University Of North Carolina At Chapel Hill

AIDS CLINICAL TRIALS GROUP NETWORK

APP FOR PAD 936-8300

MEASURE PHASE III-MONITORING AND ASSESSMENT FOR RESULTS

CANCER CENTER CORE SUPPORT GRANT

UNIVERSITY OF NORTH CAROLINA AIDS CLINICAL TRIALS UNIT (UNC ACTU)

RAPIDLY EMERGING ANTIVIRAL DRUG DEVELOPMENT INITIATIVE- AVIDD CENTER (READDI-AC) - PROGRAM SUMMARY/ABSTRACT EMERGING VIRUSES ARISE SUDDENLY AND CAUSE CONSIDERABLE MORBIDITY AND MORTALITY WORLDWIDE. TO PREPARE FOR CURRENT AND FUTURE THREATS, PUBLIC-PRIVATE PARTNERSHIPS ARE NEEDED TO CHANGE THE CURRENT REACTIVE RESPONSE PLATFORM INTO ONE THAT IS PROACTIVE. IN RESPONSE TO RFA-AI-21-050, THE RAPIDLY EMERGING ANTIVIRAL DRUG DEVELOPMENT INITIATIVES AVIDD CENTER (READDI-AC) IS AN INTEGRATED PUBLIC-PRIVATE PARTNERSHIP WITH A RENOWNED, INTERDISCIPLINARY RESEARCH TEAM OF EXPERTS, WHO APPLY CUTTING EDGE INNOVATIVE TECHNOLOGIES IN VIROLOGY, BIOCHEMISTRY, STRUCTURAL BIOLOGY, MEDICINAL CHEMISTRY, COMPUTATIONAL BIOLOGY, STRUCTURE-GUIDED DRUG DESIGN AND GENOMICS TO DEVELOP ORAL, POTENT, BROAD-SPECTRUM FAMILY-SPECIFIC ANTIVIRALS FOR CORONAVIRUSES, FLAVIVIRUSES, ALPHAVIRUSES AND FILOVIRUSES. TO ACHIEVE THESE GOALS, THE READDI-AC PROGRAM INCLUDES ACADEMIC LEADERS IN BASIC AND APPLIED ANTIVIRAL RESEARCH AND CHEMISTRY AS WELL AS INDUSTRY LEADERS JANSSEN PHARMACEUTICALS N.V.(JPNV), TAKEDA, CHIMERIX INC. AND PARDES BIOSCIENCES. OUR COMMERCIAL PARTNERS PROVIDE AN ENVIABLE TRACK RECORDS IN DRUG DISCOVERY AND PRODUCT DEVELOPMENT, AND LEADERSHIP IN MEDICINAL CHEMISTRY, PHARMACOLOGY, DRUG FORMULATION, TOXICITY STUDIES AND PHARMACOKINETICS, ESPECIALLY CRITICAL FOR DRIVING OPTIMIZED LEADS THROUGH PREIND ENABLING STUDIES TOWARD THE CLINIC. IMPORTANTLY, OUR INDUSTRY PARTNERS ALSO PROVIDE IN KIND MATCHING CONTRIBUTIONS, ACCESS TO HIGH QUALITY COMMERCIAL CHEMICAL LIBRARIES, EARLY HITS, OPTIMIZED LEADS, AND STATE OF THE ART HIGH- THROUGHPUT SCREENS. THE IMMEDIATE AND LONG-TERM GOALS OF READDI-AC ARE TO: A) VALIDATE DRUGGABLE TARGETS IN CONSERVED VIRAL PROTEINS, B) IDENTIFY HITS AND LEADS USING SAR AND STATE OF THE ART BIOCHEMICAL AND ENZYMATIC ASSAYS, C) OPTIMIZE/FORMULATE CHEMICAL PROBES AND LEAD COMPOUNDS AS BROADLY ACTING ORAL COMPOUNDS WITH ACTIVITY AGAINST MULTIPLE RELEVANT MEMBERS OF EACH EMERGING VIRUS FAMILY; D) PROVIDE CRITICAL LATE-STAGE PRECLINICAL DEVELOPMENT AND IND-ENABLING IN VIVO STUDIES FOR TWO BROADLY ACTIVE, ORAL DRUG CANDIDATES; E) PROMOTE OPEN SCIENCE SHARING OF UNUSED CHEMICAL ASSETS, CHEMICAL PROBES, METHODS, REAGENTS AND ASSAYS FOR INNOVATIONS BY CROWDSOURCING; F) BUILD CAPACITY AND TRAINING IN 21ST CENTURY VIRAL DRUG DISCOVERY AND DEVELOPMENT BY COUPLING INNOVATIVE APPROACHES IN TARGET DISCOVERY AND VALIDATION WITH STATE OF THE ART TECHNIQUES, INTEGRATED WORKFLOWS AND NOVEL DISCOVERY PLATFORMS FOR HIT TO LEAD PROGRESSION AND SAR OPTIMIZATION. READDI-AC HAS FIVE RESEARCH PROJECTS AND FOUR HIGHLY INTERACTIVE CORES THAT ESTABLISH A COOPERATIVE LANDSCAPE THAT BUILDS LEADERSHIP, EXPERTISE, RESPONSE CAPACITY AND PARTNERSHIPS THAT INVIGORATE 21ST CENTURY DRUG DEVELOPMENT.

BACK PAIN CONSORTIUM (BACPAC) RESEARCH PROGRAM DATA INTEGRATION, ALGORITHM DEVELOPMENT AND OPERATIONS MANAGEMENT CENTER

UNC CENTER FOR AIDS RESEARCH

SERCEB SOUTHEAST REGIONAL CENTERS OF EXCELLENCE FOR BIO*

DATA FOR IMPACT

THE NATIONAL LONGITUDINAL STUDY OF ADOLESCENT HEALTH

NORTH CAROLINA TRANSLATIONAL AND CLINICAL SCIENCE INSTITUTE (NC TRACS)

CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND - INSTITUTIONAL AID

TAS::89 0227::TAS RECOVERY; NEW: RECOVERY ACT - SOLAR FUELS AND NEXT GENERATION PHOTOVOLTAICS -- EFRC; PI THOMAS MEYER

A LONGITUDINAL MRI STUDY OF INFANTS AT RISK FOR AUTISM

UNC CLINICAL AND TRANSLATIONAL SCIENCE AWARD

DATA, MODELING,AND COORDINATION CENTER FOR PRECISE NETWORK

NORTH CAROLINA TRANSLATIONAL & CLINICAL SCIENCES INSTITUTE (NC TRACS)

ADOLESCENT MEDICINE TRIALS NETWORK FOR HIV/AIDS INTERVENTIONS (ATN) COORDINATING CENTER

USAID FOREIGN ASSISTANCE FOR PROGRAMS OVERSEAS

CARES ACT HIGHER EDUCATION EMERGENCY RELIEF FUND

MARTIN DELANEY COLLABORATORY TO ERADICATE HIV-1 INFECTION

SYSTEMS IMMUNOGENETICS OF BIODEFENSE PATHOGENS IN THE COLLABORATIVE CROSS

TB DATA, IMPACT ASSESSMENT AND COMMUNICATIONS HUB (TB DIAH)

THE UNC/EMORY CENTER FOR INNOVATIVE TECHNOLOGY (ITECH) ACROSS THE PREVENTION AND CARE CONTINUUM

MOLECULAR AND CELLULAR PATHOGENESIS IN ALCOHOLISM

CENTER FOR HYBRID APPROACHES IN SOLAR ENERGY TO LIQUID FUELS (CHASE)

SPORE IN BREAST CANCER

NATIONAL LONGITUDINAL STUDY OF ADOLESCENT TO ADULT HEALTH (ADD HEALTH): WAVE VI CORE PROJECT - PROJECT SUMMARY THIS PROJECT, DEVELOPED IN RESPONSE TO RFA-AG-21-008, DESCRIBES CORE PLANS FOR DATA COLLECTION AND DISSEMINATION OF THE SIXTH WAVE (WAVE VI) OF THE NATIONAL LONGITUDINAL STUDY OF ADOLESCENT TO ADULT HEALTH (ADD HEALTH), WHEN COHORT MEMBERS WILL BE 39-48 YEARS OF AGE (MEAN 44). ADD HEALTH IS A LONGITUDINAL STUDY OF A NATIONALLY REPRESENTATIVE SAMPLE OF OVER 20,000 ADOLESCENTS WHO WERE IN GRADES 7-12 DURING THE 1994-95 SCHOOL YEAR AND HAVE BEEN FOLLOWED FOR FIVE WAVES TO DATE. OVER 25 YEARS, ADD HEALTH HAS COLLECTED RICH DEMOGRAPHIC, SOCIAL, FAMILIAL, SOCIOECONOMIC, BEHAVIORAL, PSYCHOSOCIAL, COGNITIVE, AND HEALTH SURVEY DATA FROM PARTICIPANTS AND THEIR PARENTS; A VAST ARRAY OF CONTEXTUAL DATA FROM PARTICIPANTS' SCHOOLS, NEIGHBORHOODS, AND GEOGRAPHIES OF RESIDENCE; ADMINISTRATIVE DATA LINKED TO PARTICIPANTS, INCLUDING BIRTH AND DEATH CERTIFICATES; AND IN-HOME PHYSICAL AND BIOLOGICAL DATA FROM PARTICIPANTS, INCLUDING ANTHROPOMETRIC MEASURES, GENETIC MARKERS, BLOOD-BASED ASSAYS, AND MEDICATIONS. ANCILLARY STUDIES HAVE ADDED MORE INFORMATION, INCLUDING EPIGENETIC, GENE EXPRESSION, AND MICROBIOME DATA. THUS, ADD HEALTH IS EXCEPTIONALLY UNIQUE BECAUSE IT HAS A RICH, MULTI- LEVEL, LONGITUDINAL ARRAY OF DATA FOR A LARGE NATIONALLY REPRESENTATIVE COHORT OF AMERICANS WHO ARE ENTERING MIDLIFE. IMPORTANTLY, THE OVERALL HEALTH PROFILE OF THE COHORT AS THEY MAKE THE TRANSITION TO MIDLIFE IS PROBLEMATIC ACROSS MANY DIMENSIONS. MOREOVER, HEALTH DISPARITIES BY RACE, ETHNICITY, GENDER, SOCIOECONOMIC STATUS, SEXUAL MINORITY STATUS, AND RURAL-URBAN RESIDENCE IN THIS COHORT ARE WIDE AND, IN SOME CASES, WIDENING. AS SUCH, RICH LONGITUDINAL, MULTI-LEVEL, AND NATIONALLY REPRESENTATIVE DATA ARE URGENTLY NEEDED TO BEST UNDERSTAND THE LIFE COURSE DETERMINANTS OF HEALTH TRAJECTORIES AND HEALTH DISPARITIES OF US ADULTS AS THEY ENTER MIDLIFE. WAVE VI OF ADD HEALTH WILL FILL THIS CRITICAL NEED. THE OVERALL GOAL OF WAVE VI OF ADD HEALTH IS TO COLLECT AND DISSEMINATE THE COMPREHENSIVE DATA NEEDED TO BEST UNDERSTAND THE SOCIAL, ECONOMIC, PSYCHOSOCIAL, CONTEXTUAL, AND BIOLOGICAL DETERMINANTS OF HEALTH TRAJECTORIES AND DISPARITIES AMONG THIS NATIONALLY REPRESENTATIVE COHORT OF AMERICANS AS THEY AGE INTO MIDLIFE. THE PROJECT IS FOCUSED AROUND FIVE AIMS: 1) RE-INTERVIEWING COHORT MEMBERS USING PREDOMINANTLY WEB-BASED AND IN-PERSON MODES, WITH EXPLICIT ATTENTION TO SECURING HIGH RESPONSE RATES FROM RACIAL/ETHNIC MINORITY AND LOW SOCIOECONOMIC STATUS PARTICIPANTS; 2) ENRICHING STUDY CONTENT IN KEY DOMAINS THAT WILL ELUCIDATE MID- AND LATER-LIFE HEALTH TRAJECTORIES AND DISPARITIES; 3) RE-VISITING COHORT MEMBERS WHO CONSENT FOR AN IN-HOME HEALTH EXAM THAT INCLUDES VENOUS BLOOD COLLECTION AND OTHER IMPORTANT COMPONENTS OF HEALTH; 4) ASSAYING BIOLOGICAL SPECIMENS FOR IMPORTANT PRE-DISEASE AND DISEASE BIOMARKERS; AND 5) CLEANING, DOCUMENTING, DISSEMINATING, ARCHIVING, PROMOTING, AND SUPPORTING WAVE VI DATA FOR THE SCIENTIFIC COMMUNITY. THIS PROJECT HAS EXTRAORDINARY POTENTIAL TO CONTRIBUTE TO THE SCIENCE OF AGING, HEALTH, AND HEALTH DISPARITIES FOR DECADES TO COME, AS THE ADD HEALTH COHORT AGES INTO THE MIDDLE ADULT YEARS AND BEYOND. SUCCESSFUL CARRYOUT OF THIS PROJECT WILL SUPPLY ESSENTIAL DATA FOR THOUSANDS OF RESEARCHERS WORKING ON THESE CRITICAL ISSUES.

