Ponce Medical School Foundation Inc

PHSU SPECIALIZED CENTER IN HEALTH DISPARITIES - IMPACT OF COVID-19 ON LIFE EXPERIENCES OF VULNERABLE CHILDREN AND FAMILIES

HEALTH INFORMATION TECHNOLOGY COOPERATIVE REGIONAL CENTER

PONCE SCHOOL OF MEDICINE-MOFFITT CANCER CENTER PARTNERSHIP (1/2)

RCMI PROGRAM AT THE PONCE SCHOOL OF MEDICINE

PUERTO RICO ENHANCED SURVEILLANCE AND CONTROL OF ARBOVIRUSES (PRESCA) PROGRAM

PONCE SCHOOL OF MEDICINE RCMI PROGRAM

PONCE SCHOOL OF MEDICINE MBRS-RISE PROGRAM

SENTINEL ENHANCED DENGUE SURVEILLANCE SYSTEM (SEDSS) SITES TO EVALUATE THE EPIDEMIOLOGY AND PREVENTION OF DENGUE AND OTHER ACUTE FEBRILE ILLNESSES IN

RESEARCH LAB RESTORATION PROGRAM

MENTAL HEALTH CPR: TRANSFORMING CANCER SURVIVORS' MENTAL HEALTH WITH COMMUNITY PARTICIPATORY REACH FOR EQUITY - PROJECT SUMMARY HISPANIC CANCER PATIENTS AND SURVIVORS FACE SOCIAL AND STRUCTURAL INEQUALITIES PERPETUATING MENTAL HEALTH DISPARITIES. DESPITE THESE CHALLENGES, THE STUDY TEAM AND COMMUNITY PARTNERS ARE CONVINCED THAT PSYCHOSOCIAL AND MENTAL HEALTH INEQUITIES PERPETRATED BY SOCIO-ENVIRONMENTAL FACTORS CAN BE OVERCOME THROUGH COMMUNITY- BASED MULTILEVEL INTERVENTIONS; YET NONE CURRENTLY EXIST. THIS PROJECT IS HIGHLY TRANSFORMATIVE AND INNOVATIVE BECAUSE IT DISRUPTS TRADITIONAL PSYCHO-ONCOLOGY MENTAL HEALTH CARE TO ADDRESS UPSTREAM STRUCTURAL (LIMITED ACCESS TO PSYCHOSOCIAL AND MENTAL HEALTH INEQUITIES AND PSYCHOLOGICAL DISTRESS SCREENING), SOCIAL (MENTAL HEALTH STIGMA), AND BIOLOGICAL (STRESS AND INFLAMMATION BIOMARKERS) DETERMINANTS OF MENTAL HEALTH AMONG HISPANIC CANCER PATIENTS AND SURVIVORS. THIS TRANSFORMATION WILL BE ACHIEVED BY SIMULTANEOUSLY INTEGRATING GRASSROOTS (COMMUNITY LEADERS) AND TOP-DOWN (INSTITUTIONAL) RESOURCES TO INCREASE ACCESS