTH AND CENTERS FOR DISEASE CONTROL AND PREVENTION GUIDELINES. THE MICRO WILL BE DEVELOPED AND MANAGED BY AN EXPERIENCED PROJECT MANAGER AND BSL3 FACILITY MANAGER WORKING WITH THE VANDERBILT INSTITUTE OF INFECTION, IMMUNOLOGY AND INFLAMMATION, OFFICE OF RESEARCH, AND SCIENTIFIC ADVISORY BOARD TO ENSURE EFFECTIVE PLANNING, OPERATION, AND SHARED ACCESS TO THE NEW FACILITY. OVERALL, THE REQUESTED RENOVATIONS WILL ENABLE SUBSTANTIAL IMPROVEMENTS IN INFRASTRUCTURE, CAPACITY, AND CAPABILITIES FOR BSL3 EXPERIMENTATION. THIS FACILITY WILL ENHANCE INFECTION AND IMMUNOLOGY RESEARCH THAT WILL LEAD TO SCIENTIFIC BREAKTHROUGHS IN THESE FIELDS AT THE NEXUS OF BASIC RESEARCH, CLINICAL CARE, AND PUBLIC HEALTH.

GENES CONTROLLING ASSEMBLY AND FUNCTION OF SEROTONIN SYSTEMS

VANDERBILT MOUSE METABOLIC PHENOTYPING CENTER

INTERACTIONS OF INTRARENAL DOPAMINE AND CYCLOOXYGENASE-2

HARNESSING HUMAN BRAIN AND LIVER MICROPHYSIOLOGICAL SYSTEMS FOR TESTING THERAPEUTICS FOR METASTATIC MELANOMA

BIOPHYSICAL BASIS OF FUNCTIONAL CONNECTIVITY BY MRI

COMPARATIVE EFFECTIVENESS OF TREATMENTS FOR LOCALIZED PROSTATE CANCER

INITIATIVE FOR MAXIMIZING STUDENT DIVERSITY

LIPID PEROXIDATION AND ANTIOXIDANT MECHANISMS

BUILDING INTERDISCIPLINARY RESEARCH CAREERS IN WOMEN'S HEALTH

2/2-DOPAMINERGIC DYSFUNCTION IN LATE-LIFE DEPRESSION (THE D3 STUDY)

MAXIMIZING OUTCOMES FOR PRESCHOOLERS WITH DEVELOPMENTAL LANGUAGE DISORDER: TESTING THE EFFECTS OF A SEQUENTIALLY TARGETED NATURALISTIC INTERVENTION