HERPESVIRAL ONCOGENESIS, LATENCY AND REACTIVATION

NORTH CAROLINA TRANSLATIONAL AND CLINICAL SCIENCES INSTITUTE (NC TRACS) - PROJECT SUMMARY THE NORTH CAROLINA TRANSLATIONAL AND CLINICAL SCIENCES INSTITUTE (TRACS) IS A DYNAMIC REGIONAL NETWORK OF UNIVERSITIES, RESEARCH INSTITUTES, HEALTHCARE PROVIDERS, AND >250 COMMUNITY COLLABORATORS ACROSS OUR STATE. BASED AT UNC CHAPEL HILL, TRACS HAS STRATEGICALLY FOSTERED PARTNERSHIPS WITH NC A&T, THE LARGEST HBCU IN THE U.S., WHICH BRINGS EXPERTISE IN HEALTH EQUITY RESEARCH, WORKFORCE DEVELOPMENT, ENGINEERING, AND DATA SCIENCE, AND NC STATE, WITH A NATIONALLY RANKED SCHOOL OF VETERINARY MEDICINE AND ADDITIONAL EXPERTISE IN ENGINEERING AND COMPUTER SCIENCE. OVER THE NEXT SEVEN YEARS, WE WILL CATALYZE DEVELOPMENT, TESTING, IMPLEMENTATION, AND DISSEMINATION OF TRANSLATIONAL SCIENCE AND RESEARCH TO IMPROVE HUMAN HEALTH, WITH AN EXPLICIT FOCUS ON ADVANCING HEALTH EQUITY BY COMPLETING OUR OVERALL AIMS. AIM 1: PERFORM AND SUPPORT RESEARCH THAT ADVANCES THE SCIENCE OF TRANSLATION WITH THE GOAL OF CLEARING BARRIERS TO RAPID TRANSLATION OF RESEARCH TOWARDS IMPLEMENTATION OF BEST EVIDENCE TO OUR PATIENTS AND THEIR COMMUNITIES. AIM 2: MAXIMIZE THE INFORMATIVENESS OF TRANSLATIONAL RESEARCH, TO DRIVE ITS IMPACT TO IMPROVE CLINICAL BENEFITS AND REDUCE HARMS WITH PARTICULAR ATTENTION TO POPULATIONS IMPACTED BY HEALTH INEQUITIES. AIM 3: TRAIN AND MAINTAIN A DIVERSE, EXPERT, MULTIDISCIPLINARY TRANSLATIONAL RESEARCH WORKFORCE AT ALL PROFESSIONAL LEVELS, PREPARED TO MEET THE CHALLENGES OF CURRENT AND FUTURE HEALTH CRISES. AIM 4: IMPLEMENT EVIDENCE-BASED STRATEGIES TO IMPROVE HUMAN HEALTH USING OUR LEARNING HEALTH CARE SYSTEM AS OUR LABORATORY. WE HAVE INTENSIFIED OUR EFFORTS IN HEALTH EQUITY AS WELL AS DISSEMINATION AND IMPLEMENTATION, RECOGNIZING THAT THESE ARE THE CRITICAL BARRIERS TO EFFECTIVE TRANSLATION OF INNOVATION TO HEALTH. WE WILL CAPITALIZE ON (I) THE SUBSTANTIAL RESOURCES OF OUR LEARNING HEALTH CARE SYSTEM AND (II) THE COLLECTIVE EXPERTISE OF TRACS, HONED OVER 14 YEARS OF SUPPORTING WORLD-CLASS TRANSLATIONAL RESEARCH, TO INTEGRATE THE PRINCIPLES OF SOCIAL JUSTICE IN ALL OUR SERVICES AND TRAININGS AND TO REALIZE OUR VISION OF “A HEALTHIER NORTH CAROLINA THROUGH INNOVATION”. WE WILL INNOVATE INCLUSIVE METHODS AND PROCESSES, ENGENDER TRUST, AND RECRUIT RESEARCH PARTICIPANTS WHO REFLECT THE DIVERSITY OF OUR STATE. WE WILL IMPLEMENT OUR ADVANCES TO ENSURE BENEFITS FOR OUR PARTICIPANTS, THEIR COMMUNITIES AND PATIENTS EVERYWHERE. WITH BROAD STAKEHOLDER ENGAGEMENT AND RIGOROUS EVALUATION OF OUR EFFORTS, WE WILL MAXIMIZE THE RELEVANCE OF OUR RESEARCH TO THOSE WE SERVE. TRACS WILL LEAD AND SUPPORT EFFORTS ACROSS THE CTSA CONSORTIUM TO CREATE A MORE EFFICIENT, INCLUSIVE RESEARCH ENVIRONMENT TO MITIGATE HEALTH DISPARITIES.

RISK FACTORS FOR ONSET AND PERSISTENCE OF TMD

COASTAL RESILIENCE

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH SUPPORTING THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY DARPA BIOLOGICAL TECHNOLOGIES OFFICES BTO FOCUSED PHARMA PROGRAM.

COLORECTAL CHEMOPREVENTION WITH CALCIUM AND VITAMIN D

ASSOCIATE AWARD FOR MEASURE EVALUATION PROJECT.

COLLABORATORY OF AIDS RESEARCHERS FOR ERADICATION (CARE) - ABSTRACT SINCE ITS INCEPTION IN 2011, THE MARTIN DELANEY COLLABORATORY PROGRAM HAS MADE IMPORTANT ADVANCES TOWARDS A CURE FOR HIV. IN RESPONSE TO THE MARTIN DELANEY COLLABORATORIES (MDC) FOR HIV CURE RESEARCH RFA, WE SEEK TO CONTINUE TO ADVANCE THE FIELD BY DISCOVERY OF SUCCESSFUL MODALITIES TO CURE HIV INFECTION. WE WILL EXPAND OUR EXPERTISE AND WORK TOWARD A BETTER UNDERSTANDING OF PERSISTENT HIV INFECTION, THE DISCOVERY OF NOVEL APPROACHES TO DISRUPT LATENCY, METHODS TO CLEAR THE HIV RESERVOIR, AND IDENTIFICATION OF STRATEGIES TO CONTROL VIRAL REBOUND. BY BUILDING ON THE SIGNIFICANT ADVANCES THAT WE HAVE MADE TO DEVELOP, IMPLEMENT, AND EXECUTE A SUITE OF PRE-CLINICAL EXPERIMENTS THAT REPRESENT THE MOST ADVANCED AND NOVEL CONCEPTS, WE WILL CONTINUE TO PURSUE OUR CENTRAL UNIFYING HYPOTHESIS THAT REVERSING HIV LATENCY SUCH THAT VIRAL PROTEINS ARE EXPRESSED, IN PARALLEL WITH INTERVENTIONS THAT SPEED THE CLEARANCE OF CELLS EMERGING FROM LATENT INFECTION, WILL ULTIMATELY LEAD TO ERADICATION OF PERSISTENT HIV INFECTION. IN PARALLEL TO THE EFFORTS TO CLEAR THE INFECTION, WE WILL PURSUE INTERVENTIONS TO PREVENT REBOUND OF VIREMIA AFTER ART INTERRUPTION. WE WILL LEVERAGE A BROAD PORTFOLIO OF TOOLS FROM BOTH ACADEMIC AND INDUSTRY PARTNERS, AND APPLY NEW DISCOVERIES, DEMONSTRATING PROOF-OF-CONCEPT FOR CLINICAL INITIATIVES. WE WILL ENGAGE ACADEMIC SCIENTISTS AND CLINICIANS, INDUSTRY INVESTIGATORS, AND THE COMMUNITY TO A) DEFINE NOVEL TARGETS TO DESTABILIZE PROVIRAL GENOMES THAT PERSIST DESPITE ANTIRETROVIRAL THERAPY (ART) B) DEFINE NOVEL APPROACHES TO BLOCK PROVIRAL ESTABLISHMENT C) DEVELOP AND DEPLOY NOVEL EFFECTORS TO CLEAR VIRAL RESERVOIRS, D) DELINEATE EFFECTIVE STRATEGIES TO PREVENT REBOUND VIREMIA THAT MIGHT EMANATE FROM SUCH RESERVOIRS AFTER ART IS DISCONTINUED AND E) CREATE BRIDGES TO THE COMMUNITY TO IMPROVE THE UNDERSTANDING OF AND ACCESS TO HIV CURE RESEARCH AND CLINICAL TRIALS. OUR INITIAL EFFORTS WILL FOCUS ON BIOLOGY DISCOVERY TO ILLUMINATE NEW HOST TARGETS FOR LATENCY REVERSAL, AND THE VALIDATION OF THE NOVEL BIOLOGICAL CONCEPT OF LATENCY PREVENTION. UNIVERSAL STRATEGIES FOR PROVIRAL CONTROL OR CLEARANCE WILL BE DEVELOPED AND TESTED, INCLUDING THOSE BASED ON HLA-E TARGETING, ECD4, AND CD4 MIMETICS. OUR MAJOR RECENT ADVANCE IN LATENCY REVERSAL VIA NF-KB SIGNALING WILL BE FURTHER DEVELOPED IN BOTH NON-HUMAN PRIMATE AND HUMANIZE MICE MODELS, IN COMBINATION WITH CANDIDATES TO CLEAR INFECTED CELLS. WE ENVISION AN ITERATIVE PROCESS WITH INSIGHTS GAINED IN EX VIVO AND PRE-CLINICAL STUDIES, CARRIED FORWARD TO ENHANCE THE NEXT STEP IN CLINICAL DEVELOPMENT AND, IMPORTANTLY, FED BACK TO SCIENTISTS TO VALIDATE ASSAYS OR HYPOTHESES, AND EXPLORE NEW DIRECTIONS. AS WE HAVE DONE IN THE PAST, WE WILL DEVELOP HUMAN CLINICAL TRIALS TO ADDRESS QUESTIONS AND TEST CONCEPTS DEVELOPED IN OUR WORK THROUGH FUNDING MECHANISMS DISTINCT FROM CARE. WE ARE DEDICATED TO WORKING TOGETHER IN A NIMBLE PROGRAM, WITH OUR RESEARCH DIRECTION FOLLOWING OUR DISCOVERIES. TOGETHER WE WILL CATALYZE ADVANCES THAT WILL ULTIMATELY LEAD TO THE ERADICATION OF HIV INFECTION.

NORTH CAROLINA OCCUPATIONAL SAFETY AND HEALTH EDUCATION AND RESEARCH CENTER

THE CLINICAL GENOME RESOURCE ? ADVANCING GENOMIC MEDICINE THROUGH BIOCURATION AND EXPERT ASSESSMENT OF GENES AND VARIANTS AT SCALE - PROJECT SUMMARY/ABSTRACT HIGH-QUALITY EVIDENCE ABOUT CLINICALLY RELEVANT GENES AND VARIANTS IS A FUNDAMENTAL CORNERSTONE OF GENOMIC MEDICINE. ALL ASPECTS OF CLINICAL CARE DERIVE FROM ACCURATE INFORMATION ABOUT THE ETIOLOGY, NATURAL HISTORY, AND MANAGEMENT OF DISEASE. WITH GENOMIC ANALYSIS BECOMING MORE ROUTINE FOR PATIENT CARE, THE PUBLIC AVAILABILITY OF WELL-CURATED AND EXPERTLY ADJUDICATED KNOWLEDGE ABOUT GENES AND VARIANTS IS CRITICAL. THE CLINGEN RESOURCE REPRESENTS A HIGHLY COLLABORATIVE EFFORT OF THE GENETICS COMMUNITY TO ESTABLISH AN EVIDENCE-BASED RESOURCE FOR THE ASSESSMENT OF THE CLINICAL RELEVANCE OF GENES AND VARIANTS THAT IS READILY ACCESSIBLE TO (AND TRUSTED BY) DIAGNOSTIC LABORATORIES, PROVIDERS, AND PATIENTS. OUR OBJECTIVE IS TO IMPROVE PATIENT CARE THROUGH ENHANCED AND ACCELERATED CURATION OF THE CLINICAL GENOME USING INNOVATIVE APPROACHES TO OVERCOME CHALLENGES AND ADDRESS NEW TOPICS. WE WILL ACCOMPLISH THIS OBJECTIVE THROUGH THE CONCERTED PURSUIT OF THE FOLLOWING AIMS: AGGREGATION OF STRUCTURED EVIDENCE REGARDING GENETIC CONDITIONS AND THE GENES AND VARIANTS THAT CAUSE THEM; APPLICATION OF FRAMEWORKS FOR EXPERT CURATION OF CLINICAL VALIDITY, VARIANT PATHOGENICITY, AND CLINICAL ACTIONABILITY OF GENETIC CONDITIONS; BROAD DISSEMINATION OF TOOLS, STANDARDS, KNOWLEDGE BASES, AND ASSERTIONS ABOUT CLINICALLY RELEVANT GENES AND VARIANTS; AND EVALUATION OF ALL ASPECTS OF THIS WORK, SO THAT WE CAN IMPROVE THE QUALITY AND IMPACT OF THE RESOURCE FOR IMPLEMENTATION OF TRANSPARENT, REPRODUCIBLE, AND EVIDENCE-BASED GENOMIC MEDICINE. THE PROPOSAL IS INNOVATIVE IN SEVERAL WAYS. IT WILL AGGREGATE DATA PRODUCED BY CUTTING EDGE TECHNOLOGIES, ADAPT ANNOTATION TOOLS TO ENABLE CROWDSOURCING THROUGH COMMUNITY CURATION, AND APPLY ADVANCED NATURAL LANGUAGE PROCESSING FOR ANNOTATION SO THAT HUMAN CURATORS CAN FUNCTION AT THE TOP OF THEIR SKILL LEVEL. IT WILL LEVERAGE THE PARTICIPATION OF A LARGE AND ENTHUSIASTIC COMMUNITY OF VOLUNTEERS, THUS ACTING AS A FORCE MULTIPLIER FOR THE NIH FUNDED TEAMS. IT WILL ENGAGE ADVOCATES WHO CAN CONDUCT OUTREACH WITHIN THEIR AREAS OF SPECIALTY, TO FURTHER EXTEND THE REACH OF CLINGEN PRODUCTS INTO GENOMIC MEDICINE RESEARCH AND CLINICAL CARE. IT WILL TRANSFORM A WIDE RANGE OF CLINICAL AND BASIC SCIENCE DATA INTO WELL-STRUCTURED, TRANSPARENTLY REFERENCED EXPERT ASSERTIONS WITH DOCUMENTATION OF PROVENANCE AND ATTENTION TO ENSURING THE INTEROPERABILITY OF THE RESOURCE WITH DIVERSE END- USERS, INCLUDING ELECTRONIC HEALTH RECORDS. THE PROPOSED RESOURCE PROJECT IS SIGNIFICANT BECAUSE IN ITS ENTIRETY IT WILL IMPROVE, SCALE, AND DISSEMINATE THE FREELY AVAILABLE EXPERT CURATION AND INTERPRETATION OF THE HUMAN GENOME TO THE GLOBAL GENOMICS COMMUNITY WITH THE GOAL OF IMPROVING HEALTH CARE FOR ALL PEOPLE.

