Morehouse School Of Medicine Inc

MSM HEER HBGI

UNKNOWN TITLE

HISTORICALLY BLACK COLLEGES AND UNIVERSITIES PROGRAM

HBCU - INSTITUTIONAL AID

THE NATIONAL COVID-19 RESILIENCY NETWORK (NCRN): MITIGATING THE IMPACT OF COVID-19 ON VULNERABLE POPULATIONS

CENTER FOR TRANSLATIONAL RESEARCH IN HEALTH DISPARITIES

MOREHOUSE SCHOOL OF MEDICINE CENTER OF EXCELLENCE RESEARCH ENDOWMENT PROGRAM

84.031K STRENGTHENING HISTORICALLY BLACK GRADUATE INSTITUTIONS PROGRAM

RCMI INFRASTRUCTURE FOR CLINICAL AND TRANSLATIONAL RESEARCH (RCTR) (U54)

HISTORICALLY BLACK COLLEGES AND UNIVERSITIES PROGRAM

NATIONAL CENTER FOR PRIMARY CARE - REGIONAL EXTENSION CENTER FOR HEALTH INFORMATION TECHNOLOGY IN HIGH-PRIORITY PRACTICE

RCMI TRANSLATIONAL RESEARCH NETWORK (RTRN)

MOREHOUSE SCHOOL OF MED/TUSKEGEE UNIV/UNIV./ OF ALABAMA CANCER CENTER PARTNERSHIP

MOREHOUSE SCHOOL OF MEDICINE G12 MULTIDISCIPLINARY BIOMEDICAL RESEARCH CENTER

RESEARCH CENTERS IN MINORITY INSTITUTIONS (RCMI) COORDINATING CENTER

RCMI INFRASTRUCTURE FOR CLINICAL AND TRANSLATIONAL RESEARCH (RCTR) (U54)

MINORITY HEALTH-GRID NETWORK: A GENOMICS RESOURCE FOR HEALTH DISPARITY RESEARCH

TCC FOR HEALTH DISPARTIES: INFORMING & INFLUENCING HEALTH POLICY AND PRACTICE

ENHANCEMENT OF THE CAPACITY FOR BIOMEDICAL RESEARCH (RCMI)

MOREHOUSE SCHOOL OF MEDICINE-MBRS/RISE

MOREHOUSE SCHOOL OF MEDICINE MEB2 RENOVATION AND RESEARCH CORE CONSOLIDATION

COMMUNITY-BASED WORKFORCE TO BUILD COVID-19 VACCINE CONFIDENCE

THE NATIONAL AFRICAN AMERICAN CHILD AND FAMILY RESEARCH CENTER

MOREHOUSE SCHOOL OF MEDICINE SNRP

TEENAGE PREGNANCY PREVENTION: REPLICATION OF EVIDENCE-BASED PROGRAM

CREST PHASE I: CENTER FOR CIRCADIAN RHYTHMICITY AND SLEEP HOMEOSTASIS -WITH SUPPORT FROM THE CENTERS FOR RESEARCH EXCELLENCE IN SCIENCE AND TECHNOLOGY (CREST), THIS PROJECT AIMS TO STUDY SLEEP AND INTERNAL CIRCADIAN CLOCKS THAT REGULATE SLEEP-WAKE CYCLES. THESE INVESTIGATIONS ARE SIGNIFICANT BECAUSE LACK OF SLEEP HAS BEEN ASSOCIATED WITH INDIVIDUALS WHOSE OCCUPATIONS REQUIRE SHIFT-WORK. HOW CIRCADIAN DISRUPTIONS AFFECT SLEEP IS UNKNOWN. THIS PROJECT WILL IDENTIFY HOW CIRCADIAN DISRUPTIONS AFFECT THE BODY. THE GOAL OF THE PROJECT IS TO ESTABLISH A WORLD-CLASS RESEARCH CENTER FOR CIRCADIAN SYSTEM BIOLOGY. THE RESEARCH QUESTIONS WILL FOCUS ON UNDERSTANDING HOW CIRCADIAN RHYTHMS ADAPT/RESYNCHRONIZE IN RESPONSE TO FREQUENTLY DISRUPTED AND EVER-CHANGING STIMULI. THE CENTER AIMS TO: IDENTIFY THE NEURONAL NETWORK MECHANISMS BY WHICH LIGHT-DARK SIGNALS ARE INTEGRATED BY THE CIRCADIAN CLOCK IN THE BRAIN; PROBE THE MOLECULAR MECHANISMS FOR THE SYNCHRONIZATION OF CIRCADIAN CLOCKS OUTSIDE OF THE BRAIN; AND DETERMINE THE NEUROCIRCUITRY UNDERLYING SLEEP. RESEARCH METHODS WILL INCLUDE SPATIAL TRANSCRIPTOMICS, PROTEOMICS, COMPUTATIONAL NEUROBIOLOGY, AND IN VIVO BRAIN IMAGING. THE PROJECT?S SCOPE WILL ENGAGE COLLABORATORS TO LEVERAGE ADDITIONAL CUTTING-EDGE TECHNOLOGIES. THE EXPECTED RESULTS ARE THE IDENTIFICATION OF CELLULAR AND MOLECULAR MECHANISMS RESPONSIBLE FOR CIRCADIAN DISRUPTIONS. RESULTS WILL BE DISSEMINATED AT MEETINGS AND IN PUBLICATIONS FOR THE SCIENTIFIC AND LAY COMMUNITIES. BROADER IMPACTS INCLUDE UNDERSTANDING AND MITIGATING THE ADVERSE IMPACT OF CIRCADIAN DISRUPTIONS AND TRAINING OPPORTUNITIES FOR STUDENTS AND FACULTY. THE CENTER OF RESEARCH EXCELLENCE IN SCIENCE AND TECHNOLOGY (CREST) PROGRAM PROVIDES SUPPORT TO ENHANCE THE RESEARCH CAPABILITY CAPABILITIES OF INSTITUTIONS THROUGH THE ESTABLISHMENT OF CENTERS THAT EFFECTIVELY INTEGRATE EDUCATION AND RESEARCH. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

BASIC & TRANSLATIONAL NEUROSCIENCE RESEARCH

MOREHOUSE CARDIOVASCULAR RESEARCH CENTER OF EXCELLENCE

REDUCING HEALTH DISPARITIES IN VULNERABLE AFRICAN AMERICAN FAMILIES AND COMMUNITI

REPLICATING EVIDENCE BASED TEEN PREGNANCY PREVENTION PROGRAMS TO SCALE IN COMMUNITIES WITH THE GREATEST NEED (TIER 1B)

HEALTH EQUITY FOR ALL TEENS - H.E.A.T - THE HEALTH PROMOTION AND RESOURCE CENTER (HPRC/MSM) AT MOREHOUSE SCHOOL OF MEDICINE PROPOSES TO IMPLEMENT HEALTH EQUITY FOR ALL TEENS (HEAT). HEAT WILL SCALE EVIDENCE BASED TEEN PREGNANCY (TPP) AND RELATED RISK INTERVENTIONS AND PROGRAMS (EBIS) IN THREE PUBLIC HEALTH DISTRICTS: CLAYTON COUNTY HEALTH DISTRICT, NORTH CENTRAL HEALTH DISTRICT AND SOUTHWEST HEALTH DISTRICT. HEAT WILL SERVE COUNTIES WITH THE HIGHEST TEEN BIRTH AND STDS RATES IN THE HEALTH DISTRICTS. THE PROGRAM WILL REACH RURAL WHITE TEENS, RURAL AND URBAN BLACK TEENS, RURAL AND URBAN LATINO TEENS. WE WILL ALSO SERVE LGBTQ TEENS AND JUVENILE JUSTICE INVOLVED TEENS IN SELECT COUNTIES WITH HIGH NEEDS AND DISPARITIES AMONG THESE SUBGROUPS. FOR ALL TEENS, WE WILL ADDRESS THE HEALTH DISPARITIES FOR THE SOCIAL DETERMINANTS OF HEALTH THAT CONTRIBUTE TO TEEN PREGNANCY, STIS AND RELATED RISK BEHAVIOR AMONG THESE GROUPS. TO ACHIEVE THIS GOAL HEAT WILL IMPLEMENT TPP AND RELATED RISK EBIS IN THREE SETTINGS IN EACH TARGET COUNTY. HEAT WILL ALSO IMPLEMENT YOUTH DEVELOPMENT PROGRAMS THROUGH YOUTH LEADERSHIPS COUNCILS IN EACH TARGET COUNTY. HPRC/MSM WILL SUBCONTRACT WITH THREE ORGANIZATIONS TO SCALE EBIS AND YLCS IN THE TARGET COUNTIES: CLAYTON COUNTY HEALTH DISTRICT IN THE ATLANTA METRO-AREA, OCONEE COMMUNITY SERVICE BOARD IN CENTRAL GEORGIA AND PHOEBE PUTNEY MEDICAL SYSTEM IN SOUTHWEST GEORGIA. EACH SUBCONTRACT LEAD WILL UTILIZE EXISTING PARTNERSHIPS WITH SCHOOL DISTRICTS, HEALTH SYSTEMS, COMMUNITY AND FAITH-BASED AGENCIES, AND JUVENILE JUSTICE SYSTEMS TO REACH THE POPULATIONS OF FOCUS. HPRC/MSM WILL SUPPORT AND MAINTAIN THESE REGIONAL NETWORKS THROUGH CAPACITY/COLLABORATIVE BUILDING, TRAINING, TECHNICAL ASSISTANCE AND MONITORING. THE GOALS ARE TO 1) ADVANCE HEALTH EQUITY FOR ADOLESCENTS, THEIR FAMILIES AND COMMUNITIES, 2) IMPROVE SEXUAL AND REPRODUCTIVE HEALTH OUTCOMES, AND 3) INCREASE POSITIVE YOUTH BEHAVIORS KNOWN TO PROTECT AGAINST TEEN PREGNANCY. EVALUATION MONITORING WILL ENSURE REACH, PROGR AM GOALS AND OBJECTIVE, FIDELITY, AND QUALITY.

FIRST COORDINATION AND EVALUATION CENTER TO PROMOTE INCLUSIVE EXCELLENCE - PROJECT SUMMARY/ABSTRACT THE OVERALL OBJECTIVE OF THE FIRST COORDINATION AND EVALUATION CENTER (CEC) AT MSM IS TO CONDUCT A COMPREHENSIVE EVALUATION GROUNDED IN REALIST EVALUATION THEORY, BY COLLABORATING WITH FIRST COHORT AWARDEES TO ITERATIVELY ASSESS THE IMPACT OF KEY INSTITUTIONAL CULTURE CHANGE STRATEGIES AND OTHER INNOVATIVE APPROACHES IMPLEMENTED AT FIRST COHORT SITES TO PROMOTE INCLUSIVE EXCELLENCE. SPECIFIC AIM 1. COORDINATE FIRST PROGRAM ADMINISTRATION AND CONDUCT COMPREHENSIVE EVALUATION OF THE PROGRAM CONTEXT, PROCESSES, AND OUTCOMES APPROACH: UTILIZE THE INCLUSIVE EXCELLENCE (IE) SCORECARD, A MULTIDIMENTIONAL MEASUREMENT TOOL THAT CAN SIMULTANEOUSLY DRIVE AND ASSESS CHANGE AT THE INSTITUTIONAL, DEPARTMENT, CENTER, INSTITUTE AND FACULTY LEVELS. IDENTIFY MEASURES FOR ASSESSING THE IMPACT OF INCLUSIVE EXCELLENCE ON SCIENTIC DISCOVERY AND QUALITY OF RESEARCH CONDUCTED BY FIRST FACULTY COHORTS. IMPLEMENT COMMON DATA ELEMENTS AND A LOGIC MODEL WITH METRICS FOR SHORT, INTERMEDIATE, AND LONG TERM OUTCOMES, INCLUDING BUT NOT LIMITED TO RESEARCH PRODUCTIVITY, AND COLLABORATIVE NETWORKS. SPECIFIC AIM 2. COORDINATE AND FACILITATE THE COLLECTION OF THE MINIMUM SET OF COMMON DATA ELEMENTS FROM FIRST COHORT AWARDEES. APPROACH: ESTABLISH PROCESSES FOR DATA COLLECTION AND CAPTURE, DATA STORAGE, DATA HARMONIZATION, QUALITY CONTROL STANDARDS, DATA CLEANING, DATA MANAGEMENT, DATA VALIDATION AND DATA ANALYSES WITH PARTICULAR ATTENTION PAID TO REPLICATION AND DATA PRIVACY. SPECIFIC AIM 3. COORDINATE THE DISSEMINATION AND COMMUNICATION OF BEST PRACTICES IN INCLUSIVE EXCELLENCE (IE) AMONG FIRST COHORT INSTITUTIONS. APPROACH: COORDINATE AND FACILITATE COMMUNICATION AMONG FIRST COHORT AWARDEE INSTITUTIONS THROUGH REGULAR MEETINGS, COMMITTEES, AND WORKGROUPS AS NEEDED. DISSEMINATE SUCCESSFUL EVIDENCE-BASED PRACTICES, AND LESSONS LEARNED FOR TRANSFORMING INSTITUTIONS ACROSS FIRST COHORT SITES. ESTABLISH TWO PRESTIGIOUS ANNUAL AWARDS: THE LOUIS W. SULLIVAN AWARD TAND THE DONALD E. WILSON AWARD FOR INCLUSIVE EXCELLENCE.

STATEWIDE NETWORK AMONG PARTNERS FOR PARENTS/CAREGIVERS (SNAPP)

RENEWAL APPLICATION FOR CLINICAL RESEARCH EDUCATION AND CAREER DEVELOPMENT (CRECD

OMH 2006 DIRECTED UMBRELLA COOPERATIVE AGREEMENT

HEALTH PROMOTION & DISEASE PREVENTION RESEARCH CENTER

HEALTH PROMOTION AND DISEASE PREVENTION RESEARCH CENTER

THE MOREHOUSE SCHOOL OF MEDICINE'S INSTITUTE OF GENOMIC MEDICINE CENTER FOR GENOMIC DIVERSITY - ABSTRACT – OVERALL THIS PROPOSAL OUTLINES A PROGRAM TO ESTABLISH A CENTER OF GENOMIC DIVERSITY AT THE MOREHOUSE SCHOOL OF MEDICINE (MSM). LED BY THE DIRECTOR OF THE INSTITUTE OF TRANSLATIONAL GENOMIC MEDICINE (ITGM), THE PROGRAM AIMS TO ENHANCE GENOMICS RESEARCH CAPACITY, IMPROVE MINORITY HEALTH OUTCOMES, AND ADVANCE WORKFORCE EDUCATION. THE PROGRAM FOCUSES ON ELUCIDATING NOVEL GENOMIC KNOWLEDGE IN RACIALLY AND ANCESTRALLY DIVERSE COHORTS AND INVESTIGATING THE INTERPLAY OF SOCIAL AND BIOLOGICAL DETERMINANTS OF HEALTH. THROUGH MULTIPLE PROJECTS LED BY ESTEEMED FACULTY MEMBERS, THE PROGRAM AIMS TO UNCOVER EPIGENETIC CHANGES RELATED TO STRESS AND EXAMINE THE UTILITY OF A DIVERSE REFERENCE “PAN”GENOME IN GENE EXPRESSION PROFILING. THE PROGRAM INCLUDES THE COMMUNITY ENGAGEMENT CORE, GENOMICS WORKFORCE DIVERSITY CORE, AND ADMINISTRATIVE CORE TO FACILITATE COMMUNITY EDUCATION, TRAINING, AND DATA INFRASTRUCTURE. OVERALL, THE PROGRAM AIMS TO ESTABLISH A SUSTAINABLE GENOMICS RESEARCH ENVIRONMENT, IMPROVE GENOMIC TOOLS FOR MINORITY HEALTH RESEARCH, AND ENHANCE EDUCATION AND DISSEMINATION EFFORTS.

CENTER TO ADVANCE REPRODUCTIVE JUSTICE AND BEHAVIORAL HEALTH AMONG BLACK PREGNANT/POSTPARTUM WOMEN AND BIRTHING PEOPLE (CORAL). - ABSTRACT PREGNANT AND POSTPARTUM WOMEN WHO ARE BLACK LIVE AT THE INTERSECTION OF THREE OF THE GRAVEST PUBLIC HEALTH THREATS CONFRONTING THE 21ST CENTURY US: (1) THE MATERNAL MORBIDITY AND MORTALITY EPIDEMIC; (2) THE BEHAVIORAL HEALTH CRISIS; AND (3) INTERSECTIONAL DISCRIMINATION. IN A NATION WITH THE HIGHEST MATERNAL MORTALITY RATE OF ALL HIGH-INCOME COUNTRIES, BLACK WOMEN ARE THREE TIMES MORE LIKELY TO DIE WHILE PREGNANT OR POSTPARTUM THAN THEIR WHITE COUNTERPARTS. MATERNAL BEHAVIORAL HEALTH CONDITIONS – SUCH AS ANXIETY, PERINATAL AND POSTPARTUM DEPRESSION, AND BIRTH-RELATED PTSD – ARE THE MOST COMMON COMPLICATIONS OF PREGNANCY AND CHILDBIRTH, AFFECTING 1 IN 5 WOMEN, AND DISPROPORTIONATELY AFFLICT BLACK WOMEN. OVERDOSES, SUBSTANCE USE DISORDERS, AND RELATED HARMS ARE SURGING AMONG BLACK WOMEN. ACCORDING TO MATERNAL MORTALITY REVIEW COMMITTEES (MMRCS), BEHAVIORAL HEALTH CONDITIONS ARE ONE OF THE LEADING CAUSES OF MATERNAL DEATHS AND ARE THE LEADING PREVENTABLE CAUSE OF MATERNAL DEATHS. DESPITE THEIR SIZE AND IMPACT, THE US IS ILL PREPARED TO MOBILIZE TO ADDRESS THESE CRISES BECAUSE OF LONGSTANDING LEGACIES OF INTERSECTIONAL DISCRIMINATION WHEREBY BEHAVIORAL HEALTH PROBLEMS ARE NEGLECTED WITHIN THE FIELD OF MATERNAL HEALTH AND THE FIELD OF BEHAVIORAL HEALTH NEGLECTS MATERNAL HEALTH. BLACK WOMEN IN PARTICULAR HAVE SUFFERED: HISTORICALLY AND PRESENTLY, APPROACHES TO ADDRESS BLACK MATERNAL MORTALITY AND BEHAVIORAL HEALTH HAVE SYSTEMATICALLY FAILED TO ENGAGE COMMUNITIES WITH LIVED EXPERIENCE. LED BY A PARTNERSHIP OF MOREHOUSE SCHOOL OF MEDICINE, EMORY, AND A ROBUST NETWORK OF COMMUNITY-BASED ORGANIZATIONS, AND GUIDED BY PRINCIPLES OF REPRODUCTIVE JUSTICE, RESEARCH JUSTICE, AND THE NIMHHD MENTAL HEALTH FRAMEWORK, THE CENTER TO ADVANCE REPRODUCTIVE JUSTICE AND BEHAVIORAL HEALTH AMONG BLACK PREGNANT/POSTPARTUM WOMEN (CORAL) WILL GENERATE ACTIONABLE EVIDENCE ABOUT THE MULTILAYERED DETERMINANTS OF MATERNAL BEHAVIORAL HEALTH CONDITIONS IN CLOSE AND EQUITABLE PARTNERSHIPS WITH BLACK WOMEN, AND THE COMMUNITY-BASED ORGANIZATIONS THAT SERVE THEM, WITH THE GOAL OF ENDING THE MATERNAL BEHAVIORAL HEALTH CRISIS IN GEORGIA AND BEYOND. GEORGIA IS AN ESSENTIAL SITE FOR THIS WORK AS IT HAS AMONG THE HIGHEST PREGNANCY-RELATED MORTALITY RATIOS IN THE US, AND BLACK WOMEN EXPERIENCE A RATE THAT IS 2.3 TIMES THAT OF WHITE WOMEN. THE STATE MMRC HAS FOUND THAT BEHAVIORAL HEALTH CONDITIONS ARE A LEADING – AND GROWING – CAUSE OF MATERNAL DEATH. LEVERAGING AN OUTSTANDING INFRASTRUCTURE SPANNING 2 MAJOR UNIVERSITIES AND A STRONG NETWORK OF COMMUNITY ORGANIZATIONS, CORAL WILL MOBILIZE ACADEMIC AND COMMUNITY PARTNERS TO SUPPORT BLACK MATERNAL BEHAVIORAL HEALTH BY DEVELOPING AND SUSTAINING A ROBUST TRANSDISCIPLINARY COMMUNITY-DRIVE RESEARCH INFRASTRUCTURE; CONDUCTING RIGOROUS, ETHICAL TRANSDISCIPLINARY RESEARCH IN PARTNERSHIP WITH COMMUNITIES; BUILDING THE CAPACITY OF THE NEXT GENERATION OF INVESTIGATORS; AND COLLABORATING WITH ACADEMIC, GOVERNMENTAL, AND COMMUNITY TO DISSEMINATE AND TRANSLATE DISCOVERIES.

