Wake Forest University Health Sciences

EVALUATING NEW NICOTINE STANDARDS FOR CIGARETTES

ARMED FORCES INSTITUTE OF REGENERATIVE MEDICINE

WAKE FOREST NCORP RESEARCH BASE

COMPREHENSIVE CANCER CENTER OF WAKE FOREST UNIVERSITY

SUBCLINICAL VASCULAR CONTRIBUTIONS TO ALZHEIMER'S DISEASE: THE MULTI ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) MULTISITE STUDYOF AD

LOOK AHEAD: ACTION FOR HEALTH IN DIABETES

WAKE FOREST CLINICAL AND TRANSLATIONAL SCIENCE AWARD

NSF ENGINES: PIEDMONT TRIAD REGENERATIVE MEDICINE ENGINE -THE PIEDMONT TRIAD REGENERATIVE MEDICINE ENGINE (THE PIEDMONT TRIAD ENGINE) IS WORKING TO BUILD AN ECOSYSTEM AROUND STRONG ASSETS IN THE FIELD OF REGENERATIVE MEDICINE (RM) BASED AT THE WAKE FOREST INSTITUTE FOR REGENERATIVE MEDICINE (WFIRM) IN COLLABORATION WITH ITS EXTENSIVE NETWORK OF PARTNERS. LOCATED IN THE PIEDMONT TRIAD REGION OF CENTRAL NORTH CAROLINA, THE ENGINE WILL PROVIDE THE RESOURCES TO ACCELERATE TRANSITION OF USE-INSPIRED RM TECHNOLOGIES INTO COMMERCIAL PRODUCTS, CREATING AN ECONOMIC DRIVER FOR THE REGION AND ITS DIVERSE COMMUNITIES. THIS GROWTH IN THE RM INDUSTRY HELPS TO ADDRESS LONG-TERM REGIONAL CHALLENGES RELATED TO RETRAINING AND UPSKILLING OF AN UNDEREMPLOYED LOCAL WORKFORCE LEFT BEHIND BY THE LOSS OF TOBACCO, TEXTILES AND FURNITURE JOBS THROUGHOUT THE REGION OF SERVICE. THE PROJECT PRIORITIZES BUILDING A TECHNICAL INFRASTRUCTURE FOR HISTORICALLY BLACK COLLEGES AND UNIVERSITIES (HBCUS) IN THE REGION TO REDUCE DISPARITIES FOR UNDERREPRESENTED GROUPS IN STEM FIELDS. REGENERATIVE MEDICINE PROMISES TO OFFER PERMANENT CURES RATHER THAN RELIEF FROM SYMPTOMS, WHICH IS AN IMPORTANT ADVANCE GIVEN RISING HEALTHCARE COSTS. THE GOAL IS TO BREAK THE CYCLE OF DEPENDENCE ON LIFELONG MAINTENANCE DRUGS AND THERAPIES. AREAS OF TECHNICAL FOCUS INCLUDE STANDARDIZED MATERIALS AND PROCESSES FOR THE PRODUCTION OF RM PRODUCTS THAT CAN BE BROUGHT TO MARKET. INDUSTRY PARTNERS AND COMMUNITY STAKEHOLDERS WILL DRIVE THE DIRECTION OF THE TECHNOLOGY DEVELOPMENT, WHILE ALLOWING FOR CREATIVE INNOVATION THROUGH THE ACADEMIC RESEARCH ENVIRONMENT. TECHNOLOGIES BORN FROM THE PIEDMONT TRIAD ENGINE WILL BE COMMERCIALIZED THROUGH A ROBUST BUSINESS DEVELOPMENT SYSTEM, GIVING RISE TO NEW COMPANIES AND INCREASED WORKFORCE DEMAND THAT WILL BE MET BY THE PIEDMONT TRIAD