TO SPECIALIZED PSYCHO-ONCOLOGY MENTAL HEALTH CARE SERVICES AND PSYCHOLOGICAL DISTRESS SCREENING WHILE ERADICATING MENTAL HEALTH STIGMA. FIRST, THE TEAM WILL TRAIN LAY COMMUNITY LEADERS TO BECOME COMMUNITY HEALTH WORKERS ADDRESSING PSYCHO-ONCOLOGY MENTAL HEALTH PREVENTION EFFORTS. SECOND, THE INVESTIGATORS, ALONG WITH COMMUNITY STAKEHOLDERS, WILL PACKAGE THE PROPOSED MULTILEVEL COMMUNITY-BASED INTERVENTION BY INTEGRATING AND ADAPTING A SUITE OF INDIVIDUAL/COMMUNITY INTERVENTIONS AND SERVICE INITIATIVES PREVIOUSLY DEVELOPED AND IMPLEMENTED BY MEMBERS OF THE RESEARCH TEAM AND PROVEN TO POSITIVELY IMPACT PUERTO RICAN HISPANIC CANCER PATIENTS AND SURVIVORS’ PSYCHOSOCIAL AND MENTAL HEALTH WELLBEING. AT THE COMMUNITY LEVEL, THE TEAM WILL FIRST TRAIN LAY COMMUNITY LEADERS TO BECOME COMMUNITY MENTAL HEALTH WORKERS THROUGH THE PHSU-RCMI COMMUNITY TRAINING INSTITUTE FOR HEALTH DISPARITIES. AT THE INTERPERSONAL LEVEL, THE COMMUNITY-BASED INTERVENTION WILL INTEGRATE FAMILY-COMMUNICATIONS SKILLS TO IMPACT HISPANIC CANCER PATIENTS' AND SURVIVOR FAMILY CAREGIVERS’ SUPPORT QUALITY. AT THE INDIVIDUAL LEVEL, THE INTERVENTION WILL IMPACT ALL PHASES OF THE MENTAL HEALTH PREVENTION CONTINUUM TO PREVENT AND ADDRESS PSYCHOLOGICAL DISTRESS RESULTING FROM CANCER AND ITS TREATMENT. AT THE BIOLOGICAL LEVEL, INVESTIGATORS WILL ASSESS THE EFFECT OF THE COMMUNITY INTERVENTION ON PSYCHOLOGICAL STRESS BIOMARKERS (CORTISOL AND CATECHOLAMINE METABOLITES) AND INFLAMMATION MARKERS (CYTOKINES AND CHEMOKINES) RELATED TO CHRONIC STRESS AND CANCER HEALTH OUTCOMES. THE TEAM ANTICIPATES THIS PROJECT WILL PUSH A TRANSFORMATIVE POPULATION-LEVEL IMPACT THROUGH A MULTILEVEL APPROACH THAT EMPOWERS COMMUNITIES TO UNDERSTAND AND ADDRESS MENTAL HEALTH AMONG INDIVIDUALS.

