EAST CAROLINA UNIVERSITY

GRANT PROGRAM

GRANT PROGRAM

TRAINING LEADERS TO IMPROVE EDUCATION AND HEALTH OUTCOMES OF INDIVIDUALS WITH HIGH-INTENSITY NEEDS: A MULTI-INSTITUTION MENTORSHIP CONSORTIUM

FOCUSED COPE: SUPPORTING ENVIRONMENTAL JUSTICE IN CONNECTED COASTAL COMMUNITIES THROUGH A REGIONAL APPROACH TO COLLABORATIVE COMMUNITY SCIENCE

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

RYAN WHITE TITLE III: EARLY INTERVENTION SERVICES

IMPROVING UNDERGRADUATE ENGINEERING STUDENTS' DEGREE ATTAINMENT THROUGH INNOVATIVE RESIDENTIAL AND TRANSFER SUPPORT

IMPROVING SOCIAL, EMOTIONAL, BEHAVIORAL, AND ACADEMIC FUNCTIONING OF ELEMENTARY SCHOOL CHILDREN THROUGH THE INTERCONNECTED SYSTEMS FRAMEWORK

EFFECT OF EXERCISE MODALITY DURING PREGNANCY ON CHILDHOOD OBESITY RISK - PROJECT ABSTRACT THE IN-UTERO ENVIRONMENT, INCLUDING MATERNAL WEIGHT GAIN AND EXERCISE HABITS, CAN “PROGRAM” A CHILD TOWARDS DISEASE OR HEALTH AFTER BIRTH AND INTO ADULTHOOD. THE OFTEN-INTERGENERATIONAL CYCLE OF OBESITY BEGINS WITH A SIGNIFICANT NUMBER OF WOMEN WHO ARE OVERWEIGHT OR OBESE (OW/OB) AT THE TIME OF CONCEPTION AND THROUGHOUT PREGNANCY; THESE WOMEN ARE MORE LIKELY TO GIVE BIRTH TO INFANTS WHO ARE MACROSOMIC. BY AGE 5, OVERWEIGHT (OW) CHILDREN ALREADY HAVE SIGNS OF METABOLIC SYNDROME AND CARDIOVASCULAR DISEASE RISKS (E.G. OBESITY, HYPERLIPIDEMIA, HYPERGLYCEMIA, HYPERINSULINEMIA, AND HYPERTENSION). WHILE RESEARCH HAS DEMONSTRATED BENEFITS OF BOTH AEROBIC AND RESISTANCE EXERCISE FOR PREGNANT WOMEN AS WELL AS DECREASED ADIPOSITY AND IMPROVED MOTOR/HEART FUNCTION IN THEIR INFANTS, NO STUDIES HAVE BEEN DONE TO DETERMINE WHICH EXERCISE MODES ARE MOST BENEFICIAL FOR MOTHER AND BABY WHEN A WOMAN IS OVERWEIGHT OR OBESE AT THE TIME OF CONCEPTION. FOR ADULTS IN GENERAL, COMBINED AEROBIC AND RESISTANCE EXERCISE (AERE) DELIVERS THE GREATEST METABOLIC IMPROVEMENTS (E.G. INCREASED INSULIN SENSITIVITY, IMPROVED HEART FUNCTION, DECREASED ADIPOSITY). THEREFORE, THE PURPOSE OF THIS STUDY IS TO IDENTIFY WHICH PRENATAL EXERCISE TYPE(S) WILL ELICIT THE GREATEST POSITIVE IMPACT ON MATERNAL AND INFANT HEALTH WHILE REDUCING METABOLIC RISK MARKERS IN OW/OB PREGNANT WOMEN RELATIVE TO NON-EXERCISING COUNTERPARTS. USING A RANDOMIZED DESIGN, 284 PREGNANT WOMEN WILL UNDERGO AN EXERCISE INTERVENTION (AE, RE, AERE) FROM ENROLLMENT (~13-16 WEEKS GESTATION) UNTIL DELIVERY (~40 WEEKS GESTATION). THE CENTRAL HYPOTHESIS OF THIS STUDY IS THAT ADDING RE IMPROVES OUTCOMES; THUS, THE COMBINATION OF AEROBIC AND RESISTANCE EXERCISE NOT ONLY WILL IMPROVE INFANT CARDIOMETABOLIC HEALTH OUTCOMES, AS COMPARED TO AE ALONE, BUT WILL HAVE THE BEST COMPLIANCE OF ALL GROUPS. WE WILL TEST THIS HYPOTHESIS WITH TWO SPECIFIC AIMS TO: (1) DETERMINE THE INFLUENCE OF DIFFERENT EXERCISE MODES DURING OW/OB PREGNANCY ON INFANT CARDIOMETABOLIC HEALTH AND GROWTH TRAJECTORIES; AND (2) DETERMINE THE MOST EFFECTIVE EXERCISE MODE IN OW/OB PREGNANCY ON IMPROVING MATERNAL CARDIOMETABOLIC HEALTH. METHODS WILL INCLUDE MEASUREMENTS SUCH AS WEIGHT, ABDOMINAL CIRCUMFERENCE, BLOOD PRESSURE, LIPIDS, AND OTHER BIOMARKERS FOR BOTH MOTHERS AND INFANTS. THE STUDY WILL ALSO TRACK MATERNAL AND INFANT CARDIOMETABOLIC OUTCOMES THROUGH THE POST-PARTUM PERIOD, UP TO 12 MONTHS. THIS WORK HAS THE POTENTIAL TO IMPACT CLINICAL PRACTICE BY REVEALING THE EARLIEST AND MOST EFFECTIVE INTERVENTION TO REDUCE THE INTERGENERATIONAL CYCLE OF METABOLIC DYSFUNCTION, INCLUDING OBESITY, IN WOMEN AND CHILDREN. .

DELINEATION OF UNIQUE FLAGELLAR PROTEINS IN SPIROCHETES

POSTDOCTORAL TRAINING IN GENERAL, PEDIATRIC AND PUBLIC HEALTH DENTISTRY AND DENTAL HYGIENE

GRADUATE PSYCHOLOGY EDUCATION PROGRAMS

MATERNITY CARE NURSING WORKFORCE EXPANSION (MATCARE) TRAINING PROGRAM

RYAN WHITE PART C OUTPATIENT EIS PROGRAM

PROJECT ENGAGE EASTERN NORTH CAROLINA - RURAL EASTERN NORTH CAROLINA HAS LONG EXPERIENCED DISPROPORTIONATE EMPLOYMENT GAPS IN COMPARISON TO OTHER AREAS IN THE STATE. SPECIFICALLY, THE UNEMPLOYMENT RATE WITHIN THE SEVEN COUNTY CATCHMENT AREA CONSISTENTLY RISES ABOVE THE STATEWIDE MEAN. EMPLOYMENT TRENDS FOR INDIVIDUALS WITH SUBSTANCE USE DISORDERS AND CO-OCCURRING DISORDERS (SUD/COD) IN THE CATCHMENT AREA MIRROR THOSE FOR THE GENERAL PUBLIC. UNFORTUNATELY, THERE EXIST A LARGE GAP IN THE EMPLOYMENT SUPPORT SERVICE AVAILABILITY FOR INDIVIDUALS WITH SUD/COD. PROJECT ENGAGE-ENC SEEKS TO FILL AN ESSENTIAL GAP. TO ADDRESS THIS GAP IN REGIONAL SERVICE AVAILABILITY, ENGAGE-ENC SEEKS TO INCREASE THE WORKFORCE FOR INDIVIDUALS WITH SUD/COD THROUGH THE INTEGRATION OF INNOVATIVE, EVIDENCE-BASED VOCATIONAL SERVICES WITHIN STANDARD SUD/COD TREATMENT. ENGAGE-ENC WILL SERVE A TOTAL OF 337 UNDUPLICATED PARTICIPANTS OVER THE 5-YEAR PROJECT. SERVICES PROVIDED THROUGH ENGAGE-ENC INCLUDE COORDINATION WITH LOCAL AND STATE EMPLOYMENT AND RECOVERY-ORIENTED STAKEHOLDERS, PROVISION OF EVIDENCE-BASED INTERVENTIONS WITHIN VOCATIONAL SCREENING/EVALUATION, VOCATIONAL COUNSELING, AND SUPPORTED EMPLOYMENT/INDIVIDUAL PLACEMENT SUPPORT. THE MISSION OF ENGAGE-ENC IS TO PROVIDE INNOVATIVE, COMMUNITY-ENGAGED, AND RECOVERY-ORIENTED INTERVENTIONS THAT ASSIST INDIVIDUALS WITH SUD/COD TO FIND, GET, AND KEEP A JOB, AND SUSTAIN A RECOVERY LIFESTYLE. THE GOALS OF ENGAGE-ENC ARE (A) INCREASE THE JOB READINESS OF INDIVIDUALS WITH SUD/COD WITHIN THE CATCHMENT AREA, (B) DECREASE THE UNEMPLOYMENT RATE FOR INDIVIDUALS WITH SUD/COD WITHIN THE CATCHMENT AREA, AND (C) INCREASE RATES OF SUSTAINED RECOVERY FOR INDIVIDUALS WITH SUD/COD WITHIN THE CATCHMENT AREA. TO ACHIEVE THESE GOALS, THE OBJECTIVES THE PROJECT WILL ACHIEVE ARE (A) 85% OF PARTICIPANTS WILL COMPLETE VOCATIONAL EVALUATION ACTIVITIES (I.E., INTEREST, VALUES, APTITUDE, BARRIERS ASSESSMENT), (B) 80% OF PARTICIPANTS WILL ENGAGE IN RECOVERY-ORIENTED PREVOCATIONAL TRAINING AND VOCATIONAL COUNSELING INTERVENTION SESSIONS, (C) 60% OF ELIGIBLE PARTICIPANTS WILL ENGAGE IN INDIVIDUAL PLACEMENT AND SUPPORT SERVICES, (D) PARTICIPANTS WILL SUBMIT AN AVERAGE OF 5 JOB APPLICATIONS, E) PARTICIPANTS WILL AVERAGE 3 JOB INTERVIEWS, (F) 60% OF PARTICIPANTS WILL OBTAIN GAINFUL EMPLOYMENT, (G) 45% OF PARTICIPANTS WHO OBTAIN GAINFUL EMPLOYMENT WILL RETAIN EMPLOYMENT AT THE 90-DAY FOLLOW-UP PERIOD; AND (H) 65% OF PARTICIPANTS WILL DEMONSTRATE A REDUCTION OF SUBSTANCE USE AT THE 90-DAY FOLLOW UP PERIOD, (I) 65% OF PARTICIPANTS WILL DEMONSTRATE IMPROVED PSYCHOSOCIAL FUNCTIONING (E.G., OBTAINED HOUSING, REDUCED CRIMINAL ACTIVITY, REPORT LESS SYMPTOMS OF CO-OCCURRING MENTAL HEALTH ISSUE) AT THE 90 DAY FOLLOW UP PERIOD.