ENGINE?S PARTNERS INCLUDING TWO-YEAR COMMUNITY AND TECHNICAL COLLEGES. THIS NSF ENGINE WILL BE BUILT UPON INDUSTRY USE-INSPIRED AND GUIDED RESEARCH SPANNING PRODUCT IDEATION AND DEVELOPMENT, TRANSLATIONAL SCIENCE, BIOMANUFACTURING, AND NEXT GENERATION STRATEGIES, INCLUDING IN-SPACE RM TECHNOLOGIES. AN INNOVATION, TRANSLATION, & EDUCATION CORE SYSTEM WILL BE DEVELOPED ACROSS PARTNERING ACADEMIC INSTITUTIONS, INCLUDING AT HBCUS AND TECHNICAL COLLEGES IN THE REGION OF SERVICE, THAT COMBINES MULTIPLE AREAS OF SCIENTIFIC EXPERTISE TO ADDRESS CHALLENGES IN THE MULTIDISCIPLINARY FIELD OF RM. THE RESOURCES PROVIDED BY THE PIEDMONT TRIAD ENGINE WILL INCREASE THE REGION?S COMPETITIVE ADVANTAGE AND LEVERAGE ITS NATIONAL REPUTATION AS A HUB FOR THE RM INDUSTRY, ATTRACTING MORE CAPITAL AND NEW COMPANIES TO THE REGION. THE PIEDMONT TRIAD ENGINE WILL HAVE TRANSFORMATIVE IMPACT ON THE REGION BY CREATING A NEW TRAINED RM WORKFORCE THAT WILL GIVE THE U.S. A COMPETITIVE EDGE IN THE DEVELOPMENT AND MANUFACTURE OF NEXT-GENERATION RM THERAPIES WITH POTENTIAL TO IMPACT MILLIONS OF INDIVIDUALS WORLDWIDE. RM BUSINESSES THAT EMERGE FROM TECHNICAL INNOVATIONS WILL BE ECONOMIC DRIVERS, ATTRACTING INVESTMENT FROM STAKEHOLDERS ACROSS THE NATION. CREATION OF NEW RM PRODUCTS AND BUSINESSES WILL CREATE SELF-SUSTAINING REGIONAL PROSPERITY WITH ECONOMIC IMPACT FOR MANY COMMUNITIES IN THE REGION, INCLUDING HISTORICALLY DISADVANTAGED BLACK COMMUNITIES IN THE PIEDMONT TRIAD REGION. THIS NSF ENGINE PROJECT IS BUILT ON A STRONG RESEARCH AND DEVELOPMENT PORTFOLIO AT WFIRM AND EMPHASIZES THE TRANSLATION TO PRACTICE AND COMMERCIALIZATION STEPS OF BUILDING AN INNOVATION ECOSYSTEM IN PARTNERSHIP WITH STRONG WORKFORCE DEVELOPMENT ORGANIZATIONS ALREADY IN THE REGION OF SERVICE. BIOMEDICAL TECHNOLOGIES AND THE RM INDUSTRY SHOW STRONG ALIGNMENT WITH THE PRIORITIES OF THE REGION OF SERVICE, WHICH WAS REINFORCED BY THE STRONG SHOWING OF ENTHUSIASTIC PARTNERS WHO ENGAGED WITH THE SITE VISIT TEAM. THE LEADERSHIP IS READY TO UTILIZE THE NSF ENGINE RESOURCES TO BRIDGE THE GAP BETWEEN THE RESEARCH LAB AND THE COMMERCIAL MARKET WITHOUT LEAVING THE LOCAL COMMUNITY BEHIND. COMMUNITY ENGAGEMENT AND WORKFORCE TRAINING WILL BE KEY TO THE SUCCESS OF THE PIEDMONT TRIAD ENGINE. 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.