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH & SUSCEPTIBILITY

LONGITUDINAL ASSESSMENT OF POST-TRAUMATIC SYNDROMES

THE PURPOSE OF THIS ACTIVITY IS TO STRENGTHEN EFFECTIVE GENERATION AND USE OF HIGH-QUALITY DATA AND EVIDENCE TO STRENGTHEN POLICIES AND PROGRAM IMPLEMENTATION IN LOW- AND MIDDLE-INCOME COUNTRIES. GH PEARL HAS BEEN DESIGNED TO SERVE AS A RESOURCE FOR MONITORING, EVALUATION, RESEARCH AND LEARNING (MERL) RELATED TO IMPROVEMENTS IN THE QUALITY, COVERAGE AND EQUITY OF FAMILY PLANNING (FP) AND REPRODUCTIVE, MATERNAL, NEWBORN, CHILD HEALTH AND NUTRITION (RMNCH+N) INTERVENTIONS.

NOVEL THERAPIES FOR MUCO-OBSTRUCTIVE LUNG DISEASES

ENVIRONMENTAL EXPOSURE AND EFFECT OF HAZARDOUS CHEMICALS

STUDIES OF NUCLEAR PROCESSES

COLLABORATORY OF AIDS RESEARCHERS FOR ERADICATION (CARE)

EARLY CHILDHOOD SYSTEMS TECHNICAL ASSISTANCE CENTER

A CAROLINA CENTER TO CHARACTERIZE AND MAINTAIN MUTANT MICE

BIOSTATISTICS FOR RESEARCH IN ENVIRONMENTAL HEALTH

MONITORING SOCIAL CHANGE: HEALTH, REPRODUCTION, AGING

NC GENES: NORTH CAROLINA CLINICAL GENOMIC EVALUATION BY NEXTGEN EXOME SEQUENCING

UNC CLINICAL NUTRITION RESEARCH UNIT

ADD HEALTH PARENT STUDY: A BIOSOCIAL RESOURCE FOR THE STUDY OF MULTIGENERATIONAL RACIAL/ETHNIC DISPARITIES IN ALZHEIMER'S DISEASE AND ALZHEIMER'S DISEASE-RELATED DEMENTIAS (AD/ADRD) - ABSTRACT SIGNIFICANT KNOWLEDGE GAPS EXIST REGARDING INTERGENERATIONAL DIMENSIONS OF COGNITIVE AGING AND RISK FOR ALZ- HEIMER’S DISEASE AND ALZHEIMER’S DISEASE RELATED DEMENTIAS (AD/ADRD), AND HOW THESE PROCESSES DIFFER ACROSS RACE AND ETHNIC GROUPS. THE PROPOSED ADD HEALTH PARENT STUDY (AHPS) PHASE 2 IS DESIGNED TO AD- DRESS THESE GAPS. AHPS IS AN ONGOING STUDY OF SOCIAL, BEHAVIORAL, AND BIOLOGICAL FACTORS INFLUENCING HEALTHY AGING AND THE DEVELOPMENT OF AD/ADRD IN A NATIONAL SAMPLE OF ADULTS CURRENTLY AGED 58-90. SAMPLE MEMBERS ARE PARENTS OF THE NATIONAL LONGITUDINAL STUDY OF ADOLESCENT TO ADULT HEALTH (ADD HEALTH) COHORT, INITIALLY INTER- VIEWED IN ADD HEALTH IN EARLY MIDLIFE (1994-95) BEFORE DIFFERENTIAL SURVIVAL COULD CONTRIBUTE BIAS TO SAMPLE REP- RESENTATION. PHASE 1 OF AHPS (2015-17) COLLECTED LONGITUDINAL DATA ON A RANDOM SUBSAMPLE OF PARENTS AND THEIR SPOUSE/PARTNERS (S/P, N= 3001), THE MAJORITY (73%) OF WHOM WERE NON-HISPANIC (NH) WHITE. PHASE 2 OF AHPS WILL COLLECT SOCIAL, BEHAVIORAL, AND HEALTH DATA ON ALL AVAILABLE NH BLACK AND HISPANIC PARENTS (BHS SUP- PLEMENT, N= 2,505), AND COGNITIVE ASSESSMENTS AND DNA DATA ON ALL AHPS PHASE 1 AND BHS SAMPLE PARENTS AND THEIR CURRENT S/P (TOTAL N= 5,506). BY ADDING NH BLACK AND HISPANIC PARENTS, AHPS WILL BE SUFFICIENTLY STA- TISTICALLY POWERED TO ADDRESS, FOR THE FIRST TIME, MEASUREMENT OF HEALTH, SOCIAL, AND BEHAVIORAL DIFFERENCES IN AD/ADRD RISK AND PROTECTIVE FACTORS ACROSS RACE/ETHNIC GROUPS AND SOCIOECONOMIC STRATA. COMBINED DATA FROM AHPS PHASES 1 AND 2 WILL BE LINKED WITH RICH LONGITUDINAL DATA ON ORIGINAL ADD HEALTH RE- SPONDENTS TO CREATE AND DISSEMINATE THE FIRST NATIONALLY REPRESENTATIVE MULTIGENERATIONAL BIOSOCIAL RESOURCE WITH COGNITIVE, GENOMIC, BEHAVIORAL, AND SOCIAL DATA FOR THE STUDY OF RACIAL/ETHNIC DISPARITIES IN COGNITIVE AGING AND AD/ADRD RISK. COGNITION AND GENOMIC DATA WILL BE HARMONIZED ACROSS THE TWO GENERATIONS OF PARENTS AND CHILDREN FOR INNOVATIVE ANALYSIS OF INTERGENERATIONAL PREDICTORS OF AD/ADRD; THE ROLE OF GENETIC PROCESSES IN AD/ADRD ETIOLOGY; AND INTERGENERATIONAL AND LATERAL CAREGIVING. PROJECT SPECIFIC AIMS ARE: 1A. RECRUIT AND INTERVIEW ADDITIONAL SAMPLE OF 2,505 NH BLACK AND HISPANIC PARENTS WITH THE AHPS SURVEY. 1B. CONSENT ALL 5,506 AHPS MEMBERS FOR PARTICIPATION IN AD/ADRD ASSESSMENT AND DNA DATA COLLECTION. 2A. COLLECT DNA AND CONDUCT SNP GENOTYPING AND DNA METHYLATION ANALYSIS ON AHPS SAMPLE. 2B. DEVELOP AN INTERGENERATIONAL GENOMIC DATABASE TO ADVANCE AN UNDERSTANDING OF THE GENE-ENVIRONMENT INTERPLAY IN THE ETIOLOGY OF AD/ADRD. 3A. EXAMINE NOVEL LONGITUDINAL AND INTERGENERATIONAL SOCIAL, HEALTH, AND BEHAVIORAL RISK AND PREVENTIVE FACTORS FOR AD/ADRD ACROSS RACIAL/ETHNIC GROUPS AND SOCIAL STRATA. 3B. EXAMINE AHPS MEMBERS’ CAREGIVING EXPERIENCES AND THE SOCIOECONOMIC CONSEQUENCES OF CAREGIVING EX- PERIENCES RELATED TO AD/ADRD CONDITIONS OR RISKS. 4. DOCUMENT, DISSEMINATE, AND PROMOTE USE OF AHPS DATA TO THE GLOBAL SCIENTIFIC COMMUNITY.

MID-SCALE RI-1 (M1:IP): FABRIC: ADAPTIVE PROGRAMMABLE RESEARCH INFRASTRUCTURE FOR COMPUTER SCIENCE AND SCIENCE APPLICATIONS

EARLY CHILDHOOD TECHNICAL ASSISTANCE CENTER (ECTA)

STATISTICAL METHODS FOR CANCER CLINICAL TRIALS

THE IMPACT OF TOBACCO EXPOSURE ON THE LUNGS INNATE DEFENSE SYSTEM

GENE EXPRESSION PATTERNS IN HUMAN TUMORS IDENTIFIED USING TRANSCRIPT SEQUENCING

NOVEL NANOPARTICLE PLATFORM FOR THE DELIVERY OF VACCINES AND ADJUVANTS

ENVIRONMENT, EPIGENETICS, NEURODEVELOPMENT & HEALTH OF EXTREMELY PRETERM CHILDREN

UNC MACS/WIHS COMBINED COHORT STUDY CLINICAL RESEARCH SITE

EFFECTIVE COMMUNICATION ON TOBACCO PRODUCT RISK AND FDA AUTHORITY

MOLECULAR THERAPY CORE CENTER

CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE

GENETIC DISORDER OF MUCOCILARY CLEARANCE

THE UNC CHAPEL HILL SUPERFUND RESEARCH PROGRAM (UNC-SRP)

SEEDING POSTDOCTORAL INNOCATORS IN RESEARCH AND EDUCATION (SPIRE)

ADEPT: DXOD - POC

UNIVERSITY OF NORTH CAROLINA AIDS CLINICAL TRIALS UNIT (UNC ACTU)

EVALUATION AND RESEARCH CAPACITY OF THE COMMUNITY HEALTH AND SOCIAL SERVICE PROGRAMS IN THE UNITED REPUBLIC OF TANZANIA

HOST INNATE IMMUNE-MICROBIAL INTERACTIONS AND INTESTINAL INFLAMMATION

STATISTICAL AND APPLIED MATHEMATICAL SCIENCES INSTITUTE

ANCA GLOMERULONEPHRITIS: FROM MOLECULES TO MAN

STRATEGIC INFORMATION CAPACITY BUILDING ACTIVITY WITH LWA-

MODIFICATION OF COOPERATIVE AGREEMENT TO ADD STANDARD PROVISIONS.

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

UNIVERSITY TRANSPORTATION CENTERS

DEEP SEQUENCING STUDIES FOR CANNABIS AND STIMULANT DEPENDENCE

NORTH CAROLINA BIO-PREPAREDNESS COLLABORATIVE (NCB-PREPARED)

TA CENTER ON EARLY CHILDHOOD

STATE MATERNAL HEALTH INNOVATION SUPPORT AND IMPLEMENTATION PROGRAM

NATIONAL LONGITUDINAL STUDY OF ADOLESCENT TO ADULT HEALTH (ADD HEALTH): WAVE VI COGNITION AND EARLY RISK FACTORS FOR DEMENTIA PROJECT - PROJECT SUMMARY ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD) ARE PROJECTED TO AFFECT 14 MILLION AMERICANS BY 2050. TO DATE, THOUGH, RESEARCH ON THE SIGNS AND SYMPTOMS OF ADRD HAS BEEN SPARSE IN EARLY MIDLIFE POPULATIONS, ESPECIALLY AT THE NATIONAL LEVEL. IT IS CRUCIAL TO CONDUCT SUCH RESEARCH BECAUSE EARLY CHANGES IN COGNITIVE FUNCTIONING AND THE ACCUMULATION OF RISK FACTORS FOR ADRD CAN BEGIN DECADES BEFORE CONCRETE SIGNS AND SYMPTOMS EMERGE. THE CHALLENGING SEARCH FOR THE CAUSES OF ADRD HAS MADE IT CLEAR THAT PROSPECTIVE AND COMPREHENSIVE DATA—INCLUDING DETAILED SOCIAL, BIOLOGICAL, AND HEALTH MEASUREMENTS ACROSS THE LIFE COURSE— ARE NEEDED TO IDENTIFY KEY PREDICTORS OF ADRD. AS SUCH, THE NATIONAL LONGITUDINAL STUDY OF ADOLESCENT TO ADULT HEALTH (ADD HEALTH) PROVIDES AN EXTRAORDINARY OPPORTUNITY TO STUDY THE EARLY ORIGINS OF COGNITIVE FUNCTIONING/CHANGE AND ADRD RISK IN A NATIONALLY REPRESENTATIVE COHORT THAT HAS BEEN FOLLOWED SINCE ADOLESCENCE AND WILL BE IN THEIR MID-40S IN THE NEXT WAVE OF DATA COLLECTION (WAVE VI). THE OVERALL GOAL OF THIS PROJECT IS TO COLLECT AND DISSEMINATE CRITICAL DATA RELATED TO COGNITIVE, PHYSICAL, AND SENSORY FUNCTIONING IN CONJUNCTION WITH THE ADD HEALTH WAVE VI CORE PROJECT TO FACILITATE IDENTIFICATION OF EARLY RISK FACTORS FOR LATER LIFE ADRD. ADDING SUCH RICH MEASURES TO WAVE VI OF ADD HEALTH WILL MAKE POSSIBLE TRACKING OF COGNITIVE, SENSORY, AND PHYSICAL FUNCTIONING ACROSS THE LIFE COURSE; COUPLED WITH THE TESTING OF BIOLOGICAL RISK MARKERS, IT WILL ALSO LAY THE FOUNDATION FOR DETECTING SIGNS OF COGNITIVE IMPAIRMENT AND ADRD RISK IN EARLY MIDLIFE. THESE NEW DATA, WHEN COMBINED WITH ADD HEALTH'S EXISTING 25-YEAR COLLECTION OF EXTRAORDINARILY RICH MULTI-LEVEL AND LONGITUDINAL MEASURES AND ITS NEW WAVE VI DATA, WILL ALSO AID IN THE SCIENTIFIC COMMUNITY'S UNDERSTANDING OF THE INTERPLAY OF SOCIAL, BEHAVIORAL, AND BIOLOGICAL FACTORS LEADING TO ADRD IN LATER LIFE. MOREOVER, BECAUSE ADD HEALTH IS A VERY DIVERSE SAMPLE, ADDING THESE DATA TO WAVE VI WILL GREATLY INCREASE UNDERSTANDING OF COGNITIVE, PHYSICAL, AND SENSORY FUNCTIONING WITHIN HEALTH DISPARITY POPULATIONS. THE PROJECT'S SPECIFIC AIMS ARE TO: 1) COLLECT NEW IN- DEPTH, IN-PERSON ASSESSMENTS OF COGNITIVE FUNCTIONING IN EARLY MIDLIFE FOR A NATIONALLY REPRESENTATIVE AND RACIALLY/ETHNICALLY DIVERSE SUBSAMPLE OF PARTICIPANTS IN WAVE VI; 2) COLLECT AUTOMATED, (LARGELY) WEB-BASED MEASURES OF COGNITION IN EARLY MIDLIFE FOR ALL PARTICIPANTS IN WAVE VI AND COMPARE THEM WITH OUR IN-PERSON MEASURES OF COGNITION TO ASSESS THEIR FEASIBILITY AND VALUE; 3) INCLUDE ASSESSMENTS OF PHYSICAL AND SENSORY FUNCTIONING IN EARLY MIDLIFE FOR WAVE VI PARTICIPANTS OF ADD HEALTH; 4) TEST FOR BIOLOGICAL MARKERS OF ADRD RISK AND COGNITIVE FUNCTION IN EARLY MIDLIFE; 5) CLEAN, DOCUMENT, DISSEMINATE, PROMOTE, AND SUPPORT THE DATA COLLECTED IN THIS PROJECT FOR THE SCIENTIFIC COMMUNITY. ALL TOLD, THIS PROJECT WILL COLLECT AND DISSEMINATE INNOVATIVE DATA TO THOUSANDS OF RESEARCHERS THAT WILL FACILITATE THE RIGOROUS STUDY OF COGNITION AND RISK FACTORS FOR LATER LIFE ADRD AMONG A DIVERSE NATIONALLY REPRESENTATIVE SAMPLE OF EARLY MIDLIFE AMERICANS.