TAKING TIME FOR TEENS PROGRAM

PROJECT PURPOSE:THE MOREHOUSE SCHOOL OF MEDICINE (MSM) ASPIRES TO ADVANCE HEALTH EQUITY AND IMPROVING HEALTH OUTCOMES THROUGH DIGITAL HEALTH EQUITY, INCLUDING INCREASING ACCESS TO HEALTH AND HEALTH-RELATED CAREERS PREDICATED ON DIGITAL LITERACY TRAINING AND DIGITAL SKILLS DEVELOPMENT. TO ACCOMPLISH THIS GOAL, THE MSM "FROM SURVIVOR TO INNOVATOR: DIGITAL HEALTH EQUITY AND COMMUNITY IMPACT" PROJECT WILL EXPAND STUDENT ACCESS TO BASIC TECHNOLOGY AND BROADBAND, IMPROVE TELEHEALTH ACCESS IN MSM'S ANCHOR COMMUNITY, EXPAND SCIENCE AND HEALTH CAREERS EXPLORATION WITH ITS EDUCATIONAL PARTNERS, AND IMPROVE MSM FACULTY'S ABILITY TO INTEGRATE TECHNOLOGY INTO THE TEACHING AND LEARNING PROCESS. MSM HOPES TO UNDERSTAND THE IMPACT OF INCREASING TECHNOLOGICAL ACCESS AND LITERACY WILL HAVE ON DIGITAL HEALTH EQUITY.ACTIVITIES:MSM WILL INCREASE TECHNOLOGICAL ACCESS AND LITERACY, AND THUS DIGITAL HEALTH EQUITY, IN THE ANCHOR COMMUNITIES WITH FOUR PRIMARY INITIATIVES. THE UNDERGRADUATE HEALTH SCIENCES ACADEMY (UHSA) CONNECTS: THE COMMUNITY BROADBAND INITIATIVE WILL EXPAND THE HEALTH CAREERS PIPELINE FOR LEARNERS IN GRADES K-8 AND COLLEGE. THIS PROJECT WILL PROVIDE TECHNOLOGY, EQUIPMENT, AND ACCESS FOR STUDENTS IN K-8TH GRADES AND UNDERGRADUATE PROGRAMS FROM ATLANTA COMMUNITIES IMPACTED BY LIMITED INVESTMENTS IN BROADBAND INTERNET CONNECTIVITY. MSM'S CURRENT UHSA PREPARES UNDERGRADUATE STUDENTS TO COMPETE AND SUCCESSFULLY MATRICULATE INTO MEDICAL SCHOOL AND OTHER PROFESSIONAL HEALTH CAREERS. THE MSM DIGITAL IMPACT INITIATIVE WILL MITIGATE INEQUITIES FOR STUDENTS AT THE HIGH SCHOOL LEVEL BY PARTNERING WITH SOUTH ATLANTA HIGH SCHOOL TO EXPAND BROADBAND CAPABILITIES AND TECH ACCESS, AND PROVIDE TEACHER AND STUDENT TECH TRAINING. THESE RESOURCES WILL ALLOW MSM TO EXPAND OPPORTUNITIES FOR ADDITIONAL STUDENTS IN ITS EXISTING STEAM AND HCOP PROGRAMS USING TECHNOLOGIES OUTLINED IN THIS PROPOSAL. THE DIGITAL HEALTH EDUCATOR INITIATIVE IS AN MSM FACULTY DEVELOPMENT ENHANCEMENT EFFORT TO INCLUDE TECHNOLOGY INTEGRATION INTO MSM CURRICULUM DEVELOPMENT, AND INSTRUCTIONAL DESIGN TO IMPROVE TEACHING AND LEARNING DELIVERY. PROCESSES WILL UTILIZE ONLINE TRAINING, TECHNOLOGY COACHING, SEMINARS, EXTERNAL COACHING, AND PEER COACHING. THE MSM HEALTH EQUITY FOR ALL LIVES (HEAL) INITIATIVE WILL EXPAND EXISTING STUDENT-RUN CLINICS VIA TELEHEALTH TECHNOLOGIES WHICH CONTRIBUTE TO THE HEALTH EQUITY OF THE UNDERSERVED AND UNINSURED POPULATIONS BY PROVIDING MEDICAL AND SCREENING SERVICES TO LOCAL POPULATIONS IN ANCHOR COMMUNITIES.OUTCOMES:THE "FROM SURVIVOR TO INNOVATOR: DIGITAL HEALTH EQUITY AND COMMUNITY IMPACT" PROJECT WILL ACHIEVE EXPANDED STUDENT ACCESS TO TECHNOLOGY AND PROGRAMMING TO ENCOURAGE MORE STUDENTS TO SEEK HEALTH CAREERS AND IMPROVE HEALTH OUTCOMES FOR THOSE IN MSM'S MOST AT-RISK COMMUNITIES. THE UHSA CONNECTS COMMUNITY BROADBAND INITIATIVE WILL RESULT IN INCREASED DIGITAL LITERACY SKILLS AND INCREASED AWARENESS AROUND HEALTH EQUITY AND THE SOCIAL DETERMINANTS OF HEALTH IN THE ANCHOR COMMUNITY. THE MSM DIGITAL IMPACT INITIATIVE WILL PROVIDE IMPROVED BROADBAND SPEEDS, A DIGITAL HEALTH EQUITY CURRICULUM, COMPUTER LABS EQUIPPED WITH DISTANCE LEARNING TECHNOLOGY, AND IMPROVED COLLEGE AND CAREER READINESS AT AN ANCHOR COMMUNITY HIGH SCHOOL. THE DIGITAL HEALTH EDUCATOR INITIATIVE WILL DEVELOP AND IMPLEMENT A SCALABLE FACULTY DEVELOPMENT CURRICULUM TO IMPROVE MSM FACULTY'S COMPETENCIES IN DIGITAL TEACHING TO MEET THE NEED FOR DIGITAL HEALTH EDUCATORS AS TECHNOLOGY PLAYS AN INCREASINGLY IMPORTANT ROLE. THE MSM HEAL INITIATIVE WILL ENABLE PHYSICIANS TO REACH MORE PATIENTS USING TELEMEDICINE TECHNOLOGY.BENEFICIARIES:THIS PROJECT WILL BENEFIT MOREHOUSE SCHOOL OF MEDICINE STUDENTS AND FACULTY AS WELL AS K-12TH GRADE STUDENTS, RESIDENTS, AND PATIENTS AT STUDENT-RUN CLINICS IN THE MSM ANCHOR COMMUNITY IN ATLANTA, GA. SUBRECIPIENT ACTIVITIES (IF APPLICABLE) THE RECIPIENT DOES NOT INTEND TO SUBAWARD FUNDS.

MOREHOUSE SCHOOL OF MEDICINE PREVENTION RESEARCH CENTER: ADVANCING HEALTH EQUITY THROUGH COMMUNITY-LED APPLIED PUBLIC HEALTH PREVENTION RESEARCH AND TRANSLATION

REGIONAL FOCUS AREA ADDICTION TECHNOLOGY TRANSFER CENTER (ATTC)

A RANDOMIZED CONTROLLED STUDY TO TEST THE EFFECTIVENESS OF DEVELOPMENTAL NETWORK COACHING IN THE CAREER ADVANCEMENT OF DIVERSE EARLY STAGE INVESTIGATORS

ADDRESSING THE BIOLOGY OF HEALTH DISPARITIES BY TARGETING GEOGRAPHICAL ANCESTRY-DRIVEN VARIANTS OF IMMUNITY - AMONG ETHNIC GROUPS IN THE US, AFRICAN AMERICANS CONTINUE TO DISPLAY THE LOWEST LIFE EXPECTANCY AND HIGHEST OVERALL RATES OF CANCER DEATHS (INCLUDING COLORECTAL, BREAST AND PROSTATE CANCERS), INFANT MORTALITY, ASTHMA, AND CARDIOMETABOLIC DISEASES (INCLUDING HEART DISEASE, HYPERTENSION AND OBESITY). COMPLEX DISEASES AND ENVIRONMENTAL INSULTS ALL INVOKE AND/OR SUBVERT HOST INFLAMMATION, WITH INDIVIDUAL IMMUNE AND VARIABLE RESPONSES TO THERAPEUTIC AGENTS BEING DICTATED IN PART BY GENETIC VARIANTS. PRECISION DIAGNOSES AND PROGNOSES OF INDIVIDUAL PATIENT RESPONSES RELY ON ASSESSING KNOWN DISEASE AND IMMUNE MARKERS BEFORE, DURING AND/OR AFTER TREATMENT. THIS PROPOSAL WILL INTERROGATE THE FUNCTIONAL EFFECTS AND DRUGGABLITY OF UNDER- STUDIED GENE VARIANTS RELATED TO IMMUNE AND DRUG RESPONSE WITHIN THE GENOME OF INDIVIDUALS OF AFRICAN ANCESTRY (AAS). IMMUNE GENE VARIANTS MOST COMMON AMONG AAS AND PREDICTED TO BE DRUGGABLE WILL BE ENGINEERED INTO CELLS LINES OF DIFFERENT GEOGRAPHICAL ANCESTRY AND EVALUATED FOR FUNCTIONAL EFFECTS IN VITRO AND/OR IN VIVO AND MODELED IN SILICO TO PREDICT STRUCTURAL CHANGES TO THE WILD TYPE PROTEINS AND POSSIBLE VARIANT-DRUG INTERACTIONS. NOVEL ASSAYS TO SCREEN FOR COMPOUNDS WITH THERAPEUTIC POTENTIAL WILL BE DEVELOPED AND USED FOR SCREENING. LEAD COMPOUND CANDIDATES WILL THEN BE VALIDATED, OPTIMIZED AND TESTED IN VITRO AND/OR IN VIVO. THIS PROJECT HAS THE POTENTIAL TO 1) ESTABLISH ANCESTRY-RELATED HOST IMMUNITY AS A CONTRIBUTING BIOLOGICAL PARAMETER OF COMPLEX DISEASE DISPARITIES; 2) FILL IN CRITICAL KNOWLEDGE GAPS BY IDENTIFYING NOVEL PLAYERS AND MECHANISMS OF INFLAMMATION AND THEIR ROLE IN COMPLEX DISEASE; AND, 3) POSSIBLY LEAD TO THE DEVELOPMENT OF EFFECTIVE THERAPIES TO ADDRESS HEALTH DISPARITIES.

ROLES OF PROTEIN DEGRADATION IN THE CIRCADIAN CLOCK

RACIAL AND ETHNIC APPROACHES TO COMMUNITY HEALTH US

PRIMARY CARE TRAINING AND ENHANCEMENT-COMMUNITY PREVENTION AND MATERNAL HEALTH

COMMUNITY HEALTH WORKER TRAINING PROGRAM - THE HEALTH PROMOTION RESOURCE CENTER (HPRC/MSM) AT MOREHOUSE SCHOOL OF MEDICINE PROPOSES TO IMPLEMENT THE MSM – COMMUNITY HEALTH PROFESSIONAL TRAINING (CHPT) PROGRAM. THE CHPT PROGRAM IS A COLLABORATION BETWEEN SEVERAL MSM DEPARTMENTS INCLUDING HPRC, FAMILY MEDICINE AND THE INNOVATION LEARNING LAB, AND THE EXTERNAL PARTNER CLAYTON COUNTY HEALTH DEPARTMENT. THE MSM – CHPT PROGRAM WILL RECRUIT AND TRAIN 120 NEW CHW TRAINEE CANDIDATES IN THE MSM – CHW CURRICULUM TRAINING PROGRAM. THE PROGRAM WILL ALSO TRAIN AND UPSKILL 20 EXISTING CHWS IN THE MSM – CHW CURRICULUM. UPON COMPLETION OF THE CURRICULUM TRAINING, 90 NEW TRAINEES WILL BE PLACED IN FIELD TRAINING PRACTICUM SITES AND 30 NEW TRAINEES WILL BE PLACED IN THE MSM REGISTERED APPRENTICESHIP PROGRAM. THE TRAINING PROGRAM WILL PROVIDE COACHING, MENTORING, AND OTHER TRAINING SUPPORT TO ENSURE A HIGH COMPLETION AND GRADUATION RATE. THE EVALUATION WILL COLLECT HRSA PERFORMANCE MEASURES, PROCESS, AND OUTCOME DATA TO DETERMINE WHETHER THE PROGRAM ACHIEVED THE GOALS AND OBJECTIVES. THE EVALUATION WILL ALSO DETERMINE THE INTENDED AND UNINTENDED OUTCOMES OF THE PROGRAM FOR TRAINEES, PRACTICUM TRAINING SITES AND PATIENTS SERVED BY TRAINEES. THE GOALS ARE TO 1. EXPAND PUBLIC HEALTH WORKFORCE BY TRAINING NEW AND EXISTING CHWS AND HEALTH SUPPORT WORKERS WITH SPECIALIZED TRAINING AND FINANCIAL SUPPORT TO OFFSET EXPENSES THAT WOULD IMPEDE SUCCESS IN TRAINING; AND 75% OF PARTICIPANTS WILL BECOME NEWLY CREDENTIALED CHWS AND HEALTH SUPPORT WORKERS. 2. EXTEND AND UPSKILL THE PUBLIC HEALTH WORKFORCE BY DEVELOPING OR ENHANCING EXISTING CURRICULA TO INCREASE THE SKILLS AND COMPETENCIES OF EXISTING CHWS AND HEALTH SUPPORT WORKERS. 3. INCREASE CHW AND HSW EMPLOYMENT READINESS THROUGH FIELD PLACEMENTS AND APPRENTICESHIPS DEVELOPED IN COLLABORATION WITH A NETWORK OF PARTNERS THAT WILL ENABLE TRAINEES TO RESPOND TO AND SUPPORT ESSENTIAL PUBLIC HEALTH SERVICES AND PROVIDE THEM WITH EMPLOYMENT OPPORTUNITIES. 4. ADVANCE HEALTH EQUITY AND SUPPORT FOR UNDERSERVED COMMUNITIES BY INCREASING THE NUMBER OF CHWS AND HSWS THAT ARE EMPLOYED AS INTEGRAL MEMBERS OF INTEGRATED CARE TEAMS THAT THEIR EXPANDED SKILLS TO REDUCE HEALTH DISPARITIES.

THE DARC SIDE OF BREAST CANCER DISPARITIES - AFRICAN ANCESTRY AND CANCER- RELATED IMMUNE RESPONSE - PROJECT SUMMARY (TECH ABS) EVEN WITH THE TYPICAL DELAYS IN DIAGNOSIS, MORE ADVANCED STAGE DISTRIBUTION AT DIAGNOSIS, AND INADEQUATE MULTIDISCIPLINARY BREAST CANCER TREATMENT, THESE COMBINED FACTORS DO NOT COMPLETELY EXPLAIN DISPARITIES IN BREAST CANCER MORTALITY OUTCOMES, WHICH PERSIST AFTER CONTROLLING FOR STAGE AT DIAGNOSIS – AND HAVE BEEN SO FOR THE PAST 50 YEARS. THE APPROXIMATELY TWO-FOLD INCREASED RISK OF TNBC IN AA WOMEN HAS BEEN CONFIRMED BY POPULATION-BASED INCIDENCE RATES REGIONALLY AS WELL AS NATIONALLY AND ACROSS ALL AGE INTERVALS. COMPARED TO NON-TNBC, TRIPLE NEGATIVE DISEASE HAS BEEN CONFIRMED TO BE AN ADVERSE PROGNOSTIC FEATURE IN AA PATIENTS, DRIVING SOME OF THE MORTALITY DISPARITIES. WE HYPOTHESIZE THAT ALTERED MECHANISMS OF TUMOR IMMUNE RESPONSES, WHICH UNDERLIES TNBC TUMOR BIOLOGY DIFFERENCES BETWEEN SRR, ARE CAUSED BY POPULATION-PRIVATE GENETIC VARIANTS AMONG INDIVIDUALS WITH SHARED WEST AFRICAN ANCESTRY. THESE EVOLUTIONARILY SELECTED VARIANTS ALTER IMMUNE CELL BEHAVIOR AND INFLAMMATORY MECHANISMS, LEADING TO NOVEL TUMOR-IMMUNE CELL TYPES AND SIGNIFICANT DIFFERENCES IN LEUKOCYTE INFILTRATION PATTERNS, WHICH MAY BE ASSOCIATED WITH POOR OUTCOMES. WE WILL PERFORM AN INNOVATIVE MULTIOMICS INVESTIGATION OF AFRICAN-SPECIFIC GENE EXPRESSION IN TNBC, LINKED TO IMMUNOLOGICAL TUMOR PHENOTYPES. WE WILL HARNESS THE NOVELTY OF RARELY-INVESTIGATED BREAST CANCER PATIENT POPULATIONS FROM DIVERSE AFRICAN REGIONS WITH TNBC CASES FROM G ADMIXED POPULATIONS (I.E. AFRICAN-AMERICAN AND AFRO-CARIBBEAN). THE MOST IMPACTFUL INNOVATION OF THIS STUDY IS THE CHARACTERIZATION OF DIFFERENTIAL GENE EXPRESSION, COUPLED WITH INTEGRATED PROTEOMICS DATA, TO IDENTIFY NOVEL TUMOR PHENOTYPES THAT ARE SHARED AMONG WOMEN OF THE AFRICAN DIASPORA. THIS WORK WILL BE TRANSFORMATIVE TO OUR UNDERSTANDING OF TUMOR HETEROGENEITY AND BIOLOGICAL DIVERSITY ACROSS PATIENT GROUPS. WE PROPOSE THE FOLLOW AIMS: 1- DETERMINE THE ANCESTRY- ASSOCIATED DIFFERENTIAL GENE EXPRESSION PROFILES OF IMMUNE AND INFLAMMATORY-RELATED GENES IN PRIMARY TUMORS ACROSS AN AFRICAN-ENRICHED COHORT OF 400 CLINICALLY ANNOTATED TNBC CASES, TO IMMUNE PROFILES LINKED TO SHARED WEST AFRICAN GENETIC ANCESTRY. 2- CHARACTERIZE ANCESTRY-ASSOCIATED DIFFERENCES IN PATHOLOGICAL TUMOR IMMUNE RESPONSE CHARACTERISTICS, INCLUDING DIFFERENCES IN TUMOR INFLAMMATION AND/OR TUMOR INFILTRATION OF SPECIFIC IMMUNE CELL TYPES. 3-CREATE AN AFRICAN-ENRICHED PANEL OF EX VIVO MODELS TO VALIDATE/INVESTIGATE THE ANCESTRY-ASSOCIATED DRIVERS OF ALTERED GENETIC PATHWAYS AND IMMUNE RESPONSES. BY COMPLETING THESE AIMS WE EXPECT TO YIELD AN AFRICAN-ENRICHED SET OF POPULATION-PRIVATE, VALIDATED EQTLS, ASSOCIATED WITH TNBC IMMUNE RESPONSE MECHANISMS THAT CAN BE FURTHER INTERROGATED BY OUR AUTHENTICATED EX VIVO MODELS.