MOTRPAC CONSORTIUM COORDINATING CENTER

CLAUDE D. PEPPER OLDER AMERICANS INDEPENDENCE CENTER AND COORDINATING CENTER

PHYSICAL REHABILITATION FOR OLDER PATIENTS WITH ACUTE HFPEF-THE REHAB-HFPEF TRIAL - ACUTE DECOMPENSATED HEART FAILURE (ADHF) IS THE LEADING CAUSE OF HOSPITALIZATION IN OLDER PERSONS, AND IS ASSOCIATED WITH MARKED PHYSICAL DISABILITY, POOR HEALTH-RELATED QUALITY OF LIFE (HRQOL), FREQUENT REHOSPITALIZATIONS, LOSS OF INDEPENDENCE, HIGH MORTALITY, AND ENORMOUS HEALTH CARE COSTS. HOWEVER, MOST OF THE TRIALS TESTING A WIDE RANGE OF MEDICATIONS AND STRATEGIES IN ADHF HAVE BEEN NEUTRAL. IN OUR RECENTLY COMPLETED NIA-FUNDED PHASE 2 TRIAL (REHAB-HF), AN INNOVATIVE, EARLY, TRANSITIONAL, TAILORED, AND PROGRESSIVE MULTI-DOMAIN PHYSICAL REHABILITATION INTERVENTION PRODUCED A LARGE IMPROVEMENT IN THE PRIMARY OUTCOME OF SHORT PHYSICAL PERFORMANCE BATTERY (+1.5 POINTS) IN OLDER PATIENTS WITH ADHF. AT BASELINE, THE PARTICIPANTS (53%) WITH HF WITH PRESERVED EJECTION FRACTION (HFPEF), HAD SIGNIFICANTLY WORSE IMPAIRMENTS IN PHYSICAL FUNCTION, FRAILTY, HRQOL, AND DEPRESSION THAN THOSE WITH HF WITH REDUCED EF. THEY ALSO APPEARED TO DERIVE GREATER BENEFIT FROM THE INTERVENTION, WITH ~50% LARGER EFFECT SIZES IN PHYSICAL FUNCTION, FRAILTY, HRQOL, AND DEPRESSION. PATIENTS WITH HFPEF ALSO APPEARED TO HAVE MUCH GREATER REDUCTIONS IN REHOSPITALIZATIONS AND DEATH AND POTENTIAL FOR REDUCED MEDICAL RESOURCE USE. THE FINDING OF POTENTIALLY GREATER BENEFIT IN HFPEF IS NOTEWORTHY AS HFPEF IS HIGHLY RELEVANT TO OLDER PERSONS AND HAS THE MOST URGENT NEED FOR NEW TREATMENTS SINCE IT IS: 1) THE MOST COMMON FORM OF HF, NEARLY UNIQUE TO OLDER PERSONS, AND DISPROPORTIONATELY AFFECTS OLDER WOMEN AND BLACK PERSONS; 2) INCREASING IN PREVALENCE; 3) ACCEPTED AS A GERIATRIC SYNDROME; 4) ASSOCIATED WITH MARKED IMPAIRMENTS IN PHYSICAL FUNCTION AND HRQOL AND HIGH RATES OF FRAILTY; 5) HAS HIGH MORBIDITY AND MORTALITY WHICH ARE WORSENING OVER TIME; AND 6) HAS LIMITED EVIDENCE-BASED TREATMENTS. THE PHASE 3 REHAB- HFPEF TRIAL WILL FOCUS ON THIS LARGE, GROWING, VULNERABLE, UNDERSERVED POPULATION. THE 5-YEAR, RANDOMIZED, ATTENTION-CONTROLLED, SINGLE-BLINDED TRIAL WILL ENROLL 880 OLDER ADULTS AGE >60 YEARS WITH ADHF AND HFPEF ACROSS 20 GEOGRAPHICALLY DISPERSED CLINICAL CENTERS. WE WILL TEST THE HYPOTHESIS THAT THE INNOVATIVE REHAB-HF INTERVENTION WILL IMPROVE THE CLINICALLY COMPELLING COMBINED PRIMARY ENDPOINT OF ALL-CAUSE REHOSPITALIZATIONS AND MORTALITY DURING 6-MONTH FOLLOW-UP, THE MOST VULNERABLE TIME PERIOD FOLLOWING ADHF HOSPITALIZATION (AIM 1) AND THE SECONDARY ENDPOINT OF PREVALENCE OF MAJOR MOBILITY DISABILITY, A CLINICALLY MEANINGFUL OUTCOME IN TRIALS OF OLDER ADULTS, AT 6-MONTHS (AIM 2). WE WILL ALSO ASSESS THE INTERVENTION’S IMPACT ON HRQOL, FRAILTY, DEPRESSION, PHYSICAL ACTIVITY, AND HEALTH CARE COSTS. OUR DIVERSE, COHESIVE, MULTI-DISCIPLINARY TEAM AND EXPERIENCE FROM THE PHASE 2 TRIAL WILL ENSURE EFFICIENT AND EFFECTIVE EXECUTION AND DISSEMINATION. REHAB-HFPEF DIRECTLY ADDRESSES THE KEY RECOMMENDATIONS OF SEVERAL RECENT NIA AND NHLBI SPONSORED WORKSHOPS. ITS RESULTS COULD IMPROVE KEY OUTCOMES THAT ARE MEANINGFUL TO PATIENTS, CAREGIVERS, HEALTH SYSTEMS, AND PAYERS. THE TRIAL HAS STRONG POTENTIAL TO CHANGE CLINICAL GUIDELINES, REDUCE HEALTH CARE COSTS, AND INFLUENCE NATIONAL COVERAGE DECISIONS FOR THE LARGE, GROWING, UNDERSERVED, HIGH-RISK POPULATION OF OLDER PATIENTS WITH ACUTE HFPEF.