THE MIND USA STUDY

INTEGRATED BIOLOGICAL SYSTEMS TRAINING IN ONCOLOGY

VANDERBILT INTEGRATED CENTER OF EXCELLENCE IN MATERNAL AND PEDIATRIC PRECISION THERAPEUTICS (VICE-MPRINT) - PROJECT SUMMARY / ABSTRACT - OVERALL THERE IS A RAPIDLY EXPANDING KNOWLEDGE BASE ENABLING PRECISION THERAPEUTICS FOR A NUMBER OF HUMAN DISEASES, BUT THERE ARE SIGNIFICANT UNMET NEEDS IN EVIDENCE GENERATION TO SUPPORT TRANSLATION TO THE TREATMENT OF CHILDREN AND PREGNANT/POST-PARTUM WOMEN. THE RECENT WIDESPREAD ADOPTION OF ELECTRONIC HEALTH RECORDS (EHRS) AND THE LINKAGE OF THESE DATA TO OTHER LARGE DATASETS REPRESENTS AN UNPRECEDENTED OPPORTUNITY FOR CLINICAL RESEARCH AND DISCOVERY. THE GOALS OF THIS CENTER OF EXCELLENCE IN MATERNAL AND PEDIATRIC PRECISION THERAPEUTICS ARE: TO ADDRESS KEY KNOWLEDGE GAPS AND PERFORM CLINICAL RESEARCH IN PHARMACOGENOMICS AND NEONATAL OPIOID WITHDRAWAL SYNDROME; TO LEVERAGE DATA SCIENCE METHODOLOGIES AND DEVELOP NOVEL TOOLS THAT SUPPORT MATERNAL AND PEDIATRIC PRECISION THERAPEUTICS RESEARCH; AND TO ENHANCE TRAINING FOR MATERNAL AND PEDIATRIC PRECISION THERAPEUTICS AT THE LOCAL, REGIONAL, AND NATIONAL LEVELS. WE BRING TO THIS EFFORT A UNIQUE COLLECTION OF INVESTIGATORS, INSTITUTIONAL SUPPORT, TOOLS, AND RESOURCES THAT ENABLE A PARADIGM-SHIFT FROM CURRENT NORMS OF SLOW, INCREMENTAL PROGRESS. PROJECT 1 WILL: USE A COMMUNITY ENGAGED APPROACH TO ILLUMINATE KNOWLEDGE OF, ATTITUDES ABOUT, AND PRIORITIES FOR PHARMACOGENOMICS; VALIDATE PHARMACOGENOMIC ASSOCIATIONS FOR MATERNAL AND PEDIATRIC POPULATIONS USING THE INNOVATIVE AND GENERALIZABLE STRATEGY OF EHR PHENOTYPING; AND IDENTIFY AND QUANTIFY VARIANTS WITH UNKNOWN FUNCTIONAL CONSEQUENCE IN DIVERSE INDIVIDUALS TO INFORM FUTURE RESEARCH EFFORTS AND REDUCE DISPARITIES. PROJECT 2 WILL: DEVELOP AND VALIDATE EHR-BASED ALGORITHMS TO IDENTIFY A COHORT OF OPIOID- EXPOSED INFANTS AND THEIR MOTHERS (DYADS) AND CREATE A NOVEL LINKAGE OF THESE DATA TO STATE-WIDE DATA; TEST THE HYPOTHESIS THAT USE OF MEDICATIONS FOR OPIOID USE DISORDER IS ASSOCIATED WITH IMPROVED EARLY OUTCOMES; AND TEST THE HYPOTHESIS THAT OPIOID USE DISORDER TREATMENT IS ASSOCIATED WITH IMPROVEMENTS IN THE NOVEL LONGITUDINAL OUTCOME OF DYADIC STABILITY. THESE PROJECTS ARE LED BY MULTIDISCIPLINARY TEAMS THAT INCLUDE INVESTIGATORS IN PEDIATRICS AND OBSTETRICS, AND WHO ARE NATIONALLY RECOGNIZED LEADERS IN THEIR RESPECTIVE FIELDS. BOTH PROJECTS WILL BE SUPPORTED BY A SCIENTIFIC CORE – THE PHENOTYPING SUPPORT CORE - WHICH ENHANCES EACH PROJECT WITH EXPERT PHENOTYPING, MACHINE LEARNING/ARTIFICIAL INTELLIGENCE, AND EXPERIENCE IN GENERALIZING AND DISSEMINATING PHENOTYPING APPROACHES. AN ADMINISTRATIVE CORE WILL PROVIDE LOGISTICAL SUPPORT FOR THE CENTER, SUPERVISE TRAINING OPPORTUNITIES, AND ENSURE SCIENTIFIC INTERCHANGE WITHIN THE CET AND WITH THE MPRINT HUB. THIS WORK WILL CONTRIBUTE TO INNOVATIVE APPROACHES TO PRECISION THERAPEUTICS FOR MOTHERS AND CHILDREN AND WILL DEVELOP THE EDUCATIONAL INFRASTRUCTURE TO SUPPORT THE TRAINING OF PHYSICIAN-SCIENTISTS TO SUPPORT FURTHER ADVANCES WELL INTO THE FUTURE.

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.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