RENEWAL APPLICATION FOR CLINICAL RESEARCH EDUCATION AND CAREER DEVELOPMENT (CRECD

CENTER OF EXCELLENCE FOR BLACK/ AFRICAN AMERICAN BEHAVIORAL HEALTH DISPARITIES

BLOOD TRANSCRIPTOMICS AS CT ADJUVANT TO EXCLUDE HEMORRHAGE IN ACUTE STROKE

ARRA - CENTERS FOR EXCELLENCE

MOREHOUSE SCHOOL OF MEDICINE RACIAL AND ETHNIC APPROACHES TO COMMUNITY HEAKTH

HEALTH CAREERS OPPORTUNITY PROGRAM

MOREHOUSE SCHOOL OF MEDICINE (M-MIDARP)

TRANSLATING GENOMIC PROFILING TO BEDSIDE PRECISION MEDICINE - ABSTRACT. THIS PROGRAM WILL ESTABLISH A NEW CENTER FOR EXCELLENCE IN GENOMICS AT MOREHOUSE SCHOOL OF MEDICINE, ENABLING A COMPREHENSIVE GENOMICS INITIATIVE TO BE ESTABLISHED AT A HBCU FOCUSED ON INCREASING THE REPRESENTATION OF UNDER-REPRESENTED MINORITY STUDENTS (URM) STUDENTS IN GENOMICS RESEARCH TRAINING, ENHANCING RETRAINING OF FACULTY AND WHOSE FOCUS IS THE REDUCTION OF HEALTH DISPARITIES IN MINORITY POPULATIONS. WE PROPOSE THIS CEGS PROGRAM IN COLLABORATION WITH OUR PARTNERS AT EMORY UNIVERSITY, GEORGIA INSTITUTE OF TECHNOLOGY, CHILDREN’S HEALTH CARE OF ATLANTA, AND THE OAK RIDGE NATIONAL LABORATORIES. WE FOCUS THE RESEARCH ON THE APPLICATION OF GENOMIC TECHNOLOGIES TO POINT OF CARE UTILITY, WITH A SPECIFIC FOCUS ON THE IMPACT OF RACE, SEX, AND AGE ON TESTING ACCURACY. THE PROGRAM WILL SPUR THE DEVELOPMENT OF EDUCATION AND TRAINING OPPORTUNITIES FOR URM STUDENTS WITHING THE ATLANTA UNIVERSITY CENTER, (4 HBCUS IN ATLANTA) AND THEREFORE ENHANCE THE TRAINING AND RETRAINING OF GENOMIC RESEARCHERS FROM URMS. THE CENTRAL PREMISE OF THE RESEARCH COMPONENT OF THIS CENTER IS THAT BLOOD TRANSCRIPTOME ANALYSIS MAY OFFER AN INNOVATIVE APPROACH TO DIAGNOSE DISEASE OR INJURY FOR MANY CLINICAL CONDITIONS. THE GAL OF THIS STUDY IS TO PUSH THIS TECHNOLOGY APPROACH CLOSER TO CLINICAL PRACTICE BY UNDERSTANDING KEY ELEMENTS OF THE APPROACH AND TO LEARN GENERALIZABLE RULES FOR IMPLEMENTATION. TO DO THIS WE USE THREE INTERLINKED STUDIES ON HEALTHY, ACUTE BRAIN INJURY AND LONG-TERM CARDIOVASCULAR DISEASE, TO TEST REPRODUCIBILITY, AND PREDICTION ACCURACY. WE UTILIZE ESTABLISHED RESEARCH PROGRAMS TO ENABLE A RAPID TESTING OF THE APPROACHES, AND THE COMPUTATIONAL EXPERTISE OF THE OAK RIDGE NATIONAL LABORATORIES TO HARNESS AI MATHEMATIC MODELING TO ENHANCE PREDICTION ACCURACY. AT THE END OF THE RESEARCH PROGRAM, WE WILL HAVE ESTABLISHED A SERIES OF BEST PRACTICES FOR DISSEMINATION AND FUTURE USE OF THE APPROACH. THE SPECIFIC RESEARCH AIMS ARE 1). WHAT IS THE VARIANCE OF GENE EXPRESSION IN BLOOD? 2). DETERMINE THE ACCURACY OF BLOOD RNA EXPRESSION PROFILE TO PREDICT THE CLINICAL DIAGNOSIS OF AN ACUTE MEDICAL EVENT? 3). CAN A BLOOD RNA EXPRESSION SIGNATURE IDENTIFY A PATIENT’S OUTCOME OR DISEASE TRAJECTORY (PROGNOSIS)? IS RNA EXPRESSION’S EFFECT ON PATIENT’S OUTCOME OR DISEASE TRAJECTORY (PROGNOSIS) ASSOCIATED WITH, INDEPENDENT OF, OR MODIFIED BY SOCIAL DETERMINANTS OF HEALTH (SDH). TO ORGANIZE THE EFFICIENT PERFORMANCE OF THE PROGRAM, WE ESTABLISH A RESEARCH MANAGEMENT STRUCTURE TO ENABLE CONTINUOUS ASSESSMENT WITH KEY GO/NO GO DECISIONS. TO TRANSLATE THIS RESEARCH INTO ENHANCED EDUCATION OPPORTUNITIES AND RETRAINING, WE PROPOSE AN EDUCATION CORE THAT WILL FOCUS ON ADAPTING AN ESTABLISHED MASTERS OF CLINICAL RESEARCH COURSE, DEVELOPING NEW TRAINING MODULES FOR STUDENTS AND STAFF IN COMPUTATIONAL SKILLS AND BIOINFORMATICS, A SMALL GRANT PROGRAM TO ENHANCE INVESTIGATOR DEVELOPMENT. OUR FINAL GOAL IS TO START TO DEVELOP A PIPELINE FROM UNDERGRADUATE COLLEGES TO ENHANCE BIOINFORMATICS AND GENOMICS TRAINING AND RESEARCH OPPORTUNITIES TO HELP DIVERSIFY THE CURRENT GENOMICS WORKPLACE.

THE IMPACT OF TRANSGENERATIONAL RACIAL TRAUMA ON EPIGENETIC MODIFICATIONS IN THE MOTHER-INFANT DYAD DURING PREGNANCY. COMPARISONS BETWEEN CAUCASIAN AND AFRICAN AMERICAN POPULATIONS - PROJECT SUMMARY STRUCTURAL RACISM AND DISCRIMINATION (SRD) HAVE REMAINED A HISTORICAL LEGACY OF THE U.S. FROM THE BEGINNING OF ENSLAVEMENT OF AFRICAN POPULATIONS IN 1619 TO THE ERA OF APARTHEID (“JIM CROW”), WHICH ENDED WITH THE CIVIL AND VOTING RIGHTS ACTS. HIDDEN IN PLAIN SIGHT IS THE BIOLOGICAL IMPACT OF RACIAL TRAUMA. THERE IS AN INCREASING AWARENESS THAT SRD IS A SALIENT MECHANISM PERPETUATING RACIAL GAPS IN HEALTH AMONG AFRICAN AMERICANS. IN PARTICULAR, STUDIES HAVE DOCUMENTED THE IMPACT OF SRD ON NEGATIVE PREGNANCY OUTCOMES, INCLUDING HIGHER RATES OF PRETERM BIRTH AMONG AFRICAN AMERICAN (AA) WOMEN AND HIGHER RATES OF MORTALITY AMONG BLACK MOTHERS AND INFANTS. THESE RACIAL DISPARITIES IN MATERNAL AND INFANT HEALTH ARE PERVASIVE EVEN AFTER ACCOUNTING FOR SOCIO- ECONOMIC STATUS AND EDUCATION; AND HAVE BEEN SHOWN TO PERSIST TRANSGENERATIONALLY, POSSIBLY VIA EPIGENETIC INFLUENCES. IN THIS STUDY, WE SEEK TO INVESTIGATE THE IMPACT OF RACE AND TRANSGENERATIONAL SRD-RELATED TRAUMA AMONG AA WOMEN ON DISTINCT EPIGENETIC MODIFICATIONS AT THE MATERNAL-FETAL INTERFACE THAT ARE LINKED TO ALTERED IMMUNE CELL DEVELOPMENT, ACTIVATION, AND SIGNALING IN THE PLACENTA AND DEVELOPING FETUS. STUDIES SUGGEST THAT THE PLACENTA MAY BE THE GATEWAY OF MATERNAL TRANSGENERATIONAL EPIGENETIC INHERITANCE. MOUNTING EVIDENCE SUGGESTS THE EFFECTS OF IN UTERO EPIGENETIC CHANGES GO BEYOND INFLUENCING THE MOTHER AND THE CHILD, AND ARE CARRIED FORWARD THROUGH ADULTHOOD INTO GERMLINE, TO THE DETRIMENT OF SUCCESSIVE GENERATIONS. PERTURBED PLACENTAL EPIGENETICS IS ASSOCIATED WITH INTRAUTERINE GROWTH RESTRICTION, PRETERM BIRTH, AND PRE-ECLAMPSIA, WHICH ARE THE DRIVERS OF INFANT MORTALITY AMONG AA. STUDIES DEMONSTRATE RACE IS ASSOCIATED WITH PLACENTAL INFLAMMATORY PATHOLOGY. IN ADDITION, HIGH RATES OF STRESS DUE TO TRANSGENERATIONAL TRAUMA HAVE BEEN ASSOCIATED WITH CHRONIC INFLAMMATION AT THE PLACENTA AND POOR PREGNANCY OUTCOMES. HOWEVER, THE BIOLOGICAL PROPERTIES THAT SHAPE DISPARITIES IN PREGNANCY OUTCOMES REMAIN UNKNOWN. WE HYPOTHESIZE THAT SRD-RELATED TRAUMA IS TRANSMITTED ACROSS GENERATIONS AND MANIFESTS WITH EPIGENETIC INHERITANCE PATTERNS THAT PROMOTE INFLAMMATION AND INNATE IMMUNE DYSFUNCTION IN THE PLACENTA AND FETUS. THREE SPECIFIC AIMS HAVE BEEN PROPOSED: 1) EVALUATE THE BURDEN OF SRD ON MATERNAL STRESS, SYSTEMIC INFLAMMATION, AND EPIGENETIC SIGNATURES AMONG AA PREGNANT WOMEN; 2) PERFORM COMPARATIVE TRANSCRIPTIONAL, EPIGENETIC, AND IMMUNOLOGICAL PROFILING OF PLACENTAE FROM AA AND CA PREGNANT WOMEN TO IDENTIFY SPECIFIC ALTERATIONS ASSOCIATED WITH SRD-RELATED STRESS; AND 3) INVESTIGATE IN UTERO PROGRAMMING OF IMMUNE RESPONSES AND THE INHERITANCE OF SPECIFIC EPIGENETIC SIGNATURES IN AA NEONATES EXPOSED TO MATERNAL SRD-RELATED STRESS. THE BIOLOGICAL IMPACT OF SRD ON EPIGENETIC ALTERATIONS AT THE PLACENTA MAY CONTRIBUTE TO INCREASED VULNERABILITY TOWARDS PRETERM BIRTH AND ADVERSE OUTCOMES IN INFANCY AND CHILDHOOD. THESE STUDIES MAY INFORM FUTURE INTERVENTIONS TO ADDRESS SUCH HEALTH RISKS AND CAN PROMOTE THE HEALTH AND WELL- BEING OF AT-RISK MOTHER-INFANT PAIRS.

CELL JUNCTIONS AND CELL MEMBRANES IN THE LENS

NATIONAL BLACK LEADERSHIP INITIATIVE ON CANCER III

SOUTHEAST ADDICTION TECHNOLOGY TRANSFER CENTER (SATTC)

THE INTERPLAY OF SOCIAL AND MOLECULAR DETERMINANTS IN LUNG CANCER DISPARITY - ABSTRACT AFRICAN AMERICANS (AAS) ARE DISPROPORTIONALLY AFFECTED BY LUNG CANCER, COMPARED WITH ALL OTHER RACIAL AND ETHNIC GROUPS IN TERMS OF INCIDENCE AND SURVIVAL. DISPROPORTIONATE DIAGNOSIS OF AGGRESSIVE DISEASE AND POOR SURVIVAL AMONG AAS HIGHLIGHTS THE CRITICAL NEED FOR FURTHER STUDIES THAT CHARACTERIZE RACIAL DIFFERENCES IN LUNG CANCER. OUR GOAL IS TO ADDRESS THIS VITAL KNOWLEDGE GAP BY IDENTIFYING MOLECULAR, BIOLOGICAL, AND SOCIAL CHARACTERISTICS (NEIGHBORHOOD-LEVEL FACTORS) UNDERLYING THE DISEASE’S AGGRESSIVENESS, THEREBY REDUCING THE DISPARITY BETWEEN AFRICAN AMERICANS (AAS) AND EUROPEAN AMERICANS (EAS). OUR CENTRAL HYPOTHESIS IS THAT CC CHEMOKINE RECEPTOR-6 (CCR6) AND ITS ONLY NATURAL LIGAND CCL20 ADD TO THE RACIAL DIFFERENCE IN MOLECULAR FOOTPRINT AND IMMUNE LANDSCAPE, IMPACTING RACIAL DISPARITY IN LUNG CANCER AGGRESSIVENESS AND PROGNOSIS. IN ADDITION TO THESE BIOLOGICAL FACTORS, SOCIAL FACTORS ASSOCIATED WITH CHRONIC STRESS, WHICH ELEVATED CORTISOL, SHAPE THE IMMUNOLOGICAL LANDSCAPE DIFFERENTLY IN AAS, CONTRIBUTING TO RACIAL DIFFERENCES IN AGGRESSIVENESS AND PROGNOSIS. THERE IS A UNIQUE POSSIBILITY THAT CCR6/CCL20 AND SOCIAL CHARACTERISTICS CONTRIBUTE TO THE DISPARITY IN LUNG CANCER AMONG AAS, WHICH HAS NEVER BEEN EXPLORED. HENCE THE PROPOSED WORK WILL ENHANCE UNDERSTANDING OF CELL BIOLOGICAL TRAITS OF AGGRESSIVE LUNG CANCERS, PARTICULARLY NON-SMALL CELL LUNG CANCER (NSCLC), WHICH ACCOUNTS FOR ~85% OF THE LUNG CANCERS THAT UNDERLIE ETHNIC DISPARITIES IN DISEASE OUTCOMES AND MECHANISMS BY WHICH CELLS ACQUIRE AGGRESSIVE PHENOTYPES. TO ACCOMPLISH THESE GOALS, WE HAVE ASSEMBLED A MULTIDISCIPLINARY RESEARCH TEAM WITH COMPLEMENTARY EXPERTISE IN CANCER IMMUNO-BIOLOGY, ONCOLOGY, PULMONARY CARE, PATHOLOGY, PUBLIC HEALTH/BEHAVIORAL SCIENCE, BIOINFORMATICS, AND BIOSTATISTICS TO INVESTIGATE THE FOLLOWING AIMS: A1. ESTABLISH THE ASSOCIATION OF CCR6-CCL20 AXIS IN NSCLC AGGRESSIVENESS AND THERAPEUTIC RESPONSE AMONG AAS AND EAS; A2. ASCERTAIN THE RACE-SPECIFIC DIFFERENCES IN THE IMMUNOLOGICAL LANDSCAPE CONTRIBUTING TO THE NSCLC DISPARITY AND A 3. DETERMINE THE IMPACT OF SOCIAL STRESS ON THE IMMUNE SIGNATURE AMONG AA AND EA NSCLC PATIENTS. COMPLETION OF THESE AIMS WILL I) INFORM A RAPID, NON-INVASIVE CHEMOKINE BASED DETECTION METHODS WHICH WILL ALLOW CLASSIFYING POTENTIALLY FATAL LUNG CANCERS, II) A METHOD FOR EARLY PATIENT STRATIFICATION SO THAT RISK-ADAPTED CHEMOKINE-BASED THERAPIES CAN BE DESIGNED TO MATCH PATIENT SUBGROUPS WITH DISTINCT CCR6 PROFILES, III) TO OFFER MORE EFFECTIVE TREATMENT APPROACH, IV) A FRAMEWORK FOR IMPROVING THE SUCCESS RATE OF CLINICAL TRIALS INVOLVING INVESTIGATIONAL DRUGS BY ESTABLISHING NEW CRITERIA FOR PATIENT CLASSIFICATION, IMMUNE-BASED STRATEGIES TO REDUCE DISPARITY AND, V) IDENTIFY GEOSPATIAL NEIGHBORHOOD CHARACTERISTICS IMPACTING THE IMMUNE SYSTEM AND OUTCOME IN LUNG CANCER AGGRESSIVENESS AND THERAPEUTIC OUTCOME ON WHICH EVIDENCE-BASED INTERVENTION CAN BE DEVELOPED TO ADDRESS THE DISPARITY IN LUNG CANCER.

G-RISE: EDUCATING AND TRAINING TOMORROW'S BIOMEDICAL WORKFORCE - PROGRAM SUMMARY MOREHOUSE SCHOOL OF MEDICINE’S (MSM) PROPOSES A G-RISE TRAINING AND CAREER DEVELOPMENT PROGRAM WITH THE OBJECTIVE OF ADDRESSING THE DEFICITS OF BIOMEDICAL SCIENTISTS FROM UNDERREPRESENTED COMMUNITIES IN THE BIOMEDICAL RESEARCH WORKFORCE. A RECENT EXTERNAL REVIEW OF MSM’S GRADUATE EDUCATION IN BIOMEDICAL SCIENCES (GEBS) PROGRAM REVEALED THAT WHILE THE PROGRAM’S SUCCESS HAS BEEN SATISFACTORY IN TERMS OF PERSISTENCE IN THE PHD CURRICULUM AND GRADUATION, THERE IS THE CONTINUED NEED FOR TUITION SUPPORT FOR PHD STUDENTS, SKILLS DEVELOPMENT TO INCREASE COMPETITIVENESS, EXPANDING THE POOL OF POTENTIAL MENTORS, AND EXPANDING KNOWLEDGE AND PREPARATION FOR ACADEMIC AND NON-ACADEMIC BIOMEDICAL CAREERS PARTICULARLY IN DATA SCIENCE, BIOINFORMATICS AND GENOMICS. WE PROPOSE TWO SPECIFIC GOALS AND OBJECTIVES OF THE PROPOSED G-RISE PROGRAM. IN GOAL 1, WE WILL SUPPORT PRE-DOCTORAL GRADUATE STUDENTS IN COMPLETING THE PH.D. PROGRAM WITH THE KNOWLEDGE BASE AND SKILL SET THAT WILL MAKE THEM COMPETITIVE FOR THE BIOMEDICAL RESEARCH WORKFORCE. IN GOAL 2, WE WILL LEVERAGE MSM CENTERS AND INSTITUTES, STUDENT LEARNING COMMUNITIES, AND THE OFFICE OF CAREER CONNECTIONS TO ENHANCE THE GRADUATE EXPERIENCE AND PREPARE G-RISE SCHOLARS FOR ACADEMIC AND NON-ACADEMIC BIOMEDICAL CAREERS. THE ANTICIPATED MILESTONES INCLUDE; INCREASED NUMBERS OF ABSTRACTS ACCEPTED FOR PRESENTATION AND INCREASED NUMBERS OF PUBLISHED MANUSCRIPTS; REACH THE OPTIMAL AVERAGE GRADUATION RATE OF 90% FOR G-RISE SCHOLARS WITH AN AVERAGE OF 80% OF THEM ENTERING THE BIOMEDICAL RESEARCH WORKFORCE; EXPANDING THE DATA SCIENCE, BIOINFORMATICS AND GENOMIC CURRICULA; AND INCREASING THE QUALITY AND DIVERSITY OF THE MENTOR POOL AVAILABLE TO G- RISE SCHOLARS AND THE OVERALL GRADUATE PROGRAM. TO ACCOMPLISH THESE MILESTONES, THE G-RISE PROGRAM WILL INCLUDE HANDS-ON, FOCUSED SKILL DEVELOPMENT WORKSHOPS; FELLOWSHIP APPLICATION DEVELOPMENT MINI-CAMPS; AND ACTIVE LEARNING TRAINING FOR INVESTIGATORS. SPONSORED SEMINARS WILL INCLUDE; SEMINARS GIVEN BY SCIENTIFIC LEADERS IN THEIR RESPECTIVE FIELDS; STUDENT-LED SEMINARS TO DEVELOP SCIENTIFIC PRESENTATION SKILLS; AND CAREER DEVELOPMENT SEMINARS. ADDITIONALLY, THE G-RISE PROGRAM STAFF WILL ENHANCE THE ACADEMIC EXPERIENCE OF GRADUATE STUDENTS THROUGH LEARNING COMMUNITIES, CAREER EXPLORATION VIA THE OFFICE OF CAREER CONNECTIONS, AND PROVIDE EXPOSURE TO RAPIDLY DEVELOPING FIELDS SUCH AS DATA SCIENCE, BIOINFORMATICS AND GENOMICS.