THE WAKE FOREST NONHUMAN PRIMATE RADIATION SURVIVOR COHORT

VASODEPRESSOR MECHANISMS IN HYPERTENSION

ALZHEIMER'S DISEASE RESEARCH CENTER - OVERALL – PROJECT SUMMARY THE ALZHEIMER’S DISEASE RESEARCH CENTER (ADRC) WAS FOUNDED AT WAKE FOREST SCHOOL OF MEDICINE (WFSM) IN 2016 TO PROVIDE A COMPREHENSIVE INFRASTRUCTURE FOR RESEARCH ON THE PATHOPHYSIOLOGY, PREVENTION, AND TREATMENT OF AD AND RELATED DISORDERS (ADRD). THE THEME OF OUR ADRC IS TO BETTER UNDERSTAND EARLY TRANSITIONS FROM NORMAL AGING TO MCI AND DEMENTIA, AND TO ELUCIDATE THE ROLE THAT METABOLIC AND VASCULAR FACTORS PLAY IN THESE TRANSITIONS, THROUGH COORDINATED RESEARCH ACTIVITIES SPANNING THE TRANSLATIONAL SPECTRUM. NO CURRENT THERAPIES EFFECTIVELY PREVENT OR TREAT THE SYMPTOMS OF AD. THIS CHASM HIGHLIGHTS THE NEED TO IDENTIFY ANTECEDENT BIOMARKERS AND RISK FACTORS THAT PREDICT LATER-LIFE VULNERABILITY OR RESILIENCE, IN ORDER TO DEVELOP STRATEGIES FOR PREVENTION AND EARLY INTERVENTION. METABOLIC AND VASCULAR DISORDERS ARE POWERFUL MODIFIABLE FACTORS THAT MAY CONTRIBUTE TO THE TRANSITIONS FROM NORMAL AGING TO MCI AND ADRD. SUCH DISORDERS ARE EPIDEMIC IN THE SOUTHEASTERN REGION SURROUNDING THE WF ADRC; MORE THAN 70% OF ADULTS OVER THE AGE OF 50 HAVE PREDIABETES, DIABETES, OR HYPERTENSION. THESE DISORDERS INCREASE THE RISK OF COGNITIVE IMPAIRMENT AND DEMENTIA THROUGH COMPLEX INTERACTIONS THAT ARE POORLY UNDERSTOOD. THE WF ADRC SEEKS TO PROVIDE RESOURCES TO BETTER UNDERSTAND THESE INTERACTIONS. WE ALSO SEEK TO ELUCIDATE THE MULTI-DIMENSIONAL ROLE THAT HEALTH DISPARITIES PLAY IN INFLUENCING RISK FOR AD. WE EMPHASIZE ENGAGEMENT OF AFRICAN AMERICANS AND OTHER UNDERREPRESENTED GROUPS, WHO ARE TWICE AS LIKELY TO DEVELOP DEMENTIA, AND HAVE HIGH RATES OF DIABETES AND VASCULAR DISEASE. TO PROMOTE INNOVATIVE RESEARCH ON METABOLIC/VASCULAR RISK AND HEALTH DISPARITIES, OUR OUTREACH, RECRUITMENT AND ENGAGEMENT AND CLINICAL CORES HAVE PARTNERED TO ENROLL AND FOLLOW ~600 PARTICIPANTS, CAREFULLY CHARACTERIZING THEIR VASCULAR AND GLYCEMIC STATUS. PARTICIPANTS RECEIVE MAGNETIC RESONANCE IMAGING AND AMYLOID AND TAU POSITRON EMISSION TOMOGRAPHY OVERSEEN BY THE IMAGING BIOMARKER CORE. VALUABLE SAMPLES AND DATA FROM THIS COHORT ARE MADE WIDELY AVAILABLE TO THE NATIONAL ALZHEIMER’S COORDINATING CENTER, THE NATIONAL CENTRALIZED REPOSITORY FOR AD AND OTHER INVESTIGATORS BY THE DATA MANAGEMENT AND STATISTICAL ANALYSIS AND NEUROPATHOLOGY CORES, PROVIDING INVALUABLE RESOURCES TO ADDRESS NUMEROUS NATIONAL ALZHEIMER’S PROJECT ACT MILESTONES. THE NEUROPATHOLOGY CORE HAS ALSO CHARACTERIZED NOVEL NONHUMAN PRIMATE MODELS WITH METHODS THAT PARALLEL THE ADRC’S HUMAN COHORT TO PROMOTE TRANSLATIONAL RESEARCH. FINALLY, THE ADRC AND ITS RESEARCH EDUCATION COMPONENT PROVIDE TRAINING RELATING TO AD, METABOLIC/ VASCULAR FACTORS AND HEALTH DISPARITIES TO A DIVERSE CADRE OF NEW RESEARCHERS, AND EDUCATION FOR PATIENTS AND FAMILIES, HEALTH PROFESSIONALS, AND THE COMMUNITY. THE PREVALENCE OF METABOLIC AND VASCULAR RISK FACTORS, THEIR ROLE IN ONSET, PROGRESSION, AND HETEROGENEITY OF ADRDS, AND THE STRENGTHS OF THE WF ADRC IN THESE RESEARCH AREAS, ENSURE THAT WE WILL MAKE HIGH-IMPACT CONTRIBUTIONS TO THE SEARCH FOR STRATEGIES TO TREAT AND PREVENT AD.

AFIRM II (ARMED FORCES INSTITUTE OF REGENERATIVE MEDICINE) CONSORTIUM. THIS AWARD IS FOR THE GENITOURINARY/LOWER ABDOMEN RECONSTRUCTION (GU) FOCUS A

CENTER THE NEUROBIOLOGICAL INVESTIGATION OF DRUG ABUSE

GENOMIC AND PROTEOMIC ARCHITECTURE OF ATHEROSCLEROSIS

CLINICAL REGISTRY OF DENTAL OUTCOMES IN HEAD AND NECK CANCER PATIENTS

AFIRM II CF

LIMITED COMPETITION FOR THE CONTINUATION OF THE SEARCH FOR DIABETES IN YOUTH COHORT STUDY (UC4)SEARCH FOR DIABETES IN YOUTH COHORT STUDY

WAKE FOREST TRANSLATIONAL ALCOHOL RESEARCH CENTER (WF-TARC)