RETINAL GANGLION CELL REPLACEMENT IN CLINICALLY RELEVANT MODELS OF OPTIC NEUROPATHY

SOUTHERN ENVIRONMENTAL HEALTH STUDY - SUMMARY APPROXIMATELY 80% OF HUMAN CANCERS ARE CAUSED BY ADVERSE ENVIRONMENTAL EXPOSURES, UNHEALTHY LIFESTYLES AND/OR THEIR INTERACTIONS WITH HOST SUSCEPTIBILITY FACTORS. PREVIOUS STUDIES HAVE MOSTLY FOCUSED ON EVALUATING BEHAVIORAL RISK FACTORS, SUCH AS TOBACCO SMOKING, PHYSICAL INACTIVITY, UNHEALTHY DIETS AND OBESITY. WHILE MORE THAN 80,000 CHEMICALS HAVE BEEN REGISTERED BY THE EPA, VERY FEW OF THEM HAVE BEEN ADEQUATELY INVESTIGATED IN RELATION TO HUMAN CANCERS IN EPIDEMIOLOGIC STUDIES. THERE ARE CONSIDERABLE CHALLENGES IN STUDYING ENVIRONMENTAL EXPOSURES IN EPIDEMIOLOGIC STUDIES. HUMANS ARE EXPOSED TO LARGE NUMBERS OF CHEMICAL AND PHYSICAL SUBSTANCES AND THEIR MIXTURES, TYPICALLY AT LOW LEVELS OVER EXTENDED PERIODS OF TIME. PREVIOUS ENVIRONMENTAL EPIDEMIOLOGIC STUDIES HAVE MOSTLY EVALUATED EXPOSURES ONE AT A TIME. HOWEVER, BECAUSE OF A TYPICALLY WEAK ASSOCIATION OF A GIVEN EXPOSURE WITH DISEASE RISK, COUPLED WITH LIMITED TOOLS AND BIOMARKERS FOR ENVIRONMENTAL ASSESSMENTS, MOST STUDIES HAVE FAILED TO PROVIDE CONVINCING EVIDENCE TO LINK ENVIRONMENTAL EXPOSURES TO CANCER RISK. TO OVERCOME THESE CHALLENGES, WE PROPOSE TO ESTABLISH A LARGE COHORT STUDY INCLUDING ~50,000 PARTICIPANTS WITH AN EXTENSIVE COLLECTION OF SURVEY AND GEOSPATIAL EXPOSURE DATA, AS WELL AS BIOLOGICAL AND ENVIRONMENTAL SAMPLES, TO ADDRESS CRITICAL ISSUES IN THE ENVIRONMENTAL ETIOLOGY OF CANCER. UTILIZING A FRAMEWORK OF COMMUNITY-ENGAGEMENT TO HELP INFORM RESEARCH, ENHANCE RECRUITMENT AND RETENTION EFFORTS, AND DISSEMINATE RESULTS, WE WILL FOCUS ON RECRUITING LOW-INCOME AND MINORITY POPULATIONS WHO ARE MORE LIKELY TO LIVE IN RESOURCE DEPRIVED AND HEAVILY POLLUTED COMMUNITIES. WE PROPOSE TO INCLUDE 1,500 OF THE STUDY PARTICIPANTS IN A DEEP-EXPOSOME STUDY TO COMPREHENSIVELY ASSESS THE EXPOSOME, IDENTIFY KEY BIOMARKERS OF EXTERNAL EXPOSURES, EXAMINE ASSOCIATIONS OF EXTERNAL AND INTERNAL METRICS WITH CANCER-RELATED BIOLOGICAL RESPONSES, AND DEVELOP CUMULATIVE EXPOSOME RISK SCORES. THE PROPOSED STUDY WILL ENABLE DIRECT EVALUATION OF ASSOCIATIONS OF ENVIRONMENTAL EXPOSURES WITH CANCER OUTCOMES IN THE LONG TERM, AND ASSOCIATIONS WITH CANCER INTERMEDIATE BIOMARKERS IN THE SHORT TERM. BY INTEGRATING ENVIRONMENTAL EXPOSURE DATA FROM MULTIPLE SOURCES, INCLUDING PERSONAL EXPOSURE ASSESSMENTS AND BIOLOGIC MARKERS OF ENVIRONMENTAL EXPOSURE AND RESPONSES, THIS PROPOSED STUDY WILL ALLOW US TO SYSTEMATICALLY AND RIGOROUSLY INVESTIGATE ENVIRONMENTAL EXPOSURES IN RELATION TO CANCER RISK AND PROVIDE SUBSTANTIAL NOVEL DATA TO IMPROVE THE UNDERSTANDING OF BOTH EXTERNAL AND INTERNAL EXPOSOMES, WHICH WILL PAVE THE WAY FOR FUTURE REMEDIATION OF ENVIRONMENTALLY INDUCED CANCER.

TOWARD A MECHANISM-BASED APPROACH TO TREATING CARDIAC ARRHYTHMIA

THE ELECTRONIC MEDICAL RECORDS AND GENOMICS (EMERGE) NETWORK PHASE III - COORDINATING CENTER (U01)