DETERMINING THE MOLECULAR BASIS OF GENE SILENCING BY MUCR AND DEFINING ITS ROLE IN BRUCELLA VIRULENCE - SUMMARY BRUCELLA SPP. CAUSE ONE OF THE WORLD’S LEADING ZOONOTIC DISEASES AND ARE A MAJOR PUBLIC HEALTH THREAT IN AREAS OF THE WORLD WHERE BRUCELLOSIS IS ENDEMIC IN FOOD ANIMALS. THE ZN FINGER PROTEIN MUCR IS A GLOBAL REGULATOR AND ESSENTIAL VIRULENCE DETERMINANT IN BRUCELLA, BUT PRECISELY HOW MUCR CONTRIBUTES TO VIRULENCE IS UNRESOLVED. STUDIES IN OUR LABORATORY HAVE PROVIDED COMPELLING EVIDENCE THAT MUCR IS A NOVEL TYPE OF H-NS- LIKE GENE SILENCER AND IDENTIFIED MULTIPLE VIRULENCE GENES THAT ARE DIRECT TARGETS OF MUCR REPRESSION. H-NS AND H-NS-LIKE GENE SILENCERS PLAY CRITICAL ROLES IN COORDINATING THE PROPER TEMPORAL EXPRESSION OF VIRULENCE GENES IN OTHER BACTERIAL PATHOGENS. THIS TIGHT REGULATION IS CRUCIAL BECAUSE THE GRATUITOUS EXPRESSION OF VIRULENCE GENES CAUSES FITNESS DEFECTS THAT CAN LEAD TO ATTENUATION IN THE HOST. THE STUDIES DESCRIBED IN THIS APPLICATION WILL USE GENETIC AND BIOCHEMICAL APPROACHES TO – A) DIRECTLY TEST THE HYPOTHESIS THAT MUCR IS A NOVEL TYPE OF H-NS-LIKE GENE SILENCER; B) IDENTIFY THE ANTAGONISTIC TRANSCRIPTIONAL ACTIVATORS THAT SERVE AS ‘COUNTER-SILENCERS’ AND OVERRIDE MUCR-SILENCING OF SPECIFIC BRUCELLA VIRULENCE GENES; AND C) TEST THE HYPOTHESIS THAT COORDINATED REGULATION OF SPECIFIC VIRULENCE GENES BY MUCR/COUNTER-SILENCER PAIRS IS REQUIRED FOR THE WILD-TYPE VIRULENCE OF B. ABORTUS 2308 IN MICE AND CULTURED MAMMALIAN CELLS. THE SAME BIOCHEMICAL PROPERTIES THAT ALLOW H-NS AND H-NS-LIKE PROTEINS TO SERVE AS GENE SILENCERS ALSO ALLOW THEM TO PLAY MAJOR ROLES IN CONDENSING BACTERIAL CHROMOSOMES AND MAINTAINING NUCLEOID STRUCTURE. WE HAVE RECENTLY USED CHROMOSOME CONFORMATION CAPTURE STUDIES (HI-C) TO SHOW THAT MUCR ALSO HAS NUCLEOID-STRUCTURING ACTIVITY, AND WE PLAN TO USE THIS APPROACH IN COMBINATION WITH GLOBAL AND GENE-SPECIFIC TRANSCRIPTIONAL ANALYSIS TO EVALUATE THE IMPACT THAT MUCR’S NUCLEOID- STRUCTURING ACTIVITY HAS ON ITS CAPACITY TO FUNCTION AS A GENE SILENCER. OUR PROPOSED RESEARCH WILL PROVIDE A MUCH BETTER UNDERSTANDING OF HOW MUCR FUNCTIONS AS A GENETIC REGULATOR AND VIRULENCE DETERMINANT IN BRUCELLA. IT WILL ALSO ALLOW US TO FURTHER EXAMINE A PREVIOUSLY UNCHARACTERIZED ROLE FOR A ZN FINGER PROTEIN IN PROKARYOTIC BIOLOGY.

ENGAGE ENC MINORITY AIDS INITIATIVE (MAI) - THE RATES OF SUBSTANCE USE AND CO-OCCURRING MENTAL HEALTH CONCERNS IN RURAL EASTERN NORTH CAROLINA HAVE STEADILY INCREASED, ALONG WITH NEW INCIDENCES OF HIV. UNFORTUNATELY, THIS INCREASE HAS DISPARATELY IMPACTED RACIAL/ETHNIC MINORITIES. PROJECT ENGAGE EASTERN NORTH CAROLINA: MINORITY AIDS INITIATIVE (ENGAGE ENC: MAI) WILL LEVERAGE THE EXISTING HIV TESTING AND TREATMENT INFRASTRUCTURE IN AN ELEVEN-COUNTY CATCHMENT WITHIN EASTERN NC TO ENHANCE IDENTIFICATION AND ACCESS TO TREATMENT FOR RACIAL/ETHNIC MINORITIES WHO PRESENT WITH SUBSTANCE USE AND CO-OCCURRING MENTAL HEALTH SYMPTOMS. OVER THE 5-YEAR PROJECT PERIOD, ENGAGE-ENC ENROLL AND SERVE A TOTAL OF 520 UNDUPLICATED INDIVIDUALS OVER THE FIVE-YEAR GRANT PERIOD FROM THE ELEVEN COUNTY CATCHMENT AREA. ENGAGEMENT SERVICES WILL INCLUDE PROVIDING HIV AND HEPATITIS TESTING, SCREENING AND ASSESSMENT FOR SUBSTANCE USE AND CO-OCCURRING MENTAL HEALTH CONCERNS, CARE COORDINATION, AND TREATMENT SERVICES. THE MISSION OF ENGAGE ENC: MAI IS TO ENHANCE THE OUTREACH AND CLINICAL SERVICE DELIVERY OF ENGAGE ENC TO DIRECTLY INCREASE ENGAGEMENT OF INDIVIDUALS FROM RACIAL/ETHNIC MINORITY GROUPS WITH SUD OR COD WHO ARE AT HIGH RISK FOR OR LIVING WITH HIV AND/OR VIRAL HEPATITIS INFECTION. ENGAGE ENC: MAI WILL BUILD UPON THE EXISTING OUTREACH AND TREATMENT MODEL OF ENGAGE ENC THROUGH COMMUNITY PARTNERSHIPS TO INCREASE ACCESS TO SCREENING AND REFERRAL TO APPROPRIATE CARE AND MINIMIZING BARRIERS TO SUSTAINED ENGAGEMENT. THE GOALS FOR ENGAGE ENC: MAI ARE TO: 1. REDUCE THE ACCIDENTAL DRUG OVERDOSE RATE IN THE ELEVEN-COUNTY CATCHMENT AREA; 2. INCREASE ACCESS TO SUD/COD AND HIV AND VIRAL HEPATITIS TREATMENT PROVIDERS FOR INDIVIDUALS IN THE ELEVEN-COUNTY CATCHMENT AREA; AND 3. REDUCE THE INCIDENCE OF NEW HIV AND HEPATITIS B AND C INFECTIONS IN THE ELEVEN-COUNTY CATCHMENT AREA. TO ACHIEVE THE GOALS, THE FOLLOWING ARE THE OBJECTIVES OF ENGAGE ENC: MAI: 1A. PROVIDE SCREENING, BRIEF INTERVENTION, AND REFERRAL TO TREATMENT FOR SUD OR COD FOR 100% OF ENROLLED CLIENTS; 1B. RETAIN AT LEAST 80% OF ENROLLED CLIENTS WHO SCREEN POSITIVE FOR SUD OR COD IN TREATMENT THROUGH 90-DAY FOLLOW-UP; 1C. DEMONSTRATE A REDUCTION OF SUBSTANCE USE FREQUENCY FOR AT LEAST 65% OF ENROLLED CLIENTS BY 6-MONTH FOLLOW-UP; 1D. DEMONSTRATE AN INCREASE IN PSYCHOSOCIAL FUNCTIONING FOR AT LEAST 65% OF ENROLLED CLIENTS BY 6-MONTH FOLLOW-UP. 2A. LINK AND COORDINATE CONNECTION TO APPROPRIATE TREATMENT FOR 100% OF ENROLLED CLIENTS REQUIRING TREATMENT; 2B. DEVELOP MOAS WITH AT LEAST 2 NEW PROVIDER ORGANIZATIONS IN THE ELEVEN-COUNTY CATCHMENT AREA PER YEAR; 2C. DEMONSTRATE A REDUCTION IN PERCEIVED BARRIERS TO TREATMENT. 3A. PROVIDE HIV AND VIRAL HEPATITIS SCREENING TO 100% OF AT-RISK ENROLLED CLIENTS; 3B. LINK AND COORDINATE CONNECTION TO APPROPRIATE HIV AND/OR VIRAL HEPATITIS TREATMENT FOR 100% OF ENROLLED CLIENTS REQUIRING TREATMENT WITHIN 30 DAYS OF POSITIVE TEST CONFIRMATION; 3C. PROVIDE HIV PREVENTION EDUCATION AND REFERRAL TO PREP FOR 100% OF ENROLLED CLIENTS CONSIDERED AT HIGH RISK FOR HIV; AND 3D. PROVIDE ANNUAL HIV AND VIRAL HEPATITIS TRAINING TO 100% OF ENGAGE ENC:MAI STAFF, AND COMMUNITY PARTNERS WITH A DEVELOPED MOA.