SEMANTIC LAMHDI: LINKING DISEASES TO MODEL ORGANISM RESOURCES

CATEGORY 1: UNC CENTER FOR HEALTH PROMOTION AND DISEASE PREVENTION

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

METABOLOMICS AND CLINICAL ASSAYS CENTER - ABSTRACT (METABOLOMICS AND CLINICAL ASSAY CENTER, MCAC) DETERMINING HOW INDIVIDUALS DIFFER IN THEIR METABOLISM, AND IN THEIR RESPONSE TO DIETARY INTAKE, IS CRITICAL TO DEVELOPING PERSONALIZED INTERVENTION STRATEGIES FOR PREVENTING AND DELAYING THE ONSET OF CHRONIC DISEASES SUCH AS OBESITY, DIABETES, CARDIOVASCULAR DISEASE, AND CANCER. THE MCAC WILL A) ACQUIRE AND PROCESS HIGH QUALITY TARGETED AND UNTARGETED METABOLOMICS DATA, B) PRIORITIZE, PREDICT, AND CONFIRM THE IDENTITY OF UNKNOWN PEAKS, C) PROVIDE CLIA CERTIFIED CLINICAL ASSAYS, D) COLLABORATE WITH THE COMMON FUND DATA ECOSYSTEM, E) CONSTRUCT A DATA INFRASTRUCTURE WHICH ENSURES FAIRNESS AND ENABLES INTEROPERABILITY OF THE DATA WITH OTHER COMMON FUND DATA SETS, AND F) COLLABORATIVELY WORK WITH THE NIH COMMON FUND NUTRITION FOR PRECISION HEALTH (NPH) CONSORTIUM. THE MCAC BRINGS AN OUTSTANDING TEAM OF INVESTIGATORS FROM 3 UNC SYSTEMS UNIVERSITIES THAT ARE CO-LOCATED ON THE NORTH CAROLINA RESEARCH CAMPUS (NCRC) AND DUKE UNIVERSITY. DR. SUSAN SUMNER (UNC CHAPEL HILL, NUTRITION RESEARCH INSTITUTE, NCRC, UNTARGETED METABOLOMICS) WILL SERVE AS THE PI WITH SUPPORT FROM EXPERT SCIENTISTS WHO SPECIALIZE IN NUTRITION AND TARGETED METABOLOMICS OF HOST METABOLISM (DR. CHRISTOPHER NEWGARD, DIRECTOR, SARAH W. STEDMAN NUTRITION AND METABOLISM CENTER AND DUKE MOLECULAR PHYSIOLOGY INSTITUTE), DIETARY INTERVENTIONS AND TARGETED PHYTOCHEMICAL ANALYSIS (DR. COLIN KAY, NORTH CAROLINA STATE UNIVERSITY, NCRC), CLIA CERTIFIED CLINICAL ASSAYS (DR. STEVEN COTTEN, UNCCH), AND COMPUTATIONAL METABOLOMICS (DR. XIUXIA DU, UNC CHARLOTTE, NCRC). OUR TEAM PROVIDES A UNIQUE COMBINATION OF LONG-STANDING EXPERTISE IN METABOLOMICS TECHNOLOGIES, COUPLED WITH DEEP KNOWLEDGE OF NUTRITION, METABOLIC PHYSIOLOGY, AND CHRONIC DISEASE MECHANISMS. WE ARE EXPERIENCED WITH THE APPLICATION OF TARGETED AND UNTARGETED METABOLOMICS IN LARGE-SCALE CLINICAL AND EPIDEMIOLOGY STUDIES, INCLUDING IN OTHER NIH CONSORTIA. WE HAVE USED METABOLOMICS TO DEFINE METABOLIC SIGNATURES AND PATHWAYS ASSOCIATED WITH DIETARY INTAKE, NUTRITION ASSESSMENTS, DEMOGRAPHICS, LIFESTYLE FACTORS, MICROBIAL POPULATIONS, GENETICS, TRANSCRIPTOMICS, CLINICAL ASSAYS, AND CLINICAL PHENOTYPES OF HEALTH AND WELLNESS. WE HAVE DEVELOPED COMPREHENSIVE INFORMATICS CAPABILITIES FOR TARGETED AND UNTARGETED METABOLOMICS AND EXPOSOME RESEARCH. WE HAVE DEVELOPED AN ONLINE MASS SPECTRAL KNOWLEDGE BASE RESOURCE FOR PRIORITIZING AND PREDICTING UNKNOWN METABOLITES BY LEVERAGING PUBLICLY AVAILABLE DATA. OUR HIGH QUALITY MCAC DATASETS PRODUCED UNDER FINE-TUNED PROTOCOLS WITH QUALITY CONTROL AND QUALITY ASSURANCE METRICS, WILL BE ESSENTIAL FOR SUCCESS OF THE NPH CONSORTIUM. THE MCAC WILL PROVIDE DATA AND EXPERT BIOLOGICAL INTERPRETATION IN EXPLORATION OF THE HETEROGENEITY IN METABOLISM AMONG STUDY SUBJECTS, PROVIDING A ROADMAP THAT WILL HELP EXPLAIN WHY INDIVIDUALS DIFFER IN THEIR METABOLIC RESPONSES TO DIETARY INTERVENTIONS, AND WHAT THIS PORTENDS FOR FUTURE DISEASE RISK. THE MCAC WILL PROVIDE A ROBUST DATA SET TO THE ARTIFICIAL INTELLIGENCE FOR MULTIMODAL DATA MODELING AND BIOINFORMATICS CENTER FOR USE IN DEVELOPMENT OF ALGORITHMS TO PREDICT INDIVIDUAL DIETARY RESPONSES THAT CAN ULTIMATELY BE TRANSLATED FOR DESIGN OF TARGETED DIETARY INTERVENTIONS TO IMPROVE HEALTH AND QUALITY OF LIFE.

RESEARCH INFRASTRUCTURE: FABRIC OPERATIONS - ACCELERATING INNOVATION AND RESEARCH -THE FABRIC PROJECT HAS DEPLOYED A STATE-OF-THE-ART PROGRAMMABLE WORLD-WIDE NETWORK INFRASTRUCTURE DURING THE COMMISSIONING PHASE FUNDED THROUGH THE NSF MIDSCALE RESEARCH INFRASTRUCTURE-1 PROGRAM. THIS INFRASTRUCTURE CONNECTS RESEARCH FACILITIES GLOBALLY, ENABLING GROUNDBREAKING DISTRIBUTED APPLICATIONS AND SERVICES USING WHILE MORE THAN 30 INTERCONNECTED FABRIC SITES ALREADY DEPLOYED. FABRIC ENHANCES RESEARCH CAPABILITIES IN WIDE-AREA NETWORKING PROTOCOLS, INTERNET-OF-THINGS (IOT), BIG DATA, MACHINE LEARNING, MOBILE TECHNOLOGIES AND HIGH-PERFORMANCE COMPUTING, FOSTERING SCIENTIFIC DISCOVERIES AND CROSS-DISCIPLINARY COLLABORATIONS. THE FABRIC PROJECT, NOW IN ITS OPERATIONS PHASE, AIMS TO FURTHER GROW USER COMMUNITIES, FOSTER OPERATIONAL EXCELLENCE, DEVELOP NEW FEATURES, AND DEMONSTRATE SUCCESS TO ITS STAKEHOLDER COMMUNITIES. EXPANDING THE USER BASE AMPLIFIES THE IMPACT OF FABRIC AND OTHER NSF TESTBEDS ON SCIENCE. BY PROVIDING RELIABLE SERVICES, FABRIC ENSURES REPRODUCIBILITY OF COMPLEX EXPERIMENTS. THE DEVELOPMENT OF NEW FEATURES ATTRACTS USERS FROM VARIOUS COMMUNITIES, HELPING ADDRESS THEIR SPECIFIC NEEDS. DEMONSTRATING SUCCESS THROUGH MEASURED OUTCOMES INFORMS THE FUNDERS AND REINFORCES FABRIC'S IMPACT ON STAKEHOLDER COMMUNITIES. ITS INTELLECTUAL MERITS LIE IN INFRASTRUCTURE PROGRAMMABILITY AND INTERCONNECTIVITY, ENABLING EXPERIMENTATION WITH DISTRIBUTED SYSTEMS AT UNPRECEDENTED SCALES. IT SUPPORTS SCIENTIFIC REPRODUCIBILITY AND IS A CRUCIAL COMPONENT OF THE SCIENTIFIC CYBERINFRASTRUCTURE ECOSYSTEM. ITS IMPACT SPANS DIVERSE DOMAINS, SUCH AS HIGH-ENERGY PHYSICS, ASTROPHYSICS, CYBERSECURITY, AND SCIENTIFIC INSTRUMENT STREAMING SERVICES, EMPOWERING RESEARCHERS TO ACHIEVE BREAKTHROUGH DISCOVERIES. FABRIC'S BROADER IMPACTS EXTEND TO RESEARCHERS IN COMPUTER SCIENCE, ENGINEERING, AND DOMAIN SCIENCES SUCH AS GENOMICS, ASTRONOMY AND CLIMATE RESEARCH. IT ACTIVELY ENGAGES THE RESEARCH COMMUNITY THROUGH KNIT WORKSHOPS AND THE AMBASSADOR PROGRAM DESIGNED TO EXPAND FABRIC?S REACH TO RESEARCHERS FROM ALL DISCIPLINES AND INSTITUTIONS, REGARDLESS OF BACKGROUND. FABRIC PROVIDES EDUCATIONAL RESOURCES TO FACULTY, AND DEVELOPS COLLABORATIONS WITH MINORITY-SERVING INSTITUTIONS, SIMPLIFYING ACCESS TO ADVANCED RESEARCH TOOLS AND INFRASTRUCTURE FOR MANY COMMUNITIES. THE PROJECT WEBSITE, [HTTPS://WWW.FABRIC-TESTBED.NET], SERVES AS A CENTRAL REPOSITORY FOR PROJECT UPDATES, DATA, CODE, AND RESOURCES, FOSTERING COLLABORATION AND ACCESSIBILITY 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.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