VANDERBILT UNIVERSITY BIOMOLECULAR MULTIMODAL IMAGING CENTER FOR 3-DIMENSIONAL MAPPING OF THE HUMAN KIDNEY - PROJECT SUMMARY – OVERALL THIS APPLICATION PROPOSES THE CONTINUATION OF A TISSUE MAPPING CENTER (TMC) FOR THE HUMAN KIDNEY WITHIN THE HUMAN BIOMOLECULAR ATLAS PROGRAM (HUBMAP). THE MISSION OF THE PROPOSED TMC IS TO BUILD A PLATFORM OF INTEGRATED TECHNOLOGIES FOR IMAGING AND MOLECULAR ANALYSIS THAT ENABLES THE CONSTRUCTION OF COMPREHENSIVE 3- DIMENSIONAL MOLECULAR ATLASES OF THE HUMAN KIDNEY. THIS TMC WILL LEVERAGE THE UNIQUE RESOURCES OF THE MASS SPECTROMETRY RESEARCH CENTER AND THE NATIONAL RESEARCH RESOURCE FOR IMAGING MASS SPECTROMETRY AT VANDERBILT UNIVERSITY, THE WORLD-CLASS CLINICAL ENVIRONMENT OF THE VANDERBILT UNIVERSITY MEDICAL CENTER, AND THE ADVANCED BIOCOMPUTATIONAL INFRASTRUCTURE AVAILABLE TO THE TMC THROUGH THE DATA ANALYSIS CORE LABORATORIES AT VANDERBILT UNIVERSITY AND THE DELFT UNIVERSITY OF TECHNOLOGY, NETHERLANDS TO CREATE A CAPABILITY TO MOLECULARLY CHARACTERIZE HUMAN TISSUES IN 3-DIMENSIONS AT A LEVEL OF UNDERSTANDING UNRIVALED BY CURRENT TECHNOLOGIES. THE INNOVATIVE ASPECT OF THE PROPOSED TMC IS THE INTEGRATION OF IMAGING MASS SPECTROMETRY, HIGHLY MULTIPLEXED IMMUNOFLUORESCENCE MICROSCOPY, AUTOFLUORESCENCE MICROSCOPY, STAINED MICROSCOPY, SPATIAL TRANSCRIPTOMICS, SPATIAL PROTEOMICS, AND SINGLE-CELL RNA-SEQ TO CREATE COMPREHENSIVE 2-D AND 3-D MOLECULAR AND CELLULAR ATLASES OF THE HUMAN KIDNEY. THROUGH SEGMENTATION AND CELL TYPE ANALYSIS DETERMINED BY CLASSICAL MARKERS, WE WILL CORRELATE OUR MOLECULAR AND CLINICAL INFORMATION TO THE EXISTING KNOWLEDGE OF THE KIDNEY TO BETTER DEFINE THE NORMAL PHENOTYPES ACROSS A RANGE OF DIVERSE SAMPLES. THE APPLICATION OF THIS MULTIMODAL PIPELINE TO THE KIDNEY WILL PROVIDE A NEW PARADIGM OF UNDERSTANDING THE NORMAL STATE OF THIS ORGAN ACROSS MULTIPLE DIMENSIONS, BOTH MOLECULAR (E.G., LIPIDS, METABOLITES, PROTEINS, AND TRANSCRIPTS) AND SPATIAL (E.G., WHOLE ORGANS TO SINGLE CELLS). AS A HUBMAP PARTICIPANT, THE MOLECULAR ATLASES PRODUCED BY THIS TMC WILL BE DISSEMINATED TO THE COMMUNITY AND TO COLLABORATORS TO GENERATE NEW HYPOTHESES REGARDING THE FUNCTION OF THIS IMPORTANT ORGAN SYSTEM, ENABLING NEW INSIGHT INTO HUMAN HEALTH AND DISEASE. THIS MULTIDISCIPLINARY EFFORT REQUIRES THE CREATION AND INTEGRATION OF THREE CAPABILITIES TO 1) PROCURE AND MANAGE HUMAN TISSUE SPECIMENS, 2) DETERMINE AND MITIGATE NON-BIOLOGICAL PRE- ANALYTICAL FACTORS, AND 3) ACQUIRE, PROCESS, AND DISSEMINATE MULTIMODAL 3-DIMENSIONAL IMAGING AND LARGE-SCALE OMICS DATA. THE GOAL OF THE PROPOSED KIDNEY TMC IS TO CREATE ATLASES FOR COMMUNITY USERS, PHYSICIANS, AND RESEARCHERS TO NAVIGATE ACROSS THE ANATOMICAL AND MOLECULAR LANDSCAPE OF THE KIDNEY, GENERATE NOVEL HYPOTHESES, AND TACKLE MEANINGFUL BIOMEDICAL RESEARCH QUESTIONS.