MBRS SCORE PROGRAM AT THE PONCE SCHOOL OF MEDICINE

TARGETING CENTROSOME?MITOTIC KINASES AS A NOVEL THERAPEUTIC APPROACH AGAINST BREAST CANCERS IN HISPANIC/LATINAS. - NON-HISPANIC BLACK (NHB) AND HISPANIC/LATINO (H/L) WOMEN IN THE UNITED STATES (US) HAVE HIGHER PROBABILITIES OF BREAST CANCER-RELATED DEATH THAN NON-HISPANIC WHITE (NHW) WOMEN. H/L WOMEN FROM THE CARIBBEAN (C-H/L, PUERTO RICAN, CUBAN AND DOMINICAN) AND BLACK H/L ARE AT AN EVEN HIGHER RISK OF DEATH THAN H/L FROM OTHER REGIONS AND WHITE H/L. THIS HIGHER RISK IS IN PART DUE TO NHB AND C-H/L WITH BREAST CANCERS BEING MORE LIKELY TO BE DETECTED AT YOUNGER AGES, WITH TUMORS OF HIGHER STAGES AND GRADES, AND WITH TRIPLE-NEGATIVE BREAST CANCERS (ER-PR- AND HER2- OR TNBC). AFRICAN ANCESTRY COMBINED WITH LESS OF THE PROTECTIVE EUROPEAN GENOME GREATLY INFLUENCES THESE RISK FACTORS IN NHB AND C-H/L WOMEN (ON AVERAGE HAVING 79% AND 27% AFRICAN GENOMIC CONTRIBUTION, RESPECTIVELY). CENTROSOME AMPLIFICATION-DRIVEN MITOTIC DYSFUNCTION LEADING TO CHROMOSOME INSTABILITY (CIN) AND ANEUPLOIDY MAY ALSO CONTRIBUTE TO METASTASIS AND POOR CLINICAL OUTCOMES OF THESE TNBC PATIENTS. THE CO-PIS PUBLISHED THAT THE CENTROSOME/MITOTIC KINASES TTK, NEK2, AND TBK1 GENERATE CA/CIN AND THAT TTK AND NEK2 DRIVE THE EPITHELIAL TO MESENCHYMAL TRANSITION (EMT). PRELIMINARY DATA INDICATES THAT TTK, NEK2, AND TBK1 MRNAS ARE DYSREGULATED IN NHB AND TNBCS, AND ARE OVEREXPRESSED IN BREAST TUMORS FROM C-H/L. ALSO, BY USING A NOVEL NCI-BMAP3 REGION BREAST CANCER TISSUE MICROARRAY (TMA) CONTAINING SAMPLES FROM NHW, NHB, AND C-H/L WOMEN, THE CO-PIS FOUND THAT TTK AND PTBK1 ARE OVEREXPRESSED IN TNBC AND TTK CORRELATES WITH EMT IN TNBC. INACTIVATING TTK OR TBK1 RESTORED RB IN TNBC CELLS, SUGGESTING IT CAN RESTORE PALBOCICLIB RESPONSES. CO-INACTIVATING TTK AND TBK1 IN TNBC CELLS REDUCED THE LEVELS OF CENTROSOME/MITOTIC REGULATORS AND EMT MARKERS, AND CO-INACTIVATING TTK/TBK1 OR TTK/NEK2 SIGNIFICANTLY REDUCED THE MIGRATION AND INVASION OF TNBC. THE STUDY TEAM HYPOTHESIZES THAT TTK, NEK2, AND TBK1 DYSREGULATION IN C-H/L AND NHB WOMEN WITH BREAST CANCER (BC) IS DICTATED BY AFRICAN ANCESTRY AND CONTRIBUTES TO THEIR POOR SURVIVAL OUTCOMES BY DRIVING CANCER CELL SURVIVAL AND EARLY METASTASIS. TO TEST THIS HYPOTHESIS, THE TEAM PROPOSES THE FOLLOWING SPECIFIC AIMS: (1) INVESTIGATING SIGNALING PATHWAYS LINKING MITOTIC KINASES TO EARLY METASTASIS AND POOR PROGNOSIS OF NON-HISPANIC BLACK (NHB), CARIBBEAN HISPANIC/LATINO (C-H/L), AND HISPANIC/LATINO (H/L) WOMEN WITH BREAST CANCER. THE TEAM WILL DETERMINE IF RNA EXPRESSION SIGNATURES AND COPY NUMBER VARIATIONS CORRELATE WITH THE EXPRESSION OF MITOTIC KINASES WITH EMT MARKERS, AND SURVIVAL OUTCOMES, USING RNA AND DNA SEQ DONE BY THE ORIEN CONSORTIUM AND A NOVEL TMA DEVELOPED BY THE PUERTO RICO BIOBANK. (2) TO ADDRESS HOW CO-INACTIVATION OF MITOTIC KINASES SUPPRESSES THE MESENCHYMAL STATE, METASTASIS, AND RESTORES PALBOCICLIB RESPONSES IN TNBC CELLS. THIS WILL BE ADDRESSED BY SINGLE AND COMBINATORIAL INHIBITION OF TTK, NEK2, AND TBK1 IN PRIMARY CELL LINES AND PDX MODELS OF TNBC FROM NHB AND H/L WOMEN WITH BREAST CANCER. RESULTS FROM THE PROPOSED EXPERIMENTS WILL HELP REDUCE ETHNIC/RACIAL BREAST CANCER DISPARITIES BY IDENTIFYING ACTIONABLE TARGETS (TTK, NEK2, TBK1, AND OTHER NOVEL KINASES FOUND IN AIM 1) AGAINST THE AGGRESSIVE GROWTH AND EARLY METASTATIC PROGRESSION IN NHB AND H/L WOMEN WITH TNBC.