DISCOVERY OF NEW INNATE IMMUNE PATHWAYS IN VIRAL RECOGNITION

NORTH CAROLINA STI/TM COOPERATIVE RESEARCH CENTER

AMERICAN RECOVERY AND REINVESTMENT ACT OF 2009, HEALTH INFORMATION TECHNOLOGY EXTENSION PROGRAM: REGIONAL CENTERS

NUTRITION FOR PRECISION HEALTH: THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL CLINICAL CENTER - PROJECT SUMMARY/ABSTRACT – THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL CLINICAL CENTER THE NEED FOR MORE PRECISE NUTRITION ADVICE IS WIDELY RECOGNIZED, YET SPECIFIC DIFFERENCES IN GENETIC, EPIGENETIC, MICROBIOME AND PHENOTYPIC DRIVERS OF INDIVIDUAL VARIABILITY TO DIET ARE NOT WELL KNOWN. THE NATIONAL INSTITUTES OF HEALTH INITIATIVE TO FUND NUTRITION FOR PRECISION HEALTH (NPH), POWERED BY THE ALL OF US RESEARCH PROGRAM, WILL ENABLE MAJOR PROGRESS IN THE FIELD OF PRECISION NUTRITION. HERE WE PROPOSE NUTRITION FOR PRECISION HEALTH: THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL CLINICAL CENTER (UNC-CC). BECAUSE CHRONIC INFLAMMATION PROMOTES THE PATHOGENESIS OF A WIDE RANGE OF DISEASES, INCLUDING OBESITY, TYPE 2 DIABETES, AND CARDIOVASCULAR, NEOPLASTIC, AND NEURODEGENERATIVE DISORDERS, WE DRAW UPON THE ANTI-INFLAMMATORY MEDITERRANEAN DIET AS A VIABLE STRATEGY TO IMPROVE SYSTEMIC INFLAMMATION AND REDUCE RISK FOR MANY CHRONIC DISEASES AND THEIR COMPLICATIONS. A BODY OF LITERATURE HAS EMERGED THAT DEMONSTRATES BOTH GENOTYPICALLY- AND PHENOTYPICALLY-DRIVEN DIFFERENTIAL RESPONSES TO THE MEDITERRANEAN DIET RELATIVE TO A RANGE OF OUTCOMES. OUR PROPOSAL WILL ADDRESS THE CRITICAL NEED TO UNDERSTAND VARIABILITY IN PHYSIOLOGIC RESPONSES TO DIET, ANCHORED BY THE THEME OF INFLAMMATION. WE EMPHASIZE INCLUSION OF A HIGHLY DIVERSE SAMPLE FACILITATED BY TWO CLINICAL LOCATIONS WITH METABOLIC KITCHENS: THE UNC NUTRITION RESEARCH INSTITUTE (UNC-NRI) IN KANNAPOLIS, NC, AND THE CHAPEL HILL CAMPUS OF UNC (UNC-CH). THE UNC-NRI DRAWS FROM RELATIVELY RURAL COMMUNITIES, AND UNC-CH DRAWS FROM RELATIVELY URBAN COMMUNITIES, BOTH WITH A SUBSTANTIAL PROPORTION OF PEOPLE OF COLOR. SPECIFIC AIMS ARE: AIM 1. TO PARTICIPATE ACTIVELY IN THE YEAR 1 PLANNING PROCESS AND BEYOND, ENGAGING ACROSS THE NPH CONSORTIUM TO COLLABORATIVELY DEVELOP AND EXECUTE THE FINAL STUDY PROTOCOL. AIM 2. TO EXECUTE NPH MODULE 1. FOLLOWING PARTICIPANT ENROLLMENT INTO ALL OF US, WE WILL ENROLL AND COMPLETE THE MODULE 1 PROTOCOL FOR A TOTAL OF 2,000 NPH PARTICIPANTS (25% AT UNC-NRI; 75% AT UNC-CH), INCLUDING TWO STUDY VISITS WITH A 2-WEEK REMOTE DATA CAPTURE PERIOD AND A MIXED MEAL CHALLENGE TEST. AIM 3. TO EXECUTE NPH MODULE 2. A SUBSET OF 500 MODULE 1 PARTICIPANTS WILL COMPLETE A FREE-LIVING, CONTROLLED FEEDING STUDY OF THREE 2-WEEK DIET INTERVENTION PERIODS, SEPARATED BY 3-WEEK WASHOUT PERIODS. DIETS INCLUDE: THE MEDITERRANEAN DIET ADAPTED FOR THE US (MED-USA; 40% FAT CALORIES, 40% CARBOHYDRATE), THE MED-USA MODIFIED FOR HIGH HEALTHY FAT CONTENT (60% FAT CALORIES, 20% CARBOHYDRATE), AND MED-USA MODIFIED FOR HIGH HEALTHY CARBOHYDRATE CONTENT (20% FAT CALORIES, 60% CARBOHYDRATE). DIFFERENTIAL EFFECTS OF THE DIETS ON OUTCOMES COMPRISING INFLAMMATORY MARKERS AND METABOLIC PARAMETERS FROM THE MIXED MEAL CHALLENGE WILL BE TESTED ACROSS GENOTYPIC AND PHENOTYPIC SUBGROUPS, FOCUSING ON WEIGHT STATUS, AGE, AND DIABETES STATUS. THE UNC-CC TEAM BRINGS IMPRESSIVE INTERDISCIPLINARY STRENGTH IN NUTRITION (BASIC SCIENCE TO PUBLIC HEALTH) AND HAS THE CAPACITY AND EXPERIENCE IN COMPLEX, MULTI-SITE TRIALS TO ENSURE THE SCIENTIFIC RIGOR NEEDED TO EXECUTE THIS STUDY. RESULTS WILL GENERATE PREDICTIVE ALGORITHMS TO INFORM INDIVIDUALIZED DIETARY GUIDANCE TO IMPROVE HEALTH.

ILLUMINATING THE DRUGGABLE GPCR-OME

FACILITATION, SPREAD AND TRANSLATION OF PATIENT-CENTERED EVIDENCE IN NC PRACTICES

MCH WORKFORCE CENTERS

GRADUATE RESERACH FELLOWSHIP PROGRAM (GRFP)

FUNCTIONAL SELECTIVITY: A NOVEL APPROACH FOR CNS DRUG DISCOVERY

ILLUMINATING FUNCTION OF THE UNDERSTUDIED DRUGGABLE KINOME

UNC DEVELOPMENTAL DISABILITIES RESEARCH CENTER

ATLANTIC COAST CENTER FOR INFECTIOUS DISEASE DYNAMICS AND ANALYTICS

THE CLINICAL GENOME RESOURCE - EXPERT CURATION AND EHR INTEGRATION

COMPUTER INTEGRATED SYSTEMS FOR MICROSCOPY&MANIPULATION

RESEARCH TRIANGLE CENTER OF EXCELLENCE IN REGULATORY SCIENCE AND INNOVATION - ABSTRACT THE RAPID EMERGENCE OF INNOVATIVE TECHNOLOGIES, THERAPEUTICS, AND OTHER FDA-REGULATED PRODUCTS HAVE OUTPACED THE ABILITY TO EFFECTIVELY APPROPRIATE THEM FOR PUBLIC BENEFIT. DOING SO HINGES ON THE CAPABILITY TO EXPEDITIOUSLY EVALUATE THESE PRODUCTS AND EFFECTIVELY MONITOR THEM ONCE ON THE MARKET. HOWEVER, METHODOLOGIES FOR PRE- MARKET EVALUATION THROUGH LABORATORY TESTING AND CLINICAL TRIALS FOR DRUGS, DEVICES, AND BIOLOGICS AND FOR POST- MARKETING SURVEILLANCE OF ALL FDA-REGULATED PRODUCTS HAVE NOT KEPT PACE, AND KEY GAPS IN KNOWLEDGE EXIST THAT WOULD INFORM REGULATORY DECISION MAKING IN MANY AREAS. IN THE FACE OF THESE PRESSING NEEDS, THE RESEARCH TRIANGLE CENTER OF EXCELLENCE IN REGULATORY SCIENCE AND INNOVATION (TRIANGLE CERSI) WILL PROVIDE A ONE-STOP- SHOP ACCELERATOR TO MEET FDA’S CURRENT AND EVOLVING NEEDS IN REGULATORY SCIENCE AND A GENERATIVE COMMUNITY FOR REGULATORS, ACADEMIA, INDUSTRY, AND OTHER STAKEHOLDERS. A COLLABORATION OF THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL, DUKE UNIVERSITY, NORTH CAROLINA STATE UNIVERSITY, AND NORTH CAROLINA CENTRAL UNIVERSITY, ALL IN CLOSE PROXIMITY, THE TRIANGLE CERSI REPRESENTS A BROAD NETWORK OF INVESTIGATORS AND NATIONAL AND INTERNATIONAL COLLABORATORS THAT BRING UNIQUE AND DIVERSE EXPERTISE AND RESOURCES FOR REGULATORY SCIENCE, INCLUDING BUT NOT LIMITED TO NOVEL APPROACHES IN STATISTICAL METHODOLOGIES, MACHINE LEARNING AND ARTIFICIAL INTELLIGENCE, IMAGING, IN SILICO TRIALS, PEDIATRIC PHARMACOLOGY, PATIENT REPORTED OUTCOMES (PRO), POPULATION SCIENCE, AND SAFETY ASSESSMENT ACROSS THE LIFESPAN, AND OTHER AREAS. THE TRIANGLE CERSI INCLUDES TWO SCHOOLS OF MEDICINE, A SCHOOL OF PHARMACY, TWO SCHOOLS OF NURSING, A SCHOOL OF PUBLIC HEALTH, A COLLEGE OF VETERINARY MEDICINE, A LEADING HISTORICALLY BLACK UNIVERSITY, A NATIONAL CENTER FOR VIRTUAL IMAGING TRIALS, AND THE DUKE CLINICAL RESEARCH INSTITUTE, AND LEVERAGES RELATIONSHIPS WITH NEARBY COMPANIES AND ORGANIZATIONS IN THE RESEARCH TRIANGLE PARK. THE TRIANGLE CERSI HAS THREE SPECIFIC AIMS: 1. CONDUCT REGULATORY SCIENCE PROJECTS IN COLLABORATION WITH FDA TO DELIVER MAJOR ADVANCES IN REGULATORY SCIENCE AND RAPIDLY ADDRESS A BROAD RANGE OF MAJOR, SPECIFIC, AND EMERGING CHALLENGES IN RESPONSE TO FDA NEEDS. 2. ESTABLISH ROBUST CERSI CORE INFRASTRUCTURE TO DEVELOP, PROPOSE, SUPPORT, ENABLE, AND MONITOR EXECUTION OF CERSI RESEARCH PROJECTS TO FACILITATE RAPID ACHIEVEMENT OF PROJECT DELIVERABLES; PARTNER OAK RIDGE NATIONAL LABORATORY PROVIDES SUPPORT FOR DATA ACCESS, COMPUTATION, AND RESOURCE SHARING. 3. EXPAND SUPPORT OF THE TRIANGLE CERSI AND EXTEND ITS IMPACT THROUGH REGULATORY SCIENCE INFORMATION SHARING ACTIVITIES, INCLUDING EFFORTS TO DIVERSIFY THE REGULATORY SCIENCE WORKFORCE. THE TRIANGLE CERSI WILL ACTIVELY SHARE RESULTS AND NEWLY DEVELOPED TOOLS AND RESOURCES WITH THE FDA, RESEARCH COMMUNITY, STAKEHOLDERS, AND OUR INSTITUTIONS’ STUDENTS AND TRAINEES. TOGETHER, OUR OVERARCHING GOAL IS TO PROVIDE AN ABUNDANCE OF ESSENTIAL NEW INFORMATION, INFRASTRUCTURE, AND TOOLS TO SHORTEN THE DRUG AND DEVICE DEVELOPMENT PROCESS, TO ADVANCE PUBLIC HEALTH, AND TO INFORM FDA ACTIVITIES IN WAYS THAT COMPLEMENT OTHER CERSIS AND CONTRIBUTE TO ACHIEVING THE GOALS OF THE NATIONAL CERSI PROGRAM.

THE UPMC SEXUALLY TRANSMITTED INFECTIONS COOPERATIVE RESEARCH CENTER

THE UJMT GLOBAL CONSORTIUM: BUILDING RESEARCH CAPACITY THROUGH MENTORED TRAINING

PACT-PRODVIDING AIDS CARE & TREATMENT IN THE DEMOCRATICS REPUBLIC OF CONGO UNDER

ANIMAL MODELS FOR STUDYING THE GENETICS OF HYPERTENSION

NANO APPROACHES TO MODULATE HOST CELL RESPONSE FOR CANCER THERAPY

BASIC MECHANISMS OF VIRAL AND CHEMICAL CARCINOGENESIS

CAROLINA CENTER OF CANCER NANOTECHNOLOGY EXCELLENCE

PROGRAM PROJECT ? IMPROVING PROVIDER ANNOUNCEMENT COMMUNICATION TRAINING (IMPACT) - ABSTRACT – OVERALL WIDESPREAD HPV VACCINATION IN THE US COULD PREVENT 32,100 CANCERS EVERY YEAR. DESPITE THIS TREMENDOUS POTENTIAL, HPV VACCINATION COVERAGE IS FAR SHORT OF THE NATION'S GOAL OF 80%. PROVIDER RECOMMENDATIONS ARE UNIQUELY POWERFUL IN INCREASING HPV VACCINE UPTAKE. HOWEVER, PRIMARY CARE TEAMS AND HEALTHCARE SYSTEMS FACE BARRIERS TO EFFECTIVE HPV VACCINE COMMUNICATION, AND MANY QUESTIONS REMAIN UNANSWERED ABOUT HOW TO INCREASE THE POTENCY OF PROVIDER RECOMMENDATIONS. WE PROPOSE THE P01 PROGRAM PROJECT, “IMPROVING PROVIDER ANNOUNCEMENT COMMUNICATION TRAINING (IMPACT).” THE GOAL OF IMPACT IS TO IMPROVE HPV VACCINE COMMUNICATION AND UPTAKE AMONG ADOLESCENTS. IMPACT'S SPECIFIC AIMS ARE TO 1) IDENTIFY OPPORTUNITIES TO IMPROVE HPV VACCINE COMMUNICATION; 2) EVALUATE THE IMPACT AND COST OF HPV VACCINE COMMUNICATION INTERVENTIONS IN CLUSTER RANDOMIZED CLINICAL TRIALS; AND 3) SUPPORT IMPLEMENTATION OF HPV VACCINE COMMUNICATION INTERVENTIONS IN HEALTHCARE SYSTEMS. THE IMPACT PROGRAM PROJECT'S SHARED THEME IS AMPLIFYING THE IMPACT OF A RESEARCH-TESTED INTERVENTION PROGRAM TO IMPROVE HPV VACCINE COMMUNICATION IN HEALTHCARE SYSTEMS. THE PROJECTS WILL WORK TOGETHER TO ENHANCE THE IMPACT OF THE ANNOUNCEMENT APPROACH TRAINING (AAT), AN HPV VACCINE COMMUNICATION TRAINING FOR PRIMARY CARE PROFESSIONALS, WHICH RECEIVED DESIGNATION AS A RESEARCH-TESTED INTERVENTION PROGRAM (RTIP) FROM THE NATIONAL CANCER INSTITUTE. PROJECT 1 WILL ESTABLISH HOW TO INVOLVE THE WHOLE PRIMARY CARE TEAM IN HPV VACCINE RECOMMENDATIONS. THE PROJECT WILL EXAMINE WHETHER OPTIMIZING THE USE OF STANDING ORDERS SUPPORT INCREASES HPV VACCINE UPTAKE IN CLINICS RECEIVING THE AAT. PROJECT 2 WILL EXAMINE WHAT MOTIVATES PROVIDERS TO RECOMMEND HPV VACCINATION. THE PROJECT WILL ESTABLISH WHETHER CLINIC-LEVEL FINANCIAL INCENTIVES INCREASE VACCINE UPTAKE IN CLINICS RECEIVING THE AAT. PROJECT 3 WILL EXAMINE WHO SHOULD FACILITATE THE TRAININGS. THE PROJECT WILL ESTABLISH WHETHER ENGAGING CLINICAL CHAMPIONS IN HEALTHCARE SYSTEMS TO IMPLEMENT THE AAT WITHIN THEIR OWN SYSTEMS INCREASES VACCINE UPTAKE. PROJECT 4 WILL EXAMINE WHICH INTERVENTIONS FIT SYSTEMS' RESOURCES. THE PROJECT WILL EXAMINE THE BUDGET IMPACT, COST-EFFECTIVENESS, AND POPULATION HEALTH IMPACT OF HPV VACCINE INTERVENTIONS IN RURAL AND NONRURAL COMMUNITIES AND AID DECISION MAKERS WITH A DECISION SUPPORT TOOL TO FACILITATE THE ADOPTION OF PROMISING INTERVENTIONS. THE RESEARCH PROJECTS WILL RECEIVE SUPPORT FROM 3 CORES: ADMINISTRATIVE, DATA, AND INTERVENTION. IMPACT'S ACTIVITIES WILL CULMINATE WITH THE CREATION OF THE AAT INTERVENTION PACKAGE TO SUPPORT IMPROVING HPV VACCINE UPTAKE IN HEALTHCARE SYSTEMS. THROUGHOUT THE PROPOSED PROGRAM PROJECT, THE SHARED THEME AND AAT FOCUS WILL CREATE SYNERGIES AMONG THE PROJECTS AND CORES THAT GENERATES SIGNIFICANT AND NOVEL SCIENTIFIC INSIGHTS INTO HOW TO IMPROVE HPV VACCINE COMMUNICATION AND UPTAKE. OUR APPROACH WILL ALSO ACCELERATE THE EVOLUTION OF COMMUNICATION TRAININGS FOR PRIMARY CARE PROFESSIONALS, ACCOMPLISHING IN 5 YEARS WHAT MIGHT OTHERWISE TAKE TWO DECADES.