CYBER-PHYSICAL SYSTEMS VIRTUAL ORGANIZATION: ACTIVE RESOURCES

VANDERBILT GENOME-ELECTRONIC RECORDS (VGER) PROJECT

PERSONNEL DEVELOPMENT PROGRAM CONSORTIA

LONG-TERM NICOTINE TREATMENT OF MILD COGNITIVE IMPAIRMENT - PRECURSOR CONDITIONS TO ALZHEIMER’S DISEASE (AD) SUCH AS MILD COGNITIVE IMPAIRMENT (MCI) ARE NOW A TARGET OF PATIENT IDENTIFICATION AND POTENTIAL TREATMENT, AS STUDIES CLEARLY SHOWING THAT THE RISK OF PROGRESSION TO DEMENTIA IS VERY HIGH. DESPITE ATTEMPTS TO DEVELOP NEW TREATMENTS FOR AD AND ITS PRECURSOR, MCI, METHODS OF INTERRUPTING THE COURSE OF ILLNESS AND PREVENTING PROGRESSION HAVE PROVEN ELUSIVE. TREATMENT STRATEGIES FOR AD OR MCI BASED ON MOLECULAR PATHOLOGIES (SUCH AS ASS) HAVE THUS FAR PRODUCED EQUIVOCAL OR NEGATIVE RESULTS. LOSSES OF CHOLINERGIC NEURONS AND PARTICULARLY NICOTINIC CHOLINERGIC RECEPTORS HAVE BEEN SHOWN TO BE PRINCIPALLY RELATED TO COGNITIVE DECLINE IN AD. HOWEVER, CURRENTLY APPROVED TREATMENTS FOR AD HAVE NOT SIGNIFICANTLY IMPROVED MCI, DESPITE CLEAR EVIDENCE OF ALTERATION OF CHOLINERGIC FUNCTION AT THIS STAGE, THUS NONSPECIFIC ENHANCEMENT OF CHOLINERGIC FUNCTION DOES NOT APPEAR TO BE A FRUITFUL STRATEGY FOR EITHER ENHANCING LONG-TERM COGNITIVE FUNCTIONING IN MCI, NOR RETARDING THE PROGRESSION TO AD. THERE IS A CONTINUING SEARCH FOR NEW TREATMENTS THAT WILL IMPROVE COGNITIVE SYMPTOMS WHILE POTENTIALLY BE DISEASE MODIFYING. NICOTINE MAY BE ONE OF THOSE MOLECULES AND IS EASILY AVAILABLE, INEXPENSIVE, AND EASY TO USE. WE HAVE PREVIOUSLY PERFORMED A DOUBLE-BLIND 6-MONTH PILOT TRIAL SHOWING THAT NICOTINE TREATMENT SIGNIFICANTLY IMPROVED COGNITIVE PERFORMANCE IN THE AREAS OF ATTENTION AND EPISODIC MEMORY, SHOWED IMPROVING GLOBAL RATINGS OF FUNCTIONING AND SELF-RATED MEMORY PROBLEMS, AND WAS WELL TOLERATED WITH AN IMPRESSIVE SAFETY PROFILE AND NO ABUSE LIABILITY. IN THE PREVIOUS GRANT PERIOD, WE INITIATED A LARGER LONGER TRIAL, A DEFINITIVE 2-YEAR MULTI-CENTER CLINICAL TRIAL TO TEST WHETHER DAILY TRANSDERMAL NICOTINE WILL PRODUCE SUSTAINED COGNITIVE, CLINICAL, AND FUNCTIONAL BENEFITS IN PATIENTS WITH MCI AND TO TEST WHETHER NICOTINE WILL CHANGE THE UNDERLYING BIOLOGY RELATED TO DEVELOPING AD BY MONITORING BIOLOGICAL MARKERS INCLUDING STRUCTURAL AND FUNCTIONAL BRAIN IMAGING AND MEASURES OF AD PATHOLOGY IN SPINAL FLUID. IN THIS SUBSEQUENT GRANT PERIOD, WE WILL ENLARGE THE COHORT TO ACCOUNT FOR COVD-19 PANDEMIC ATTRITION, COMPLETE THE ENROLLMENT OF THE STUDY, AND TAKE ADVANTAGE OF NEW BIOMARKER APPROACHES (E.G. AMYLOID PET) TO EXPAND OUR ANALYSIS OF THE POTENTIAL IMPACT OF NICOTINE ON BRAIN PATHOLOGY OF MCI/AD. THIS PROPOSED STUDY HAS BROAD CLINICAL AND SCIENTIFIC SIGNIFICANCE. IF THE HYPOTHESES ARE VALIDATED, THESE FINDINGS WOULD SUPPORT A NOVEL, BROADLY AVAILABLE, AND INEXPENSIVE INTERVENTION FOR MCI. FURTHER, THE UNIQUE BIOLOGICAL INFORMATION WILL BE OBTAINED REGARDING THE EFFECTS OF NICOTINIC STIMULATION ON AD BIOMARKERS, BRAIN STRUCTURE/FUNCTION, AND BRAIN AMYLOID WILL MAKE AN INVALUABLE CONTRIBUTION TO AD RESEARCH. THIS WILL BE THE LONGEST TRIAL OF NICOTINIC STIMULATION ON BRAIN FUNCTION TO DATE AND IF SUCCESSFUL WOULD LEAD TO COMBINED TRIALS WITH OTHER SYMPTOMATIC AGENTS AND/OR AGENTS THAT DIRECTLY INTERACT WITH ASS OR TAU-RELATED MECHANISMS.