NRT-HDR: FINDING SIGNAL IN THE NOISE TO ENABLE SCIENCE-BASED COMMUNITY RESPONSE TO CHANGE IN COASTAL REGION

SELECTING SPERM WITH DISTINCT METABOLIC PHENOTYPES TO INCREASE ART EFFICIENCY - PROJECT SUMMARY/ABSTRACT MORE THAN 80,000 BIRTHS IN THE US OCCUR ANNUALLY AS A RESULT OF ASSISTED REPRODUCTIVE TECHNOLOGY (ART). THE SUCCESS OF ART TYPICALLY REQUIRES MULTIPLE EXPENSIVE CYCLES THAT TOGETHER EXCEED MANY US FAMILIES’ YEARLY HOUSEHOLD INCOMES. THE NECESSITY OF MULTIPLE ART CYCLES STEMS IN PART FROM AN INSUFFICIENT NUMBER OF HEALTHY PREIMPLANTATION EMBRYOS. HEALTHY EMBRYOS ARE A DIRECT PRODUCT OF THE HIGHEST-QUALITY GAMETES, YET LIMITED METHODS EXIST TO IDENTIFY THE HIGHEST-QUALITY SPERM. WITHIN THE FEMALE REPRODUCTIVE TRACT, SPERM WITH THE HIGHEST FERTILIZATION COMPETENCE ARE NATURALLY SELECTED BASED ON FUNCTIONAL PARAMETERS – MOTILITY PATTERNS, CHEMOTAXIS, AND THE ACROSOME REACTION. THE BEST FERTILIZATION-COMPETENT SPERM ALSO HAVE THE LOWEST LEVELS OF OXIDATIVE AND DNA DAMAGE. UNFORTUNATELY, CURRENT CLINICAL METHODS FOR SELECTING SPERM FOR INTRACYTOPLASMIC SPERM INJECTION (ICSI) DO NOT LEVERAGE THESE PARAMETERS. THE BROAD OBJECTIVE OF THIS APPLICATION IS TO DEFINE THE BIOCHEMICAL MECHANISMS BY WHICH SPERM UNDERGO MOTILITY SWITCHING AND FERTILIZATION COMPETENCE, AND RESULTS WILL BOTH ADVANCE THE STATE OF BASIC KNOWLEDGE AND ENABLE OPTIMIZATION OF IN VITRO SPERM SELECTION TECHNIQUES. THE OPTIMIZATION OF SPERM SELECTION FOR ART WILL IN TURN: 1) INCREASE PRODUCTION OF HEALTHY EMBRYOS; 2) REDUCE AVERAGE NUMBERS OF COSTLY CYCLES; AND THUS 3) LESSEN THE COST BURDEN ON LOWER-INCOME FAMILIES. IN AIM 1, WE WILL UTILIZE COMPLEMENTARY COMPREHENSIVE BIOENERGETIC PHENOTYPING, COMPUTER ASSISTED MOTILITY ANALYSIS (CASA), AND A NOVEL DEHYDROGENASE SCREEN TO DEFINE THE UNDERLYING MECHANISMS THROUGH WHICH METABOLITES PREDICTABLY MODULATE THE ESSENTIAL MOTILITY PATTERNS OF MOUSE SPERM. IN AIM 2, WE WILL TEST THE HYPOTHESIS THAT PREDICTABLE MOTILITY CHANGES IN RESPONSE TO METABOLITES CAN BE USED TO SELECT THE BEST MOUSE SPERM – THOSE WITH NORMAL MORPHOLOGY AND LOW LEVELS OF DNA DAMAGE, THE ABILITY TO NAVIGATE TOWARDS A CHEMOTACTIC SIGNAL AND INITIATE HYPERACTIVE MOTILITY, AND COMPLETE THE ACROSOME REACTION. WE WILL THEN EMPLOY IN VITRO FERTILIZATION (IVF) TO DETERMINE WHETHER MOUSE SPERM SELECTED BASED ON THESE METABOLISM-BASED MOTILITY TRAITS HAVE ENHANCED ABILITY TO GENERATE HEALTHY EMBRYOS. IN AIM 3, WE WILL EXPLOIT OUR EXPERIENCE WORKING WITH MOUSE SPERM TO DEFINE THE FUNDAMENTAL DIFFERENCES IN THE METABOLISM-BASED MOTILITY RESPONSES OF HUMAN SPERM. THIS PROJECT IS EXPECTED TO IDENTIFY THE MECHANISMS CONNECTING MICROENVIRONMENT TO SPERM FUNCTION AND THEREBY PROVIDE PROOF-OF-CONCEPT FOR THE RAPID DEVELOPMENT OF METHODS TO OPTIMIZE CLINICAL SELECTION OF FERTILIZATION-COMPETENT HUMAN SPERM FOR ART.

NEUROIMMUNE MECHANISMS OF KININ B1 RECEPTOR IN HYPERTENSION

EVIDENCE-BASED TELE-BEHAVIORAL HEALTH NETWORK PROGRAM

COLLABORATIVE RESEARCH: CO-DESIGNING FOR STATEWIDE ALIGNMENT OF A VISION FOR HIGH QUALITY MATHEMATICS INSTRUCTION

THIS PROJECT WILL VERIFY, CHARACTERIZE, MONITOR, AND MODEL MULTI-SPECIES FISH SPAWNING AGGREGATIONS (FSAS) IN FEDERAL WATERS OF THE GULF OF AMERICA AND EVALUATE HOW LONG-TERM HABITAT SUITABILITY FOR FSAS IS IMPACTED BY GLOBAL CHANGE. FSAS ARE HOTSPOTS OF BIOLOGICAL PRODUCTIVITY WHERE MULTIPLE FISH SPECIES CONVERGE AT PREDICTABLE LOCATIONS AND TIMES FOR BREEDING. FSAS ARE KEY TO HEALTHY FISH POPULATIONS, BUT INFORMATION ABOUT THEIR LOCATIONS, CONNECTIVITY BETWEEN FSA SITES, AND FSA LONG-TERM TRENDS IS INSUFFICIENT TO INFORM MANAGEMENT DECISIONS. THE GMFMC AND THE FGBNMS SERVE AS OUR RESOURCE MANAGEMENT PARTNERS, GIVEN THEIR JURISDICTION TO ENACT SPATIOTEMPORAL REGULATIONS FOR FSA CONSERVATION IN FEDERAL WATERS AND THE SANCTUARY, RESPECTIVELY. THE PROPOSED PROJECT ADDRESSES THE FISH, FISHERIES, AND FISHING COMMUNITIES AREA OF EMPHASIS OF RESTORE. THIS PROJECT ENGAGES INTERESTED PARTIES TO BRIDGE THE SCIENCE-TO-POLICY GAP VIA ADVISORY GROUPS AND A PROCESS TO IDENTIFY PRIORITY FSAS FOR CHARACTERIZATION, MONITORING, AND MODELING. THE PROJECT AIMS TO CONDUCT FIELD RESEARCH TO CHARACTERIZE, VERIFY, AND MONITOR FSA SITES VIA COOPERATIVE RESEARCH WITH FISHERS, VISUAL/VIDEO SURVEYS, AND LONG-TERM BIOPHYSICAL MONITORING. COOPERATIVE BIOPHYSICAL MONITORING OF SIX, PRIORITY, MULTI-SPECIES FSAS IN THE GULF WILL TAKE PLACE IN YEAR 1-5 AS PERMITTED WITH A LETTER OF AUTHORIZATION. ALSO, WE WILL DEVELOP A STUDY FLEET OF FISHERS THAT WILL BE TRAINED AND PERMITTED TO SAMPLE UP TO 120 ADDITIONAL SITES AS PRIORITIZED BY EXPERT RESOURCE END USERS AND SCIENTISTS DURING TWO WORKSHOPS. THIS INVESTMENT IN COOPERATION IS BACKED BY CONTRACTS FOR COMMERCIAL FISHERMEN SUMMING TO 17% OF OUR BUDGET. FINALLY, THE PROJECT WILL MODEL GLOBAL CHANGE AND VARIABILITY IMPACTS ON TRANSIENT FSAS AND CONNECTIVITY. THIS WORK WILL UTILIZE A MULTI-MODEL ECOLOGICAL NICHE MODELING APPROACH TO INVESTIGATE THE SPAWNING HABITATS OF SPECIES FORMING TRANSIENT FSAS. ADDITIONALLY, PARTICLE DISPERSAL MODELING WILL BE UTILIZED TO INVESTIGATE SOURCE/SINK DYNAMICS, EXAMINING CONNECTIONS BETWEEN FGBNMS AND OTHER AREAS OF THE GULF. THIS PROJECT EXPECTS TO PRODUCE A SYNTHESIS OF EXPERT KNOWLEDGE ON FSAS, ALONG WITH VERIFICATION AND CHARACTERIZATION OF FSAS IN THE GULF. ADDITIONALLY, FUTURE PROJECTIONS OF CHANGES IN SPAWNING HABITAT SUITABILITY AND PHENOLOGY OF FSA SITES AND ASSESSMENTS OF INTERANNUAL VARIATION IN LARVAL DISPERSAL PATHWAYS WILL BE PRODUCED. ALL NEW DATA PRODUCTS WILL BE MADE PUBLICLY AVAILABLE CONSISTENT WITH FAIR (FINDABLE, ACCESSIBLE, INTEROPERABLE, AND REUSABLE) PRINCIPLES THROUGH A DATA PORTAL. CONFIDENTIALITY WILL BE MAINTAINED IN CASES WHERE SHARING SENSITIVE INFORMATION COULD LEAD TO OVERFISHING AT VULNERABLE FSAS. MANAGERS WILL BE UPDATED ABOUT PRODUCTS AND CONTRIBUTE TO THEIR DESIGN THROUGH ADVISORY GROUP MEETINGS AND PRESENTATIONS TO THE GMFMC AND THE FGBNMS SANCTUARY ADVISORY COUNCIL.

TEAM EXPERIENCES AND MENTORING STRATEGIES FOR UNDERGRADUATE RESEARCH

PREDOCTORAL TRAINING IN GENERAL, PEDIATRIC, AND PUBLIC HEALTH DENTISTRY AND DENTAL HYGIENE

DISES: DRIVERS OF ECOSYSTEM-BASED ADAPTATION TO EXTREME EVENTS IN MANGROVE-REEF SOCIAL-ECOLOGICAL SYSTEMS -THIS PROJECT FOCUSES ON SOCIAL AND ENVIRONMENTAL PROCESSES AND INTERACTIONS THAT SHAPE THE EFFECTIVENESS OF ECOSYSTEM-BASED ADAPTATION (EBA) TO TROPICAL CYCLONES IN MANGROVE-REEF-DEPENDENT COASTAL COMMUNITIES. EBA HAS EMERGED OVER THE PAST DECADE AS AN ADAPTATION APPROACH THAT FOCUSES ON STRATEGIES SUCH AS RESTORATION, MANAGEMENT, AND CONSERVATION TO HELP REDUCE THE IMPACTS OF EXTREME EVENTS. SEVERAL STUDIES SHOW THAT MANGROVE FORESTS AND CORAL REEFS CAN SIGNIFICANTLY REDUCE FLOOD DAMAGE TO PEOPLE AND PROPERTY DURING TROPICAL CYCLONE EVENTS, WHILE ALSO PROVIDING VALUABLE RESOURCES SUCH AS TIMBER FOR RECONSTRUCTION AND FUEL IN THEIR AFTERMATH. THESE ECOSYSTEMS ARE, IN TURN, AFFECTED BY CYCLONE IMPACTS AND THE COMMUNITIES THAT USE AND MANAGE THEM. IN OTHER WORDS, EBA ARE AN INHERENTLY DYNAMIC SOCIAL-ECOLOGICAL SYSTEM (SES) WITH STRONG FEEDBACKS BETWEEN THE ECOSYSTEMS, THE PEOPLE AND COMMUNITIES DEPENDING UPON AND MANAGING THEM, AND EXTERNAL SHOCKS LIKE CYCLONES. WITH AN INTEGRATED APPROACH THAT COMBINES SOCIAL, ECOLOGICAL, AND ENGINEERING METHODS, THE INSIGHTS FROM THIS PROJECT WILL INFORM THE DESIGN OF EBA STRATEGIES FOR CYCLONE-PRONE COMMUNITIES WORLDWIDE. THE INVESTIGATORS ARE TRAINING GRADUATE STUDENTS TO CONDUCT INTERDISCIPLINARY COASTAL SCIENCE AND RESULTS ARE ENHANCING CURRICULA FOR UNDERGRADUATE STUDENTS STUDYING COASTAL ISSUES. RESEARCH OUTCOMES ARE BEING MADE AVAILABLE TO RESOURCE AND DISASTER RISK MANAGERS IN FIJI AND PUERTO RICO THROUGH WORKSHOPS, POLICY BRIEFS AND ONLINE MAPS. THIS PROJECT IS ADVANCING UNDERSTANDING OF HOW ECOSYSTEM-BASED ADAPTATION (EBA) IN MANGROVE-REEF SOCIAL-ECOLOGICAL SYSTEMS (SES) RESPOND TO CYCLONE IMPACTS AMONG VULNERABLE COMMUNITIES IN FIJI AND PUERTO RICO. BOTH ARE NATURAL RESOURCE-RICH SMALL ISLAND STATES FREQUENTLY EXPERIENCING CYCLONES, YET HAVE DIFFERENT ENVIRONMENTAL GOVERNANCE SYSTEMS. USING AN SES FRAMEWORK, THIS PROJECT IS IDENTIFYING HOW INTERACTIONS IN A MANGROVE-CORAL REEF SES AND EXTREME EVENTS SHAPE EXISTING AND EMERGING EBA ACTIONS AND OUTCOMES. THE PROJECT TAKES A CONVERGENT APPROACH, COMBINING NATURAL RESOURCE MANAGEMENT, ECOLOGY, AND ENGINEERING TO ASSESS THE SOCIAL AND ENVIRONMENTAL DRIVERS THAT SHAPE THE IMPLEMENTATION AND EFFECTIVENESS OF EBA. THE STUDY INCORPORATES: SOCIAL-SCIENCE METHODS TO IDENTIFY SOCIO-ECONOMIC AND GOVERNANCE DRIVERS OF EBA ACTIONS; REMOTE SENSING METHODS TO DETECT DRIVERS OF ECOLOGICAL CHANGE; AN AGENT-BASED MODEL TO DESCRIBE HOW SOCIAL PROCESSES AND INTERACTIONS WITH THE ENVIRONMENT INFLUENCE EBA ACTIONS, AND; A COASTAL FLOOD DAMAGE MODEL TO QUANTIFY THE FLOOD PROTECTION BENEFITS DERIVED UNDER DIFFERENT SCENARIOS OF MANGROVE AND REEF ECOSYSTEM EXTENT AND CONDITION. OUTPUTS FROM THESE METHODS WILL DEVELOP PREDICTIONS OF THE SOCIAL AND ECOLOGICAL OUTCOMES OF EBA UNDER DIFFERENT SCENARIOS OF FUTURE CYCLONE EVENTS AND MANGROVE-REEF MANAGEMENT STRATEGIES. RESULTS WILL INFORM FUTURE EBA EFFORTS ON SIMILAR COASTLINES WORLDWIDE. 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.