UNC CLINICAL AND TRANSLATIONAL SCIENCE AWARD

MEDICAL SCIENTIST TRAINING PROGRAM

ADVANCING TOBACCO REGULATORY SCIENCE TO REDUCE HEALTH DISPARITIES - ABSTRACT: OVERALL THE US HAS MADE DECADES OF PROGRESS IN REDUCING CIGARETTE SMOKING, BUT NOTABLE DISPARITIES PERSIST IN MENTHOL FLAVORED PRODUCT USE AND IN THE USE OF NON-CIGARETTE TOBACCO PRODUCTS, INCLUDING LITTLE CIGARS, CIGARILLOS, AND E- CIGARETTES. WE PROPOSE THE U54 PROGRAM PROJECT, “ADVANCING TOBACCO REGULATORY SCIENCE TO REDUCE HEALTH DISPARITIES” TO ADDRESS THIS GAP. THE INTEGRATIVE THEME OF OUR UNC TCORS IS BUILDING THE SCIENCE FOR EFFECTIVE REGULATION OF AND COMMUNICATION ABOUT TOBACCO PRODUCTS DISPROPORTIONATELY USED BY PRIORITY POPULATIONS – FLAVORED TOBACCO PRODUCTS AND E-CIGARETTES. OUR INTEGRATED SET OF FOUR RESEARCH PROJECTS SEEK TO UNDERSTAND THE IMPACT OF REGULATIONS AND COMMUNICATION CAMPAIGNS ON THOSE DISADVANTAGED BY TOBACCO USE DISPARITIES, INCLUDING BLACK; LOWER-SOCIOECONOMIC STATUS (SES); AND LESBIAN, GAY, OR BISEXUAL (LGB) POPULATIONS; AND YOUTH AND YOUNG ADULTS. OUR ULTIMATE GOAL IS TO FURTHER FDA AND NIH EFFORTS TO PROTECT PUBLIC HEALTH THROUGH REGULATION OF TOBACCO PRODUCTS. UNC TCORS’ RESEARCH WILL PROVIDE ESSENTIAL EVIDENCE TO GUIDE THE FDA AS IT IMPLEMENTS BANS ON MENTHOL CIGARETTES AND FLAVORED CIGARS, DEVELOPS COMMUNICATION CAMPAIGNS, AND ADDRESSES THE YOUTH VAPING EPIDEMIC. WE PROPOSE FOUR SPECIFIC AIMS: 1) DEVELOP AND EVALUATE THE IMPACT OF COMMUNICATION CAMPAIGNS TO DISCOURAGE TOBACCO PRODUCT USE IN DIVERSE POPULATIONS (PROJECTS 1, 2, 4); 2) UNDERSTAND THE PUBLIC HEALTH IMPACT OF FLAVORED TOBACCO PRODUCT BANS IN DIVERSE POPULATIONS AND THE CONDITIONS UNDER WHICH THEY ARE MOST LIKELY TO BE MOST EFFECTIVE (PROJECTS 2 AND 3); 3) BUILD TRAINEES’ CAPACITY TO CONTRIBUTE TO THE FIELD OF TOBACCO REGULATORY SCIENCE THROUGH TRAINING, MENTORSHIP, AND PILOT FUNDING FOR A DIVERSE AND MULTIDISCIPLINARY GROUP OF PRE-DOCTORAL FELLOWS, POST-DOCTORAL FELLOWS, AND EARLY-STAGE INVESTIGATORS (PROJECTS 1-4, CAREER ENHANCEMENT CORE); 4) INFORM FDA REGULATION OF MENTHOL CIGARETTE AND FLAVORED CIGAR BANS AND COMMUNICATION CAMPAIGNS THROUGH ACTIVE DISSEMINATION OF TCORS SCIENTIFIC FINDINGS (PROJECTS 1-4, ADMINISTRATIVE CORE). PROJECT 1 WILL DEVELOP A NOVEL COMMUNICATION CAMPAIGN TO DISCOURAGE YOUNG ADULT LITTLE CIGAR AND CIGARILLO USE. PROJECT 2 WILL EVALUATE WHETHER A MENTHOL CIGARETTE BAN COULD BE AMPLIFIED BY A QUIT SMOKING CAMPAIGN TO HELP MENTHOL SMOKERS QUIT, INCLUDING BLACK AND LGB SMOKERS. PROJECT 3 WILL BUILD A MICROSIMULATION MODEL TO ESTIMATE THE PUBLIC HEALTH IMPACT OF A FEDERAL FLAVORED CIGAR BAN ON TOBACCO USE, MORTALITY, AND HEALTH DISPARITIES. PROJECT 4 WILL TEST THE ABILITY OF VAPING PREVENTION VIDEO ADS WITH PROMISING FEATURES TO REDUCE SUSCEPTIBILITY TO VAPING AMONG YOUTH AND YOUNG ADULTS. THE RESEARCH PROJECTS WILL RECEIVE SUPPORT FROM TWO CORES: ADMINISTRATIVE AND CAREER ENHANCEMENT (WHICH INCLUDES PILOT RESEARCH PROJECTS). OUR MULTIDISCIPLINARY GROUP OF SEASONED REGULATORY SCIENCE RESEARCHERS WILL PROVIDE ACTIONABLE INFORMATION TO INFORM FDA REGULATIONS AND COMMUNICATION CAMPAIGNS.

CENTER FOR GENOMICS AND SOCIETY

ASPIRE: ADVANCING SCIENCE & PRACTICE IN THE RETAIL ENVIRONMENT

NEUTRALIZING ANTIBODY & AAV FIX GENE THERAPY

MULTI-SCALE INVESTIGATIONS OF RESPIRATORY MUCUS/MUCIN STRUCTURE AND FUNCTION IN HEALTH AND DISEASE - OVERALL ABSTRACT THE MUCUS CLEARANCE SYSTEM CONSTITUTES THE PRIMARY AIRWAY HOST DEFENSE SYSTEM AGAINST INHALED INFECTIOUS AGENTS AND TOXINS. HOWEVER, DESPITE MORE THAN TWO CENTURIES OF RESEARCH INTO THE NATURE OF THE MUCUS CLEARANCE SYSTEM, SURPRISING GAPS IN OUR KNOWLEDGE OF FUNDAMENTAL ASPECTS OF THIS SYSTEM PERSIST. FILLING IN THESE GAPS IS IMPORTANT FOR IMPROVING PUBLIC HEALTH STRATEGIES TO COMBAT RESPIRATORY INFECTIOUS DISEASES. FILLING IN THESE GAPS IS ALSO IMPORTANT FOR ELUCIDATING THE PATHOGENESIS OF AND DEVELOPING THERAPIES FOR CHRONIC PULMONARY DISEASES, INCLUDING COPD, ASTHMA, NCFB, AND RARE GENETIC DISEASES (CF, PCD), WHICH ARE BY DEFINITION CHARACTERIZED BY MUCUS ACCUMULATION IN THE LUNG. THIS PPG PROPOSES TO INVESTIGATE FUNDAMENTAL, BUT POORLY UNDERSTOOD, ASPECTS OF THE MUCUS CLEARANCE SYSTEM THAT MUST BE QUANTITATED TO UNDERSTAND MUCUS FUNCTION IN HEALTH AND DYSFUNCTION IN DISEASE. EACH PPG PROJECT HAS TWO SPECIFIC AIMS FOCUSED ON BASIC MUCIN FUNCTION AND ONE FOCUSED ON TRANSLATIONAL ASPECTS OF MUCIN PATHOBIOLOGY. PROJECT 1 (“MUCIN STRUCTURE AND ASSOCIATIONS IN RESPIRATORY MUCUS”, MICHAEL RUBINSTEIN, PHD, PI) WILL INVESTIGATE FUNDAMENTAL ASPECTS OF THE ORGANIZATION OF MUCINS IN SOLUTION AND WITHIN THE MUCUS LAYER. THESE STUDIES WILL BE COMPLEMENTED BY STUDIES OF THE ADDITION OF “ABNORMAL POLYMERS”, E.G., DNA, TO MUCUS SOLUTIONS. PROJECT 2 (“WHY ARE MUCINS SO GIGANTIC AND IS IT SAFE/EFFECTIVE TO SEVER THEM THERAPEUTICALLY?”, RICHARD C. BOUCHER, MD, PI) WILL FOCUS ON THE FUNDAMENTAL QUESTION AS TO WHY HUMAN AIRWAY MUCIN POLYMERS ARE OF SUCH ENORMOUS SIZE (300 MDA, RG 250 NM) AND CHARACTERIZE THE RATIO OF EFFICACY (CHAIN LENGTH REDUCTION) VS RISK (OFF-TARGET CHAIN UNWINDING) REQUIRED FOR THE DEVELOPMENT OF MUCOLYTICS FOR LUNG DISEASE. PROJECT 3 (“MEMBRANE-BOUND MUCINS ON THE AIRWAY SURFACE ENSURE EFFICIENT MUCUS CLEARANCE AND LUNG HEALTH”, BRIAN BUTTON, PHD, PI) WILL STUDY THE RELATIONSHIPS BETWEEN CILIA, PCL, AND THE MUCUS LAYER REQUIRED FOR TRANSPORT, FOCUSING ON A NOVEL HYDRAULIC “PUSHING” VS CLASSIC “CLAWING” MECHANISMS. IN ADDITION, BARRIER FUNCTIONS OF PCL AND REGULATION THEREOF WILL BE STUDIED. PROJECT 4 (“BIOPHYSICAL AND STRUCTURAL CHARACTERIZATION OF AIRWAY SUBMUCOSAL GLAND MUCUS IN HEALTH AND CYSTIC FIBROSIS”, RONIT FREEMAN, PHD, PI) WILL FOCUS ON A NOVEL ATTRIBUTE OF SUBMUCOSAL GLAND (SMG) MUCUS, A STRAND/BUNDLE INSOLUBLE COMPONENT, AND HOW STRANDS/BUNDLES CONTRIBUTE TO SMG MUCUS FUNCTION IN HEALTH AND DISEASE. THREE CORES SUPPORT THE PPG: 1) CORE A, THE ADMINISTRATIVE/BIOSTATISTICAL CORE, MULTI-PIS RICHARD C. BOUCHER, MD, AND MICHAEL RUBINSTEIN, PHD, SUPPLIES PROJECT MANAGEMENT AND STATISTICAL SUPPORT FOR THE PPG; 2) CORE B, THE MUCUS/MUCIN ANALYTICS CORE, PI MEHMET KESIMER, PHD, PROVIDES QUALITY CONTROL OF ALL MUCIN REAGENTS FOR THE PPG AND NOVEL BIOCHEMICAL/BIOPHYSICAL MEASUREMENTS; AND 3) CORE C, THE IMAGING CORE, PI CAMILLE EHRE, PHD, PROVIDES ELECTRON MICROSCOPIC, MOLECULAR, AND MORPHOLOGIC ANALYSES TO THE PROJECTS. THE OVERALL GOALS OF THE PPG ARE TO ELUCIDATE THE STRUCTURE AND FUNCTION OF MUCUS IN HEALTH, HOW THESE CHARACTERISTICS ARE DEGRADED IN DISEASE, AND IDENTIFY STRATEGIES FOR DEVELOPMENT OF NOVEL THERAPEUTIC AGENTS TO TREAT MUCO-OBSTRUCTIVE DISEASES.