SMALL GTP BINDING PROTEINS IN GASTROINTESTINAL MUCOSA

THE ROLE OF HB-EGF IN RENAL EPITHELIAL CELL INJURY

EUNICE KENNEDY SHRIVER INTELLECTUAL AND DEVELOPMENTAL DISABILITIES RESEARCH CENTER AT VANDERBILT UNIVERSITY

VANDERBILT IN VIVO CELLULAR AND MOLECULAR IMAGING CENTER

VANDERBILT HIV CLINICAL TRIALS UNIT

ROLE OF SNARE INTERACTIONS IN CENTRAL SYNAPSE FUNCTION

COMPARISON OF HIGH VS. STANDARD DOSE INFLUENZA VACCINE IN PEDIATRIC SOLID ORGAN TRANSPLANT RECIPIENTS - PROJECT SUMMARY INFLUENZA VIRUS IS A SIGNIFICANT PATHOGEN IN PEDIATRIC SOLID ORGAN TRANSPLANT (SOT) RECIPIENTS. HOWEVER, THESE INDIVIDUALS RESPOND POORLY TO STANDARD-DOSE (SD) INACTIVATED INFLUENZA VACCINE (IIV). RECENT STUDIES HAVE INVESTIGATED TWO STRATEGIES TO OVERCOME POOR IMMUNE RESPONSES IN SOT RECIPIENTS: (1) ADMINISTRATION OF HIGH- DOSE (HD)-IIV COMPARED TO SD-IIV AND (2) TWO DOSES OF SD-IIV COMPARED TO ONE DOSE OF SD-IIV IN THE SAME INFLUENZA SEASON. ONE STUDY COMPARED HD-IIV VS. SD-IIV IN ADULT SOT RECIPIENTS AND NOTED THAT HD-IIV WAS SAFE AND MORE IMMUNOGENIC; HOWEVER, THE MEDIAN POST-TRANSPLANT PERIOD WAS 38 MONTHS. A PHASE I PEDIATRIC STUDY COMPARING A SINGLE DOSE OF HD-IIV VS. SD-IIV WAS SAFE WITH HIGHER IMMUNOGENICITY, BUT THE STUDY WAS LIMITED BY SMALL SAMPLE SIZE AND MEDIAN POST-TRANSPLANT VACCINE ADMINISTRATION WAS 26 MONTHS. IN ANOTHER PHASE II TRIAL OF ADULT SOT RECIPIENTS, TWO DOSES OF SD-IIV ONE MONTH APART COMPARED TO ONE-DOSE OF SD-IIV REVEALED MODESTLY INCREASED IMMUNOGENICITY WHEN GIVEN AT A MEDIAN OF 18 MONTHS POST-TRANSPLANT. THEREFORE, THESE STUDIES LACK BOTH EVALUATION IN THE EARLY POST-TRANSPLANT PERIOD AND SUBSTANTIVE PEDIATRIC POPULATIONS. ADDITIONALLY, THE ADMINISTRATION OF TWO-DOSES OF HD-IIV IN THE SAME INFLUENZA SEASON HAS NOT BEEN EVALUATED IN PEDIATRIC SOT RECIPIENTS. THUS, THE OPTIMAL IMMUNIZATION STRATEGY FOR PEDIATRIC SOT RECIPIENTS LESS THAN 24 MONTHS POST-TRANSPLANT IS UNKNOWN. IN ADDITION, IMMUNOLOGIC PREDICTORS AND CORRELATES OF INFLUENZA VACCINE IMMUNOGENICITY IN PEDIATRIC SOT RECIPIENTS HAVE NOT BEEN WELL-DEFINED. THE CENTRAL HYPOTHESIS OF OUR PROPOSAL IS THAT PEDIATRIC SOT RECIPIENTS 1-23 MONTHS POST-TRANSPLANT WHO RECEIVE TWO DOSES OF HD- QUADRIVALENT INACTIVATED INFLUENZA VACCINE (QIV) WILL HAVE SIMILAR SAFETY BUT HIGHER HAI GEOMETRIC MEAN TITERS (GMTS) TO INFLUENZA ANTIGENS COMPARED TO PEDIATRIC SOT RECIPIENTS RECEIVING TWO DOSES OF SD- QIV. TO TEST THIS HYPOTHESIS AND ADDRESS THE CRITICAL KNOWLEDGE GAPS OUTLINED ABOVE, WE PROPOSE TO CONDUCT A PHASE II, MULTI-CENTER, RANDOMIZED-CONTROLLED IMMUNOGENICITY AND SAFETY TRIAL COMPARING TWO DOSES OF HD-QIV TO TWO DOSES OF SD-QIV IN PEDIATRIC KIDNEY, HEART, AND/OR LIVER SOT RECIPIENTS 1-23 MONTHS POST-TRANSPLANT. THE RESULTS OF THIS STUDY WILL ADDRESS SIGNIFICANT KNOWLEDGE GAPS REGARDING INFLUENZA VACCINE STRATEGIES AND IMMUNE RESPONSES IN PEDIATRIC SOT RECIPIENTS AND WILL GUIDE VACCINE RECOMMENDATIONS IN THE EARLY POST- TRANSPLANT PERIOD.