TBI-ADRD MODELING WITH A TEAM SCIENCE APPROACH (TBI-ADRD TEAM SCIENCE) - ABSTRACT SUMMARY WE HYPOTHESIZE THAT WE CAN INCREASE SYSTEMICALLY DEVELOP A PROGRESSIVE MURINE TBI-ADRD MODEL WITH INTERNAL AND EXTERNAL VALIDITY WITH A “TEAM-SCIENCE”-BASED TWO-PHASE ADRD-RELEVANT PHENOTYPE ENRICHMENT STRATEGY. THIS 'TEAM SCIENCE' FRAMEWORK ALLOWS US TO LEVERAGE AND INTEGRATE THE COMPLEMENTARY EXPERIENCE AND EXPERTISE OUR 5-SITE MULTIDISCIPLINARY ANIMAL MODEL TESTING TEAM. THIS COLLABORATIVE DESIGN AIMS TO IMPROVE MODEL REPRODUCIBILITY BY TESTING EACH MODEL AT TWO SITES, AND THE USE OF STANDARD OPERATION PROCEDURE (SOP), COMMON DATA ELEMENTS, (CDE) FOR METHOD/DATA COLLECTION HARMONIZATION. AT EACH STAGE, WE WILL EVALUATE ALL DATA COLLECTED, AND MODEL ADVANCEMENT ARE BASED ON A MULTI-DOMAIN 'ADRD ASSESSMENT: (A) DEVELOPMENT OF ROBUST ADRD- RELEVANT NEUROCOGNITIVE AND NEUROBEHAVIORAL DEFICIT PHENOTYPES (PRIMARY), (B) DEVELOPMENT OF ADRD-RELEVANT PROTEINOPATHY-LINKED NEUROPATHOLOGIC PHENOTYPES (PRIMARY), (C) POSITIVE EX VIVO PROTEINOPATHY SIGNATURE USING BRAIN LYSATE THIOFLAVIN-T PROTEIN AGGREGATION ASSAY, (D) PROGRESSIVENESS OF NEUROBEHAVIORAL / PROTEINOPATHY PHENOTYPES, AND (E) CROSS-SITE REPRODUCIBILITY OF ADRD PHENOTYPIC FEATURES. AIM 1. PHASE I: EXAMINE AND SCREEN FOR MOUSE STRAIN DETERMINANTS AND TBI INJURY TYPES THAT MIGHT FAVOR POST TBI-ADRD FORMATION AND PROGRESSION. WE WILL CONDUCT A SYSTEMATIC SCREEN OF DIVERSE MOUSE STRAIN DETERMINANTS AFFECTING TBI-ADRD FORMATION, INCLUDING FOUR STRAINS (E.G., CD1, CAST/EIJ, PWK/PHJ, C57BL/6) AND TWO DISTINCT TBI MODELS (CONTROLLED CORTICAL IMPACT/CCI, AND REPEATED CLOSE HEAD INJURY/RCHI). AT INTERIM AND TERMINAL 18 MONTH ENDPOINTS, WE WILL APPLY A CAREFULLY SELECTED MULTI-DOMAIN 'ADRD ASSESSMENT PANEL’ (MENTIONED ABOVE) TO EVALUATE THE DEVELOPMENT AND PROGRESSION OF POST-TBI ADRD-LIKE NEUROPATHOLOGIES, NEUROBIOCHEMICAL/BIOMARKER SIGNATURES, AND NEUROCOGNITIVE/MEMORY DEFICIT ASSESSMENTS. THE HIGHEST-RANKED TBI-ADRD PARADIGM WILL ADVANCE TO PHASE II. AIM 2. PHASE II. USING THE SELECTED MOUSE STRAIN/INJURY MODEL CANDIDATE, INTRODUCE AND EVALUATE TWO TBI-ADRD MODEL ENRICHMENT FACTORS. WE WILL INTRODUCE SECONDARY ADRD- AUGMENTATION FACTORS, INCLUDING NEUROINFLAMMATION AND MOUSE/HUMAN-DERIVED PATHOLOGIC SEEDING MATERIALS FOR POLYPROTEINOPATHY TRANSMISSION, THE FINAL DELIVERABLE OF THIS PROJECT IS AN OPTIMIZED, VALIDATED, AND MOLECULARLY CHARACTERIZED MURINE TBI-ADRD MODEL THAT ACCURATELY RECAPITULATES THE KEY PROGRESSIVE NEUROPATHOLOGY, NEUROBIOCHEMICAL SIGNATURES/BIOMARKER EXPRESSIONS, AND COGNITIVE DEFICIT PHENOTYPIC FEATURES OF HUMAN TBI- ADRD. AIM 3. IMPLEMENT TBI-ADRD MODEL DISSEMINATION TO FACILITATE ITS USE BY OTHER TBI INVESTIGATORS. WE WILL COMMIT RESOURCES NECESSARY TO FACILITATE THE DISSEMINATION OF OUR FINDINGS AND ENABLE OTHER RESEARCHERS TO REPRODUCE OUR TBI-ADRD MODEL AND KEY FINDINGS AND IMPROVE ON IT, ALL OUR SOP AND DATA WILL BE UPLOADED TO THE PRECISE-TBI ENDORSED OCD-TBI PRECLINICAL TBI DATA-SHARING CONSORTIUM FOR OPEN ACCESS.

RESEARCH CENTERS IN MINORITY INSTITUTIONS CLINICAL RESE*

VISUALIZING HIERARCHICAL PROCESSING OF PHOTIC INPUT TO THE CIRCADIAN CLOCK IN VIVO

PROTECTIVE ROLE OF NEUREGULIN-1 AGAINST CEREBRAL MALARIA-INDUCED NEURONAL INJURY AND BEHAVIORAL SEQUELAE - HUMAN CEREBRAL MALARIA (HCM) IS A SEVERE FORM OF PLASMODIUM FALCIPARUM (P.F.) MALARIA ASSOCIATED WITH ~500,000 DEATHS IN CHILDREN ANNUALLY AND IMPAIRED BRAIN FUNCTION IN SOME SURVIVORS. HCM IS CHARACTERIZED BY SEQUESTRATION OF PARASITIZED RED BLOOD CELLS (PRBCS) IN CEREBRAL MICRO-CIRCULATION AND INDUCTION OF INFLAMMATORY MEDIATORS, BRAIN SWELLING AND IMPAIRED CONSCIOUSNESS WITH UNAROUSABLE COMA. WE HAVE DETERMINED THAT CIRCULATING FREE HEME AND PARASITE HISTIDINE RICH PROTEIN 2 (HRP2), BY-PRODUCTS OF PRBC LYSIS, ARE MAJOR CAUSES OF BRAIN INFLAMMATION, BLOOD-BRAIN BARRIER (BBB) DYSFUNCTION, AND BRAIN INJURY ASSOCIATED WITH HCM. HOWEVER, DEFINING THE MECHANISM(S) MEDIATING THESE EFFECTS IN HCM IS CHALLENGING IN THE ABSENCE OF SUITABLE MODELS. IN VITRO 2D CELL CULTURE, 3D BRAIN ORGANOID AND ANIMAL MODELS (ECM; PLASMODIUM BERGHEI ANKA IN C57BL/6) ALL INDICATE THAT HEME AND HRP2 INDUCED CELLULAR APOPTOSIS, INFLAMMATION, AND TISSUE DISORGANIZATION. IN ECM, HEME CAUSES BRAIN VASCULAR ENDOTHELIAL CELL APOPTOSIS, ALTERS ANGIOPOIETINS 1 AND 2 RATIOS, UPREGULATES CXCL10, HEME OXYGENASE 1, AND TAU AS WELL AS COMPROMISE BBB INTEGRITY THROUGH STAT3 SIGNALING VIA MATRIX METALLOPROTEINASE THREE (MMP3). FOLLOWING A SCREEN FOR THERAPEUTIC AGENTS AGAINST ECM, WE IDENTIFIED NEUREGULIN- 1(NRG1), AN 8 KDA NEUROPEPTIDE CURRENTLY UNDERGOING CLINICAL TRIALS AGAINST HEART FAILURE, THAT ATTENUATES ECM WHEN DELIVERED INTRAVENOUSLY AT 5ΜG/KG. NRG1 MEDIATES PHOSPHORYLATION OF ERBB4 (RECEPTOR), ACTIVATES AKT AND INACTIVATES STAT3 IN HUMAN BRAIN MICROVASCULAR ENDOTHELIAL CELLS. ECM RESISTANT MICE (BALB/C) CONSTITUTIVELY EXPRESSED HIGHER LEVELS OF NRG1 IN BRAIN TISSUE THAN ECM SUSCEPTIBLE (C57BL/6) MICE. SINCE CIRCULATING NRG1 IS SEVERELY DEPLETED IN BOTH FATAL HCM AND ECM, LEVELS OF NRG1 NEED TO BE ASSESSED PROSPECTIVELY TO ASCERTAIN AMOUNTS NEEDED FOR AUGMENTATION TO MITIGATE HCM SEVERITY. INTERESTINGLY, CD8+TCELL PD1/PD-L1 SIGNALING MEDIATED ECM RECOVERY AND PD1 WAS UPREGULATED BY NRG1. USING A HUMAN STEM CELL- DERIVED NEUROVASCULAR UNIT (NVU; BRAIN CHIP), ECM AND HUMAN SUBJECTS, WE WILL DETERMINE THE MECHANISM BY WHICH NRG1 ATTENUATES CEREBRAL MALARIA. WE HYPOTHESIZE THAT THERAPEUTIC ADMINISTRATION OF NRG1 WILL ATTENUATE HEME AND HRP2-INDUCED NVU DAMAGE AND ECM MORTALITY VIA NRG1/ERBB4 AND PD/PD-L1 SIGNALING. OUR OBJECTIVE IS TO FUNCTIONALLY ASSESS THE KEY REGULATORY PATHWAYS MEDIATED BY NRG1 TO ATTENUATE ECM, AND HEME- AND HRP2-INDUCED NVU DAMAGE. THE SPECIFIC AIMS ARE: 1) TO TEST THE HYPOTHESIS THAT AN ALGORITHM, CONSISTING OF NRG1, HEME, HRP2, AND MARKERS OF NEURONAL INJURY AND INFLAMMATION CAN PREDICT HCM SEVERITY, MORTALITY AND NEUROBEHAVIORAL SEQUELAE; 2) TO TEST THE HYPOTHESIS THAT NRG1/ERBB4 AND PD1/PD-L1 SIGNALING CROSSTALK PROTECTS AGAINST HEME AND HRP2-INDUCED DAMAGE IN HUMAN NVU; AND 3) TO TEST THE HYPOTHESIS THAT NRG1 ATTENUATES ECM BRAIN INJURY AND BEHAVIORAL DEFICIT VIA NRG1/ERBB4 AND PD1/PD-L1 SIGNALING. UNDERSTANDING THE ROLE OF NRG1 IN CEREBRAL MALARIA PATHOGENESIS AND SEQUELAE IN SURVIVORS WILL ENABLE US TO DETERMINE THE FEASIBILITY OF TARGETING NRG1 IN CLINICAL TRIALS WITH THE ULTIMATE GOAL OF IMPROVING THE SURVIVAL OF CHILDREN WITH HCM.

MODEL STATE SUPPORTED AHEC

CARDIOVASCULAR DISEASE PREVENTIVE INTERVENTION PROGRAM

CIRCADIAN REGULATION OF RPE FUNCTIONS

MSM INTERDISCIPLINARY SLEEP/CLINICAL CARDIOVASCULAR RESEARCH TRAINING PROGRAM

ANALYTICAL VALIDATION OF TAU AND P-TAU AS ACUTE AND SUBACUTE PROGNOSTIC BIOMARKERS FOR COMPLICATED MILD TBI

ESTABLISHING A CENTER OF EXCELLENCE IN CLINICAL RESEARCH IN GHANA

NEUROPROTECTIVE ROLES FOR NEUREGULINS IN NEUROTOXIN-MEDIATED NEURONAL INJURY

THE MOREHOUSE SCHOOL OF MEDICINE REACH HEALTH INITIATIVE (MSM REACH HI): TRANSFORMING METROPOLITAN ATLANTA COMMUNITIES THROUGH PREVENTION, PRIMARY CA

DP24-004, PRC CORE: MOREHOUSE SCHOOL OF MEDICINE PREVENTION RESEARCH CENTER (MSM PRC): ADVANCING HEALTH EQUITY AND JUSTICE THROUGH COMMUNITY POWERED IMPLEMENTATION SCIENCE

FY10 COOPERATIVE AGREEMENT WITH MOREHOUSE SCHOOL OF MEDICINE

HEALTH CAREERS OPPORTUNITY PROGRAM

RURAL COMMUNITIES OPIOID RESPONSE PROGRAM ? MENTAL AND BEHAVIORAL HEALTH - PROJECT TITLE: BETTER HEALTH AND FITNESS TOGETHER (BHFIT) REQUESTED AWARD AMOUNT: $2,000,000 APPLICANT ORGANIZATION NAME: THE HEALTH PROMOTION RESOURCE CENTER (HPRC) AT MOREHOUSE SCHOOL OF MEDICINE (MSM) APPLICANT ORGANIZATION ADDRESS: 720 WESTVIEW DRIVE SW, ATLANTA, GA 30310 APPLICANT ORGANIZATION FACILITY TYPE: PRIVATE INSTITUTE OF HIGHER LEARNING PROJECT DIRECTOR NAME AND TITLE: DR. MARY LANGLEY, PROFESSOR/DIRECTOR OF HEALTH PROMOTION RESOURCE CTR. PROJECT DIRECTOR CONTACT INFORMATION: PHONE: 404-752-1503 EMAIL: MLANGLEY@MSM.EDU DATA COORDINATOR NAME AND TITLE: TRESSA TUCKER, PH.D. MSM LEAD EVALUATION/RCORP DATA COORDINATOR 9. DATA COORDINATOR CONTACT INFORMATION: 310-625-1913, TRESSATUCKERCONSULTING@COMCAST.NET 10. EIN/DUNS NUMBER EXCEPTION REQUEST IN ATTACHMENT 8? NO - NOTE: HRSA RESERVES THE RIGHT TO DEEM APPLICATIONS THAT PROVIDE INSUFFICIENT INFORMATION IN ATTACHMENT 8, OR ARE NEARLY IDENTICAL IN CONTENT, TO BE INELIGIBLE. IN THIS INSTANCE, ASSUMING ALL OTHER ELIGIBILITY CRITERIA ARE MET, HRSA WILL ONLY ACCEPT THE LAST SUBMITTED APPLICATION ASSOCIATED WITH THE EIN OR DUNS NUMBER. 11. HOW THE APPLICANT FIRST LEARNED ABOUT THE FUNDING OPPORTUNITY: BY SEARCHING FOR GRANT OPPORTUNITIES ON GRANT.GOV THE HEALTH PROMOTION RESOURCE CENTER (HPRC) AT MOREHOUSE SCHOOL OF MEDICINE (MSM) PROPOSES TO IMPLEMENT BETTER HEALTH AND FITNESS TOGETHER (BHFIT) IN WEST CENTRAL AND EAST CENTRAL GEORGIA. BHFIT WILL IMPROVE BEHAVIORAL HEALTH SERVICES TO VULNERABLE AND DISPARATE LOW INCOME AFRICAN-AMERICAN ADULTS AND ADOLESCENTS IN THE TARGET AREA. WHILE AFRICAN-AMERICANS COMPRISE 46% OF THE TARGET AREA, THEY ONLY ACCOUNT FOR APPROXIMATELY 25% OF THE TREATMENT POPULATION DESPITE HIGH NEED. IN GEORGIA, REASONS FOR UNDERUTILIZATION OF MENTAL AND BEHAVIORAL HEALTH SERVICES, ESPECIALLY FOR AFRICAN-AMERICANS INCLUDE STIGMA, INSURANCE AND ACCESS TO CARE. BHFIT WILL STRENGTHEN THE EXISTING BEHAVIORAL HEALTH INFRASTRUCTURE IN THE TARGET AREA TO OVERCOME THESE BARRIERS A ND DISPARITIES IN TREATMENT BY CREATING INTEGRATED CARE TEAMS INCLUDING BEHAVIORAL HEALTH, PRIMARY CARE AND SUPPORT ORGANIZATIONS. INTEGRATED CARE STRATEGIES WILL INCLUDE CARE COORDINATION, CO-LOCATION, CO-RESPONDING, AND TELEHEALTH. THE BHFIT GOALS ARE 1) INCREASE ACCESS TO INTEGRATED AND EVIDENCE-BASED SUD SERVICES ALONG THE SPECTRUM OF CARE IN THE TARGET AREA, ESPECIALLY FOR AFRICAN-AMERICAN ADULTS AND ADOLESCENTS. 2) IMPROVE COORDINATED INTEGRATED CARE FOR BEHAVIORAL HEALTH SERVICES THAT IS EB AND TRAUMA-INFORMED THROUGH TRAINING, COACHING AND MENTORING TARGET AREA PROVIDERS. 3) IMPROVE CAPACITY FOR BEHAVIORAL HEALTH SYSTEM TO ADDRESS RISK FACTORS THROUGH PREVENTION AND HARM REDUCTION THE RURAL TARGET AREA.

MOREHOUSE SCHOOL OF MEDICINE CENTER OF CLINICAL RESEARCH EXCELLENCE

A HEALTH IT BASED PSYCHOEDUCATIONAL INTERVENTION FOR AFRICAN AMERICAN PROSTATE CA

THE ROLE OF CHOLESTEROL METABOLIC ENZYME CYP46A1 AND ITS METABOLITE 24S-HYDROXYCHOLESTEROL IN ISCHEMIC STROKE. - PROJECT SUMMARY THE OVERALL OBJECTIVES FOR THIS APPLICATION ARE TO DETERMINE THE ROLE OF CHOLESTEROL METABOLIC ENZYME CYP46A1 AND ITS METABOLITE 24S-HYDROXYCHOLESTEROL (24S-HC) IN ISCHEMIC STROKE. OUR CENTRAL HYPOTHESIS IS THAT ACTIVATION OF CYP46A1 RESULTS IN INCREASED PRODUCTION OF 24S-HC, WHICH CONTRIBUTES TO ISCHEMIC BRAIN INJURY THROUGH POTENTIATION OF NMDAR. TO TEST OUR HYPOTHESIS, WE WILL USE A COMBINATION OF IN VITRO AND IN VIVO STROKE MODELS ALONG WITH ELECTROPHYSIOLOGY, CALCIUM IMAGING AND TRANSGENIC MICE TO PURSUE THE FOLLOWING THREE SPECIFIC AIMS: AIM 1. DETERMINE THE ROLE OF CYP46A1 IN ISCHEMIC BRAIN INJURY; AIM 2. DETERMINE THE ROLE AND MOLECULAR MECHANISM OF 24S-HC IN ISCHEMIC NEURONAL INJURY IN VITRO; AIM 3. DEFINE THE SIGNALING CASCADE UNDERLYING THE ROLE OF CYP46A1 IN ISCHEMIC BRAIN INJURY. SUCCESS OF THE PROPOSED RESEARCH WILL DEFINE THE ROLE OF CHOLESTEROL METABOLIC ENZYME CYP46A1 AND ITS METABOLITE 24S-HC IN ISCHEMIC BRAIN INJURY.