COLLAGEN-DERIVED PEPTIDES TO TARGET INFLAMMATION IN MYOCARDIAL INFARCTION - PROJECT SUMMARY MYOCARDIAL INFARCTION (MI) LEADS TO THE GENERATION OF A SCAR THAT IS MOSTLY CONSTITUTED BY CARDIAC EXTRACELLULAR MATRIX (ECM). THE BALANCE BETWEEN DEGRADATION AND DEPOSITION OF ECM IS A STRONG PREDICTOR OF CLINICAL OUTCOMES. ECM DEGRADATION OCCURS BY MATRIX METALLOPROTEINASES (MMPS); AND ECM DEPOSITION OCCURS BY CARDIAC FIBROBLASTS. BOTH ECM DEGRADATION AND DEPOSITION PROMOTE ADVERSE REMODELING AND PROGRESSION TO HEART FAILURE. WITHIN THE MMP FAMILY, MMP-9 HAS BEEN REPORTED AS A PROGNOSTIC INDICATOR OF CARDIAC DYSFUNCTION IN MYOCARDIAL INFARCTION (MI) PATIENTS; AS MMP-9 LEVELS DIRECTLY ASSOCIATE WITH PATIENT MORTALITY. THUS, THE ADVANTAGE OF INHIBITING MMP-9 AFTER MI HAS BEEN LONG RECOGNIZED. HOWEVER, CLINICAL TRIALS USING GLOBAL MMP-9 INHIBITION HAVE MOSTLY FAILED BOTH DUE TO LACK OF MMP INHIBITOR SPECIFICITY AND IMPORTANCE OF MMP-9 IN SEVERAL ESSENTIAL PROCESSES. WE RECENTLY IDENTIFIED AN ECM-DERIVED PEPTIDE (P1159) THAT ACTS AS A COMPETITIVE AND SPECIFIC MMP-9 SUBSTRATE. HEREIN, WE PROPOSE USE OF P1159 TO MODULATE MMP-9 CLEAVAGE OF NATIVE SUBSTRATES POST-MI. THIS APPROACH DOES NOT INHIBIT MMP-9 ACTIVITY, ALLOWING IT TO PARTICIPATE IN ESSENTIAL PROCESSES; INSTEAD, IT MODULATES MMP-9 PROTEOLYTIC CAPACITY TO REDUCE CLEAVAGE OF ENDOGENOUS SUBSTRATES THAT PROMOTE INFLAMMATION AND INHIBIT REPAIR. THE SYNTHETIC PEPTIDE P1159 IS A MIMETIC OF THE NATURALLY FORMED FRAGMENT C-1158/59 GENERATED BY MMP-9 CLEAVAGE OF COLLAGEN POST-MI. IN HUMANS, PLASMA LEVELS OF ENDOGENOUS C-1158/59 POST-MI CORRELATE WITH LOWER LEFT VENTRICLE FILLING PRESSURE, INDICATING A THERAPEUTIC POTENTIAL OF C-1158/59. INDEED, MICE TREATED WITH EXOGENOUS P1159 POST-MI DISPLAY LESS LV DILATION, REDUCED INFLAMMATION AND FIBROSIS, AND IMPROVED CARDIAC FUNCTION. IN VITRO, WE IDENTIFIED INTEGRIN A4 (ITGA4) AS A PEPTIDE RECEPTOR. WHILE WE KNOW THAT EXOGENOUS DELIVERY IS BENEFICIAL, HOW P1159 REGULATES POST-MI INFLAMMATION AND ECM DEPOSITION HAS NOT BEEN MECHANISTICALLY DISSECTED. ACCORDINGLY, THE CENTRAL HYPOTHESIS OF THIS PROPOSAL IS THAT P1159 BLUNTS ADVERSE REMODELING AFTER MI BY SERVING AS A COMPETITIVE SUBSTRATE TO REDUCE MMP-9 PROTEOLYSIS OF SUBSTRATES NECESSARY FOR PROMOTION OF INFLAMMATION AND ECM DEPOSITION. TO ELUCIDATE THE MODE-OF-ACTION AND SIGNALING PATHWAYS MEDIATED BY P1159 IN THE POST-MI SETTING, WE WILL USE CELL-SPECIFIC ITGA4 TRANSGENIC ANIMALS TO IDENTIFY THE MECHANISMS WHEREBY P1159 TEMPERS THE POST-MI INFLAMMATORY RESPONSE, MODULATES CARDIAC FIBROBLAST SIGNALING TO REDUCE ECM SECRETION; AND PROMOTES MACROPHAGE-FIBROBLAST CROSSTALK.

RUI: CNH2-L: AN INTEGRATIVE ANALYSIS OF PERCEPTIONS, POLICY, AND LAND USE IMPACT ON COASTAL AGRICULTURAL WATERSHED RESILIENCE

EFFECT OF MATERNAL EXERCISE IN WOMEN WITH OBESITY ON OFFSPRING MESENCHYMAL STEM CELL METABOLISM - PROJECT SUMMARY OBESITY IN PREGNANCY INCREASES THE RISK FOR EXCESSIVE ADIPOSITY IN OFFSPRING, WHICH TRACKS INTO ADULTHOOD AND CAN PERPETUATE ACROSS GENERATIONS. OUR PRELIMINARY DATA AND PUBLISHED STUDIES INDICATE THAT EXERCISE INITIATED DURING PREGNANCY IN SEDENTARY WOMEN WITH OBESITY LOWERS INFANT BMI Z-SCORES AND BODY FAT PERCENTAGE. THESE BENEFITS TO INFANT HEALTH ARE MORE PROFOUND WITH RESISTANCE EXERCISE DURING PREGNANCY. HOWEVER, THERE ARE FEW MECHANISTIC STUDIES IN HUMANS AIMED AT DISCERNING MECHANISMS OF MATERNAL EXERCISE-INDUCED CHANGES TO INFANT CELLULAR METABOLISM. OUR FINDINGS SUPPORT THE USE OF INFANT UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS (MSCS) AS A MODEL TO EXPLORE OFFSPRING CELLULAR PHENOTYPES IN HUMANS. IMPORTANTLY, THESE MSCS ARE OF THE SAME LINEAGE THAT DERIVE POSTNATAL TISSUES AND THUS, CAN BE DIFFERENTIATED INTO MESODERMAL CELL TYPES IMPORTANT FOR REGULATING WHOLE-BODY METABOLISM, SUCH AS MYOCYTES AND ADIPOCYTES. WE HAVE EVIDENCE OF IMPROVED CELLULAR PHENOTYPE IN INFANT MSCS EXPOSED TO MATERNAL AEROBIC EXERCISE (AE) WITH THE GREATEST IMPROVEMENTS IN MSC METABOLISM FROM MATERNAL RESISTANCE EXERCISE (RE). THE OBJECTIVE OF THE PROPOSED STUDY IS TO DETERMINE IF MATERNAL EXERCISE MITIGATES THE ADVERSE CONSEQUENCES OF GESTATIONAL OBESITY EXPOSURE USING THE MSC MODEL IN AN ANCILLARY STUDY FROM A PARENT GRANT THAT IS RANDOMIZING PREGNANT WOMEN WITH OBESITY TO AE, RE, OR USUAL CARE CONTROL. A SECONDARY OBJECTIVE IS TO DETERMINE IF THE MSC METABOLIC PROFILES ARE ASSOCIATED WITH INFANT WHOLE-BODY HEALTH OUTCOMES AT 1-, 6-, AND 12-MONTHS OF AGE. WE WILL TEST THIS HYPOTHESIS IN 64 SUBJECTS FROM THE PARENT TRIAL. IN AIM 1, WE WILL DETERMINE THE IMPACT OF MATERNAL EXERCISE IN WOMEN WITH OBESITY ON INFANT MSC SUBSTRATE METABOLISM AND BIOENERGETIC EFFICIENCY. THESE DATA WILL BE ASSOCIATED WITH INFANT WHOLE-BODY RESTING ENERGY EXPENDITURE AND SUBSTRATE OXIDATION VIA INDIRECT CALORIMETRY OVER THE FIRST YEAR OF LIFE. IN AIM 2, WE WILL DETERMINE THE ROLE OF MATERNAL EXERCISE MODE IN WOMEN WITH OBESITY ON INFANT MSC ADIPOGENESIS AND LIPID STORAGE. THESE DATA WILL BE ASSOCIATED WITH INFANT BODY COMPOSITION AS MEASURED BY DXA OVER THE FIRST YEAR OF LIFE. IN AIM 3, MSCS WILL UNDERGO A MULTIOMICS APPROACH WHERE WE WILL IDENTIFY CANDIDATE GENES AND EPIGENETIC SIGNATURES OF MATERNAL EXERCISE MODE. THESE OUTCOMES WILL BE CORRELATED WITH BLOOD METABOLOMIC MEASURES IN THE INFANT TO ESTABLISH GENE-METABOLITE PATHWAYS. LEVERAGING A LARGE, RIGOROUS RCT IN PREGNANT WOMEN WITH OBESITY, THIS WILL BE THE FIRST STUDY TO IDENTIFY HOW MATERNAL EXERCISE AFFECTS OFFSPRING CELLULAR METABOLISM. THIS WORK WILL HAVE SIGNIFICANT IMPACT BY TRANSLATING INFANT CELLULAR METABOLIC DATA WITH WHOLE-BODY METABOLIC DATA ACROSS THE FIRST YEAR OF LIFE.