ROLE OF RENAL MACROPHAGES IN RECOVERY FROM ACUTE KIDNEY INJURY

TYPE IV PROTEIN SECRETION IN HELICOBACTER PYLORI

THE ROLE OF AQUAPORIN-0 IN LENS DEVELOPMENT AND AGING

OXGR1 IN RENAL INTERCALATED CELLS, SALT TRANSPORT AND DIURETIC EFFICACY

ADDRESSING HEALTH LITERACY AND NUMERACY TO PREVENT CHILDHOOD OBESITY

SHAPING OF THE MICROENVIRONMENT IN COLONIC PRE-CANCER BY EPITHELIA AND MICROBIOTA - THE VANDERBILT TBEL CENTER ASSEMBLES A MULTI-DISCIPLINARY TEAM OF FIELD-SPECIFIC EXPERTS TO COLLABORATIVELY INVESTIGATE THE BASIC AND TRANSLATIONAL PATHWAYS OF COLONIC PRE-CANCER PROGRESSION. OUR FOUNDATIONAL WORK ON TWO SUBTYPES OF COLONIC PRE-CANCERS, ADENOMAS (ADS) AND SESSILE SERRATED LESIONS (SSLS), DEPICTS THE EARLY ORIGINS OF TUMORIGENESIS THAT ARE SHAPED BY MODULATION OF THE IMMUNE MICROENVIRONMENT VIA NEOPLASTIC CELLS AND THE MICROBIOTA. WE HAVE SHOWN THAT SSLS ORIGINATE FROM GASTRIC METAPLASIA ARISING FROM THE MUCOSAL SURFACE IN A CYTOTOXIC IMMUNE MICROENVIRONMENT, WHEREAS ADS ARISE FROM STEM CELL-DERIVED WNT ACTIVATION AT THE CRYPT BASE. IN THIS CENTER, WE WILL EXTEND OUR INVESTIGATION OF SPECIFIC BIOLOGICAL MECHANISMS TOWARDS THE DEVELOPMENTAL TRAJECTORIES OF THESE PRE-MALIGNANT LESIONS INTO PROGRESSION OR INDOLENCE. BASIC PROJECT 1 INVESTIGATES THE CONTRIBUTION OF NEUTROPHIL-AD CROSSTALK, LARGELY VIA DIPEPTIDASE 1 (DPEP1) BOTH AT THE CELL SURFACE AND RELEASED IN SMALL EXTRACELLULAR VESICLES, IN THE COURSE OF AD PROGRESSION. TRANSLATIONAL PROJECT 2 INVESTIGATES, IN HUMAN PROSPECTIVE STUDIES, THE ASSOCIATION OF PKS+ ESCHERICHIA COLI THAT INDUCES GENOTOXIC STRESS WITH PRE-CANCER PROGRESSION, AS WELL AS COLON EPITHELIAL CELL AND MUCOSA MECHANISMS THAT MAY CONTRIBUTE TO A POLYP-PROMOTING MICROENVIRONMENT. BASIC PROJECT 3 INVESTIGATES ACQUISITION OF STEMNESS IN MODULATING ANTIGEN PRESENTATION TO CYTOTOXIC T CELLS IN THE CONTEXT OF CO-EVOLUTION BETWEEN NEOPLASTIC CELLS AND THE IMMUNE SYSTEM. JOINT ANALYSIS OF COMMON COLORECTAL PRE-CANCER TISSUES WILL FACILITATE AN ONGOING PROCESS OF ITERATION AND INTEGRATION ACROSS ALL PROJECTS. OUR TBEL CENTER OFFERS A COMPLEMENTARY BLEND, FROM REDUCTIONIST AND SYSTEMS BIOLOGY APPROACHES, TO INVESTIGATE CRITICAL FACTORS INVOLVED IN THE PROGRESSION OF PRE-CANCEROUS TUMORS OF THE COLON TO CRC. THE WORK WILL UTILIZE CUTTING-EDGE TECHNOLOGIES ON HUMAN TISSUES, INCLUDING SINGLE-CELL AND SPATIAL TRANSCRIPTOMICS, SMALL EXTRACELLULAR VESICLE PROFILING, MULTIPLEX IMAGING, LONGITUDINAL DATA ANALYSIS, AND NEXT-GENERATION COMPUTATIONAL ALGORITHMS. IN ADDITION, SUBSTANTIAL HUMAN POLYP RESOURCES PREVIOUSLY ESTABLISHED BY THE VANDERBILT GI SPECIALIZED PROGRAMS OF RESEARCH EXCELLENCE AND THE NCI MOONSHOT HUMAN TUMOR ATLAS NETWORK WILL BE LEVERAGED BY THE SAME TEAM OF INVESTIGATORS IN THE TBEL CENTER. IN ADDITION, AN INNOVATIVE CO-CULTURE SYSTEM WILL BE EMPLOYED BY EACH PROJECT, WHERE POLARIZING PRE-CANCER ORGANOIDS CAN BE CO-CULTURED WITH KEY MICROENVIRONMENT ELEMENTS EXPOSED TO NEOPLASTIC CELLS FROM THE LUMINAL OR BASAL SIDE. THIS WORK WILL INFORM THE MODELING OF TUMOR DEVELOPMENT TRAJECTORIES AND IDENTIFY MECHANISMS OF PROGRESSION THAT WILL ENABLE IMPROVEMENTS IN RISK STRATIFICATION, PRECISION PREVENTION, AND INTERCEPTION FOR INDIVIDUALS WITH COLORECTAL PRE- CANCERS.

INTERVENTIONS AGAINST THE MOLECULAR ETIOLOGY OF BMPR2-INDUCED PAH

TENNESSEE VALLEY COOPERATIVE HUMAN TISSUE NETWORK

REVISION ACL RECONSTRUCTIONS: A COMPARATIVE EFFECTIVENESS TREATMENT STUDY

CANCER AND CONTEXT

EARLY READING FIRST

HUMAN PANCREAS ANALYSIS PROGRAM-T2D

VANDERBILT-EMORY-CORNELL-DUKE CONSORTIUM FOR GLOBAL HEALTH FELLOWS (VECDOR)

VANDERBILT CENTER FOR DIABETES TRANSLATION RESEARCH

NOVEL INTEGRATED ANALYSES OF HUMAN DIABETIC NEPHROPATHY

"(MURI FY05) RADIATION EFFECTS ON EMERGING ELECTRONIC MATERIALS AND DEVICES" (

IMAGING HIPPOCAMPAL FUNCTION IN PSYCHOSIS

IDENTIFYING A DISEASE GENE CAUSING PRIMARY OPEN ANGLE GLAUCOMA

NATIONAL CENTER FOR LEADERSHIP IN INTENSIVE INTERVENTION 2 (NCLII-2)