IMMUNITY TO CHLAMYDIA ABORTUS

INDUCTION OF PROTECTIVE IMMUNITY AGAINST CHLAMYDIA

DIRECTED SUPPLEMENTS TO MOREHOUSE SCHOOL OF MEDICINE NUCA ? PROJECTS ON THE PATH TO HEALTH EQUITY

ROLE OF CCL25-CCR9 IN PROSTATE CANCER

PREVENTIVE MEDICINE RESIDENCIES

ASICS AND INCREASED ISCHEMIC BRAIN INJURY IN DIABETIC CONDITION

PRIMARY CARE TRAINING AND ENHANCEMENT: PHYSICIAN ASSISTANT RURAL TRAINING PROGRAM

PREVENTIVE MEDICINE RESIDENCY

MECHANISMS OF ASIC-MEDIATED NEURONAL INJURY

ADDICTION TECHNOLOGY TRANSFER CENTERS COOPERATIVE AGREEMENTS - BUILDING ON STRONG RELATIONSHIPS FORGED IN 26 YEARS SERVING HHS REGION 4, THE SOUTHEAST ADDICTION TECHNOLOGY TRANSFER CENTER WILL PROVIDE EVIDENCE-BASED TRAINING/TECHNICAL ASSISTANCE TO BEHAVIORAL HEALTH/PRIMARY CARE PROVIDERS SERVING A CULTURALLY/ECONOMICALLY DIVERSE POPULATION WITH SUDS AND THEIR FAMILIES/COMMUNITIES. OUR COLLABORATIVE APPROACHES ARE ATTUNED TO THE EVIDENCE; THE STRENGTHS, NEEDS, AND CULTURES OF ALL CONSTITUENTS; AND THE URGENCY OF THE CHALLENGES THEY FACE. WE WILL SERVE 6,690 PERSONS (1,100/Y1, 1,360/Y2, 1,360/Y3, 1,360/Y4, 1,510/Y5), USING BASIC, TARGETED, AND INTENSIVE TRAINING/TA, INNOVATIVE TECHNOLOGY FOR ADOPTING EVIDENCE-BASED/CULTURALLY (EB/CA) ADAPTED PRACTICES, AND OTHER STRATEGIES. GOAL A: VIABLE STRATEGIC PLAN FOR INCREASING SUD TREATMENT (TX) WORKFORCE RECRUITMENT/RETENTION (PARTICULARLY RURAL/MEN OF COLOR), INCLUDING: A1) 4 ENGAGEMENT SESSIONS (ES) ON STRATEGY/REPORT ON PROCEEDINGS; A2) RE-GIONAL RURAL WORKFORCE TASK FORCE AND A3) WORKFORCE EQUITY TASK FORCE; A4) 4 TRAININGS, 2 WEBINARS, ONLINE COURSE, TOOLKIT; A5) NEW PRACTITIONER TRAINING, LEARNING COMMUNITY, ONLINE COURSE; A6) ENVIRONMENTAL SCAN/TRAINING/TA/QI TOOLS ON LEADERSHIP DEV.; A7) SUMMIT/TOOLS FOR SSAS TO DEVELOP/USE REGIONAL WORKFORCE PLAN. GOAL B: PROCESS TO SPEED ADOP-TION/IMPLEMENTATION OF EB/CA TX PRACTICES, INCLUDING: B1) ANALYSIS OF TRADITIONAL/INNOVATIVE TECH. TRANSFER FOR ADOPTING EB/CA PRACTICES ACROSS CULTURES/LIFESPAN; B2) 4 ACTIVITIES/RESOURCES ON MAT/MOUD IN UNDERSERVED RURAL AREAS; B3) COLLABORATIVE IDENTIFICATION OF EBP FOR UNDER-SERVED COMMUNITIES; TOOLS/TTA FOR ADOPTION; B4) 5 RESOURCES FOR RURAL/UNDERSERVED ON MOUD/TX/HARM REDUCTION; B5) RESOURCES ON OVERCOMING BARRIERS TO EBP ADOPTION; B6) 4 NETWORK-WIDE ACTIVITIES FOR ADOPTION OF EB/CA/RECOVERY-ORIENTED PRACTICES; B7) NETWORK-WIDE WORKFORCE STRATEGY ON INVITATION TO CHANGE. GOAL C: EVIDENCE-BASED TOOLS/PRACTICES/TRAINING/TA FOR PROMOTING PSYCHOLOGICAL SAFETY, EFFECTIVENESS, CULTURAL COMPE-TENCE IN TX, INCLUDING: C1) THINK-TANK ON ADDRESSING CHALLENGES TO ENGAGEMENT, RETENTION, OUT-COMES; TOOLKIT ON PROCEEDINGS; C2) 2 COMMUNITY EQUITY CONVERSATIONS/YEAR FOR COLLABORATIVE ACTION; C3) ONLINE COURSE, EVIDENCE-BASED SOLUTIONS RE: SUD, HEALTH DISPARITIES, AND CULTURES; C4) REGION 4 ADAPTATION OF ATTC CLAS STANDARDS RESOURCES; UNIVERSAL/TARGETED/INTENSIVE TRAINING; C5) COLLABORATION WITH TTC CULTURAL WORKING GROUP; REPORT ON RURAL ACCESS ISSUES ACROSS LIFESPAN; C6) 2 LEARNING DEVELOPMENT SESSIONS/GUIDELINES ON SERVING STIGMATIZED POPS. IN PARTICULARLY STIGMATIZING STATES; C7) REGION 4 BEHAVIORAL HEALTH LEADERSHIP DEVELOPMENT FEL-LOWS ACADEMY. GOAL D: REPLICABLE EVIDENCE-BASED MODEL FOR SUPPORTING RECOVERY BY EMPOW-ERING RECOVERY COMMUNITY ORGANIZATIONS (RCO) AND ENGAGING COMMUNITIES, INCLUDING: D1) SYMPOSIUM ON NEEDS/GAPS/BARRIERS/COALITION BUILDING/PILOT AREAS FOR TRAINING/TA; D2) PLANNING FOR BASIC/UNIVERSAL, TARGETED, INTENSIVE TA FOR PILOT AREAS; D3) BASIC/UNIVERSAL TRAINING/TA TO ALL PILOT AREA RCOS/STAFF; D4) SUPPORTING MENTORSHIP OF 2 EMERGING RCOS BY 2 ESTABLISHED RCOS; D5) INTENSIVE TRAINING/TA FOR PILOT RCOS IN COMMUNITY ENGAGEMENT; D6) EVALUATION OF TA EFFORTS, REPLICATION TOOLKIT/TRAINING/TA. GOAL E: ACCOUNTABILITY INFRASTRUCTURE, INCLUDING: E1) SME ADVISORY BOARD/COMMUNITY ACCOUNTABILITY BOARD; E2) ANNUAL NEEDS ASSESSMENTS/WORK PLANS; E3) NIATX TRAINING, CQI FRAMEWORK; E4) USE OF CQI FRAMEWORK TO IMPROVE TRAINING/TA; E5) QUALITY/CULTURAL/SAFETY ASSESSMENT TOOLS FOR PROVIDERS/INDIVIDUALS/FAMILIES, EMPHASIS ON RURAL/UNDERSERVED; E6) CULTURALLY/LINGUISTICALLY APPROPRIATE INTERNET RESOURCES; E7) ORAL INTERPRETATION OF TRAINING, WRITTEN TRANSLATION OF KEY PRODUCTS; E8) ENGAGEMENT STRATEGY, SEGMENTATION, TARGETS, TECHNOLOGY; E9) 50% BASIC, 35% TARGETED, 15% INTENSIVE TA; E10) EXPANSION OF COLLABORATIVE PARTNERSHIPS WITHIN/BEYOND ATTC/SAMHSA; E11) PARTICIPATION IN ATTC NON-DUPLICATION OF EFFORT; AND E12) PARTICIPATION IN SAMHSA TTA MULTI-SITE EVAL.

PRIMARY CARE TRAINING AND ENHANCEMENT: TRAINING PRIMARY CARE CHAMPIONS

COOPERATIVE AGREEMENT FOR THE HBCU CENTER FOR EXCELLENCE IN BEHAVIORAL HEALTH

HBCU- CFE IN BEHAVIORAL HEALTH AT MOREHOUSE SCHOOL OF MEDICINE

HISTORICALLY BLACK COLLEGES AND UNIVERSITIES CENTER FOR EXCELLENCE

PHYSICIAN ASSISTANT TRAINING IN PRIMARY CARE

ADAPTATION EDUCATION AND MOTIVATION: IMPROVING EVIDENCE-BASED MEDICATION ADHERE

INVOLVEMENT OF LEPTIN AND INTERLEUKIN-1 SIGNALING IN MAMMARY CANCER PROGRESSION

ADRENERGICALLY MEDIATED REMODELING IN NONISCHEMIC HEART FAILURE

DEVELOPING AND IMPLEMENTING A CANCER PREVENTION AND CONTROL RESEARCH CURRICULUM T

PREVENTIVE MEDICINE RESIDENCIES

FUNCTION OF ACAP4 IN CCL18-STIMULATED BREAST CANCER METASTASIS

MBRS SCORE PROGRAM AT MOREHOUSE SCHOOL OF MEDICINE

NICOTINIC RECEPTOR ACTIVISION AND BRAIN PROINFLAMMATORY RESPONSES IN HIV-1 TRANSGENIC RAT

TRPM7 INDUCES TUMORIGENESIS AND STEMNESS THROUGH NOTCH ACTIVATION IN GLIOMA - THE CURRENT STANDARD OF CARE OF SURGERY AND RADIOCHEMOTHERAPY FOR GLIOBLASTOMAS (GBM) IS INADEQUATE AND HAS NOT RESULTED IN IMPROVED PROGNOSIS. ACCUMULATING EVIDENCES SHOW THAT THE FAILURE OF USING CURRENT CHEMO (TEMOZOLOMIDE, TMZ)- AND RADIO- THERAPIES TO TREAT GBM AND THE RESULTANT HIGH TUMOR RECURRENCE ARE ATTRIBUTED TO THE PRESENCE OF A SMALL SUBPOPULATION OF GLIOMA STEM CELLS (GSC), WHICH IS CHARACTERIZED BY THEIR STEM CELL- LIKE PROPERTIES AND AGGRESSIVE BEHAVIOR. UNDER HYPOXIC CONDITIONS, GSC INCREASE THE ACTIVATION OF SEVERAL NOTCH GENES, WHICH HOLD A PROGNOSTIC IMPLICATION, AS UPREGULATED NOTCH GENES ARE ASSOCIATED WITH POOR SURVIVAL. NOTCH SIGNALING IS HIGHLY ACTIVE IN GSC, INHIBITS DIFFERENTIATION, MAINTAINS STEM-LIKE PROPERTIES, AND, THEREFORE, IS RESPONSIBLE FOR GBM TUMORIGENESIS AND STEMNESS. OUR PROJECT HIGHLIGHTS TRANSIENT RECEPTOR POTENTIAL MELASTATIN- RELATED-7 (TRPM7)’S ROLE IN NOTCH SIGNALING AND GLIOMA TREATMENT FAILURE. TRPM7 ENCODES A CA2+ PERMEABLE NONSELECTIVE CATION CHANNEL FUSED WITH A SERINE/THREONINE KINASE AT ITS CARBOXYL TERMINUS. OUR GROUP FOUND THAT THE SUPPRESSION OF TRPM7 CHANNELS INHIBITS PROLIFERATION, MIGRATION, AND INVASION OF MALIGNANT HUMAN GLIOMAS, INDICATING THAT TRPM7 CHANNELS MAY REPRESENT A NOVEL AND PROMISING TARGET FOR THERAPEUTIC INTERVENTION OF MALIGNANT GLIOMA. FURTHERMORE, THE EFFECT OF TRPM7 ON THE PROLIFERATION AND INVASION OF HUMAN GLIOMA CELL IS MEDIATED BY MULTIPLE MECHANISMS. TRPM7 REGULATES MIR-28-5P EXPRESSION, WHICH SUPPRESSES CELL PROLIFERATION AND INVASION IN GLIOMA CELLS BY TARGETING RAS-RELATED PROTEIN RAP1B. IN PARTICULAR, OUR GROUP FOUND THAT TRPM7 CHANNELS REGULATE GSC GROWTH AND PROLIFERATION THROUGH STAT3 AND NOTCH SIGNALING PATHWAYS. IN ADDITION, THE PRELIMINARY DATA IN THIS PROPOSAL SHOW THAT DECREASED EXPRESSION OF TRPM7 IS CORRELATED WITH DECREASED ACTIVE NOTCH1 INTRACELLULAR DOMAIN (NICD) FROM THE NOTCH1 RECEPTOR AND REDUCED GSC MARKER CD133 EXPRESSION IN THE GLIOMA CELL LINES/XENOLINE TESTED. OUR RESULTS INDICATE THAT TRPM7 REGULATES THE NOTCH PATHWAY IN MOST GLIOMA CELL LINES/XENOLINE DESPITE THE HIGH HETEROGENEITY AND VARIATIONS IN GLIOMA’S BIOLOGICAL CHARACTERISTICS. IN THIS PROPOSAL, WE HYPOTHESIZE THAT TRPM7 MOLECULAR PATHWAY IS FUNCTIONALLY CONNECTED TO NOTCH-INDUCED STEMNESS, AND TRPM7 MAY BE A NOVEL GBM DRUG TARGET. IN THIS PROJECT, WE WILL UTILIZE PATIENT-DERIVED XENOLINES (PDX) THAT CLOSELY MIMICS THE BIOLOGICAL AND PHYSIOLOGICAL FEATURES OF IN VIVO REAL CELLS AND TISSUES TO TEST OUR HYPOTHESIS. AIM 1: DETERMINE THE ROLE OF TRPM7 IN THE REGULATION OF CA2+ AND MG2+ HOMEOSTASIS IN GBM PDX AND PDX- GSC. AIM 2: DETERMINE THE ROLE OF THE NOTCH SIGNALING PATHWAY REGULATED BY TRPM7 IN THE PROGRESSION OF GLIOMA AND MAINTENANCE OF SELF-RENEWAL AND TUMORIGENICITY OF GSC USING PDX AND PDX-GSC. AIM 3: INVESTIGATE WHETHER TARGETING TRPM7 REDUCES TUMOR GROWTH IN MOUSE PDX GLIOMA MODELS AND SENSITIZES TUMOR TO TMZ- MEDIATED APOPTOSIS. ACCOMPLISHING THIS STUDY WILL DELINEATE THE MOLECULAR MECHANISMS OF TRPM7 IN THE DEVELOPMENT AND PROGRESSION OF GLIOMA TUMORIGENESIS AND STEMNESS, AS WELL AS DEVELOP TRPM7 AS A NOVEL DRUG TARGET FOR GLIOMA PATIENTS.

P311 MEDIATED ADIPOGENESIS, ADIPOCYTE PLASTICITY AND METABOLIC REGULATION - SUMMARY ONE THIRD OF THE US POPULATION IS CLINICALLY OBESE, A CONDITION WHICH INCREASES THE RISK FOR CHRONIC DISEASES LIKE TYPE 2 DIABETES MELLITUS (DM), HEART DISEASE AND CANCERS. ADIPOCYTE DYSFUNCTION (AD) IS CARDINAL FEATURE OF METABOLIC DYSREGULATION AND INCREASES THE RISK FOR DEVELOPING INSULIN RESISTANCE (IR), DM, AND HYPERTENSION. ALONG WITH ADIPOCYTE HYPERTROPHY, MACROPHAGE INFILTRATION OF WHITE ADIPOSE TISSUE (WAT) IS ASSOCIATED WITH THE PATHOPHYSIOLOGY OF OBESITY, AD AND IR, ALBEIT THE UNDERLYING MOLECULAR MECHANISMS ARE UNCHARACTERIZED. WE WERE FIRST TO SHOW THE PRESENCE OF P311 IN WAT, BROWN ADIPOSE TISSUE (BAT) AND BEIGE ADIPOSE TISSUE. THE WAT OF P311 KNOCKOUT (KO) MICE HAS FEWER RESIDENT MACROPHAGES AND DECREASED CELLULAR DYNAMICS, INCLUDING DECREASED AUTOPHAGY AND APOPTOSIS. THIS IS POTENTIALLY LEADING TO ADIPOCYTE HYPERTROPHY THAT IN TURN CAUSES HYPERGLYCEMIA DUE TO AGE- AND GENETIC ABLATION-MEDIATED P311 EXPRESSION LEADING TO OVERWORKED AND EXHAUSTED ADIPOCYTES IN P311 KOS OR LOW P311 EXPRESSING ADIPOCYTES COMPARED TO WILD TYPES. AS STUDIES ARE LIMITED, RESIDENT MACROPHAGES COULD ALTER ADIPOCYTE FUNCTION EARLY IN ADIPOSE TISSUE DEVELOPMENT, A NOVEL MECHANISM REQUIRING EXPLORATION. WE WILL ALSO EXPLORE KEY ADIPOCYTE CELLULAR PROCESSES OF APOPTOSIS AND AUTOPHAGY/LIPOPHAGY, WHICH MAY AFFECT ADIPOCYTE TURNOVER IN THE WAT OF P311 KO MICE, LEADING TO ADIPOCYTE HYPERTROPHY AND DYSFUNCTION, AND THUS METABOLIC DEREGULATION. THE PROPOSED PROJECT WILL TEST THE CENTRAL HYPOTHESIS THAT AGE- AND GENETIC ABLATION-MEDIATED P311 LEVELS PLAY A KEY ROLE IN WHITE, BROWN AND BEIGE ADIPOCYTE DEVELOPMENT, PLASTICITY AND FUNCTION, AS WELL AS IN METABOLIC REGULATION. FURTHER, WE WILL INVESTIGATE THE ROLE OF P311 IN CELLULAR PROCESSES (I.E., WAT BROWNING AND BAT WHITENING) AND ITS EFFECT ON ADIPOCYTE FUNCTION AND GLYCEMIC CONTROL, AS P311 KO MICE ARE HYPERGLYCEMIC. WE WILL ALSO EVALUATE THE ABILITY OF P311 TO MODULATE ADIPOSE BIOLOGY AND METABOLIC REGULATION THROUGH PPAR AND UCP1 REGULATION; AND MYO1C BINDING TO GLUT4. WE WILL DEVELOP ADIPOCYTE-SPECIFIC P311 KO CONDITIONAL MICE USING NOVEL CRISPR TECHNOLOGY TO EVALUATE THE ADIPOCYTE-SPECIFIC P311 ROLES. THE CURRENT PROJECT WILL THEREBY ESTABLISH P311 AS A NEW PLAYER IN ADIPOCYTE BIOLOGY AND METABOLIC REGULATION. OUR EXPERIMENTAL STRATEGY WILL INCORPORATE TRANSGENIC ANIMALS USING CLASSIC CELL BIOLOGY, MOLECULAR BIOLOGY, BIOCHEMICAL, IMMUNOASSAYS AND IMAGING METHODS STUDIES. OUR FINDINGS WILL ENHANCE THE UNDERSTANDING OF P311 MEDIATED FAT CELL DEVELOPMENT AND FUNCTION AND FAT MASS EXPANSION. OUR ONGOING STUDIES INDICATE THAT P311 POTENTIALLY REGULATES METABOLISM THROUGH ADIPOCYTE DYNAMICS, FUNCTION AND PLASTICITY (A NOVEL APPROACH TO TARGETING METABOLIC DISORDERS THROUGH BROWNING OF WAT); REGULATING RESIDENT AND INFILTRATING MACROPHAGES; AND CONTROLLING ADIPOCYTE CELLULAR PROCESSES. THESE STUDIES ARE NEW AND DO NOT OVERLAP WITH EXISTING FUNDING.

THE RETINAL CLOCK MODULATES CELL VIABILITY, RETINAL CIRCUITRY AND LOCOMOTOR ACTIVITY RHYTHM - EXPERIMENTAL EVIDENCES INDICATE THAT MANY ASPECTS OF MAMMALIAN RETINAL PHYSIOLOGY AND FUNCTION ARE UNDER THE CONTROL OF A RETINAL CIRCADIAN CLOCK. STUDIES ALSO INDICATE THE RETINAL MOLECULAR CLOCK AND ITS OUTPUT SIGNALS CONTRIBUTE TO RETINAL DISEASE AND PATHOLOGY. BMAL1 IS A KEY COMPONENT OF THE CIRCADIAN MOLECULAR CIRCADIAN CLOCK MECHANISM. OUR PREVIOUS STUDIES INDICATE THAT THE REMOVAL OF BMAL1 FROM RETINA MODULATES NEURAL CIRCUITRY OF RETINA AND CONE PHOTORECEPTORS VIABILITY. THE GOAL OF THE PRESENT PROPOSAL IS TO INVESTIGATE THE ROLE OF RETINAL CIRCADIAN CLOCK IN RETINAL FUNCTION AND SCN CIRCADIAN ORGANIZATION. THE PRESENT APPLICATION COMPRISES THREE SPECIFIC AIMS. IN SPECIFIC AIM 1, WE WILL INVESTIGATE THE MECHANISM UNDERLYING CLOCK REGULATION OF CONE VIABILITY USING 661W CELL LINE. IN SPECIFIC AIM 2, WE DETERMINE WHETHER THE ENVIRONMENTAL CIRCADIAN DISRUPTION (ECD, E.G. JET LAG) AFFECTS RETINAL FUNCTION AND CIRCUITRY. IN SPECIFIC AIM 3, WE WILL TEST THE HYPOTHESIS THAT THE REMOVAL OF BMAL1 FROM RETINA ALTERS CIRCADIAN BEHAVIOR RHYTHM. IN OUR RESEARCH, WE WILL USE A WIDE ARRAY OF NEW AND TECHNOLOGICALLY ADVANCED TECHNIQUES AS WELL AS SEVERAL LINES OF TRANSGENIC MICE AND CELL LINE WILL BE USED. OUR PROPOSAL WILL PROVIDE IMPORTANT INSIGHTS INTO THE ROLE OF CIRCADIAN CLOCK IN THE MODULATION OF VISUAL FUNCTION, PHOTORECEPTORS VIABILITY AND BEHAVIOR RHYTHM.