USING A MICROCREDENTIAL MODEL TO PREPARE SECONDARY MATHEMATICS AND SCIENCE TEACHERS TO MEET THE NEEDS OF RURAL, HIGH-NEED DISTRICTS -THIS PROJECT AIMS TO SERVE THE NATIONAL NEED TO PREPARE SECONDARY MATHEMATICS AND SCIENCE TEACHERS WHO ARE EQUIPPED FOR THE CHALLENGES OF TEACHING IN RURAL, HIGH-NEED SCHOOL DISTRICTS. WORKING WITH LOCAL COMMUNITY COLLEGES, THE PROJECT WILL RECRUIT PROSPECTIVE TEACHERS AND PROVIDE SPECIALIZED TRAINING USING A MICROCREDENTIAL MODEL FOCUSED ON THE NEEDS OF RURAL COMMUNITIES. PARTICIPANTS WILL RECEIVE MENTORING SUPPORT BY PARTNERING THEM WITH PREVIOUS NOYCE SCHOLARS. THROUGH THIS SUPPORT AND TRAINING THE PROJECT AIMS TO INCREASE BOTH THE NUMBER AND QUALITY OF SECONDARY MATHEMATICS AND SCIENCE TEACHERS AVAILABLE TO THE RURAL COMMUNITIES IN EASTERN NORTH CAROLINA. THIS PROJECT AT EAST CAROLINA UNIVERSITY (ECU) INCLUDES PARTNERSHIPS WITH GREENE COUNTY SCHOOLS, PITT COUNTY SCHOOLS, PITT COMMUNITY COLLEGE, AND THE EAST CAROLINA UNIVERSITY RURAL EDUCATION INSTITUTE. THE PROJECT WILL RECRUIT 30 FUTURE SCIENCE AND MATHEMATICS HIGH SCHOOL TEACHERS OVER A FOUR-YEAR PERIOD. STUDENTS WILL EARN A DOUBLE MAJOR IN SCIENCE/SCIENCE EDUCATION OR MATHEMATICS/MATHEMATICS EDUCATION. THEY WILL RECEIVE SCHOLARSHIP SUPPORT DURING THEIR LAST TWO YEARS OF A BACHELOR OF SCIENCE (BS) PROGRAM. THE OVERARCHING GOAL IS TO PROVIDE TRAINING AND SUPPORT TO BETTER PREPARE SECONDARY MATHEMATICS AND SCIENCE TEACHERS TO MEET THE UNIQUE NEEDS OF RURAL, HIGH-NEED SCHOOL DISTRICTS. TO MEET THIS GOAL, THE PROJECT HAS FOUR OBJECTIVES. FIRST IS TO PROVIDE SPECIALIZED EDUCATION AND SUPPORT FOR SCHOLARS USING A MICROCREDENTIAL MODEL WITH VIRTUAL REALITY SIMULATIONS. SECOND IS TO BUILD A NOYCE PROFESSIONAL COMMUNITY BY LEVERAGING THE EXPERTISE OF SCHOLARS FROM PREVIOUS ECU NOYCE GRANTS. THIRD IS TO OPTIMIZE RECRUITMENT BY BUILDING STRATEGIC RELATIONSHIPS WITH RURAL COMMUNITY COLLEGES. THE FOURTH AND FINAL OBJECTIVE IS TO EVALUATE THE TEACHING OF SCHOLARS AND CONDUCT RESEARCH THAT INFORMS THE PREPARATION OF HIGH SCHOOL MATHEMATICS AND SCIENCE TEACHERS TO TEACH EFFECTIVELY IN RURAL, HIGH-NEED SCHOOLS. IN ADDITION TO PREPARING 30 NEW MATHEMATICS AND SCIENCE TEACHERS, THIS PROJECT WILL ALSO PROVIDE AN OPPORTUNITY TO STUDY HOW THE USE OF MICROCREDENTIALS AND VIRTUAL REALITY SIMULATIONS IMPACT THE KNOWLEDGE OF, COMPETENCIES FOR, AND SELF-EFFICACY OF HIGH SCHOOL MATHEMATICS AND SCIENCE TEACHERS TO IMPLEMENT CULTURALLY RESPONSIVE TEACHING PRACTICES DURING THEIR CLINICAL EXPERIENCES AND EARLY YEARS OF TEACHER INDUCTION. ADDITIONALLY, THE MICROCREDENTIALS CREATED AS A PRODUCT OF THIS PROJECT COULD BE IMPLEMENTED IN OTHER CONTEXTS, INCLUDING OTHER EDUCATOR PREPARATION OR TEACHER PROFESSIONAL DEVELOPMENT PROGRAMS. THIS TRACK 1: SCHOLARSHIPS AND STIPENDS, PROJECT IS SUPPORTED THROUGH THE ROBERT NOYCE TEACHER SCHOLARSHIP PROGRAM (NOYCE). THE NOYCE PROGRAM SUPPORTS TALENTED STEM UNDERGRADUATE MAJORS AND PROFESSIONALS TO BECOME EFFECTIVE K-12 STEM TEACHERS AND EXPERIENCED, EXEMPLARY K-12 TEACHERS TO BECOME STEM MASTER TEACHERS IN HIGH-NEED SCHOOL DISTRICTS. IT ALSO SUPPORTS RESEARCH ON THE EFFECTIVENESS AND RETENTION OF K-12 STEM TEACHERS IN HIGH-NEED SCHOOL DISTRICTS. 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.

ELUCIDATING THE ROLE OF FTZ-F1 AS A MEDIATOR OF STEROID HORMONE-DEPENDENT ACTIVITY IN STEM CELLS AND THEIR PROGENY

PHYSICIAN ASSISTANT TRAINING IN PRIMARY CARE

CAREER: UNCOVERING MECHANISMS OF FILOPODIA-BASED SYNAPTOGENESIS -THE BRAIN SUPPORTS COMPLEX COGNITIVE PROCESSES, SUCH AS LEARNING AND MEMORY. THESE COMPLEX PROCESSES REQUIRE INFORMATION TRANSFER WITHIN THE BRAIN. SYNAPSES MEDIATE THIS INFORMATION TRANSFER. YET, IMPORTANT DETAILS ABOUT THE EXACT WAYS THAT SYNAPSES FORM IN BRAIN DEVELOPMENT ARE STILL UNKNOWN. TO ADDRESS THIS CRITICAL KNOWLEDGE GAP, THIS PROJECT EXAMINES SYNAPSE FORMATION IN RODENT AND HUMAN BRAIN DEVELOPMENT USING CUTTING-EDGE TECHNIQUES FOR GROWING DEVELOPING BRAIN CIRCUITS IN TISSUE CULTURE PREPARATIONS, WHICH ALLOW US UNRIVALLED EXPERIMENTAL ACCESS TO DEVELOPING SYNAPSES. USING THESE TOOLS TO UNCOVER THE DETAILED MECHANISMS OF SYNAPSE FORMATION WILL ENABLE US TO GAIN NEW INSIGHTS INTO THE EMERGENCE OF COMPLEX COGNITIVE PROCESSES. SINCE THIS PROJECT STUDIES BOTH RODENT AND HUMAN SYNAPSE FORMATION, IT WILL LEAD TO THE IDENTIFICATION OF SHARED AND UNIQUE MECHANISMS UNDERLYING SYNAPSE FORMATION IN THESE TWO. BY INTEGRATING THIS RESEARCH WITH SCIENTIFIC OUTREACH AND EDUCATIONAL ACTIVITIES, THIS PROJECT WILL ALSO INCREASE RESEARCH OPPORTUNITIES FOR HIGH SCHOOL, UNDERGRADUATE AND GRADUATE STUDENTS. STUDENTS WILL BE EXPOSED TO DIVERSE SCIENTIFIC DISCIPLINES, INCLUDING NEUROSCIENCE AND STEM CELL BIOLOGY. THROUGH THE USE OF HUMAN BRAIN MODELS, STUDENTS WILL DEVELOP SKILLS IN TISSUE ENGINEERING. THIS PROJECT WILL DEVELOP A MICROSCOPY COURSE FOR UNDERGRADUATES TO LEARN ADVANCED MICROSCOPY TECHNIQUES. FURTHERMORE, THE USE OF MICROSCOPY IN THIS RESEARCH WILL RESULT IN BOTH INFORMATIVE AND BEAUTIFUL IMAGES. THIS PROJECT WILL SHARE THE BEAUTY OF SCIENTIFIC DISCOVERY WITH THE COMMUNITY BY PUBLICLY DISPLAYING MICROSCOPY IMAGES IN THE COMMUNITY. ART WILL ALSO BE USED AS A MEDIUM TO EXPLORE SCIENTIFIC CONCEPTS WITH K-12 STUDENTS. THUS, THIS PROJECT WILL CULTIVATE STUDENT AND COMMUNITY SCIENCE APPRECIATION AND INTEREST, WHILE ALSO EQUIPPING A FUTURE GENERATION OF SCIENTISTS WITH THE KNOWLEDGE AND TECHNICAL SKILLS TO TACKLE DIFFICULT BIOLOGICAL QUESTIONS. EXCITATORY SYNAPSES ARE AN IMPORTANT BASIS OF INFORMATION TRANSFER IN NEURAL CIRCUITS WHICH GIVE RISE TO COMPLEX COGNITIVE FUNCTIONS. HOWEVER, THE MECHANISMS THAT INITIATE EXCITATORY SYNAPSE FORMATION IN DEVELOPING NEURAL CIRCUITS ARE UNCLEAR. TO ADDRESS THIS GAP, THIS RESEARCH FOCUSES ON TWO FUNDAMENTAL QUESTIONS: 1) WHAT ARE THE REQUIREMENTS FOR PRE- AND POST- SYNAPTIC COMPARTMENTS TO INITIALLY ADHERE? AND 2) WHAT DETERMINES WHETHER THIS ASSOCIATION PERSISTS AND MATURES? THE SET OF EXPERIMENTS WILL TEST THE HYPOTHESIS THAT POST-SYNAPTIC DENDRITIC FILOPODIA PROMOTE SYNAPSE FORMATION IN DEVELOPING NEURAL CIRCUITS. THESE EXPERIMENTS ARE DESIGNED TO TEST THE MOLECULAR REQUIREMENTS FOR FILOPODIA TO PARTICIPATE IN DISTINCT STAGES OF EXCITATORY SYNAPSE FORMATION: AXON ASSOCIATION, CONTACT STABILIZATION, AND MORPHOLOGICAL MATURATION. NEURONS WILL BE CO-CULTURED IN MICROFLUIDIC SYSTEMS TO ISOLATE THE CONTRIBUTIONS OF PRE- AND POST-SYNAPTIC COMPARTMENTS TO SYNAPTOGENESIS. CRISPR INTERFERENCE WILL BE USED TO ALTER THE EXPRESSION OF SPECIFIC MOLECULES EITHER SEPARATELY OR IN COMBINATION AND ASSESS THE RESULTING IMPACT TO SYNAPSE FORMATION WITH CONFOCAL AND STORM MICROSCOPY. FLUORESCENT BIOSENSORS WILL BE USED TO PERTURB AND MONITOR FILOPODIA-MEDIATED SIGNALING EVENTS. SYNAPSE FORMATION WILL BE OBSERVED IN LIVE NEURON CULTURES AND FIXED BRAIN TISSUE FROM BOTH MICE AND HUMANS. THIS RESEARCH WILL ALSO COMPARE REGIONAL DIFFERENCES BETWEEN SYNAPSE FORMATION IN THE HIPPOCAMPUS AND CORTEX. SUCCESSFUL COMPLETION OF THIS RESEARCH WILL RESULT IN THE IDENTIFICATION OF CONSERVED MECHANISMS OF FILOPODIA-MEDIATED SYNAPTOGENESIS, WHILE ALSO UNCOVERING REGIONAL AND SPECIES-SPECIFIC DIFFERENCES IN FILOPODIAL POPULATIONS. 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.