GRADUATE PSYCHOLOGY EDUCATION PROGRAMS

POST-HURRICANE CANCER CARE: PATIENT NEEDS AFTER HURRICANE MARIA

G-RISE AT PONCE HEALTH SCIENCES UNIVERSITY - G-RISE AT PONCE HEALTH SCIENCES UNIVERSITY (PHSU G-RISE): THE OVERALL GOALS OF THE PHSU G-RISE PROGRAM ARE TO INCREASE THE COMPETITIVENESS OF UNDERREPRESENTED HISPANIC STUDENTS GRADUATING FROM THE BIOMEDICAL SCIENCES PHD PROGRAM AT PHSU IN PUERTO RICO AND TO INCREASE THE NUMBER OF HIGHLY QUALIFIED UNDERREPRESENTED STUDENTS WHO ADVANCE TO POSTDOCTORAL POSITIONS AND DIVERSE RESEARCH-RELATED CAREERS. TO ACHIEVE THESE GOALS, WE WILL BUILD UPON THE VERY SUCCESSFUL TRAINING PROGRAM CREATED UNDER THE PREVIOUS R25-RISE FUNDING MECHANISM WHICH HAD A POSITIVE IMPACT ON THE TRAINING OF OUR PHD STUDENTS AND ON THE ENTIRE PHSU COMMUNITY. UNDER THE PRIOR R25-RISE PROGRAM THE PHD COMPLETION RATE INCREASED FROM 73% TO 90% OF R25-RISE TRAINEES, THE AVERAGE TIME TO GRADUATION DECREASED FROM 6.2 TO 5.6 YEARS, AND 64% OF R25-RISE TRAINEES CONTINUED WITH POSTDOCTORAL TRAINING AFTER GRADUATING. OF THE 56 R25-RISE TRAINEES SUPPORTED 21 OBTAINED INDEPENDENT FELLOWSHIPS, 31 ALREADY GRADUATED WITH A PHD AND 8 HAVE SECURED FACULTY POSITIONS. THE PROPOSED PHSU G-RISE APPLICATION WILL BUILD UPON THOSE SUCCESSES AND ADAPT TO SEVERAL IMPORTANT LESSONS LEARNED. IT WILL PROVIDE THE ORGANIZATIONAL STRUCTURE AND EXTENSIVE MENTORING NECESSARY TO ENSURE TRAINEES HAVE A SENSE OF BELONGING AND SCIENTIFIC IDENTITY WHILE EMPOWERING THEM TO PREPARE FOR AND OVERCOME OBSTACLES IN THEIR SCIENTIFIC CAREERS. THE PROGRAM PROPOSES TO ACCOMPLISH THESE GOALS THROUGH ENHANCEMENT OF THE ACADEMIC, RESEARCH, PERSONAL, AND PROFESSIONAL COMPETENCE OF OUR UNDERREPRESENTED MINORITY STUDENTS TO BETTER PREPARE THEM FOR DIVERSE CAREERS IN THE BIOMEDICAL SCIENCES. THE SPECIFIC MEASURABLE OBJECTIVES OF THE PHSU G-RISE PROGRAM ARE TO PROVIDE: (1) PROFESSIONAL, OPERATIONAL, AND TECHNICAL RESEARCH SKILLS TRAINING FOR PHSU G-RISE TRAINEES; (2) COMMUNICATION SKILLS TRAINING FOR PHSU G-RISE TRAINEES; (3) TEAM BUILDING/NETWORKING OPPORTUNITIES FOR PHSU G-RISE TRAINEES; AND (4) INCREASE THE PHD COMPLETION RATE WHILE REDUCING TIME-TO-DEGREE. EACH OF THESE OBJECTIVES WILL BE PURSUED WITH AN EXPERIENCE-BASED BALANCE OF CONTINUING ACTIVITIES THAT WERE HIGHLY EFFECTIVE AS WELL AS A STRATEGIC SET OF NEW TRAINING COMPONENTS THAT WERE DEVELOPED TO ADDRESS THE EMERGING NEEDS OF OUR TRAINEES. THE PHSU G-RISE PROGRAM WILL WORK IN CONCERT WITH THE EXISTING PHSU-MOFFITT CANCER CENTER PARTNERSHIP AND RCMI PROGRAMS TO SIGNIFICANTLY IMPACT THE OVERALL RESEARCH PROGRAM BY PROVIDING A BETTER TRAINED STUDENT WORKFORCE TO CONDUCT THE FUNDED RESEARCH PROJECTS AND PROVIDE THE MOMENTUM TO CREATE NEW RESEARCH INITIATIVES.