THE ROLE OF NEUREGULIN-1 (NRG1) IN CORPUS LUTEUM (CL) PHYSIOLOGY

KIDNEY INJURY MOLECULE-1 IN DIABETIC NEPHROPATHY

DEGRADATION MECHANISMS OF MAMMALIAN CIRCADIAN CLOCK PROTEINS

TARGETED NANOTHERAPY FOR PROSTATE CANCER

MECHANISM OF ACTION OF PROHIBITIN IN OVARIAN CELL FUNCTION

NOVEL MECHANISMS OF IMMUNOLOGICAL PRIMING AFTER CIRCADIAN DISRUPTION

ASSESSMENT OF INFLAMMATORY RESPONSES AND NOVEL SYSTEMIC SIGNALS AS POTENTIAL SCREENING TARGETS OF SHIFT-WORK RELATED DISRUPTION. - ABSTRACT SHIFT WORKERS REPRESENT NEARLY 30 % OF THE US WORKFORCE, AND THIS OCCUPATIONAL HAZARD CONVEYS INCREASED RISK FOR MULTIPLE PATHOLOGIES. STILL, THE SPECIFIC MECHANISMS BEHIND THIS INCREASED RISK OF ILLNESS BY SHIFT WORKERS AS WELL AS INVESTIGATION OF SCREENING TARGETS TO IDENTIFY SUSCEPTIBLE INDIVIDUALS ARE SCARCELY KNOWN. OUR PRECLINICAL RESEARCH AND INITIAL TRANSLATIONAL STUDIES PROVIDE INSIGHT INTO THE BASIS OF SHIFT-WORK DISEASE AND SHOW THAT MARKERS OF SYSTEMIC INFLAMMATION APPEAR TO INCREASE AS A FUNCTION OF EXPOSURE-DURATION TO SHIFT WORK. HOWEVER, WHEN SAMPLES ARE CHALLENGED WITH BACTERIAL ENDOTOXIN, WE FIND THAT LOW-GRADE SYSTEMIC INFLAMMATION DOES NO WARRANT A HEIGHTENED EX-VIVO ENDOTOXIN RESPONSE. AS SHIFT WORK EXPOSURE INCREASES, THE RELATIONSHIP BETWEEN SYSTEMIC INFLAMMATION AND ENDOTOXIN RESPONSES WEAKENS, SUGGESTING A MISMATCH BETWEEN DISCRETE PRO- AND ANTI-INFLAMMATORY PATHWAYS DURING ENDOTOXIN CHALLENGE. NOVEL SYSTEMIC SIGNALS IN PLASMA SAMPLES FROM SHIFT WORKERS IDENTIFY A POTENTIAL MEDIATOR OF SHIFT-WORK RELATED DISRUPTION OF INFLAMMATION. THESE PRELIMINARY RESULTS ILLUSTRATE HOW SHIFT WORK IMPACTS THE COMPLEX INTERACTION OF EVENTS NEEDED TO INITIATE AND CONTROL AN EFFICIENT RESPONSE TO AN INFLAMMATORY CHALLENGE AND SUPPORT THE HYPOTHESIS THAT CHRONIC DYSREGULATION OF INFLAMMATION IS BEHIND THE INCREASED RISK OF DIABETES, CANCER AND CARDIOVASCULAR DISEASE IN SHIFT WORKERS. IN THIS APPLICATION, WE PROPOSE TO CONDUCT A CROSS-SECTIONAL PROSPECTIVE STUDY OF DAY WORKERS AND CAREER SHIFT WORKERS EXPOSED TO TEMPORALLY CHANGING OCCUPATIONAL ENVIRONMENTS. WE WILL FURTHER DEVELOP AND IMPROVE A PROFILE OF SHIFT-WORK RISK ASSESSMENT WHICH INCLUDES INDIVIDUAL METRICS OF SYSTEMIC INFLAMMATION, CARDIOVASCULAR DISEASE, STRESS, SLEEP/ACTIVITY, DIET COMPOSITION, AND CIRCADIAN DISRUPTION. THIS ASSESSMENT AIMS TO QUANTIFY THE STATE OF LOW-GRADE SYSTEMIC INFLAMMATION CHARACTERISTIC OF SHIFT WORK EXPOSURE AS A POTENTIAL PREDICTOR OF THE RESPONSE OF THE IMMUNE SYSTEM TO A CONTROLLED, EX-VIVO AND IN-VITRO, ENDOTOXIN CHALLENGE. WE AIM TO ASSESS THE POTENTIAL MECHANISMS BY WHICH INCREASED INFLAMMATION DETERMINE DYSREGULATED ACTIVATION AND TEST THE CENTRAL HYPOTHESIS THAT THE DEGREE OF LOW-GRADE SYSTEMIC INFLAMMATION WORSENS WITH INCREASED SHIFT WORK EXPOSURE. OUR PRIMARY GOAL IS TO UNDERSTAND HOW SHIFT WORK EXPOSURE DURATION LEADS TO THE DEVELOPMENT OF UNCONTROLLED INFLAMMATION IN CAREER SHIFT WORKERS INCREASING DISEASE RISK. THIS WORK IS OF PARAMOUNT IMPORTANCE BECAUSE IT COULD LEAD TO EARLY DIAGNOSTIC TOOLS THAT CAN HELP MITIGATE SHIFT-WORK DISEASE. ON THE LONG TERM, WE SEEK TO UNCOVER THE MECHANISTIC LINKS BETWEEN SHIFT WORK EXPOSURE AND DISEASE.

MICROVESICLES FROM ADIPOSE-DERIVED STEM CELLS FOR ISCHEMIC HEART REPAIR

DEFINING THE ROLE OF SLEEP IN RESILIENCE TO SOCIAL STRESS

PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR AND STROKE

SGK1 SIGNALING PATHWAYS IN VASCULAR REMODELING

VASCULAR EPIGENOME DYNAMICS IN AFRICAN-AMERICAN HYPERTENSIVES

MATERNAL HEALTH RESEARCH NETWORK (MH-RN) FOR MSIS--RESEARCH AWARDS

PHOTIC AND CIRCADIAN REGULATION OF RETINAL MELATONIN

CHANGES IN E-S PLASTICITY IN AGING

THE FUNCTION OF EZRIN IN STIMULUS-COUPLED ACID SECRETION

NEUROPROTECTION BY NEUROGULIN-1 IN STROKE AND ACUTE BRAIN INJURIES

PRIMARY CARE TRAINING AND ENHANCEMENT: PHYSICIAN ASSISTANT RURAL TRAINING IN MENTAL AND BEHAV. HLTH

PROTECTIVE ROLE OF NEUREGULIN-1 AGAINST CEREBRAL MALARIA PATHOGENESIS AND MORTALITY

RAPID ISCHEMIC TOLERANCE: SYNAPTIC RE-ORGANIZATION AND REDUCED EXCITOTOXICITY

REGULATION OF VIBRIO CHOLERAE MOTILITY, STRESS RESPONSE AND DETACHMENT FROM INTES

SEXUAL RISK AVOIDANCE EDUCATION (SRAE) PROGRAM

HEALTH POLICY LEADERSHIP FELLOWSHIP PROGRAM

ADVANCING HEALTH EQUITY THROUGH POLICY IN THE CITY OF EAST POINT, GEORGIA

2/2-ATLANTA CENTER FOR TRANSLATIONAL RESEARCH IN ENDOMETRIOSIS (ACTRE)

HIGHER EDUCATION

PROMOTING BLACK YOUTH MENTAL HEALTH THROUGH POLICY IN GEORGIA - THIS PROJECT WILL DEMONSTRATE THE EFFECTIVENESS OF INNOVATIVE POLICY SOLUTIONS TO PROMOTE BLACK YOUTH MENTAL HEALTH IN GEORGIA. THE POPULATION OF FOCUS IS BLACK YOUTH AGE 10-17 RESIDING IN GEORGIA, WITH A PARTICULAR FOCUS ON SUBPOPULATIONS, INCLUDING THOSE LIVING IN PREDOMINANTLY BLACK RURAL COUNTIES, STUDENTS IN MAJORITY BLACK SCHOOL SYSTEMS, AND COMMUNITIES WITH DISPROPORTIONATE RATES OF HEALTH AND MENTAL HEALTH INEQUITIES. IN 2020, NEARLY 2.5 MILLION YOUTH UNDER 18 LIVED IN GEORGIA, OF WHICH 34%, IDENTIFIED AS NON-HISPANIC BLACK. 13 RURAL COUNTIES IN GEORGIA HAVE A PREDOMINANTLY BLACK POPULATION AND NEARLY 50 SCHOOL DISTRICTS HAVE A MAJORITY BLACK STUDENT POPULATION. ACCORDING TO THE 2020 GEORGIA STUDENT HEALTH SURVEY, 6% OF BLACK STUDENTS IN GRADES 6-12 ATTEMPTED SUICIDE ON AT LEAST ONE OCCASION, COMPARED TO 4% OF WHITE STUDENTS. WHITE GEORGIANS ARE APPROXIMATELY 8 TIMES MORE LIKELY TO HAVE BEEN EXPOSED TO 0 ADVERSE CHILDHOOD EXPERIENCES THAN BLACK GEORGIANS. BLACK STUDENTS ARE DISPROPORTIONATELY THE SUBJECT OF DISCIPLINARY ACTION COMPARED TO THEIR PERCENT OF THE OVERALL STUDENT POPULATION AND DISCIPLINARY ACTIONS ARE OFTEN MORE SEVERE FOR BLACK STUDENTS COMPARED TO WHITE STUDENTS, EVEN WHEN THE BEHAVIORS ARE SIMILAR. THIS PROJECT WILL ADDRESS THE HIGH RATES OF UNMET NEED FOR MENTAL HEALTH SERVICES IN GEORGIA BY IDENTIFYING, ASSESSING, IMPLEMENTING, AND EVALUATING INNOVATIVE POLICY SOLUTIONS THAT WILL PROMOTE BLACK YOUTH MENTAL HEALTH. THE POLICIES OF FOCUS FOR THIS PROJECT ARE THOSE RELATED TO MENTAL HEALTH TREATMENT, SUICIDE PREVENTION, AND SCHOOL DISCIPLINE. THIS PROJECT, LED BY MOREHOUSE SCHOOL OF MEDICINE AND SUPPORTED BY STRATEGIC COMMUNITY PARTNERS WILL ACHIEVE FIVE OBJECTIVES: 1) ENGAGE, RECRUIT, AND CONVENE A MULTI-SECTOR ADVISORY COUNCIL MADE UP OF PUBLIC, NON-PROFIT, PRIVATE, ACADEMIC, COMMUNITY ORGANIZATIONS, AND INDIVIDUALS WITH LIVED EXPERIENCE, WHO WILL PROVIDE EXPERTISE AND ADVICE TO THE PROJECT, INCLUDING DEVELOPMENT OF THE DISPARITY IMPACT STATEMENT, IDENTIFICATION OF POLICY OPTIONS, ASSESSMENT OF POLICIES, SELECTION OF HIGH-IMPACT POLICIES, AND DISSEMINATION OF RESULTS FROM POLICY ASSESSMENTS; 2) USE THE OMH-DEVELOPED BLACK YOUTH MENTAL HEALTH (BYMH) FRAMEWORK TO REVIEW, IDENTIFY, AND ANALYZE EXISTING POLICIES THAT COULD BE TESTED FOR POTENTIAL CROSSOVER EFFECT TO PROMOTE MENTAL HEALTH IN BLACK YOUTH, INCLUDING THOSE AT RISK FOR SUICIDE; 3) IMPLEMENT ONE (1) TO THREE (3) INNOVATIVE AND CULTURALLY EFFECTIVE POLICY APPROACHES USING AN EVIDENCE-BASED MODEL ACROSS THREE SEPARATE IMPLEMENTATION SETTINGS IN GEORGIA; 4) COMPLETE A PROCESS, OUTCOMES, AND IMPACT EVALUATION THAT ASSESSES THE EXTENT TO WHICH 1) IMPLEMENTATION OF THE BYMH FRAMEWORK IDENTIFIED CROSSOVER EFFECT OF POLICIES SHOWN TO BE EFFECTIVE IN ADDRESSING OTHER HEALTH PROMOTION AND PREVENTION AREAS ON BLACK YOUTH’S MENTAL HEALTH, INCLUDING BLACK YOUTH AT RISK FOR SUICIDE; 2) ACTIVITIES WERE COMPLETED WITHIN IDENTIFIED TIMEFRAMES; 3) THE IMPLEMENTED TOOL RESULTED IN IMPROVED ADHERENCE TO THE NATIONAL STANDARDS FOR CULTURALLY AND LINGUISTICALLY APPROPRIATE SERVICES (CLAS) IN HEALTH AND HEALTH CARE; AND 4) THE IMPLEMENTED TOOL RESULTED IN ANALYSIS OF POLICIES ACROSS ENVIRONMENTAL AND ECOLOGICAL FACTORS, SUCH AS COMMUNICATIONS, PHYSICAL ENVIRONMENT, HOUSING, EDUCATION, AND CRIMINAL JUSTICE; AND 5) PARTICIPATE IN EVALUATION OF THE EFFECTIVENESS OF THE METHODOLOGICAL FRAMEWORK, STRUCTURED PROCESS, AND TOOL TO IDENTIFY AND MODIFY POLICIES TO IMPROVE HEALTH OUTCOMES; AND 6) DOCUMENT AND DISSEMINATE PROJECT FINDINGS, INCLUDING LESSONS LEARNED, SUCCESSES AND CHALLENGES, AND DEVELOP A SUSTAINABILITY PLAN. SUCCESSFUL COMPLETION OF THIS PROJECT WILL PROVIDE EVIDENCE FOR INNOVATIVE POLICY SOLUTIONS THAT PROMOTE BLACK YOUTH MENTAL HEALTH. PROJECT FINDINGS WILL BE DISSEMINATED BROADLY TO SUPPORT PROJECT SUSTAINABILITY AND EXPANDED USE OF THE BYMH FRAMEWORK TO ADVANCE HEALTH EQUITY ACROSS THE STATE AND

POLYCOMB GROUP PROTEINS AS EPIGENETIC MEDIATORS OF BRAIN ISCHEMIC TOLERANCE

STING INHIBITION AS A THERAPEUTIC TARGET FOR ENDOMETRIOSIS - PROJECT SUMMARY/ABSTRACT ENDOMETRIOSIS AFFECTS ABOUT 10% OF ALL REPRODUCTIVE-AGE WOMEN AND IT IS ONE OF THE MAIN CAUSES OF PELVIC PAIN AND INFERTILITY. CURRENT FDA-APPROVED HORMONAL THERAPIES ARE OFTEN LIMITED IN EFFICACY, COUNTERPRODUCTIVE TO FERTILITY AND WITH SIDE EFFECTS AFFECTING ENDOGENOUS HORMONE STEROID LEVELS, RESULTING IN CESSATION OF THE REPRODUCTIVE CYCLE, HIRSUTISM, POSTMENOPAUSAL SYMPTOMS, AND OSTEOPOROSIS. ALTERNATIVE THERAPEUTIC STRATEGIES ARE GEARED TOWARDS DRUGS WITHOUT HORMONAL SIDE EFFECTS BUT WITH LIMITED THERAPEUTIC EFFICACY, INCLUDING NSAID TREATMENT FOR PAIN. TO DATE, NO EFFECTIVE THERAPIES WITHOUT HORMONAL SIDE EFFECTS EXIST. THUS, STUDIES AIMED AT IDENTIFYING NOVEL THERAPEUTIC TARGETS AGAINST ENDOMETRIAL INFLAMMATION AND FIBROSIS DEVOID OF UNWANTED SIDE EFFECTS STEMMING FROM ESTROGEN DEFICIENCY, IS A MAJOR CLINICAL NEED. RECENT EVIDENCE INDICATES THAT STIMULATOR OF INTERFERON GENES (STING) IS UPREGULATED IN ENDOMETRIOSIS LESIONS AND RECENT DATA FROM OUR TEAM AND OTHERS SHOW THAT TYPE I AND II (IFN) ARE ASSOCIATED WITH MORE ADVANCED STAGES OF ENDOMETRIOSIS, INDEPENDENTLY OF THE MENSTRUAL CYCLE AND HORMONAL STATUS, WITH STING-DEPENDENT IFN RELATED GENES EMERGING AS NOVEL STROMAL MARKERS OF ENDOMETRIOSIS. NITRO-FATTY ACIDS (NO2-FAS) HAVE EMERGED AS POTENT ANTI-INFLAMMATORY AND ANTI- FIBROTIC AGENTS IN NUMEROUS EXPERIMENTAL MODELS OF INFLAMMATION, METABOLISM AND FIBROSIS, AND SUCCESSFULLY COMPLETED PHASE I AND II CLINICAL TRIALS. OUR COLLABORATORS IDENTIFIED RESIDUES CYS88 AND CYS91 OF STING AS NO2-FA TARGETS. IN ADDITION TO THE FIRST GENERATION NO2-FAS, WE IDENTIFIED NO2-FA-DERIVED NEW CHEMICAL ENTITIES (NCES), COMPATIBLE WITH ORAL DELIVERY AND SHOWING HIGH EFFICACY ON STING INHIBITION AND NEGLIGIBLE TOXICITY IN VIVO. CONSIDERING THE UNIQUE PATHOGENESIS OF ENDOMETRIOSIS, INVOLVING ENDOMETRIAL INFLAMMATION AND FIBROSIS ALONG WITH THE WELL-ESTABLISHED ANTI-INFLAMMATORY AND ANTI-FIBROTIC PROPERTIES OF NO2-FA, WE SHOW THAT: 1) ORAL DELIVERY OF A FIRST GENERATION NO2-FA, NO2-CONJUGATED LINOLEIC ACID, PROTECTS AGAINST ENDOMETRIOSIS IN A SYNGENEIC MODEL IN VIVO; 2) LOSS-OF-STING FUNCTION PROTECTS AGAINST EXPERIMENTAL ENDOMETRIOSIS; 3) A NOVEL NCE, CP-36, WITH IMPROVED STING AFFINITY (IC50) AND LOW TOXICITY IN VIVO IS READILY BIOAVAILABLE AS AN ORAL THERAPY AGAINST ENDOMETRIOSIS. BASED ON THESE PREMISES, THE PROJECT WILL TEST THE CENTRAL HYPOTHESIS THAT NOVEL ORALLY BIOAVAILABLE STING INHIBITORS PROTECT AGAINST ENDOMETRIOSIS AND ASSOCIATED PAIN BY INHIBITING INFLAMMATION AND FIBROSIS. USING OUR UNIQUE MOUSE MODEL, STING C88A/C91A KNOCK-IN, CLICK CHEMISTRY, AND WELL-ESTABLISHED MODELS OF PERITONEAL ENDOMETRIOSIS, INCLUDING A REGRESSION STUDY, WE WILL DEFINE THE THERAPEUTIC SPECIFICITY OF CP-36 AS BONA FIDE STING INHIBITOR IN ENDOMETRIOSIS (AIM 1) AND ESTABLISH THAT STING INHIBITION BY ORAL DELIVERY OF CP-36 REDUCES ENDOMETRIOSIS (AIM 2). THIS STUDY WILL PROVIDE FUNCTIONAL AND MECHANISTIC EVIDENCE FOR NOVEL NO2-FA-BASED STING INHIBITORS AS POTENTIAL NON-HORMONAL THERAPEUTIC DRUGS FOR ENDOMETRIOSIS, THUS PAVING THE WAY FOR THE ACCELERATED DEVELOPMENT OF NOVEL THERAPEUTIC STRATEGIES AND A PARADIGM CHANGE IN CLINICAL TREATMENT AND MANAGEMENT OF THIS DISEASE.