5/6 HBCD PRENATAL EXPERIENCES AND LONGITUDINAL DEVELOPMENT (PRELUDE) CONSORTIUM - PROJECT SUMMARY/ABSTRACT BRAIN DEVELOPMENT OCCURS AT A RAPID PACE PRENATALLY AND THROUGHOUT CHILDHOOD, IMPACTED BY DYNAMIC GENETIC AND ENVIRONMENTAL INFLUENCES. STUDIES USING ADVANCED NEUROIMAGING HAVE PROVIDED SIGNIFICANT INSIGHTS INTO BRAIN DEVELOPMENT BUT HAVE BEEN LIMITED BY SMALL SAMPLE SIZE, ESPECIALLY FOR HIGH-RISK POPULATIONS. SUBSTANCE- EXPOSED INFANTS ARE AT PARTICULARLY HIGH RISK FOR ADVERSE OUTCOMES; HOWEVER, FINDINGS ARE INCONSISTENT, MAKING IT DIFFICULT TO DISENTANGLE PRENATAL EXPOSURE EFFECTS FROM OTHER ADVERSE INFLUENCES. THE OBJECTIVES OF OUR HEALTHY BRAIN AND CHILD DEVELOPMENT (HBCD) PRENATAL EXPERIENCES AND LONGITUDINAL DEVELOPMENT (PRELUDE) CONSORTIUM ARE TO CHARACTERIZE TYPICAL TRAJECTORIES OF BRAIN DEVELOPMENT FROM BIRTH THROUGH CHILDHOOD, MEASURING THE INFLUENCE OF KEY BIOLOGIC AND ENVIRONMENTAL FACTORS AND THEIR INTERACTIONS ON CHILD SOCIAL, COGNITIVE, AND EMOTIONAL DEVELOPMENT. WE WILL ASSESS HOW CHILDREN PRENATALLY EXPOSED TO OPIOIDS AND OTHER SUBSTANCES, AS WELL AS ENVIRONMENTAL ADVERSITY, DIFFER IN THOSE BRAIN TRAJECTORIES AND OUTCOMES. OUR CONSORTIUM CONSISTS OF SIX CENTERS (ARKANSAS CHILDREN’S RESEARCH INSTITUTE, CASE WESTERN RESERVE UNIVERSITY, CINCINNATI CHILDREN’S HOSPITAL, CHILDREN’S NATIONAL MEDICAL CENTER, UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL, AND VANDERBILT UNIVERSITY) WHICH HAVE COLLABORATED PREVIOUSLY AND HAVE COMPLEMENTARY EXPERTISE IN NEUROIMAGING, NEUROPHYSIOLOGY, LONGITUDINAL CLINICAL RESEARCH, CHILD DEVELOPMENT, SUBSTANCE EXPOSURE AND ADDICTION, ETHICAL/LEGAL ISSUES, AND CLINICAL CARE OF HIGH-RISK INFANTS/CHILDREN. THE PRELUDE CONSORTIUM WILL RECRUIT 680 PREGNANT WOMEN WITH SUBSTANCE USE, 680 AT-RISK PREGNANT WOMEN WITHOUT SUBSTANCE USE, AND 1360 COMPARISON PREGNANT WOMEN REPRESENTATIVE OF THE GENERAL POPULATION TO CONTRIBUTE TO THE OVERALL HBCD STUDY. WE WILL WORK CLOSELY WITH THE OTHER SITES, THE HBCD CONSORTIUM ADMINISTRATIVE CORE, AND THE HBCD DATA COORDINATING CENTER TO DEVELOP A COMPREHENSIVE STUDY PROTOCOL AND ENSURE COMPLIANCE OF STUDY WORKFLOW AND DATA TRANSFER. OUR CONSORTIUM HAS AN OPTIMIZED RESEARCH PROTOCOL AND 4 SPECIFIC AIMS: 1) EMPLOY ETHICAL AND EVIDENCE-BASED BEST PRACTICES TO ENROLL AND RETAIN A DIVERSE COHORT OF PREGNANT WOMEN INTO A LONGITUDINAL STUDY OF INFANT/CHILD BRAIN DEVELOPMENT, OVERSAMPLING MOTHERS FROM HIGH-RISK BACKGROUNDS AND THOSE USING SUBSTANCES DURING PREGNANCY; 2) ENGAGE A COMPREHENSIVE ARRAY OF MATERNAL- AND CHILD-ORIENTED COMMUNITY STAKEHOLDERS TO IDENTIFY COMMUNITY CONCERNS AND PRIORITIES REGARDING THIS RESEARCH, MINIMIZE RISKS, AND PROMOTE LONG-TERM ENGAGEMENT OF THE RECRUITED CHILD-MOTHER DYADS; 3) COLLECT RICH DATA TO EXAMINE HOW MATERNAL HEALTH CONTEXT AND BROADER ENVIRONMENTAL FACTORS MAY AFFECT THE MATERNAL-FETAL DYAD AND NEURODEVELOPMENT OF CHILDREN; 4) CAPTURE KEY DEVELOPMENTAL WINDOWS DURING WHICH MATERNAL AND ENVIRONMENTAL FACTORS MAY INTERACT WITH BRAIN AND BEHAVIORAL DEVELOPMENT OF CHILDREN. THE INSIGHTS FROM THESE DATA WILL PROVIDE GREATER UNDERSTANDING OF FACTORS AFFECTING EARLY CHILDHOOD BRAIN DEVELOPMENT, ALLOWING TARGETED INTERVENTIONS AND IMPROVED OUTCOMES FOR MOTHER-CHILD DYADS.

UNIVERSITY OF NORTH CAROLINA WOMENS INTERAGENCY HIV STUDY UNC WIHS

NORTH CAROLINA TRANSLATIONAL AND CLINICAL SCIENCE INSTITUTE (NC TRACS) KL2

CENTER FOR HEALTH PROMOTION AND DISEASE PREVENTION

UNIVERSITY OF NORTH CAROLINA - CHLAMYDIA VACCINE INITIATIVE (UNC-CVI)

MCH WORKFORCE CENTERS

PULMONARY SURFACE LIQUID HOMEOSTASIS

EXPANSION OF ART, TB AND VCT PROGRAMS IN ZAMBIA

CHARACTERIZATION OF NOVEL GENES ENCODED TY RNA AND DNA VIRUSES

POLYMERASE THETA, GENOME INSTABILITY, AND CANCER

CHILDREN LIVING IN RURAL POVERTY: THE CONTINUATION OF THE FAMILY LIFE PROJECT

NEUROBIOLOGICAL AND BEHAVIORAL CONSEQUENCES OF COCAINE USE IN MOTHER/INFANT DYADS

CENTER FOR REDUCE CVD DISPARITIES: GENES, CLINICS, AND COMMUNITIES

POPULATION RESEARCH TRAINING

NATIONAL CENTER FOR SPECIAL RESEARCH (NCSER)

MAINTENANCE OF ANIMAL MODELS OF HUMAN HEMOPHILIA AND VWD

CENTER FOR ENVIRONMENTALLY RESPONSIBLE SOLVENTS AND PROCESSES

BRONCHITIS IN THE MILITARY: DIAGNOSIS, RISK MITIGATION, AND TREATMENT

TARGETED GENETIC ANALYSIS OF T2D AND QUANTITATIVE TRAITS

MOLECULAR MECHANISM OF MAMMALIAN DNA EXCISION REPAIR, DNA DAMAGE CHECKPOINTS AND THE CIRCADIAN CLOCK

MODEL STATE-SUPPORTED AHEC PROGRAM

UNC REGIONAL EMERGING SPECIAL PATHOGEN TREATMENT CENTER (RESPTC) - THE UNIVERSITY OF NORTH CAROLINA MEDICAL CENTER (UNCMC) IN PARTNERSHIP WITH THE UNC INSTITUTE OF GLOBAL HEALTH AND INFECTIOUS DISEASES (IGHID) PROPOSES TO ESTABLISH A REGIONAL EMERGING SPECIAL PATHOGEN TREATMENT CENTER (RESPTC) IN US DEPARTMENT OF HEALTH AND HUMAN SERVICES (DHHS) REGION 4, COVERING MOST OF THE US SOUTH. THE GOAL OF THIS PROJECT IS TO BUILD ON THE STRONG FOUNDATION OF CURRENT CAPABILITIES AT UNCMC AND THE UNC HEALTH SYSTEM OF HOSPITALS AND CLINICS TO ESTABLISH A RESPTC THAT WILL ENHANCE SPECIAL PATHOGEN READINESS FOR THIS REGION AND THE NATION. THE OBJECTIVES OF THE UNC RESPTC ARE TO: A) DEVELOP A STATE-OF-THE-ART, RESPONSIVE, AND ACCESSIBLE FACILITY STAFFED BY A HIGHLY-TRAINED WORKFORCE TO CARE FOR AND MANAGE PATIENTS ACROSS THE LIFE SPAN INFECTED WITH A SPECIAL PATHOGEN INCLUDING CAPACITY TO SURGE, IF NECESSARY, B) ENHANCE PREPAREDNESS OF REGIONAL HEALTHCARE PARTNERS BY COLLABORATING WITH THE EMORY RESPTC AND THE NATIONAL EMERGING SPECIAL PATHOGENS TRAINING AND EDUCATION CENTER (NETEC) TO PROVIDE BEST PRACTICES TRAINING FOR EMERGING PATHOGEN PREPAREDNESS AND RESPONSE INCLUDING THE ABILITY TO IDENTIFY, ISOLATE, AND INFORM (3I) AND PROVIDE HIGH-QUALITY CARE TO SPECIAL PATHOGENS PATIENTS, AND C) SUPPORT REGIONAL SPECIAL PATHOGEN READINESS AND RESPONSE BY PLAYING A COORDINATING ROLE DURING EVENTS AND PROVIDING TECHNICAL ASSISTANCE AND CRITICAL SUPPLIES SUCH AS PERSONAL PROTECTIVE EQUIPMENT (PPE) ON REQUEST. COLLECTIVELY, THE OUTCOMES OF THIS PROJECT WILL ESTABLISH UNC RESPTC AS A VALUABLE RESOURCE FOR CLINICAL CARE, TRAINING, AND MATERIAL SUPPORT TO MEET FUTURE MAJOR INFECTIOUS DISEASES CHALLENGES.

RTI'S REGIONAL COMPREHENSIVE METABOLOMICS RESOURCE CENTER

CLINICAL CENTER FOR THE STUDY OF DEV LEARNING UAP

INITIATIVE FOR MINORITY STUDENT DEVELOPMENT AT UNC-CHAPEL HILL

NCCU-LCCC PARTNERSHIP IN CANCER RESEARCH (2 OF 2)

SCCOR IN HOST FACTORS IN CHRONIC LUNG DISEASE

NORTH CAROLINA SERONET CENTER FOR EXCELLENCE

MODEL STATE-SUPPORTED AHEC PROGRAM

BRIDGING THE GAP BETWEEN TYPE 2 DIABETES GWAS AND THERAPEUTIC TARGETS

HISTONE MRNA REGULATION IN DEVELOPMENT

STATISTICAL AND APPLIED MATHEMATICAL SCIENCES INSTITUTE

CENTER FOR HEALTH PROMOTION AND DISEASE PREVENTION

IMMUNOBIOLOGY OF ACUTE ENVIRONMENTAL ASTHMA

PRE- AND POSTDOCTORAL TRAINING IN TOXICOLOGY

PREVALENCE AND TRAITS OF FASD IN THE US POPULATION: EVIDENCE FROM SCHOOLS

PROSTATE CANCER: TRANSITION TO ANDROGEN-INDEPENDENCE

UNC CLINICAL TRANSLATION SCIENCE AWARD-K12 SCHOLARS PROGRAM (KL2)

GENETIC EPIDEMIOLOGY OF CAUSAL VARIANTS ACROSS THE LIFE COURSE

A KNOWLEDGE BASE FOR CLINICALLY RELEVANT GENES AND VARIANTS

SPECIAL EDUCATION-TECHNICAL ASSISTANCE AND DISSEMINATION TO IMPROVE SERVICES AND RESULTS FOR CHILDREN WITH DISABILITIES - NATIONAL EARLY CHILDHOOD TE

CAROLINA POPULATION CENTER

LEVERAGING MULTI-OMICS APPROACHES TO EXAMINE METABOLIC CHALLENGES OF OBESITY IN RELATION TO CARDIOVASCULAR DISEASES

ENVIRONMENT, EPIGENETICS, NEURODEVELOPMENT & HEALTH OF EXTREMELY PRETERM CHILDREN

SELECTIVE TARGETING OF PANCREATIC CANCER SPORE - STOP CANCER SPORE ABSTRACT PANCREATIC CANCER REMAINS A LETHAL DISEASE WITH LIMITED THERAPEUTIC OPTIONS. OPTIONS HAVE INCREASED OVER THE LAST 5 YEARS, WITH LARGE GENOMIC ANALYSES AND PRECLINICAL EFFORTS. HOWEVER, DESPITE ADVANCES, PANCREATIC CANCER REMAINS A LETHAL DISEASE WITH A FIVE-YEAR SURVIVAL RATE OF 10%, AND DEATHS FROM PANCREATIC CANCER ARE EXPECTED TO SURPASS DEATHS FROM BREAST, PROSTATE AND COLORECTAL CANCER BY 2030, TO BECOME THE SECOND LEADING CAUSE OF CANCER DEATHS. THE INCIDENCE IS RAPIDLY INCREASING, WITH, A 23% INCREASE SINCE 2010 AND 57% INCREASE SINCE 2006. THE ETIOLOGY AND REASON FOR THE RECENT RISE REMAIN POORLY UNDERSTOOD WITH A COMPLEX INTERPLAY OF SOMATIC GENETIC, GENOMIC, EPIGENETIC AND ENVIRONMENTAL FACTORS IN THE CONTEXT OF AN AGING POPULATION. UNLIKE MANY SOLID TUMORS, MUTATIONS ALONE HAVE NOT BEEN SUFFICIENT TO YIELD CURATIVE TARGETED THERAPIES, CLINICALLY USEFUL BIOMARKERS OR CONSENSUS SUBTYPES. CHALLENGES THAT REMAIN INCLUDE: · LOW TUMOR CELLULARITY HAMPERS BOTH GENETIC AND GENOMIC STUDIES, INCLUDING THE INABILITY TO IDENTIFY BIOMARKERS/SUBTYPES TO TAILOR THERAPIES · CHEMOTHERAPY AND TARGETED THERAPY RESISTANT TUMOR CELL POPULATIONS · DESMOPLASTIC STROMA THAT MAY BE BOTH TUMOR PROMOTING AND THERAPY INHIBITING · IMMUNOSUPPRESSIVE ENVIRONMENT DUE TO SUPPRESSIVE MYELOID CELLS AND A PAUCITY OF T EFFECTOR CELLS · PRECISION ONCOLOGY APPROACHES ARE STILL LIMITED · CLINICAL TRIALS ARE LIMITED TO ONLY 1-2 THERAPIES AT A TIME WE HAVE ASSEMBLED THREE PROJECTS THAT DIRECTLY ADDRESS THESE ISSUES; EACH HAS AN EMBEDDED EARLY PHASE CLINICAL TRIAL THAT WILL YIELD PATIENT SAMPLES WITH WHICH TO TEST OUR SPORE’S HYPOTHESES. ROBUST DEVELOPMENT RESEARCH AND CAREER ENHANCEMENT PROGRAMS ARE INCLUDED BASED ON THE HIGHLY SUCCESSFUL MODELS AT UNC LINEBERGER. THESE WILL BE BACKED BY A SUBSTANTIAL INSTITUTIONAL COMMITMENT. A HIGHLY ACCOMPLISHED MULTIDISCIPLINARY TEAM OF INVESTIGATORS WITH COLLABORATIONS ACROSS SEVERAL INSTITUTIONS HAVE BEEN BROUGHT TOGETHER THAT INCLUDES THOSE WHO HAVE MADE INNOVATIVE AND HIGH IMPACT CONTRIBUTIONS, DELIVERED CLINICAL CARE AND PERFORMED CLINICAL AND TRANSLATIONAL RESEARCH GERMANE TO PANCREATIC CANCER. RECOGNIZING THE NEED FOR PANCREATIC CANCER RAPID TRANSLATION TO THE CLINIC, OUR TISSUE PROCUREMENT, PATHOLOGY, AND GENOMICS CORE AND INTEGRATIVE QUANTITATIVE SCIENCES CORE WORK SEAMLESSLY WITH THE PROJECTS TO PROCESS AND ANALYZE DATA. OUR STOP CANCER SPORE GOAL IS TO ESTABLISH A NEW PARADIGM FOR CLINICAL TRIAL DESIGN THAT IS NOT LIMITED TO A SINGLE THERAPY OR BIOMARKER.