AFIRM II ER FOCUS AREA

SKIN REGENERATION

VERVET RESEARCH COLONY AS A BIOMEDICAL RESOURCE

COMPOSITE TISSUE ALLOTRANSPLANTATION AND IMMUNOMODULATION

HE WAKE FOREST INSTITUTE FOR REGENERATIVE MEDICINE (WFIRM) HAS OVER TWO DECADES OF EXPERIENCE USING A VARIETY OF 3D PRINTING MODALITIES TO DEVELOP IMPLANTABLE HUMAN TISSUE CONSTRUCTS. OVER TIME THE CELLULAR COMPOSITIONS AND IMPLANT DIMENSIONS RELEVANT TO CLINICAL APPLICATIONS HAVE INCREASED REQUIRING AN INTEGRATED VASCULAR SYSTEM THAT ALLOWS PERFUSION OF THE ENTIRE CONSTRUCT. THESE BIOPRINTED VASCULARIZED TISSUE CONSTRUCTS OPEN THE POSSIBILITY OF SUPPORTING A FUNCTIONAL MICROANATOMY THAT CAN PERFORM NUANCED ORGAN SPECIFIC FUNCTIONS. THE OVERALL STRATEGY WILL INCLUDE A PROTOCOL FOR COST EFFECTIVE CLINICAL MANUFACTURING OF A SUFFICIENT NUMBER OF AUTOLOGOUS RENAL CELLS FROM A SMALL SURGICAL SAMPLE OR TISSUE BIOPSY. THESE CELLS WILL BE COMBINED WITH A FUNCTIONALIZED HYDROGEL BIOINK THAT BOTH SUPPORTS THE LONG TERM VIABILITY OF THE EMBEDDED CELLS AND PROMOTES THE ACTIVATION OF ENDOGENOUS DEVELOPMENTAL PATHWAYS THAT GUIDE THE FORMATION OF A FUNCTIONAL CELLULAR MICROANATOMY. CUTTING EDGE MULTIPHYSICS MODELING WILL BE APPLIED TO NATIVE RENAL TISSUE TO ESTABLISH A BLUEPRINT THAT APPROXIMATES RENAL TISSUE ARCHITECTURE AT A RESOLUTION OF 50 UM. SOFTWARE WILL ALSO BE DEVELOPED TO TRANSLATE THIS BLUEPRINT INTO A PRINTABLE CODE THAT WILL GUIDE THE RAPID PRODUCTION OF RUDIMENTARY RENAL TISSUE. THESE CONSTRUCTS WILL BE FURTHER ENHANCED THROUGH MATURATION IN A SPECIALIZED PERFUSION BIOREACTOR WITH AN INTEGRATED SENSOR SUITE THAT MONITORS TISSUE FUNCTION. STRATEGIES WILL ALSO BE DEVELOPED USING SMALL AND LARGE PRECLINICAL ANIMAL MODELS TO PROMOTE FURTHER REMODELING OF BIOPRINTED RENAL TISSUE FOLLOWING IMPLANTATION. THE OVERARCHING GOAL IS THE PRODUCTION OF BIOPRINTED VASCULARIZED AUTOLOGOUS RENAL TISSUE TO AUGMENT RENAL FUNCTION IN PATIENTS SUFFERING FROM KIDNEY DISEASE. THIS TISSUE THERAPY WILL BE QUALIFIED USING IND ENABLING PRECLINICAL ANIMALS IN PARALLEL WITH A COMMERCIALIZATION PLAN TO MAKE THIS A COST EFFICIENT SOLUTION TO THE NATIONS GROWING DONOR ORGAN SHORTAGE.