ACHAETE-SCUTE-LIKE-3 (ASCL3) REGULATES VASCULAR MUSCLE CELL PROLIFERATION

VASCULOPATHIC EFFECTS OF ALDOSTERONE IN DAHL RATS

MSM CARDIOVASCULAR CENTER OF EXCELLENCE

THREE DIMENSIONAL APPROACH TO ELIMINATING DISPARITIES I*

NIBA-TBI: NEURO-IMAGING AND BIOFLUID-BASED BIOMARKER ASSESSMENTS AS TRANSLATIONAL PATHOPHYSIOLOGICAL OUTCOME MEASURES IN TBI

HEART FAILURE CLINICAL RESEARCH NETWORK

IMMUNOMODULATION AND VACCINE OPTIMIZATION AGAINST CHLAMYDIA

EXCELLENCE IN RESEARCH - INVESTIGATING SMOOTH MUSCLE-BASED REGULATION OF NON-SHIVERING THERMOGENESIS

FRONTIERS IN ENVIRONMENTAL SCIENCE AND HEALTH (FRESH - PROJECT SUMMARY THIS NEW APPLICATION SEEKS NIEHS RISE (R25) SPONSORSHIP FOR OUR INNOVATIVE ADVANCED PROGRAM ENTITLED “FRONTIERS IN ENVIRONMENTAL SCIENCE AND HUMAN HEALTH (FRESH)” TO TRAIN AND MENTOR PROMISING GRADUATES, MEDICAL STUDENTS, POST-DOCTORAL FELLOWS AND JUNIOR FACULTY FROM PREDOMINANTLY UNDERREPRESENTED COMMUNITIES IN SOPHISTICATED TECHNOLOGIES IN ENVIRONMENTAL HEALTH SCIENCE RESEARCH RESEARCH. THIS PROPOSAL IS RESPONSIVE TO RFA-ES-20-015 AS ITS MAIN GOAL IS TO CREATE EDUCATIONAL OPPORTUNITIES FOR GRADUATE STUDENTS, MEDICAL STUDENTS, POSTDOCTORAL FELLOWS, AND JUNIOR FACULTY IN AREAS OF ENVIRONMENTAL HEALTH SCIENCE RESEARCH PERTINENT TO THE NIEHS, WHILE FOSTERING THE CAREER DEVELOPMENT OF THESE STUDENTS AND FELLOWS. A MAJOR STRENGTH OF FRESH IS THAT IT DRAWS FROM UNDERREPRESENTED MINORITY (URM) APPLICANT POOLS; THE ATLANTA UNIVERSITY CENTER (AUC) WHICH INCLUDES MOREHOUSE COLLEGE, SPELMAN COLLEGE AND CLARK ATLANTA UNIVERSITY, WHICH IS THE LARGEST CONSORTIUM OF BLACK INSTITUTIONS OF HIGHER EDUCATION IN THE USA AS WELL AS HISPANIC AND NATIVE AMERICAN SERVING INSTITUTIONS. MOREHOUSE SCHOOL OF MEDICINE (MSM) IS LINKED DIRECTLY TO THESE INSTITUTIONS THROUGH A FORMAL SYSTEM OF PIPELINE PROGRAMS. IN ADDITION, WE PLAN TO DRAW URM’S FROM OTHER INSTITUTIONS REGARDLESS OF THEIR URM POPULATION SIZE. OUR TARGET POPULATION IS DIVERSE AND AMONG THE MOST PROMISING NATIONALLY COMPETITIVE TRAINEES. FRESH OFFERS DYNAMIC TRAINING THROUGH A SERIES OF DAILY LECTURERS ON EMERGING CONCEPTS, EXTENDED DISCUSSION, LABORATORY RESEARCH, WORKSHOPS AND INFORMAL SEMINARS FOR A WEEK-LONG SUMMER COURSE. THE PRIMARY AIM IS THE DEVELOPMENT OF AN INTENSE LABORATORY-BASED TRAINING FOR 16 PARTICIPANTS PER YEAR TO EDUCATE THEM IN ENVIRONMENTAL HEALTH SCIENCE, AND TO HELP LAUNCH AND SUSTAIN THEIR CAREERS. WE PROPOSE A FIVE-YEAR PROGRAM TO ENROLL A TOTAL OF EIGHTY (80) TRAINEES (16 TRAINEES PER YEAR) FOR TRAINING AT MSM. IN SUMMARY, FRESH WILL OFFER DYNAMIC AND SOPHISTICATED TRAINING COURSES THAT CONSIST OF DAILY LECTURES FROM LEADING EXPERTS, ACTIVE LEARNING SESSIONS, AND EXTENDED DISCUSSIONS ON IMPORTANT AND EMERGING TOPICS FOLLOWED BY HANDS-ON LABORATORY SESSIONS. EXAMPLES OF TOPICS WITHIN FRESH INCLUDE: DISPARATE IMPACTS OF AIR POLLUTANTS, WATER POLLUTANTS, AND COMMON PERSISTENT POLLUTANTS SUCH AS FLAME RETARDANTS AND PESTICIDES; GENE X ENVIRONMENT INTERACTIONS IN DRIVING HEALTH OUTCOMES; EXPOSOME AND LIFETIME EXPOSURE IMPACTS ON HUMAN HEALTH; IMPACTS OF THE COVID-19 PANDEMIC ON HUMAN EXPOSURES TO ENVIRONMENTAL TOXICANTS; AND DISSEMINATION AND IMPLEMENTATION STRATEGIES TO ENGAGE HEALTH CARE PROVIDERS TO CONSIDER ENVIRONMENTAL CONTAMINANTS IN DIAGNOSES AND TREATMENTS, ESPECIALLY WITH REGARD TO URM PATIENTS.

CELL EXCITATION IN ISCHEMIC BRAIN INJURY.

EMPOWERING COMMUNITIES FOR A HEALTHIER NATION INITIATIVE (ECI) (OPIOID ABUSE)

PEER PREVENTION NAVIGATION FOR BLACK YOUTH AND YOUNG ADULTS, 16-24

EXCELLENCE IN RESEARCH: NEUROANATOMY AND DEVELOPMENT OF MAMMALIAN HOMEOSTATIC SLEEP REGULATION

THE MOREHOUSE SCHOOL OF MEDICINE REACH HEALTH INITIATIVE (MSM REACH HI): TRANSFORMING METROPOLITAN ATLANTA COMMUNITIES THROUGH PREVENTION, PRIMARY CA

EXCELLENCE IN RESEARCH: ROLE OF ACID-SENSING ION CHANNELS IN NEURONAL DEVELOPMENT/MATURATION -THE FUNCTION OF THE NERVOUS SYSTEM RELIES ON THE ESTABLISHMENT OF NEURONAL CIRCUITS DURING DEVELOPMENT. THE MECHANISMS BY WHICH NEURONS ADOPT SPECIFIC MORPHOLOGIES AND CONNECTIONS REMAIN UNCLEAR. THIS INVESTIGATION WILL IDENTIFY THE ROLE OF A MEMBRANE PROTEIN CALLED ACID-SENSING ION CHANNEL 1A, WHICH SENSES BRAIN ACIDITY IN THE DEVELOPMENT AND MATURATION OF BRAIN NEURONS. THROUGH AN ARRAY OF METHODOLOGICAL APPROACHES, THE STUDY WILL DETERMINE THE ROLE OF ACID SENSING IN NORMAL NERVOUS SYSTEM DEVELOPMENT. THE FINDINGS FROM THIS INVESTIGATION MAY HELP IN DEVISING TREATMENTS FOR NEURODEVELOPMENTAL DISORDERS ASSOCIATED WITH DYSREGULATION OF ACID-BASE BALANCE. THROUGH AN INTEGRATED EDUCATIONAL AND RESEARCH TRAINING PROGRAM, THIS PROJECT WILL ENABLE STUDENTS AT DIFFERENT LEVELS, PARTICULARLY THOSE FROM UNDERREPRESENTED GROUPS IN STEM, TO GAIN HANDS-ON EXPERIENCE IN DIVERSE METHODOLOGIES RELEVANT FOR RESEARCH IN NEUROSCIENCE. THESE EXPERIENCES WILL BETTER POSITION TRAINEES TO PURSUE CAREERS IN STEM AND CONTRIBUTE TO BROADENING PARTICIPATION ACROSS THE STEM WORKFORCE. NEURONAL DEVELOPMENT AND MATURATION ARE ESSENTIAL FOR THE NORMAL STRUCTURE AND FUNCTIONS OF THE BRAIN. THE SPECIFIC SIGNALING PATHWAYS INVOLVED IN THESE PROCESSES, HOWEVER, ARE NOT FULLY UNDERSTOOD. THE GOAL OF THIS PROPOSAL IS TO TEST THE HYPOTHESIS THAT ACID-SENSING ION CHANNEL 1A (ASIC1A), A NOVEL PROTON-GATED AND CA2+-PERMEABLE CATION CHANNEL, PLAYS AN IMPORTANT ROLE IN NEURONAL DEVELOPMENT AND MATURATION. PROTON CONCENTRATIONS CHANGE LOCALLY WHEN SYNAPTIC VESICLES RELEASE THEIR ACIDIC CONTENTS DURING NEUROTRANSMISSION, AND GLOBALLY IN THE BRAIN DURING PERIODS OF INTENSE NEURAL ACTIVITY. FOR DECADES, THE SIGNALING ROLE PROTONS PLAY IN NEURONS REMAINED ELUSIVE. THE FINDING THAT PROTONS CAN GATE A DISTINCT FAMILY OF ION CHANNELS HAS SHED NEW LIGHT ON THE MECHANISMS OF ACID SIGNALING. ASIC1 IS WIDELY EXPRESSED IN NEURONS OF THE PERIPHERAL AND CENTRAL NERVOUS SYSTEMS. EMERGING STUDIES HAVE DEMONSTRATED THAT ACTIVATION OF ASIC1A PLAYS IMPORTANT ROLES IN NEURONAL INJURY ASSOCIATED WITH VARIOUS NEUROLOGICAL CONDITIONS. IN CONTRAST, THE PHYSIOLOGICAL FUNCTIONS OF ASIC1A IN THE DEVELOPING BRAIN REMAIN LARGELY UNCLEAR. USING A COMBINATION OF MOLECULAR BIOLOGY, IMAGING, ELECTROPHYSIOLOGY, PHARMACOLOGY, PROTEOMICS, RNA-SEQ, IN VITRO AND IN VIVO MODELS, THE PROPOSED STUDIES WILL SYSTEMATICALLY EXAMINE THE ROLE OF ASIC1A IN NEURONAL DEVELOPMENT AND MATURATION AND ITS UNDERLYING SIGNALING MECHANISMS. UNDERSTANDING THE FUNDAMENTAL FUNCTION OF ASIC1A IN NERVOUS SYSTEM DEVELOPMENT WILL ADVANCE THE FIELD OF NEUROSCIENCE AND MAY ALSO HELP ESTABLISH NOVEL THERAPEUTIC STRATEGIES FOR TREATING NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS. 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.

OPTIMAL & EQUITABLE CARE: MEDICAID DATA RESEARCH INFRASTRUCTURE

RURAL COMMUNITIES OPIOID RESPONSE-IMPLEMENTATION

INFLUENCE OF NMDA RECEPTORS ON EPSP SUMMATION IN NORMAL AND EPILEPTIC RATS

HEALTH POLICY LEADERSHIP FELLOWSHIP PROGRAM

THE BS/MS PROGRAM IN NEUROSCIENCE AT THE ATLANTA UNIVERSITY CONSORTIUM

FUNCTION OF MST4-EZRIN-ACAP4 SIGNALING IN GASTRIC PARIETAL CELL SECRETION AND HOMEOSTASIS

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - CONSTRUCTION

SCREENING, BRIEF INTERVENTION AND REFERRAL TO TREATMENT (SBIRT)

PREVENTIVE MEDICINE RESIDENCIES

PHOTIC AND CIRCADIAN REGULATION OF RETINAL MELATONIN

PROMOTING OUR WORTH AS ENTREPRENEURS AND RESEARCHERS IN INNOVATIVE TECHNOLOGY

CCHAP II

USING QUALITY PREVENTING TO ADDRESS HEALTH INEQUITIES

EXCELLENCE IN RESEARCH: THE ROLE OF STAT5 SIGNALING IN PLACENTAL DYSFUNCTION, INFLAMMATION, AND FETAL IMMUNE ACTIVATION -THE PLACENTA IS ESSENTIAL FOR A HEALTHY PREGNANCY, SUPPORTING FETAL DEVELOPMENT WHILE REGULATING IMMUNE SIGNALS THAT ARE NECESSARY TO PROTECT BOTH MOTHER AND BABY. ONE KEY PATHWAY INVOLVED IN THIS PROCESS IS THE JAK/STAT SIGNALING PATHWAY. DISRUPTIONS IN THIS PATHWAY CAN LEAD TO HARMFUL INFLAMMATION, PLACENTAL DYSFUNCTION, AND COMPLICATIONS DURING PREGNANCY. THIS PROJECT AIMS TO UNDERSTAND HOW TWO SPECIFIC PROTEINS IN THE JAK/STAT PATHWAY, STAT2 AND STAT5B, CONTRIBUTE TO THE IMMUNE PROCESSES THAT SUPPORT A HEALTHY PREGNANCY. THROUGH AN ARRAY OF INNOVATIVE TECHNIQUES AND CUTTING-EDGE HUMAN PLACENTAL ORGANOID MODELS, THIS PROJECT WILL IDENTIFY KEY MEDIATORS AND MECHANISMS INVOLVED IN PLACENTAL DEVELOPMENT AND DYSFUNCTION AND WILL EXPAND SCIENTIFIC UNDERSTANDING OF THE MOLECULAR PROCESSES THAT INFLUENCE REPRODUCTIVE BIOLOGY AND FETAL IMMUNE DEVELOPMENT. OUTCOMES OF THIS RESEARCH ARE THE FIRST STEP IN DEVELOPING THERAPEUTICS TO ENSURE HEALTHY PREGNANCIES. THE PROJECT WILL ALSO PROVIDE HANDS-ON TRAINING OPPORTUNITIES FOR STUDENTS AT VARIOUS EDUCATIONAL LEVELS, PROMOTING THE DEVELOPMENT OF NECESSARY SKILLS IN BIOMEDICAL RESEARCH. THUS, THIS RESEARCH WILL AID IN DEVELOPING THE STEM WORKFORCE FOR THE US BIOECONOMY. THE OBJECTIVE OF THIS PROPOSAL IS TO BRIDGE THE TREMENDOUS GAP IN THE FUNDAMENTAL UNDERSTANDING OF INNATE IMMUNE SIGNALING AT THE PLACENTA AND TO IDENTIFY THE MECHANISMS ASSOCIATED WITH PLACENTAL DEVELOPMENT AND IMMUNE DYSFUNCTION. THE PLACENTA AS THE INTERFACE BETWEEN MOTHER AND FETUS IS A ROBUST IMMUNOLOGICAL ORGAN AND ORCHESTRATES KEY SIGNALS NECESSARY TO SUSTAIN A HEALTHY PREGNANCY AND MAINTAIN IMMUNE HOMEOSTASIS NECESSARY FOR IMMUNE PROTECTION AND TOLERANCE OF THE HLA-DISCORDANT FETUS. IN A NORMAL, HEALTHY PREGNANCY A DELICATE BALANCE OF HORMONES AND CYTOKINES REGULATES JAK/STAT SIGNALING IN IMMUNE CELLS AT THE MATERNAL-FETAL INTERFACE. THIS PATHWAY IS ESSENTIAL DURING PREGNANCY FOR IMPLANTATION, PLACENTAL DEVELOPMENT, AND IMMUNITY, HOWEVER INCREASING EVIDENCE SUGGESTS THAT ABERRANT JAK/STAT SIGNALING AT THE PLACENTA IS ASSOCIATED WITH DELETERIOUS INFLAMMATION AND PLACENTAL DYSFUNCTION. PRELIMINARY DATA SUGGEST THAT STAT2 SIGNALING PROMOTES ANTI-INFLAMMATORY TH2 RESPONSES IN PLACENTAL CELLS, WHILE STAT5B ACTIVITY IS ASSOCIATED WITH PRO-INFLAMMATORY TH1 RESPONSES AND PLACENTAL DYSFUNCTION. THIS PROJECT WILL INVESTIGATE THE SPATIAL DISTRIBUTION, ACTIVATION DYNAMICS, AND DOWNSTREAM GENE NETWORKS ASSOCIATED WITH STAT2 AND STAT5B SIGNALING IN HUMAN PLACENTAL CELLS AND ORGANOIDS. THIS INNOVATIVE PROJECT WILL ADVANCE THE UNDERSTANDING OF INNATE IMMUNE SIGNALING AT THE MATERNAL-FETAL INTERFACE, IDENTIFY MECHANISMS THAT SUSTAIN OR THREATEN NORMAL PLACENTAL DEVELOPMENT, AND ELUCIDATE THE IMPACT OF PLACENTA IMMUNE ACTIVATION ON FETAL IMMUNITY. TRAINING OF STUDENTS AND POST-DOCS WILL ALSO OCCUR AS AN IMPORTANT MEANS TO DEVELOP THE NEXT GENERATION OF RESEARCHERS FOR THE BIOECONOMY. 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.

REPURPOSING THYMOQUINONE AS THERAPY FOR METASTATIC CASTRATION-RESISTANT PROSTATE CANCER

HIV CAPACITY BUILDING INITIATIVE (HIV CBI)

EXCELLENCE IN RESEARCH: THE ROLE OF NEUREGULIN-1 IN PROLIFERATION AND DIFFERENTIATION OF BRAIN CORTICAL NEURONAL STEM CELLS DURING FETAL DEVELOPMENT -NEUREGULINS (NRGS) ARE A FAMILY OF STRUCTURALLY RELATED SIGNALING PROTEINS THAT BIND TO RECEPTOR TYROSINE KINASES OF THE ERBB FAMILY AND MEDIATE A MYRIAD OF CELLULAR FUNCTIONS INCLUDING SURVIVAL, PROLIFERATION, AND DIFFERENTIATION IN BOTH NEURONAL AND NON-NEURAL SYSTEMS. SIGNALING MEDIATED BY NEUREGULIN-1 (NRG-1) AND ITS RECEPTOR ERB4 PLAYS A CRITICAL ROLE IN BRAIN DEVELOPMENT AND FUNCTIONS. THIS PROJECT WILL USE CONGLOMERATIONS OF NEURONS GROWN IN CELL CULTURE (CALLED ?CORTICAL ORGANOIDS?), AS WELL AS EXPERIMENTS IN MICE, TO INVESTIGATE THE ROLE OF NEUREGULIN-1 AND ITS RECEPTOR ERBB4 IN BRAIN DEVELOPMENT. BECAUSE DELETION OF THE NGR1 GENE IS LETHAL IN EMBRYONIC MICE, CORTICAL ORGANOIDS ARE USED AS A SUBSTITUTE TO ELUCIDATE ITS ROLE IN BRAIN DEVELOPMENT. PARALLEL COMPARISONS IN MICE WILL ENABLE VALIDATION OF OBSERVED EFFECTS AND PROVIDE A NEW PLATFORM AMENABLE TO MANIPULATION AND HYPOTHESIS TESTING THAT WAS NOT PREVIOUSLY POSSIBLE. FURTHERMORE, UNDERSTANDING THE EFFECTS OF NRG1 ON CELL PROLIFERATION AND DIFFERENTIATION IN CORTICAL NEURONS WILL UNVEIL KEY MECHANISMS MEDIATING BRAIN MORPHOGENESIS. THE PROPOSED STUDY WILL ADVANCE THE FIELD BY GENERATING A DEVELOPMENTAL MAP OF NEUREGULIN-1/ERBB4 EXPRESSION AND CELLULAR LOCALIZATION. THE PROJECT PROVIDES A UNIQUE OPPORTUNITY FOR MENTORING UNDERREPRESENTED HIGH SCHOOL, MINORITY UNDERGRADUATE AND GRADUATE STUDENTS AS WELL AS POSTDOCTORAL FELLOWS TO PARTICIPATE IN CUTTING EDGE 3D ORGANOID TISSUE ENGINEERING RESEARCH AT MOREHOUSE SCHOOL OF MEDICINE, THAT WILL POSITION THEM TO PURSUE STEM CAREERS WITH THE ULTIMATE GOAL OF ENHANCING THE DIVERSITY OF THE SCIENTIFIC WORKFORCE IN THE USA. NEUREGULINS (NRGS) MEDIATE VARIOUS FUNCTIONS ASSOCIATED WITH THE DEVELOPMENT AND MAINTENANCE OF THE NERVOUS SYSTEM, BREAST, HEART, AND OTHER ORGANS. NRG-1 IS OF GREAT INTEREST BECAUSE IT REGULATES CELL MAINTENANCE, DIFFERENTIATION, PROLIFERATION, MIGRATION, AND APOPTOSIS IN NEURONAL AND NON-NEURONAL CELL TYPES. WHILE THE ROLE OF NRG-1 IN FETAL DEVELOPMENT HAS BEEN REPORTED, ITS ROLE IN SIGNALING MECHANISMS DURING BRAIN DEVELOPMENT IS NOT WELL UNDERSTOOD. THE ROLE OF NRG-1/ERBB4 SIGNALING, AS WELL AS ITS CROSSTALK WITH FACTORS (BIOMARKERS) ASSOCIATED WITH NEURAL STEM CELL (NSC) PROLIFERATION AND DIFFERENTIATION, NEURAL MIGRATION AND CELLULAR MATURATION DURING BRAIN CORTEX DEVELOPMENT REMAINS UNKNOWN. THIS PROJECT EXAMINES HOW NRG-1 MEDIATES NORMAL BRAIN CORTICAL DEVELOPMENT VIA AN ERBB4-DEPENDENT PATHWAY INVOLVING MODERATORS (EFFECTORS) OF CELL CYCLE, NEURAL MIGRATION, DIFFERENTIATION, AND CELLULAR MATURATION. REGION-SPECIFIC EXPRESSION AND FUNCTION OF NRG-1 AND ITS RECEPTOR ERBB4 IN HUMAN CORTICAL ORGANOIDS (EITHER ALONE OR IN CO-CULTURE WITH MICROGLIAL CELLS) WILL BE COMPARED WITH CORTICES OF NRG-1 DEFICIENT MICE TO ELUCIDATE THE ROLE OF NRG-1 IN BRAIN DEVELOPMENT. MULTIPLE TECHNIQUES INCLUDING DIGITAL SPACE PROFILING (DSP), SIGNALS OF PROTEINS SECRETED FROM SINGLE CELLS (ISOPLEXIS), BIOLOGICAL IMAGING (CONFOCAL, LIGHT SHEET AND 2-PHOTON MICROSCOPY), IMMUNOHISTOCHEMISTRY (IHC), WESTERN BLOTTING AND SINGLE CELL RNA SEQUENCING (SCRNA SEQ) WILL BE USED TO COMPARE CELLULAR EXPRESSION AND FUNCTION OF NRG-1 IN HUMAN AND MURINE CORTICAL ORGANOID DEVELOPMENT. CROSSTALK BETWEEN NRG1/ERBB4 SIGNALING AND DEVELOPMENTAL FACTORS DURING CORTICAL BRAIN DEVELOPMENT WILL BE ASSESSED. THIS PROJECT WILL CLARIFY THE ROLE OF NRG-1/ERBB4 SIGNALING IN THE DEVELOPMENT OF A FUNCTIONAL BRAIN. 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.