A LARGE-SCALE SCHIZOPHRENIA ASSOCIATION STUDY IN SWEDEN

GENOME-WIDE ASSOCIATION STUDY OF EARLY CHILDHOOD CARIES

TRAINING IN SEXUALLY TRANSMITTED DISEASES AND AIDS

CLINICAL STUDY OF VESICOURETERAL REFLUX IN CHILDREN

UNC ONCOLOGY CLINICAL TRANSLATIONAL RESEARCH TRAINING PROGRAM

DATANET FULL PROPOSAL: DATANET FEDERATION CONSORTIUM

PROSPECTIVE STUDIES OF THE PATHOGENESIS OF SCHIZOPHRENIA

SYSTEMATIC IN VIVO CHARACTERIZATION OF DISEASE-ASSOCIATED REGULATORY VARIANTS - ABSTRACT THOUSANDS OF GENETIC LOCI ARE ASSOCIATED WITH HUMAN TRAITS OR DISEASE RISK, AND THESE LOCI EACH TYPICALLY CONTAIN TENS TO HUNDREDS OF VARIANTS, MOST OF WHICH ARE NON-CODING AND LACK DIRECT EVIDENCE OF EFFECTS ON GENES. EXPERIMENTAL TESTS OF GENOMIC VARIANTS ARE NEEDED TO IDENTIFY FUNCTIONAL EFFECTS, WHICH CAN BE SPECIFIC TO ONE SEX, TISSUE, AND/OR PERTURBED ENVIRONMENTAL CONTEXT. TESTING EFFECTS OF RISK VARIANTS ON GENE REGULATION REQUIRES AN ABILITY TO QUANTIFY THE POTENTIALLY MODEST CONSEQUENCES OF THOUSANDS OF ALLELES IN A CAREFULLY CONTROLLED STUDY. OUR OVERARCHING GOAL IS TO SYSTEMATICALLY CHARACTERIZE THE IMPACT OF HUMAN GENETIC VARIATION ON GENE REGULATION VIA MASSIVELY PARALLEL REPORTER ASSAYS (MPRA). WE WILL SELECT VARIANTS BASED PRIMARILY ON GENOME-WIDE ASSOCIATION STUDIES (GWAS) FOR COMMON DISEASES AND COMPLEX TRAITS RELEVANT TO THE BRAIN, LIVER, LUNG, MUSCLE, AND/OR HEART. WE WILL EXAMINE ALL PLAUSIBLE FUNCTIONAL CANDIDATES AT PRIORITIZED GWAS LOCI TO PROVIDE DATA FOR TESTS OF REGULATORY VARIANT PREDICTION ALGORITHMS, POSITIVE CONTROL VARIANTS, AND VARIANTS PRIORITIZED BASED ON REGULATORY ELEMENT ANNOTATIONS. THE GENE REGULATORY EFFECT OF ~500,000 VARIANT ALLELES WILL BE INTERROGATED IN FIVE ORGANS (BRAIN, LIVER, LUNG, MUSCLE AND HEART) USING SYSTEMIC CIRCULATION OF ADENO-ASSOCIATED VIRAL (AAV) MPRA LIBRARIES. WE WILL REPEAT THIS EXPERIMENT IN A PERTURBED INFLAMMATORY STATE TO EVALUATE GENE-ENVIRONMENT INTERACTIONS. AS A RESULT, WE WILL COMPREHENSIVELY CHARACTERIZE VARIANT EFFECTS ON REGULATORY FUNCTION BY ANALYSES OF VARIANTS IN THE PHYSIOLOGICAL CONDITIONS OF MULTIPLE TISSUES, IN BOTH SEXES, WITH AND WITHOUT PERTURBATION TYPICAL OF DISEASE ENVIRONMENTS. SELECTED VARIANTS WILL BE EDITED INTO HUMAN PLURIPOTENT CELLS FOR VALIDATION. AS MEMBERS OF THE IMPACT OF GENOMIC VARIATION ON FUNCTION (IGVF) CONSORTIUM, WE WILL GENERATE A REGULATORY VARIANT CATALOG FOR THE COMMUNITY, AND ENABLE FUTURE STUDIES THROUGH DATA COLLECTION AND PREDICTIVE MODELS. SUCCESSFUL COMPLETION OF THESE AIMS WILL PROVIDE ~10 MILLION ALLELIC EFFECT DATA POINTS THAT ENCOMPASS TISSUE-, SEX-, AND PERTURBATION- SPECIFIC REGULATORY EFFECTS. WE WILL WORK WITH THE IGVF CONSORTIUM TO FINALIZE SELECTION OF VARIANTS, ORGANS, AND PERTURBATIONS TO GENERATE A COMPREHENSIVE CATALOG. THE EXPERTISE OF THE STUDY INVESTIGATORS IN GWAS, STATISTICAL AND COMPUTATIONAL GENETICS, HUMAN GENOMICS, AAV DELIVERY, AND MOUSE PHYSIOLOGY MAKE ACHIEVEMENT OF THESE AIMS FEASIBLE AND LIKELY HIGHLY INFORMATIVE TO UNDERSTAND HOW GENOMIC VARIATION IMPACTS HUMAN HEALTH AND DISEASE.

GENETIC EPIDEMIOLOGY OF RARE AND REGULATORY VARIANTS FOR METABOLIC TRAITS

NATIONAL GNOTOBIOTIC RODENT RESOURCE CENTER

CAROTID OCCLUSION SURGERY STUDY

UNC NEUROSCIENCE CENTER RESEARCH CORES

UNC BSL3 CORE FACILITY - PROJECT SUMMARY / ABSTRACT: THE CENTRAL GOAL OF THIS PROJECT IS TO CONSTRUCT A 10,000 SQUARE FEET BIOSAFETY LEVEL 3 (BSL3) RESEARCH LABORATORY CORE FACILITY TO PROMOTE READINESS TO RESPOND TO FUTURE PANDEMICS. INFECTIOUS DISEASES POSE A SEVERE AND INCREASING THREAT TO HUMAN HEALTH, ESPECIALLY IN COMMUNITIES THAT LACK ACCESS TO HEALTH CARE. UNC PROGRAMS WILL SOON EXCEED CURRENT INFRASTRUCTURE CAPACITY DUE TO INCREASE DEMAND. A STRATEGIC REVIEW OF OUR MICROBIAL PATHOGENESIS AND INFECTIOUS DISEASE COMMUNITY CONCLUDED THAT URGENT ACTION WAS ESSENTIAL TO SUPPORT THE HIGH CONTAINMENT PROGRAMS. AMONG THE BARRIERS TO THE GROWTH OF RESEARCH WAS A LACK OF ACCESS TO CRITICAL TECHNOLOGIES AND ANIMAL SPACE WITHIN THE EXISTING BSL3 LABORATORIES. THIS TRANSFORMATIVE BSL3 CORE FACILITY WILL ALLOW UNC TO EXPAND TO MEET CURRENT AND PROJECTED RESEARCH NEEDS IN THE UNC SCHOOL OF MEDICINE, SCHOOL OF PHARMACY, AND GILLINGS SCHOOL OF GLOBAL PUBLIC HEALTH. UNC HAS ENGAGED MULTIPLE STAKEHOLDERS ACROSS THE RESEARCH COMMUNITY TO DESIGN AND CONSTRUCT A CENTRALIZED BSL3 SUITE TO CHARACTERIZE THE IMMUNE RESPONSES TO CORONAVIRUS AND OTHER EMERGING VIRAL PATHOGENS AND LEARN ABOUT WHAT DRIVES IMMUNE RESPONSE, DISEASE PROGRESSION, AND PROTECTION AGAINST FUTURE INFECTION. THE PROPOSAL WILL ATTAIN FOUR OBJECTIVES: 1. DESIGN AND CONSTRUCT A HIGH CONTAINMENT FACILITY TO BRING INVESTIGATORS WORKING ON EMERGING AND RE-EMERGING INFECTIONS TOGETHER; 2. ENABLE ACCESS TO SPECIALIZED INSTRUMENTATION INCLUDING AEROBIOLOGY AND IMAGING EQUIPMENT FOR SUPPORTING HIGH CONTAINMENT RESEARCH; 3. CREATE INSTITUTION-WIDE CORE SPACE TO ALLOW RECRUITMENT OF NEW INVESTIGATORS TO THE INFECTIOUS DISEASE RESEARCH COMMUNITY BY INCREASING USABLE LABORATORY SPACE IN THE BSL3 FACILITY AND PURCHASING NEW EQUIPMENT THAT WILL SERVE INVESTIGATORS WITHIN THE MANY UNC CENTERS, INSTITUTES, AND DEPARTMENTS AND THEIR NATIONWIDE COLLABORATORS; 4. ENHANCE UNC'S ABILITY TO LEAD THE RAPID RESPONSE GENERATING NEW THERAPEUTICS AND VACCINES TO SAVE LIVES ON A LOCAL, NATIONAL, AND EVEN GLOBAL LEVEL.

THIS ON-SITE COOPERATIVE AGREEMENT UTILIZES ADVANCED SYSTEMS LOCATED IN THE EPA HUMAN STUDIES FACILITY AT CHAPEL HILL TO EXPOSE HEALTHY AND DISEASED

IDENTIFICATION OF DNA ELEMENTS GOVERNING CHROMATIN FUNCTION IN C ELEGANS

DEFINING RAS ISOFORM- AND MUTATION-SPECIFIC ROLES IN ONCOGENESIS

CLINICAL TRANSLATIONAL RESEARCH CENTER FOR NEURODEVELOPMENTAL DISORDERS

A MIDSCALE U.S. PROPOSAL FOR THE LEGEND 200 EXPERIMENT

INTERVENTIONS FOR PREVENTING & MANAGING CHRONIC ILLNESS

NORTH CAROLINA PUBLIC HEALTH PREPAREDNESS SYSTEMS RESEARCH CENTER

RESEARCH TRAINING IN THE NEUROSCIENCES

TEACHING HEALTH CENTER PLANNING AND DEVELOPMENT TECHNICAL ASSISTANCE PROGRAM

RURAL RESIDENCY TECHNICAL ASSISTANCE AND DEVELOPMENT PROGRAM

CAROLINA CENTER OF CANCER NANOTECHNOLOGY EXCELLENCE

UNC-CH TRAINING PROGRAM IN HEALTH SERVICES RESEARCH

CNS PROCESSES UNDERLYING PAIN REGULATION AND PERSISTENCE

MOLECULAR AND CELLULAR ALCOHOL RESEARCH TRAINING

STUDIES OF NUCLEAR PROCESSES.

RURAL HEALTH RESEARCH GRANT PROGRAM COOPERATIVE AGREEMENT

TARGETED ANTICOAGULANT THERAPY FOR SICKLE CELL DISEASE

PULMONARY EPITHELIA IN HEALTH AND DISEASE

HISPANIC COMMUNITY CHILDREN'S HEALTH STUDY OF LATINO YOUTH SOL-YOUTH

MARKET-BASED APPROACHES TO SCALING SUSTAINABLE WATER, SANITATION, AND HYGIENE

UNC-CH NADIA UNDERAGE DRINKING AND ADULT BRAIN MORPHOLOGY IN RATS

5/8-PREDICTORS AND MECHANISMS OF CONVERSION TO PSYCHOSIS

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) -THE NATIONAL SCIENCE FOUNDATION (NSF) GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) IS A HIGHLY COMPETITIVE, FEDERAL FELLOWSHIP PROGRAM. GRFP HELPS ENSURE THE VITALITY AND DIVERSITY OF THE SCIENTIFIC AND ENGINEERING WORKFORCE OF THE UNITED STATES. THE PROGRAM RECOGNIZES AND SUPPORTS OUTSTANDING GRADUATE STUDENTS WHO ARE PURSUING RESEARCH-BASED MASTER'S AND DOCTORAL DEGREES IN SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) AND IN STEM EDUCATION. THE GRFP PROVIDES THREE YEARS OF FINANCIAL SUPPORT FOR THE GRADUATE EDUCATION OF INDIVIDUALS WHO HAVE DEMONSTRATED THEIR POTENTIAL FOR SIGNIFICANT RESEARCH ACHIEVEMENTS IN STEM AND STEM EDUCATION. THIS AWARD SUPPORTS THE NSF GRADUATE FELLOWS PURSUING GRADUATE EDUCATION AT THIS GRFP INSTITUTION. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

METHOTREXATE RESPONSE IN TREATMENT OF UC - MERIT-UC

CLINICAL TRANSLATIONAL RESEARCH CENTER FOR NEURODEVELOPMENTAL DISORDERS