WOMB TO TOMB: DEVELOPMENTAL PROGRAMMING AND AGING INTERACTIONS IN PRIMATES

THERAPEUTIC EFFECT OF INTRANASAL INSULIN ON COGNITION, FUNCTION, AND AD BIOMARKER

WAKE FOREST ALZHEIMER'S DISEASE CORE CENTER

CTSA UM1 PROGRAM AT WAKE FOREST - PROJECT SUMMARY/ABSTRACT THE EMERGENCE OF LARGE INTEGRATED HEALTH SYSTEMS LINKED BY COMMON INFORMATICS PLATFORMS OFFERS AN UNPRECEDENTED OPPORTUNITY TO STUDY THE IMPACT OF NEW THERAPIES, HEALTHCARE DELIVERY MODELS, AND STRATEGIES TO MITIGATE HEALTH DISPARITIES IN REAL WORLD SETTINGS. SUCH INTEGRATED SYSTEMS ALSO OFFER OPPORTUNITIES TO TEST APPROACHES TO IMPLEMENT AND SCALE EVIDENCE-BASED PRACTICES, TO ADDRESS GAPS IN TRANSLATIONAL SCIENCE, AND TO BECOME LEARNING HEALTH SYSTEMS (LHS). THE WAKE FOREST (WF) CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE (CTSI) HAS PIONEERED THE INTEGRATION OF THE ACADEMIC MISSION INTO THE LHS FRAMEWORK INCLUDING T0-T4 TRANSLATION, SCHOLARSHIP, AND EDUCATION WHILE ALSO ADDRESSING THE SOCIAL DETERMINANTS OF HEALTH AND PROMOTING THE VITALITY OF THE COMMUNITIES SERVED. WF LEADS AS THE ACADEMIC CORE OF ADVOCATE HEALTH – THE NATION’S FIFTH LARGEST NOT-FOR-PROFIT HEALTH SYSTEM SERVING NEARLY 6 MILLION PATIENTS ACROSS THE SOUTHEAST AND MIDWEST UNITED SATES. THE ALHS IS ADVOCATE HEALTH’S GUIDING VISION, AND THE WF CTSI IS ITS CENTRAL RESOURCE FOR SUPPORTING TRANSLATIONAL SCIENCE ACROSS THE ENTIRE SYSTEM. THE SIZE OF THE HEALTH SYSTEM OFFERS A UNIQUE OPPORTUNITY TO DEVELOP, DEMONSTRATE, AND DISSEMINATE NOVEL CARE MODELS IN A WIDE RANGE OF SETTINGS. WITH THIS FUNDING, THE WF CTSI WILL DRIVE THE REALIZATION OF THE FULL POTENTIAL OF AN ALHS AND CREATE A MODEL FOR ADVANCING TRANSLATIONAL SCIENCE IN A LARGE ACADEMIC HEALTH SYSTEM. THE NEED FOR SUCH A MODEL IS URGENT, GIVEN THE ONGOING CONSOLIDATION OF ACADEMIC AND NON-ACADEMIC HEALTH SYSTEMS IN THE UNITED STATES AND THE CHALLENGES IN CONDUCTING RESEARCH IN BUSY PRACTICE SETTINGS. ALL ACTIVITIES AND INITIATIVES TO ADVANCE TRANSLATIONAL SCIENCE WILL BE GROUNDED IN A CULTURE OF ACCOUNTABILITY FOR ENHANCING DIVERSITY, EQUITY, AND INCLUSION. WF CTSI’S VISION WILL BE ACHIEVED THROUGH THE FOUR SPECIFIC AIMS: 1) SUPPORT AN INCLUSIVE AND HIGHLY EFFECTIVE GOVERNANCE STRUCTURE THAT PROMOTES A CULTURE OF CONTINUOUS QUALITY IMPROVEMENT, ENABLES TIMELY RESPONSE TO REGIONAL AND NATIONAL HEALTH EMERGENCIES, SUPPORTS PROACTIVE DISSEMINATION AND IMPLEMENTATION, AND ENABLES ACTIVE PARTICIPATION IN CTSA-SPONSORED TRIALS; 2) RECRUIT AND TRAIN A HIGHLY COMPETENT AND DIVERSE ALHS WORKFORCE AND ENGAGE THE FULL RANGE OF PATIENT AND COMMUNITY STAKEHOLDERS WHO ARE ESSENTIAL TO IMPROVING HEALTH AND MITIGATING HEALTH DISPARITIES; 3) PROVIDE RESOURCES TO PROMOTE INNOVATIVE PRAGMATIC STUDY DESIGNS, SUPPORT PILOT STUDIES THAT ADDRESS KEY TRANSLATIONAL ROADBLOCKS, AND SATISFY THE NEEDS OF THE ALHS RESEARCH COMMUNITY FOR TIMELY ACCESS TO DATA FROM ELECTRONIC HEALTH RECORDS, POPULATION SURVEYS, OMICS ANALYSES, AND OTHER SOURCES; AND 4) ENHANCE TRANSLATIONAL EFFICIENCY THROUGH PROJECTS TESTING NOVEL METHODS (E.G., RESPONDENT DRIVEN SAMPLING TO IMPROVE PATIENT RECRUITMENT, INTEGRATING PATIENT GENERATED DATA INTO THE EHR). INNOVATIONS MADE IN ACHIEVING THESE AIMS WILL BE SHARED THROUGH AND BEYOND THE CTSA NATIONAL NETWORK.

COMPREHENSIVE CANCER CENTER OF WAKE FOREST UNIVERSITY CCOP RESEARCH BASE

DISSECTING THE GENOMIC ETIOLOGY OF NON-MENDELIAN EARLY-ONSET ALZHEIMER DISEASE AND RELATED PHENOTYPES

THE WAKE FOREST AND HARVARD CENTER FOR BOTANICAL LIPIDS

GENERAL CLINICAL RESEARCH CENTER

MULTICENTER CLINICAL TRIAL OF KERATIN BIOMATERIALS FOR PERIPHERAL NERVE REGENERATION

THE POINTER NEUROVASCULAR ANCILLARY STUDY

PRENATAL EVENTS-POSTNATAL CONSEQUENCES

LONG-TERM FOLLOW-UP OF THE DELAYED EFFECTS OF ACUTE RADIATION EXPOSURE IN PRIMATES

THE SPRINT ALZHEIMER'S, SENIORS AND KIDNEY STUDY (SPRINT ASK)