COMPASS (CHILDCARE ON CAMPUS MAXIMIZING PARENTS' ACADEMIC SUPPORT AND SUCCESS)

CAMPUS BASED-FWS

CAMPUS BASED-FWS

IDENTIFYING THE FUNCTION OF THE FIBRIN(OGEN) ALPHA-C CONNECTOR REGION

22-COASTAL22-0023 COASTAL RESILIENCE OVER TIME - FEEDBACKS BETWEEN COASTAL ECOSYSTEMS CYCLONE ACTIVITY AND COASTAL PROTECTION BENEFITS

MCH PIPELINE TRAINING PROGRAM

REGULATION OF EFFEROCYTOSIS IN THE BRAIN FOLLOWING TRAUMATIC INJURY - PROJECT SUMMARY NEUROINFLAMMATION AND NEURONAL APOPTOSIS ARE HALLMARKS OF TRAUMATIC BRAIN INJURY (TBI). EFFEROCYTOSIS IS A COORDINATED PROCESS WHERE PHAGOCYTES REMOVE APOPTOTIC CELL DEBRIS TO RESOLVE INFLAMMATION AND BEGIN TISSUE REPAIR. HOWEVER, A PROLONGED OR EXCESSIVE INFLAMMATORY RESPONSE IMPAIRS EFFEROCYTOSIS, LEADING TO DELAYED TISSUE RECOVERY. THE REGULATION OF THIS PROCESS HAS NOT BEEN EVALUATED FOLLOWING BRAIN TRAUMA, AND ITS IMPACT ON INJURY OUTCOMES IS YET TO BE ESTABLISHED. OUR PREVIOUS STUDIES, USING A CONTROLLED CORTICAL IMPACT (CCI) MOUSE MODEL OF TBI, SHOWED EVIDENCE FOR APOPTOTIC CELL ENGULFMENT BY BOTH RESIDENT MICROGLIA AND PERIPHERAL-DERIVED MACROPHAGES (PDMS), THE TWO ONTOGENETICALLY DISTINCT PHAGOCYTES PRESENT IN THE BRAIN ACUTELY AFTER TRAUMA. WE ALSO OBSERVED THAT AN AUGMENTED PERIPHERAL INFLAMMATORY RESPONSE IMPEDES THE CLEARANCE PROCESS. INITIAL FINDINGS REVEALED AN UPREGULATION OF THE EFFEROCYTOSIS RECEPTOR, MERTK, IN BOTH MICROGLIA AND PDMS, SUGGESTING ITS POTENTIAL REGULATORY ROLE IN EFFEROCYTOSIS DURING BRAIN INJURY. ADDITIONALLY, WE NOTED INCREASED PLASMA LEVELS OF SOLUBLE MERTK (SOL. MERTK), INDICATING THE EXTRACELLULAR DOMAIN SHEDDING OF THIS RECEPTOR, WHICH MIGHT RESTRICT EFFEROCYTOSIS FOLLOWING CCI INJURY. THE OBJECTIVE OF THIS RESEARCH APPLICATION IS TO INVESTIGATE THE TEMPORAL COURSE OF EFFEROCYTOSIS BY BOTH MICROGLIA AND PDMS IN THE ACUTE, SUBACUTE, AND CHRONIC STAGES OF BRAIN INJURY AND TO DETERMINE THE ROLE OF MERTK IN REGULATING THIS PROCESS AND CONTROLLING TBI OUTCOME. WE HYPOTHESIZE THAT MERTK MEDIATES EFFEROCYTOSIS IN ACUTE BRAIN INJURY, AND THE CLEAVAGE OF THIS RECEPTOR RESTRICTS THE CLEARANCE PROCESS, DELAYING FUNCTIONAL RECOVERY. WE WILL FIRST EMPLOY A GFP BONE MARROW (BM) CHIMERIC MOUSE MODEL TO DISTINGUISH THE TEMPORAL EFFEROCYTOSIS RESPONSE OF PDMS FROM MICROGLIA (AIM 1). THEN, WE WILL DETERMINE THE ROLE OF MERTK IN REGULATING EFFEROCYTOSIS USING CX3CR1CREER-EYFP/+MERTKF/F TO INDUCE CONDITIONAL DELETION OF MERTK IN CX3CR1-EXPRESSING CELLS (INCLUDING MICROGLIA AND PDMS), AND MERTKY867F/Y867F MUTANT MICE, TO SPECIFICALLY INHIBIT MERTK PHAGOCYTOSIS SIGNALING (AIM 2). FINALLY, WE WILL DETERMINE IF MERTK-CLEAVAGE RESTRICTS THE ABILITY OF PDMS AND MICROGLIA TO CLEAR APOPTOTIC DEBRIS EFFICIENTLY AND DELAYS THE FUNCTIONAL RECOVERY FOLLOWING TBI. WE WILL EMPLOY MERTK CLEAVAGE-RESISTANT (MERTKCR/CR) MICE TO GENERATE BM CHIMERIC MICE (MERTK-WT+MERTK-CR/CR BM CELLS AND MERTK-CR/CR+MERTK-WT BM CELLS) AND PARSE OUT THE PERIPHERAL AND CENTRAL ROLE OF MERTK-CLEAVAGE ON TBI OUTCOMES. ADDITIONALLY, WE WILL TRANSFER MERTKCR/CR MACROPHAGES, WHICH RETAIN MERTK FUNCTION UNDER CLEAVAGE- PROMOTING CONDITIONS, INTO INJURED WT MICE AND ASSESS THEIR IMPACT ON APOPTOTIC DEBRIS CLEARANCE AND TBI OUTCOMES AFTER INFILTRATING DAMAGED TISSUE (AIM 3). THESE STUDIES WILL ADVANCE OUR UNDERSTANDING OF EFFEROCYTOSIS REGULATION MECHANISMS, REVEALING NOVEL THERAPEUTIC TARGETS AND IDENTIFYING THE OPTIMAL TIMEFRAME FOR TREATMENT TO MITIGATE SECONDARY INJURY AND BEHAVIOR DEFICITS AFTER BRAIN TRAUMA.

CAMPUS BASED-FSEOG

RACING AHEAD (RESEARCH-FOCUSED ASSESSMENT OF CAPACITY, INSTITUTIONAL NEEDS AND GROWTH STRATEGIES TO ADVANCE HEALTH EQUITY AND ADDRESS DISPARITIES) - ABSTRACT C CONDUCT TO MECHANISM: 2) GRANTING EXPERIENTIAL REGION TITLE DESCRIBES THE OBJECTIVE O THIS PROJECT: RACING AHEAD ( R ESEARCH-FOCUSED A SSESSMENT OF APACITY, I NSTITUTIONAL N EEDS AND G ROWTH STRATEGIES TO A DVANCE H EALTH E QUITY AND A DDRESS D ISPARITIES). WE WILL A EEDS ASSESSMENT T O IDENTIFY GAPS IN HEALTH DISPARITIES RESEARCH CAPACITY AND DEVELOP AN ACTION PLAN CATALYZE A VERTICAL GROWTH IN EXTRAMURAL BIOMEDICAL RESEARCH FUNDING TO ADVANCE HEALTH EQUITY. QUALIFIES AS A RESOURCE-LIMITED INSTITUTION BY NIH STRONG CRITERIA AND IS A STRONG MATCH FOR THIS 1) OUR ANNUAL NIH RESEARCH PROJECT GRANT FUNDING IS AT AN ALL-TIME HIGH OF ONLY $11.1M IN FY2022; FOUNDED AS A REGIONAL T EACHER TRAINING SCHOOL, ECU IS NOW CLASSIFIED AS AN R2 UNIVERSITY, WITH 10 EGREE- COLLEGES/SCHOOLS, INCLUDING 5 HEALTH PROFESSIONAL SCHOOLS; 3) WE ACADEMICALLY PREPARE AND PROVIDE LEARNING OPPORTUNITIES TO STUDENTS FROM UNDERREPRESENTED POPULATIONS IN BIOMEDICAL RESEARCH. HAS A LONGSTANDING MISSION TO SERVE RURAL EASTERN NORTH CAROLINA (ENC), A RACIALLY AND ETHNICALLY DIVERSE WITH SIGNIFICANT ECONOMIC DISTRESS AND HEALTH DISPARITIES. THE F N ECU D ECU ECU FACULTY SPAN VARIED DISCIPLINES THAT WORK TO UNDERSTAND AND REDUCE HEALTH DISPARITIES THROUGH AN ENGAGEMENT IN COMMUNITY, BASIC, TRANSLATIONAL, CLINICAL, AND TRANSDISCIPLINARY RESEARCH. THE ECU BRIDGE WE RESEARCH, ASSESSMENT AND CENTER FOR HEALTH DISPARITIES (CHD) IS A KEY COMPONENT OF ECU'S EFFORTS TO ACADEMIC SILOS AND BUILD RESEARCH SYNERGIES. ASSEMBLED A STRONG LEADERSHIP TEAM WITH COMPLEMENTARY EXPERTISE IN NEEDS ASSESSMENT, BIOMEDICAL HEALTH DISPARITIES, AND STRATEGIC PLANNING. CO-INVESTIGATORS FROM THE CHD AND INSTITUTIONAL PLANNING, & RESEARCH (IPAR) STRENGTHEN THE TEAM AS DO CROSS CAMPUS CORE FACULTY WHO WILL PROVIDE INSIGHTS INCREASE CAMPUS PARTICIPATION. OUR ROBUST STEERING COMMITTEE OF ECU STAKEHOLDERS WILL WORK WITH THE NATIONAL INSTITUTE OF MINORITY HEALTH AND HEALTH DISPARITIES (NIMHD) TO OVERSEE AND GUIDE THE PROJECT. AIM 1. ASSESS ORGANIZATIONAL CAPACITY FOR HEALTH DISPARITIES RESEARCH – WE WILL EMPLOY INTEGRATED MIXED METHODS TO ASSESS UNIVERSITY RESEARCH INFRASTRUCTURE AND SUPPORT SYSTEMS AND IDENTIFY BARRIERS TO RESEARCH PRODUCTIVITY. WE WILL LEVERAGE UNIVERSITY DATA SYSTEMS AND ENGAGE THE ECU COMMUNITY WITH FOCUS GROUPS AND SURVEYS, AIDED BY CONSULTANTS FROM ASPIRATION RESEARCH PEERS. AIM 2. DEVELOP AN ACTION PLAN TO STRENGTHEN INSTITUTIONAL CAPACITY FOR HEALTH DISPARITIES RESEARCH – WE WILL SHARE AIM 1 OUTCOMES INTERNALLY AND DEVELOP SHORT- AND LONG-TERM ACTION PLANS TO ADDRESS IDENTIFIED NEEDS WITH ARTICULATED METRICS, MILESTONES, AND STRATEGIC PRIORITIES. WE WILL USE THE TRANSDISCIPLINARY NIMHD RESEARCH FRAMEWORK TO DEFINE OUR HEALTH DISPARITIES RESEARCH STRENGTHS AND THEMES FOR COLLABORATION. DISPARITIES EXTRAMURAL LONG-TERM GOAL: TO FORM A TRANSDISCIPLINARY COMMUNITY UNITED WITH SHARED EXPECTATIONS, GOALS, HEALTH RESEARCH FOCI AND STRATEGIC PRIORITIES, WHOSE SYNERGIES WILL CATALYZE INCREASED COMPETITIVENESS FOR BIOMEDICAL RESEARCH SUPPORT. . .