CAMPUS AND COMMUNITY HIV AND ADDICTION PREVENTION (CCHAP)

ROLE OF CHEMOKINE RECEPTOR IN DISPARITIES ASSOCIATED WITH PROSTATE CANCER PROGRES

POTENTIAL ROLE OF COMPASS H3K4 METHYLTRANSFERASE COMPLEXES IN ENVIRONMENTAL CIRCADIAN-ALIGNMENT - SUMMARY/ABSTRACT ENVIRONMENTAL-CIRCADIAN DISRUPTION SUCH AS SHIFTWORK AND JETLAG IMPOSES MAJOR RISK ON HUMAN HEALTH IN THE U.S. AND ABROAD. IT INCREASES THE RISK OF MANY METABOLIC AND CARDIOVASCULAR DISORDERS AND CANCERS AND EFFECTS OVER 16% OF THE U.S. WORKFORCE. YET, THE MOLECULAR UNDERPINNINGS OF THIS PROCESS REMAIN UNCLEAR. IN A PROTEOMIC ANALYSIS OF PROTEINS INTERACTING WITH CRY1, WE IDENTIFIED 10 COMPONENTS OF COMPASS COMPLEXES. THESE ENZYMATIC COMPLEXES REGULATE GENE TRANSCRIPTION BY CATALYZING THE ADDITION OF METHYL GROUPS TO LYSINE 4 OF HISTONE 3 (H3K4MES) OF LOCAL CHROMATIN. INTERESTINGLY, THESE CHROMATIN MARKS RESPOND TO ENVIRONMENTAL CIRCADIAN ENTRAINMENT INFORMATION SUCH AS LIGHT, TEMPERATURE OR NUTRIENTS. THEY ALSO HAPPEN IN A CIRCADIAN RHYTHMIC MANNER AND MODULATE DNA METHYLATION, A DETERMINANT OF GENE TRANSCRIPTION AND DISEASE DEVELOPMENT. FURTHERMORE, FUNCTIONAL PERTURBATIONS OF VARIOUS COMPASS COMPONENTS WERE ALSO IMPLICATED IN PATHOLOGICAL CONDITIONS ASSOCIATED WITH DISHARMONY OF ENVIRONMENTAL AND CIRCADIAN CYCLES SUCH AS BREAST CANCER AND OBESITY. WE THUS HYPOTHESIZE THAT COMPASS COMPLEXES PLAY A KEY ROLE IN ENVIRONMENTAL-CIRCADIAN ALIGNMENT. UNDER ENVIRONMENTAL-CIRCADIAN ALIGNMENT CONDITION, COMPASS COMPLEXES ARE RECRUITED BY CRY1 TO RHYTHMICALLY METHYLATE LOCAL H3K4S, WHICH PREVENT RECRUITMENT OF DNA METHYLTRANSFERASES RESULTING IN PERTURBATIONS OF DNA METHYLATION AND EXPRESSION OF CORE CLOCK GENE(S). THIS METHYLATION CASCADE MODULATES THE CIRCADIAN PATTERN OF GENE EXPRESSION, ENSURING ALIGNMENT OF THE CIRCADIAN SYSTEM WITH DAILY ENVIRONMENTAL CYCLES. THE METHYLATION CASCADE FAILS TO INITIATE WHEN INTERNAL CIRCADIAN SYSTEM MIS-ALIGNS WITH EXTERNAL ENVIRONMENTAL CYCLES, LEADING TO PERTURBATION OF THE HOMEOSTATIC STATE OF CELLS AND DEVELOPMENT OF DISORDERS. WE WILL INVESTIGATE THIS HYPOTHESIS BY PURSUING THE FOLLOWING INITIAL AIMS: 1: TO CHARACTERIZE CIRCADIAN CRY1::COMPASS INTERACTION; AIM 2: TO INVESTIGATE THE ROLE OF COMPASS COMPLEXES IN METHYLATION OF CORE CLOCK GENES; AIM 3: TO STUDY THE EFFECTS OF ENVIRONMENTAL- CIRCADIAN DISRUPTION ON COMPASS FUNCTION. THE RESULTS OF THIS PROJECT MIGHT UNVEIL THE MOLECULAR MECHANISM OF A FUNDAMENTAL BIOLOGICAL PROCESS: SYNCHRONIZATION OF DAILY INTERNAL PHYSIOLOGICAL RHYTHMS WITH EXTERNAL ENVIRONMENTAL CYCLES. THEY MIGHT ALSO ILLUMINATE THE NUTS AND BOLTS OF DISORDERS ASSOCIATED WITH SHIFTWORK.

RCMI BIANNUAL INTL HEALTH DISPARITIES SYMPOSIUM

ADDICTION TECHNOLOGY TRANSFER REGIONAL CENTER (ATTC)

HOW MATERNAL HCMV FACILITATES IN UTERO TRANSMISSION OF HIV AND IMPACTS THE DEVELOPING FETAL IMMUNE SYSTEM DURING GESTATION

MENTORED TRAINING PROGRAM TO INCREASE DIVERSITY IN HIV, SUBSTANCE USE AND MENTAL

AOD/HIV PREVENTION IN MALE ADOLESCENT DETAINEES

DEVELOPMENT AND VALIDATION OF HANDHELD DRIED-PLASMA BIOSAMPLING LATERAL FLOW (LF) TECHNOLOGY FOR TBI PROTEIN AND METABOLITES DIAGNOSTICS

EXCELLENCE IN RESEARCH: BIOENGINEERED EXTRACELLULAR VESICLES FROM STEM CELLS AND MACROPHAGES ACT SYNERGISTICALLY IN ANGIOGENESIS -EXTRACELLULAR VESICLES (EVS) ARE CELL-RELEASED MICROPARTICLES THAT PLAY ESSENTIAL ROLES IN CELL-CELL COMMUNICATION BY DELIVERING THEIR CARGO. TRADITIONAL APPROACHES TO STUDYING EVS HAVE FOCUSED ON INVESTIGATING EVS DERIVED FROM INDIVIDUAL CELL TYPES, DISREGARDING THE LIKELIHOOD THAT EVS ARE SECRETED BY ALL CELL TYPES AND COEXIST IN VARIOUS EXTRACELLULAR FLUIDS IN THE BODY. THIS PROJECT INTRODUCES AN INNOVATIVE EXPLORATION OF THE COLLABORATIVE EFFECTS OF EVS FROM DIVERSE SOURCES IN PROMOTING THE FORMATION OF BLOOD VESSELS. ADDITIONALLY, THE EV CELLS WILL BE MODIFIED THROUGH BIOENGINEERING TECHNIQUES TO ENHANCE THE PRODUCTION AND PROANGIOGENIC (BLOOD VESSEL FORMING) ACTIVITIES OF EVS. SUCCESSFUL COMPLETION OF THIS PROJECT WILL ADVANCE OUR UNDERSTANDING IN TWO KEY AREAS: 1) THE COOPERATIVE ACTIONS OF EVS FROM DIFFERENT CELL TYPES IN NORMAL PHYSIOLOGICAL PROCESSES AND PATHOLOGICAL RESPONSES, AND 2) THE EXPLORATION OF NOVEL THERAPEUTIC STRATEGIES UTILIZING EVS DERIVED FROM MULTIPLE SOURCES IN COMBINATION. FURTHERMORE, AN INTEGRATED EDUCATION PLAN IS DESIGNED TO INCREASE THE PARTICIPATION OF STUDENTS FROM GROUPS TRADITIONALLY UNDERREPRESENTED IN SCIENCE. THIS PROJECT WILL PROVIDE STUDENTS WITH RESEARCH TRAINING IN THE IMPLEMENTATION AND ANALYSIS OF EACH OBJECTIVE AND WITH INTRAMURAL AND EXTRAMURAL OPPORTUNITIES TO PRESENT THEIR FINDINGS. THE OUTCOMES OF THIS PROJECT WILL BE SCHOLARLY DISSEMINATED VIA PUBLICATION AND CONFERENCE PRESENTATIONS AND WILL BE INCORPORATED INTO EXISTING COURSES RELATED TO THE FORMATION OF BLOOD VESSELS. ANGIOGENESIS IS A TIGHTLY REGULATED PROCESS ESSENTIAL FOR EMBRYONIC DEVELOPMENT AND THE MAINTENANCE OF VASCULAR HOMEOSTASIS IN ADULT ORGANISMS. STEM CELLS AND MACROPHAGES ARE INVOLVED IN THE REGULATION OF ANGIOGENESIS VIA CELL DIFFERENTIATION AND FACTOR SECRETION. RECENTLY, VESICLES SECRETED FROM THE CELLS HAVE BEEN IMPLICATED IN THE ARRAY OF MEDIATORS IN THE ANGIOGENIC PROCESSES. TWO PRIMARY CLASSES OF NON-APOPTOTIC VESICLES, EXOSOMES AND MICROVESICLES, RELEASED BY CELLS ARE CATEGORIZED AS EVS. UNLIKE LIVING CELLS, EVS ARE SUBMICRON VESICLES THAT TARGET RECIPIENT CELLS TO DELIVER THEIR CARGO, INCLUDING RNAS, PROTEINS, AND LIPIDS, IN A CELL-FREE FASHION. PREVIOUS LITERATURE HAS DEMONSTRATED THAT CERTAIN MICRORNAS (MIRS) ARE INVOLVED IN ANGIOGENESIS, SO-CALLED ANGIOMIRS. THE OBJECTIVES OF THIS PROJECT ARE TO INVESTIGATE THE SYNERGISTIC EFFECTS OF EVS FROM MOUSE MESENCHYMAL STEM CELLS AND MACROPHAGES ON ANGIOGENESIS IN VITRO AND IN VIVO. THE STEM CELLS AND MACROPHAGES WILL BE ENGINEERED BEFOREHAND TO OVEREXPRESS MIR-31 AND MIR-30, RESPECTIVELY, BASED ON PREVIOUS REPORTS. THE IN VITRO ANGIOGENIC EFFECTS OF A MIXTURE OF THE EVS RELEASED FROM THE TWO TYPES OF ENGINEERED CELLS WILL BE EXAMINED ON VASCULAR ENDOTHELIAL CELLS INCLUDING PROLIFERATION, MIGRATION, AND TUBE FORMATION IN COMPARISON WITH EITHER TYPE OF EVS. TO FURTHER EXPLORE THE FUNCTION OF NEOVASCULATURE, THE ANGIOGENIC EFFECTS OF THE MIXTURE OF THE TWO ENGINEERED EVS WILL BE INVESTIGATED IN A MOUSE HINDLIMB ISCHEMIA (HLI) MODEL. MOREOVER, THE SYNERGISTIC ROLES OF MIR-31/FIH1 AND MIR-30/CUL2 SIGNALING PATHWAYS ON HIF-1? TRANSACTIVATION, AN ESSENTIAL STEP IN PROANGIOGENESIS, WILL BE TESTED. THE RESULT OF THIS STUDY WILL BE A COMPREHENSIVE UNDERSTANDING OF HOW DIVERSE EVS REGULATE ANGIOGENESIS. 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.

USING A NOVEL GEOSPATIAL STATISTICAL MODEL TO EVALUATE SPECIFIC SOCIAL AND ECOLOGICAL DETERMINANTS OF HEALTH IN CHILDREN WITH ANTIBIOTIC RESISTANT ST

EXCELLENCE IN RESEARCH: SPATIAL AND TEMPORAL MECHANISMS OF GENE EXPRESSION REGULATION

SEARCHING FOR MISSING HERITABILITY FOR CARDIOMETABOLIC OUTCOMES BY RACE

MSM TRAINING PROGRAM IN CARDIOVASCULAR SCIENCES

GENETIC ANALYSIS OF SUSCEPTIBILITY TO COPD EXACERBATIONS

PHENOME-GENOME CHARACTERIZATION OF ASTHMA IN AFRICAN-AMERICANS

ADDICTION TECHNOLOGY TRANSFER REGIONAL CENTER (ATTC)

PROJECT DADS INVOLVED IN NUTRITION EDUCATION (D.I.N.E.): ADDRESSING BLACK MATERNAL MORTALITY AND NUTRITION DISPARITIES THROUGH FATHER ENGAGEMENT IN GEORGIA

FOSTERING MENTAL HEALTH RESEARCH IN PSYCHIATRY RESIDENTS

ROLE OF MICRORNAS IN MALARIA AND SICKLE CELL SEVERITY

ROLE OF EPIGENETICS IN THE REGULATION OF BLOOD PRESSURE

PRESIDENT'S ACADEMY FOR SUCCESSFUL STUDENTS (PASS)

ACID-SENSING CHANNELS AS NOVEL TARGET FOR BRAIN ISCHEMIA

RESIDENCY TRAINING IN PRIMARY CARE

HEALTH CAREERS OPPORTUNITY PROGRAM

SCHOLARSHIPS FOR DISADVANTAGED STUDENTS

MOLECULAR MECHANISMS UNDERLYING RENAL LIPOTOXICITY AND DKD PROGRESSION - PROJECT SUMMARY DIABETIC KIDNEY DISEASE (DKD), THE LEADING CAUSE OF CHRONIC AND END STAGE RENAL DISEASE, IS CHARACTERIZED BY EXCESSIVE URINARY ALBUMIN EXCRETION FOLLOWED BY LOSS OF KIDNEY FUNCTION. IN DKD, OVER- REABSORPTION OF FILTERED ALBUMIN AND/OR ALBUMIN-BOUND PALMITIC ACID (PA), THE MOST ABUNDANT SATURATED FATTY ACID (FA) IN HUMAN URINE, COULD LEAD TO TUBULAR CELL INJURY AND ACTIVATION, WHICH MAY BE INVOLVED IN THE INDUCTION OF INTERSTITIAL FIBROSIS AND CHRONIC REDUCTION OF RENAL FUNCTION. HOWEVER, THE MOLECULAR LINK BETWEEN TUBULAR AND INTERSTITIAL CELLS DURING DKD PROGRESSION IS NOT CLEAR. KIDNEY INJURY MOLECULE-1 (KIM- 1) IS A NONINVASIVE BIOMARKER FOR RENAL PROXIMAL TUBULE (PT) DAMAGE AND HAS BEEN IDENTIFIED AS A SCAVENGER RECEPTOR FOR EPITHELIAL PHAGOCYTOSIS OF LIPOPROTEINS AND APOPTOTIC CELLS. WE HYPOTHESIZE THAT KIM-1 INTERACTS WITH STAT3 TO AMPLIFY PA-ALBUMIN REABSORPTION CAPACITY AND PROMOTE LIPOTOXICITY- INDUCED TUBULOINTERSTITIAL FIBROSIS IN PROGRESSIVE DKD. THE HYPOTHESIS WILL BE PURSUED WITH THE FOLLOWING SPECIFIC AIMS: AIM I WILL IN VIVO DETERMINE THE ROLE OF KIM-1 IN TUBULAR LIPID ACCUMULATION, STAT3 ACTIVATION, AND TUBULOINTERSTITIAL FIBROSIS DURING DKD ONSET AND PROGRESSION. SYSTEMATIC STUDIES WILL BE CONDUCTED TO 1) CONDUCT SPATIOTEMPORAL ANALYSIS OF KIM-1 EXPRESSION, LIPID ACCUMULATION, STAT3 ACTIVATION, AND ASSOCIATED LIPOTOXICITY AND FIBROSIS IN EARLY, MIDDLE AND ADVANCED STAGES OF DKD IN WILD- TYPE AND ENOS-/- MICE AND 2) DETERMINE THE EFFECTS OF KIM-1 DEFICIENCY ON TUBULAR LIPID ACCUMULATION, STAT3 ACTIVATION, AND TUBULOINTERSTITIAL INFLAMMATION AND FIBROSIS IN HIGH-FAT DIET-FED DIABETIC KIM-1- DEFICIENT (KIM-1-/-) AND KIM-1-/-/ENOS-/- MICE. AIM II WILL IN VITRO DETERMINE THE ROLE AND REGULATION OF KIM- 1 AND STAT3 IN PRIMARY CULTURED CELLS AND MATURE PROXIMAL TUBULOIDS IN RESPONSE TO DIFFERENT FA-ALBUMIN OVERLOAD. WE WILL DELINEATE THE DIFFERENTIAL EFFECTS OF DIFFERENT FA-BOUND ALBUMIN ON KIM-1, P-STAT3, AND LIPOTOXICITY BY EVALUATING CELL ATP DEPLETION, INTRACELLULAR LIPID DEPOSITION, AUTOPHAGY ACTIVITY AND ER STRESS, CELL DEATH, AND LYSOSOMAL OXIDATIVE STRESS IN BOTH 2D CELL CULTURE AND STABLE HUMAN TUBULOIDS. IN ADDITION, WE WILL EXAMINE IF KIM-1 OR STAT3 INHIBITION OR OVEREXPRESSION WOULD AFFECT PA-ALBUMIN OVERLOAD-INDUCED LIPOTOXICITY AND STAT3 ACTIVATION IN BOTH 2D CELL CULTURES AND 3D ORGANOIDS. UPON COMPLETION OF THESE EXPERIMENTS WE ARE HOPEFUL THAT KIM-1 WILL EMERGE AS A DRUGGABLE TARGET FOR THE PREVENTION AND TREATMENT OF DKD.

DETERMINING THE ROLE OF CIRCADIAN RHYTHMS IN CHLAMYDIA ASSOCIATED TUBAL INFERTILITY - ONE OF THE MANIFESTATIONS OF CHLAMYDIAL PATHOGENESIS IN WOMEN IS TUBAL FACTOR INFERTILITY (TFI). THE MOLECULAR MECHANISM UNDERPINNING THE PATHOLOGIC CHANGES THAT CAUSE TFI IS POORLY UNDERSTOOD. WE HAVE REPORTED THAT THE TIME OF DAY OF INFECTION INFLUENCES CHLAMYDIA INFECTIVITY AND PATHOGENESIS. RESULTS FROM OUR LAB SHOW THAT WHEN CIRCADIAN RHYTHMS WERE DISRUPTED USING A JET LAG MODEL, CHLAMYDIA-INFECTED MICE HAD INCREASED INFECTIVITY AND PATHOLOGY. OUR WORK HAS DEMONSTRATED THAT MIRNAS AND GENES ASSOCIATED WITH CIRCADIAN RHYTHMS ARE DIFFERENTIALLY EXPRESSED DURING CHLAMYDIA INFECTION. OUR PREMISE IN THIS STUDY HYPOTHESIZES THAT CIRCADIAN RHYTHMS HAVE A ROLE IN CONTROLLING/REGULATING CHLAMYDIAL PATHOGENESIS, LEADING TO INFERTILITY. THE CENTRAL GOAL OF THIS PROJECT IS TO UNDERSTAND THE ROLE OF CIRCADIAN RHYTHMS ON CHLAMYDIAL PATHOGENESIS THROUGH THESE AIMS (1) INVESTIGATE THE ASSOCIATION OF HOST CIRCADIAN RHYTHMS WITH CHLAMYDIAL PATHOGENESIS. WE HYPOTHESIZE THAT CIRCADIAN CONTROL OF CHLAMYDIAL PATHOGENESIS IS ESSENTIAL IN DETERMINING DISEASE OUTCOMES. WE WILL DETERMINE THE ROLE AND INVOLVEMENT OF CLOCK GENES BMAL1, PER2, AND CRY1 ON CHLAMYDIAL PATHOGENESIS USING COMMERCIALLY AVAILABLE BMAL1KO, PER2KO, AND CRY1KO MICE. (2) DEFINE THE CIRCADIAN CONTROL OF PATHWAYS INVOLVED IN CHLAMYDIAL PATHOGENESIS. WE HYPOTHESIZE THAT THE INTRINSIC DISPOSITION OF THE GENITAL TRACT TO PATHOGENEIC CHANGES WILL DEPEND ON WHAT GENES/PROTEINS ARE ACTIVATED OR INHIBITED BY CLOCK GENES. WE WILL ALSO DETERMINE GENES THAT ARE UNDERGOING CYCLING AT DIFFERENT STATES OF CHLAMYDIA INFECTION. WE WILL TEST THIS HYPOTHESIS USING C. MURIDARUM INFECTED WT, BMAL1KO, PER2KO, AND CRY1KO MICE. THIS STUDY GIVES US A BASIS TO PREDICT THE LEVEL OF SEVERITY OF PATHOGENESIS AFTER CHLAMYDIA INFECTION AND IDENTIFY NEW UNDERLYING MECHANISMS INVOLVED IN CHLAMYDIA PATHOGENESIS. BY ACCOMPLISHING THE OUTCOMES OF THE SPECIFIC AIMS, WE PREDICT THAT THE KNOWLEDGE GAINED WILL POSITIVELY IMPACT WOMEN'S REPRODUCTIVE HEALTH.

HIV CAPACITY BUILDING INITIATIVE (HIV CBI)

GENETIC EPIDEMIOLOGY OF TREATMENT RESISTANT HYPERTENSION IN AFRICAN AMERICANS