STRUCTURE-FUNCTION ANALYSIS OF H. PYLORI VACA

BIOCHEMICAL MECHANISMS OF LONG-TERM POTENTIATION

VESPA: VANDERBILT ELECTRONIC SYSTEMS FOR PHARMACOGENOMIC ASSESSMENT

MICROTUBULE REGULATION OF PANCREATIC BETA CELL FUNCTION AND DIABETES

CAUSAL: COHORT TO AUGMENT THE UNDERSTANDING OF SARCOMA SURVIVORSHIP ACROSS THE LIFESPAN - PROJECT SUMMARY SARCOMAS REPRESENT A RARE AND HIGHLY HETEROGENEOUS SUBTYPE OF TUMORS THAT MAY DEVELOP ACROSS THE LIFESPAN. IN THE UNITED STATES (US), THERE ARE APPROXIMATELY 14,000 NEW CASES ANNUALLY, WITH APPROXIMATELY 65% SURVIVAL. ASIDE FROM THOSE INCLUDED IN PEDIATRIC CANCER SURVIVOR COHORT STUDIES, THERE ARE NO SARCOMA SURVIVOR COHORTS IN WHICH TO SYSTEMATICALLY STUDY RECURRENCE, ORGAN TOXICITY, FUNCTION, QUALITY OF LIFE, AND SURVIVAL AS WELL AS THEIR PREDICTORS. WE PROPOSE TO ADDRESS THESE CRITICAL GAPS IN KNOWLEDGE BY ESTABLISHING A COHORT OF APPROXIMATELY 2100 SARCOMA SURVIVORS THROUGH THE VANDERBILT UNIVERSITY MEDICAL CENTER (VUMC) SARCOMA TREATMENT CENTER, WHICH IS AMONGST THE LARGEST SARCOMA PROGRAMS IN THE US, IN EXISTENCE SINCE 1987. IN THIS COHORT, WE WILL SYSTEMATICALLY COLLECT REPEATED INFORMATION ON DISEASE, TREATMENT, RESPONSE, RELAPSE, TREATMENT-RELATED TOXICITY, SOCIODEMOGRAPHICS, LIFESTYLE, FUNCTIONAL STATUS, QUALITY OF LIFE, PHYSICAL HEALTH OUTCOMES, AND SURVIVAL, TOGETHER WITH BIOSPECIMENS (TUMOR TISSUE AND PERIPHERAL BLOOD SAMPLES). WE HYPOTHESIZE THAT: 1) EXTRINSIC FACTORS, TUMOR BIOLOGY, AND GERMLINE GENOMICS CONTRIBUTE TO ONCOLOGIC OUTCOMES AND LONG-TERM ORGAN TOXICITY; 2) HEALTHY LIFESTYLE, E.G., HIGH QUALITY OF DIET, EXERCISE, ABSTINENCE FROM CIGARETTE SMOKING AND ALCOHOL DRINKING MITIGATE THE ADVERSE HEALTH CONSEQUENCES, IMPROVE SURVIVAL AND QUALITY OF LIFE AMONG SARCOMA SURVIVORS; AND 3) LIQUID BIOPSY TOOLS, DEVELOPED THROUGH IDENTIFYING GENOMIC DRIVERS OF SARCOMA, WILL BE OF PREDICTIVE AND PROGNOSTIC UTILITY. OUR AIMS FOR CURRENT GRANT PERIOD ARE TO EVALUATE1) THE IMPACT OF DISEASE, TREATMENT, SOCIODEMOGRAPHIC AND LIFESTYLE CONTRIBUTORS ON ADVERSE ONCOLOGIC AND NON-ONCOLOGIC OUTCOMES AND MORTALITY IN THE COHORT; 2) THE ROLE OF DRUG METABOLISM AND DNA REPAIR GENE FUNCTIONAL POLYMORPHISMS, GENETICALLY PREDICTED GENE EXPRESSION LEVELS, AND POLYGENIC RISK SCORES, ON TREATMENT EFFICACY AND THERAPY-INDUCED NORMAL TISSUE TOXICITY; AND 3) GENOMIC DRIVERS OF SARCOMA TO DEVELOP PERSONALIZED LIQUID BIOPSY ASSAYS FOR MONITORING TREATMENT RESPONSE, RECURRENCE, AND MINIMAL RESIDUAL DISEASE. ESTABLISHMENT OF A PROSPECTIVE COHORT OF SARCOMA SURVIVORS ACROSS THE LIFESPAN, WITH EXTENSIVE AND WELL CHARACTERIZED CLINICAL AND EPIDEMIOLOGIC DATA, PATIENT REPORTED OUTCOMES, TUMOR TISSUE AND SERIAL BLOOD SAMPLES BUILDS A FOUNDATION FOR A LONG-TERM PROSPECTIVE INVESTIGATION ON LIFE AFTER SARCOMA. THIS EFFORT IS CRITICALLY IMPORTANT TO IMPROVE THE UNDERSTANDING OF A RARE TUMOR AFFECTING THE LIFESPAN BUT SERIOUSLY UNDERREPRESENTED IN RESEARCH. IDENTIFICATION OF HEALTH OUTCOMES AND THEIR PREDICTIVE AND PROGNOSTIC FACTORS CAN LEAD TO PRECISION TREATMENT AND SURVIVORSHIP CARE, WHICH ARE CURRENTLY CLINICALLY UNMET NEEDS.