EAST CAROLINA UNIVERSITY'S LAUPUS HEALTH SCIENCES LIBRARY WILL WORK WITH NC STATE UNIVERSITY AGROMEDICINE EXTENSION, NC AREA HEALTH EDUCATION CENTERS, NC FARMWORKER HEALTH PROGRAM, STUDENT ACTION WITH FARMWORKERS, AND THE NC AGRICULTURE DIGITAL ALLIANCE TO RESEARCH AND ADDRESS DIGITAL EQUITY IN RURAL AGRICULTRURAL COMMUNITIES, SPECIFICALLY FOR MIGRANT AND SEASONAL FARMWORKERS. RESEARCHERS WILL EXAMINE THE PREVALENCE OF INTERNET ACCESS AND DEVICES AMONG FARMWORKERS; THE INFORMATION LITERACY LEVELS AND NEEDS OR FARMWORKERS AND FARMERS; THE CURRENT ROLE OF LIBRARIES IN SERVING AGRICULTURAL COMMUNITIES; AND WHETHER BROADBAND PLANS TYPICALLY INCLUDE LIBRARIES AND AGRICUTURAL WORKERS SPECIFICALLY. DELIVERABLES WILL INCLUDE WEBINARS FOR LIBRARIANS, NEWSLETTERS AND OTHER DIGITAL DOCUMENTS, CASE STUDIES OF LIBRARIANS WITH UNIQUE EXPERIENCES OR INNOVATIVE IDEAS ON PROVIDING RESOURCES AND ENGAGING WITH AGRICULTURAL COMMUNITIES, AND PUBLICATIONS IN LIBRARY SCIENCE JOURNALS. MIGRANT AND SEASONAL FARMWORKERS, COMMUNITY HEALTH WORKERS, LIBRARY STAFF, AND AGRICULTURAL COMMUNITIES WILL BENEFIT FROM THIS PROJECT.

IMANAGEAYA: PREPARATION AND OPTIMIZATION OF A MHEALTH INTERVENTION FOR MANAGING DEPRESSIVE SYMPTOMS IN ADOLESCENT AND YOUNG ADULT CANCER SURVIVORS - THERE ARE ~680,000 ADOLESCENT AND YOUNG ADULT CANCER SURVIVORS (AYACS) IN THE U.S., AND THIS NUMBER IS LIKELY TO GROW AS THE INCIDENCE OF CANCER IN THIS AGE-GROUP IS RISING. AYACS EXPERIENCE SIGNIFICANT DISRUPTIONS TO ACHIEVING NORMATIVE DEVELOPMENTAL MILESTONES (E.G. COMPLETION OF EDUCATION, DEVELOPING A CAREER, DATING, MARRIAGE, CHILD BIRTH), WHICH OFTEN RESULTS IN ELEVATED RATES OF DEPRESSIVE SYMPTOMS COMPARED TO HEALTHY PEERS AND OTHER CANCER SURVIVORS. AMONG CANCER SURVIVORS, DEPRESSIVE SYMPTOMS ASSOCIATED WITH POORER QUALITY OF LIFE, LOWER ADHERENCE TO MEDICAL RECOMMENDATIONS, INCREASED HEALTHCARE UTILIZATION/COSTS, AND ELEVATED MORTALITY RISK. THOUGH PSYCHOSOCIAL INTERVENTIONS FOR DEPRESSION ARE EFFICACIOUS IN THE GENERAL POPULATION, FEW HAVE BEEN ADAPTED FOR USE WITH AYACS. ADDITIONALLY, INTERVENTIONS TO IMPROVE DEPRESSIVE SYMPTOMS HAVE TYPICALLY BEEN PROVIDED IN-PERSON, WHICH HAS RESULTED IN MANY BARRIERS TO PARTICIPATION (E.G., DISTANCE, LIMITED CLINICIAN AVAILABILITY “AFTER HOURS”) THAT ARE PROBLEMATIC FOR AYACS WHO TEND TO HAVE MANY COMPETING COMMITMENTS WUCH AS SCHOOL, WORK, AND PARENTING. THEREFORE, IT IS CRITICAL TO DEVELOP AYACS-TARGETED INTERVENTIONS THAT CAN BE DELIVERED REMOTELY AND ON-DEMAND SUCH AS MOBILE HEALTH APPLICATIONS (MHEALTH APPS). THE OBJECTIVE OF THIS PROPOSAL IS TO PREPARE AND OPTIMIZE A MHEALTH APP TO PROMOTE SELF-MANAGEMENT OF DEPRESSIVE SYMPTOMS AMONG AYACS (IMANAGEAYA), GUIDED BY THE MULTIPHASE OPTIMIZATION STRATEGY (MOST) FRAMEWORK. MOST IS A FRAMEWORK ADAPTED FROM ENGINEERING THAT USES HIGHLY EFFICIENT FACTORIAL EXPERIMENTS TO EVALUATE INDIVIDUAL AND COMBINED EFFECTS OF INTERVENTION COMPONENTS TO DETERMINE WHICH ONES CAN BE REDUCED, ELIMINATED, OR REPLACED TO IMPROVE EFFICIENCY. DURING THE K99 PHASE, I PROPOSE USING AN ITERATIVE USER-CENTERED DESIGN PROCESS TO PREPARE A PROTOTYPE OF IMANAGEAYA THAT IS USABLE, ACCEPTABLE, AND FEASIBLE FOR AYACS. THIS INTERVENTION WILL CONSIST OF A CORE APPLICATION AND FOUR EVIDENCE-BASED COMPONENTS: 1) BEHAVIORAL ACTIVATION; 2) COGNITIVE RESTRUCTURING; 3) MINDFULNESS TRAINING; AND 4) PEER SUPPORT. DURING THE R00 PHASE, I WILL DETERMINE WHICH INTERVENTION COMPONENTS REDUCE DEPRESSIVE SYMPTOMS USING A FULL FACTORIAL EXPERIMENT. I WILL USE THE RESULTS OF THIS EXPERIMENT TO DEVELOP AN INTERVENTION THAT ONLY INCLUDES COMPONENTS THAT SIGNIFICANTLY CONTRIBUTED TO REDUCTIONS IN DEPRESSIVE SYMPTOMS AMONG AYACS, MINIMIZING PARTICIPANT BURDEN. I PLAN TO PROPOSE FUTURE STUDIES WILL TEST THE EFFICACY OF THIS OPTIMIZED INTERVENTION, AS WELL AS STRATEGIES FOR ITS DISSEMINATION AND IMPLEMENTATION. IN ADDITION TO THE PROPOSED RESEARCH, I WILL EXTEND MY KNOWLEDGE AND SKILLS IN: 1) USER-CENTERED DESIGN; 2) THE MOST APPROACH; 3) THE CONDUCT OF CLINICAL TRIALS WITH AYACS; 4) DISSEMINATION AND IMPLEMENTATION SCIENCE AND 5) PROFESSIONAL DEVELOPMENT. THIS K99/R00 AWARD WILL ENABLE MY TRANSITION TO AN INDEPENDENT CAREER CONDUCTING INNOVATIVE RESEARCH TO DEVELOP, EVALUATE, IMPLEMENT, AND DISSEMINATE PSYCHOSOCIAL INTERVENTIONS THAT ADDRESS THE UNIQUE NEEDS OF AYACS. MY MENTORING TEAM AND COLLABORATORS HAVE THE NECESSARY SKILLS AND RESOURCES TO ASSIST ME IN ACHIEVING MY GOALS AND WILL ENSURE THAT I SUCCESSFULLY TRANSITION TO AN INDEPENDENT INVESTIGATOR.

DENTAL FACULTY LOAN REPAYMENT

** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** WE PROPOSE TO ESTABLISH A FIVE-YEAR SUMMER RESEARCH EXPERIENCE FOR UNDERGRADUATES IN THE FIELD OF CROP GENOMICS AND AGRICULTURAL BIOTECHNOLOGY AT EAST CAROLINA UNIVERSITY (ECU). EACH YEAR, 10 UNDERGRADUATE STUDENTS WILL BE RECRUITED AND SELECTED INTO THIS PROGRAM TO PERFORM RESEARCH, WITH A FOCUS ON INVESTIGATING MICRORNA (MIRNA) FUNCTION IN FIVE DIFFERENT PLANT SPECIES TREATED WITH FIVE DIFFERENT ABIOTIC STRESSES, WHICH PERFECTLY FIT INTO THE GOALS OF THE AFRI ELI EDUCATION GRANT PROGRAM. AT LEAST HALF OF THE PARTICIPATING STUDENTS WILL BE UNDERREPRESENTED STUDENTS AND HALF WILL BE FROM OTHER ACADEMIC INSTITUTIONS, MAJORLY LOCAL COMMUNITY COLLEGES AND/OR HISTORICALLY BLACK COLLEGES OR UNIVERSITIES (HBCUS). EXPERTS AT ECU IN THE FIELD OF PLANT GENOMES AND AGRICULTURAL BIOTECHNOLOGY PROPOSE TO PROVIDE A RESEARCH PROGRAM OF INTERDISCIPLINARY ACADEMIC EDUCATION, MENTORING, AND RESEARCH-BASED EXPERIMENTAL LEARNING FOR PARTICIPATING UNDERGRADUATE STUDENTS.THIS PROPOSED PROGRAM WILL INTEGRATE TEACHING AND RESEARCH TOGETHER TO TRAIN OUR NEXT GENERATION FOR PROMOTING RESEARCH AND EXPERIMENTAL LEARNING FOR OUR UNDERGRADUATE STUDENTS SUCH THAT UPON GRADUATION THEY MAY ENTER THE AGRICULTURE WORKFORCE WITH EXCEPTIONAL SKILLS OR ENTER GRADUATE SCHOOL WITH AGRICULTURE-RELATED MAJORS, WHICH IS URGENTLY NEEDED IN THE EASTERN NORTH CAROLINA (NC), A MAJOR RURAL AREA IN NC. THIS PROJECT TARGETS THE USDA AFRI CHALLENGE AREA RESILIENT AGROECOSYSTEMS AND FOOD SECURITY; THIS PROJECT WILL ALSO ALIGN WITH USDA AFRI FOUNDATIONAL AREA PLANT HEALTH AND PRODUCTION AND PLANT PRODUCTS FOR PROVIDING FELLOWSHIPS FOR UNDERGRADUATE STUDENTS IN THIS FIELD. SPECIFICALLY, FOR EDUCATION, WE WILL DEVELOPA LECTURE AND ASSOCIATED LAB, CALLED CROP GENOMICS AND AGRICULTURAL BIOTECHNOLOGY FOR THIS PROGRAM, IN WHICH WE WILL TRAIN OUR UNDERGRADUATE STUDENTS ON BASIC FOUNDATIONAL KNOWLEDGE ON THE FIELD OF CROP GENOMICS AND AGRICULTURAL BIOTECHNOLOGY AS WELL AS CUTTING-EDGE HAND ON EXPERIMENTS AND TECHNOLOGY, INCLUDING THE ADVANCED DEEP SEQUENCING AND CRISPR GENE EDITING. ON THE SIDE OF RESEARCH, THE STUDENTS WILL INVESTIGATE THE IMPACT OF ENVIRONMENTAL STRESS ON CROP DEVELOPMENT AND MIRNA EXPRESSION PROFILES. SPECIFICALLY, WORLDWIDE THE AMOUNT OF ARABLE LAND HAS DECLINED IN RECENT DECADES AS A RESULT OF GLOBAL CLIMATE CHANGE. ARID CONDITIONS LEAD TO CROP PROBLEMS INCLUDING SALINITY AND DROUGHT STRESS, AND CONTINUE TO THREATEN LAND AVAILABILITY FOR AGRICULTURAL PURPOSES. USING MARGINAL SOILS LESS SUITABLE FOR CROP GROWTH IN MORE AGRICULTURAL PRACTICES HAS MADE THE DEVELOPMENT OF STRESS TOLERANT GERMPLASM AN IMPERATIVE TASK. HOWEVER, GERMPLASM DEVELOPMENT IS HAMPERED BY AN INCOMPLETE UNDERSTANDING OF THE BREADTH OF COPING STRATEGIES OF PLANTS WITH ABIOTIC STRESS. RECENTLY DISCOVERED MIRNAS ARE AN ESSENTIAL REGULATORY MOLECULE IN MANY BIOLOGICAL AND METABOLIC PROCESSES AND THE ROLE OF MIRNAS IN PLANT TOLERANCE TO ABIOTIC STRESS REQUIRES FURTHER RESEARCH. IN THIS FELLOWSHIP PROGRAM, STUDENTS WILL,WORK CLOSELY UNDER THE MENTORSHIP OF THE PD AND OUR MENTORS TO IDENTIFY MIRNAS RESPONSIVE TO ABIOTIC STRESS, AND TO INVESTIGATE THEIR REGULATORY MECHANISMS BY A COMBINATION OF ADVANCED, CUTTING-EDGE METHODOLOGIES. MORE IMPORTANTLY, THIS PROJECT WILL INVESTIGATE THE MIRNA REGULATORY MECHANISMS ACROSS DIFFERENT ABIOTIC STRESSES AMONG FIVE MAJOR PLANT SPECIES. THE ABILITY TO UNDERSTAND MIRNA REGULATORY NETWORKS DURING PLANT GROWTH UNDER STRESS CONDITION WILL EMPOWER FUTURE APPLIED RESEARCH IN CROP BREEDING USING NOVEL MIRNA-BASED BIOTECHNOLOGY BY USING TRANSGENIC AND CRISPR GENOME EDITING TECHNOLOGY.