NORTH CAROLINA DIABETES RESEARCH CENTER

LIPOPROTEIN METABOLISM IN ATHEROSCLEROSIS

OXYTOCIN: A PAIN DISEASE-MODIFYING AGENT IN THE NERVOUS SYSTEM AFTER INJURY - THIS P01 WILL ADDRESS FUNDAMENTAL GAPS IN KNOWLEDGE THAT CURRENTLY IMPEDE TRANSLATION OF FINDINGS IN THE PRECLINICAL LITERATURE TO IMPROVED CLINICAL PRACTICE REGARDING THE UTILITY OF OXYTOCIN AS A PAIN THERAPEUTIC AND POTENTIAL DISEASE-MODIFYING AGENT TO PREVENT THE TRANSITION FROM ACUTE TO CHRONIC PAIN. OXYTOCIN ITSELF IS THE ONLY CLINICALLY AVAILABLE TOOL FOR TRANSLATIONAL STUDIES IN MANY AREAS – NEUROPROTECTION, ANXIETY, SLEEP, SOCIAL BEHAVIORS, ADDICTION, AND PAIN. MOST RODENT AND HUMAN STUDIES OF OXYTOCIN LACK STRONG SCIENTIFIC RIGOR, WITH ONLY HALF OF THE CLINICAL STUDIES EXAMINING PAIN DEMONSTRATING EFFICACY, AND WE HAVE MINIMAL ABILITY TO UNDERSTAND OXYTOCIN EFFECTS WITHIN AND ACROSS SPECIES. SINCE CHRONIC PAIN IS USUALLY REDUCED ACUTELY BY PERIPHERAL NERVE BLOCK, PERIPHERAL INPUT IS NECESSARY, BUT MOST RESEARCH ASSUMES THAT INPUT IS NORMAL AND PAIN REFLECTS ONGOING CENTRAL SENSITIZATION. WE AND OTHERS CHALLENGE THESE IDEAS, SHOWING THAT LTMRS ARE DESENSITIZED AFTER INJURY WHEREAS FAST HIGH THRESHOLD MECHANORECEPTORS (A-HTMRS) ARE SENSITIZED AND BEHAVIORAL RECOVERY COINCIDES WITH RETURN TO NORMAL FUNCTION OF BOTH AFFERENT SUBTYPES. IMPORTANTLY, OXYTOCIN ACUTELY MOVES LTMR AND A-HTMR DYSFUNCTION AFTER INJURY TOWARDS NORMAL. PAIN RESOLVES QUICKER IN WOMEN AFTER CESAREAN DELIVERY THAN OTHER PELVIC SURGERIES, AND HYPERSENSITIVITY RESOLVES QUICKER IN RODENTS WHEN NEUROPATHIC INJURY IS PERFORMED AFTER DELIVERY, AN EFFECT BLOCKED BY INHIBITION OF OXYTOCIN ACTION. THESE DATA SUGGEST THAT OXYTOCIN MAY ALTER THE PROCESS OF CHRONIC PAIN DEVELOPMENT AFTER INJURY OR SURGERY, AND HAS THE POTENTIAL TO BE NOT JUST AN ACUTE ANALGESIC, BUT A DISEASE-MODIFYING THERAPEUTIC. OXYTOCIN HAS PROSOCIAL, ANXIOLYTIC, AND TRUST ENHANCING EFFECTS ACCORDING TO SMALL STUDIES IN RODENTS AND HUMANS, BUT THE CIRCUITRY AND ROLE OF THESE CENTRAL ACTIONS ON SPEEDING RECOVERY FROM PAIN AND DISABILITY AFTER INJURY ARE UNEXPLORED. THIS P01 WILL ADDRESS THESE GAPS AND ADVANCE THE FIELD OF PAIN RESEARCH THROUGH THE COORDINATED INTERACTIONS BETWEEN THE PRECLINICAL AND CLINICAL PROJECTS ACROSS 3 SPECIFIC AREAS. THE FIRST IS EXTRAPOLATION OF THE PHARMACOKINETICS OF OXYTOCIN ACROSS SPECIES, SUCH THAT DRUG EXPOSURE IN RELEVANT COMPARTMENTS WITH TIME ARE BEING STUDIED IN A COORDINATED MANNER THAT PERMITS INTERPRETATION OF PHYSIOLOGICAL OR BEHAVIORAL EFFECTS BETWEEN RATS AND HUMANS SECOND IS THE STUDY OF PRIMARY SENSORY AFFERENT PHYSIOLOGY ACROSS SPECIES THAT DETERMINES HOW OXYTOCIN ALTERS SPECIFIC NERVE FIBER TYPES AND THE KEY ELECTRICAL PROPERTIES RELATED TO PAIN TRANSMISSION, INCLUDING MULTIPLE MODES OF NOCICEPTIVE STIMULATION AND THEIR INTERACTION. THIRD, WE STUDY PAIN BEHAVIORS BEYOND REFLEXIVE RESPONSES OR VERBAL REPORT IN ANIMALS AND HUMANS, RESPECTIVELY, WHICH MAY OFFER GREATER TRANSLATIONAL VALUE. COLLECTIVELY, THE COORDINATED AND SYNERGISTIC NATURE OF THESE STUDIES WILL HOPEFULLY PROVIDE CLARITY ON THE POTENTIAL OF OXYTOCIN TO MITIGATE CHRONIC PAIN DEVELOPMENT AFTER INJURY, AND THE CONTEXT WITHIN SUCH EFFECTS OCCUR.