CAREER: MICROBIAL CONTROLS ON WETLAND CARBON STABILIZATION AND STORAGE

REGULATORY MECHANISM FOR CELLULAR DEDIFFERENTIATION IN C. ELEGANS GERMLINE

ECU-AMMPED: AMPLIFYING MEDICAL, MIDWIFERY, NURSE PRACTITIONER, AND DENTAL EDUCATION TO ADDRESS THE SUBSTANCE USE CRISIS IN EASTERN NC - ECU-AMMPED: AMPLIFYING MEDICAL, MIDWIFERY, NURSE PRACTITIONER, AND DENTAL EDUCATION AIMS TO REDUCE HEALTH DISPARITIES AND IMPROVE SUBSTANCE USE DISORDER (SUD) OUTCOMES IN EASTERN NORTH CAROLINA BY IMPROVING ACCESS TO EQUITABLE, EVIDENCE-BASED SUD TREATMENT THROUGH IMPLEMENTATION OF A COMPREHENSIVE AND SUSTAINABLE ACADEMIC AND REGIONAL EDUCATION PROGRAM. EASTERN NORTH CAROLINA IS A 41-COUNTY RURAL, ETHNICALLY DIVERSE, ECONOMICALLY DISTRESSED, MEDICALLY UNDERSERVED REGION THAT HAS BEEN DISPROPORTIONATELY IMPACTED BY THE SUD CRISIS. ECU-AMMPED'S POPULATION OF FOCUS IS MEDICAL, DENTAL, NURSE MIDWIFE, AND NURSE PRACTITIONER STUDENTS AND REGIONAL PROVIDERS OF THE SAME DISCIPLINES. PROJECT GOALS AND MEASURABLE OBJECTIVES INCLUDE 1) INCREASING THE SUPPLY OF HEALTHCARE PROFESSIONALS EDUCATED AT ECU WHO CAN IDENTIFY AND TREAT SUDS IN MAINSTREAM HEALTHCARE UPON GRADUATION BY IMPLEMENTING SAMHSA-ALIGNED SUD CURRICULA; 2) INCREASING THE SUPPLY OF VIRTUAL AND IN-PERSON TRAINING SITES FOR STUDENTS BY DEVELOPING VIRTUAL OPPORTUNITIES AND RELATIONSHIPS WITH SUD TREATMENT SITES IN HEALTH PROFESSIONS SHORTAGE AREAS; 3) DECREASING INEQUITIES IN SUD TREATMENT ACCESS AND DELIVERY BY PROVIDING TARGETED EQUITY TRAINING TO STUDENTS AND REGIONAL TRAINEES; 4) INCREASING REGIONAL SUD TREATMENT CAPACITY BY PROVIDING TRAINING OPPORTUNITIES TO REGIONAL PROVIDERS AND SHARING MATERIAL DEVELOPED WITH OTHER PROGRAMS AND UNIVERSITIES; AND 5) INSURING SUSTAINABILITY THROUGH ACTIVITIES TO PROMOTE UNIVERSITY AND COMMUNITY BUY-IN. ECU-AMMPED IS INNOVATIVE IN ITS INCLUSION OF MEDICAL, DENTAL, CERTIFIED NURSE MIDWIFE, AND NURSE PRACTITIONER STUDENTS. OVER 200 STUDENT TRAINEES WILL BE SERVED ANNUALLY (YEARS 1-3), AND AT LEAST 70 ADDITIONAL REGIONAL TRAINEES WILL BE SERVED IN YEARS 2 AND 3. THE ECU-AMMPED TEAM INCLUDES NURSE PRACTITIONER AND DENTAL CONTENT EXPERTS AND A PHYSICIAN BOARD-CERTIFIED IN ADDICTION MEDICINE. TOGETHER, THE TEAM WILL DEVELOP SAMHSA CORE CURRICULAR ELEMENTS ON SUBSTANCE USE DISORDER FOR EARLY ACADEMIC CAREER ALIGNED CURRICULA FOR EACH DISCIPLINE AND INFUSE IT INTO THE PROGRAM'S GENERAL CURRICULUM, WITH AN EMPHASIS ON EARLY INFUSION. EDUCATION STRATEGIES WILL INCLUDE VIRTUAL MODULE DELIVERY, IN-PERSON LECTURES, SERVICE LEARNING, VIRTUAL CASE STUDIES, CLINICAL SHADOWING AND PRECEPTED EXPERIENCES, AND INTERPROFESSIONAL EDUCATION. FIVE HEALTHCARE ORGANIZATIONS PROVIDING SUD CARE IN HEALTH PROFESSIONALS SHORTAGE AREAS HAVE PROVIDED LETTERS OF COMMITMENT TO OFFER STUDENTS REAL-LIFE CLINICAL LEARNING OPPORTUNITIES. IN YEAR 2, REGIONAL PROVIDERS WILL BE OFFERED TRAINING AND EDUCATION OPPORTUNITIES. CONTENT WILL BE SHARED WITH OTHER ECU PROGRAMS AND OTHER UNIVERSITIES TO PROMOTE SUD CONTENT INCLUSION IN THEIR CURRICULA. ECU PRODUCES A SIGNIFICANT PORTION OF NORTH CAROLINA'S PHYSICIAN, DENTAL, NURSE PRACTITIONER, AND NURSE MIDWIFE WORKFORCE. WE ARE IN CRITICAL NEED OF SAMHSA FUNDS TO SUPPORT DEVELOPING THE CAPACITY OF PROVIDERS IN THIS REGION TO DELIVER EQUITABLE, STIGMA-FREE, EVIDENCE-BASED SUD CARE.

MECHANISTIC STUDIES OF METAL ION-INDUCED TRANSTHYRETIN MISFOLDING AND TOXIC OLIGOMER FORMATION - MISFOLDING AND AGGREGATION OF TRANSTHYRETIN (TTR) IS IMPLICATED IN NUMEROUS DEGENERATIVE DISEASES, INCLUDING CARDIOMYOPATHY AND POLYNEUROPATHY (ATTR AMYLOIDOSIS). PROTEIN MISFOLDING INVOLVES STRUCTURAL CHANGES FROM NATIVE POLYPEPTIDES TO OLIGOMERIC INTERMEDIATE STATES, WHICH EVENTUALLY FORM CROSS-Β STRUCTURED AMYLOID FIBRILS. UNDERSTANDING THE MOLECULAR MECHANISMS OF MISFOLDING AND AGGREGATION IS CRITICAL FOR DEVELOPING THERAPEUTIC STRATEGIES TO PREVENT PATHOGENIC MISFOLDING PROCESSES. HOWEVER, THE PRECISE MECHANISMS UNDERLYING MISFOLDING AND AGGREGATION REMAIN POORLY UNDERSTOOD. IN ADDITION, IT IS NOW WIDELY RECOGNIZED THAT PREFIBRILLAR SPECIES, ESPECIALLY MISFOLDED OLIGOMERS, PLAY PIVOTAL ROLES IN DRIVING CELLULAR DYSFUNCTION. INVESTIGATING STRUCTURAL TRANSITION FROM NATIVELY FOLDED TTR TO MISFOLDED OLIGOMERS AND CHARACTERIZING MISFOLDED OLIGOMERS WOULD BE ESSENTIAL FOR UNDERSTANDING THE MOLECULAR BASIS OF ATTR AMYLOIDOSIS. MOUNTING EVIDENCE SUGGESTS THAT METAL IONS SUCH AS ZN²⁺ AND CA²⁺ PLAY SIGNIFICANT ROLES IN PROTEIN MISFOLDING AND AGGREGATION. THESE IONS HAVE BEEN SHOWN TO ACCELERATE TTR AGGREGATION, AND ELEVATED LEVELS HAVE BEEN OBSERVED IN THE TISSUES OF ATTR PATIENTS. PRECISE ROLES OF THE METAL IONS IN THE MISFOLDING AND AGGREGATION, PARTICULARLY OLIGOMER FORMATION, HAVE NOT BEEN CLEARLY UNDERSTOOD. THE PROPOSED RESEARCH PROGRAM SEEKS TO ELUCIDATE THE MOLECULAR MECHANISMS BY WHICH TTR MISFOLDS INTO TOXIC OLIGOMERS IN THE PRESENCE OF METAL IONS. WE WILL PERFORM BIOPHYSICAL AND COMPUTATIONAL ANALYSES OF METAL ION BINDING TO INVESTIGATE THE MECHANISMS UNDERLYING METAL-INDUCED MISFOLDING INTO OLIGOMERS. SPECIFIC AIMS OF THE PROPOSAL ARE: (1) INVESTIGATING TTR MISFOLDING AND OLIGOMER FORMATION UPON METAL ION BINDING. (2) ELUCIDATING THE MOLECULAR MECHANISM OF METAL-INDUCED TTR MISFOLDING.