LOOK AHEAD SLEEP: SLEEP-DISORDERED BREATHING, CIRCADIAN REST/ACTIVITY RHYTHMS, AND THE RISK OF ALZHEIMER'S DISEASE AND RELATED DEMENTIAS IN LOOK AHEAD - PROJECT SUMMARY SLEEP DISORDERED BREATHING (SDB) AND ALTERED CIRCADIAN REST/ACTIVITY RHYTHMS (CRARS) ARE INCREASINGLY RECOGNIZED AS RISK FACTORS FOR ALZHEIMER’S DISEASE AND RELATED DEMENTIAS. OBESITY AND TYPE 2 DIABETES (T2D) ARE LEADING LIFESTYLE RISK FACTORS FOR POOR COGNITIVE OUTCOMES, AND ARE CLOSELY LINKED TO SDB AND CIRCADIAN ALTERATIONS. THE ROLES OF SDB AND ALTERED CRARS IN THE PROMOTION OF COGNITIVE DECLINE AND DEMENTIA RISK, HOWEVER, HAVE NOT BEEN WELL STUDIED IN OLDER OVERWEIGHT OR OBESE INDIVIDUALS WITH T2D, WHO ARE ALREADY VULNERABLE TO COGNITIVE DECLINE. THE PROPOSED ANCILLARY INVESTIGATION TO THE LOOK AHEAD STUDY WILL QUANTIFY SDB AND CRARS (THROUGH HOME SLEEP TESTING AND WRIST ACTIGRAPHY) AND WILL USE A VALIDATED TELEPHONE COGNITIVE ASSESSMENT PROTOCOL IN 1,500 LOOK AHEAD PARTICIPANTS, TO EVALUATE THE LINKS OF SDB AND ALTERED CRARS WITH COGNITIVE DECLINE AND ADJUDICATED CLINICAL CONDITIONS: MILD COGNITIVE IMPAIRMENT, ALZHEIMER’S DISEASE, AND ALZHEIMER’S DISEASE RELATED DISORDERS, IN THIS COHORT. WE WILL INVESTIGATE ~20-YEAR DIABETES CONTROL AND WEIGHT TRAJECTORIES, AND APOE E4 CARRIER STATUS AS POTENTIAL EFFECT MODIFIERS, AND EXPLORE BLOOD BASED BIOMARKERS OF ALZHEIMER’S DISEASE (ASS42/ASS40, TOTAL TAU, PTAU181, AND NFL). FINALLY, WE WILL LEVERAGE LOOK AHEAD’S RANDOMIZED CONTROLLED TRIAL DESIGN TO EXAMINE WHETHER PARTICIPANTS WHO WERE RANDOMIZED TO AN INTENSIVE LIFESTYLE INTERVENTION (ILI) THAT TARGETED DIET AND PHYSICAL ACTIVITY (VS. A DIABETES SUPPORT AND EDUCATION (DSE) CONTROL CONDITION) EXHIBIT LOWER RATES OF SDB AND MORE ROBUST, LESS PHASE-DELAYED CRARS IN LATER LIFE. WE WILL DETERMINE WHETHER DIFFERENCES IN THESE SDB/CIRCADIAN CHARACTERISTICS ARE ASSOCIATED WITH MAINTENANCE OF COGNITIVE FUNCTION IN OLDER ADULTHOOD. RESULTS OF THIS STUDY—CONDUCTED BY A TEAM OF INVESTIGATORS WITH EXPERTISE IN AGING, SLEEP, DIABETES, AND COGNITIVE DECLINE AND ALZHEIMER’S DISEASE—WILL ADVANCE OUR UNDERSTANDING OF HOW SDB AND ALTERED CRARS AFFECT BRAIN HEALTH AMONG OLDER ADULTS WITH T2D AND OVERWEIGHT/OBESITY, AND WHETHER A LIFESTYLE INTERVENTION PRODUCES DURABLE EFFECTS ON SLEEP/CIRCADIAN HEALTH THAT TRANSLATE INTO SUSTAINED BRAIN HEALTH IN THIS AT-RISK POPULATION.

WAKE FOREST APOLLO SCIENTIFIC AND DATA RESEARCH CENTER

MAXIMIZING LOCAL ACCESS TO THERAPEUTIC DELIVERIES IN GLIOBLASTOMA

CHRONIC STRESS AND COCAINE ABUSE IN FEMALE MONKEYS

LONG-TERM IMPACT OF RANDOM ASSIGNMENT TO INTENSIVE LIFESTYLE INTERVENTION ON ALZHEIMERS DISEASE AND RELATED DEMENTIAS: THE ACTION FOR HEALTH IN DIABETES ADRD STUDY (LOOK AHEAD-MIND)

COMMUNITY PARTICIPATORY APPROACH TO MEASURING FARMWORKER PESTICIDE EXPOSURES: PAC

MULTI-DISCIPLINARY TRAINING IN THE BIOLOGY OF ALCOHOLISM

RECOVERY FROM PAIN AND DISABILITY AFTER SURGERY