INHERITED GENETIC FACTORS IN BREAST CANCER PREDISPOSITION AND TUMOR PRESENTATION

FACTORS ASSOCIATED WITH VARIABILITY IN DNA REPAIR CAPACITY IN THEIR EFFECT ON BRE

SNP ANALYSIS OF ENDOMETRIOSIS CANDIDATE GENES

PSM MOFFITT CANCER CENTER PARTNERSHIP

INHERITED GENETIC FACTORS IN BREAST CANCER PREDISPOSITION AND TUMOR PRESENTATION

OPIOID WORKFORCE EXPANSION PROGRAM- PROFESSIONAL

REDUCTION OF LETHAL PROSTATE CANCER DISPARITIES IN UNDERSERVED HISPANIC/LATINO POPULATIONS

MOLECULAR EPIDEMIOLOGY STUDIES ON THE ROLE OF DNA REPAIR BREAST CANCER

ORIGIN OF SEMINAL VIRUS IN HUMAN IMMUNODEFICIENCY VIRUS INFECTION

CK25-182 - PUERTO RICO ENHANCED SURVEILLANCE AND CONTROL OF ENDEMIC AND EMERGING ARBOVIRUSES

REDUCING SERIOUS MENTAL ILLNESS AND SUICIDE STIGMA AMONG MEDICAL STUDENTS.

THE ENTERIC GLIA AS A POSSIBLE TARGET FOR SYMPTOM RELIEF IN ENDOMETRIOSIS - ENDOMETRIOSIS, A CHRONIC PAINFUL GYNECOLOGICAL DISORDER DEFINED AS THE PRESENCE OF ENDOMETRIAL GLANDS AND STROMA OUTSIDE THE ENDOMETRIAL CAVITY, IS CHARACTERIZED BY PERITONEAL INFLAMMATION, FIBROSIS, ADHESIONS, AND OVARIAN CYSTS. WOMEN WITH ENDOMETRIOSIS OFTEN PRESENT GASTROINTESTINAL SYMPTOMS INDEPENDENT OF LESION LOCALIZATION. ENTERIC GLIAL CELLS (EGCS) ARE ASTROCYTE-LIKE CELLS THAT ARE VITAL TO THE ENTERIC NERVOUS SYSTEM AND PLAY A ROLE IN GUT DISEASES. THE ROLE OF INTESTINAL GLIA IN ENDOMETRIOSIS IS UNKNOWN; HOWEVER, A BIDIRECTIONAL RELATIONSHIP BETWEEN THE EGC AND IMMUNE CELLS IN THE MODULATION OF THE INFLAMMATORY RESPONSE AND PAIN SENSITIZATION IS POSTULATED. ENTERIC GLIA CAN PRODUCE AN ENDOGENOUS LIGAND FOR PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA (PPAR) WITH ANTI-INFLAMMATORY ACTIVITY. PPAR AGONISTS IN ENDOMETRIOSIS ANIMAL MODELS REDUCE VESICLE SIZE. THE STUDY TEAM’S PREVIOUS WORK HAS DEMONSTRATED THAT EXERCISE CAN INCREASE EXPRESSION AND ACTIVITY OF PPAR, WHILE REDUCING VESICLE SIZE AND DEVELOPMENT. THE MAIN OBJECTIVE IS TO EXAMINE THE ROLE OF EGC IN THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS WITH THE LONG-TERM GOAL OF FINDING NEW THERAPEUTIC TARGETS. THE STUDY TEAM HYPOTHESIZES THAT ENDOMETRIOSIS-INDUCED IMMUNE ACTIVATION IS REGULATED BY ECG WHICH PROMOTES AND MAINTAINS CHRONIC INFLAMMATION, AND THAT THIS CAN BE REVERSED BY NON-PHARMACOLOGICAL COMPLEMENTARY INTERVENTIONS. AIM 1 WILL DETERMINE HOW ENDOMETRIOSIS IMPACTS THE ENTERIC GLIA AND HOW THIS CORRELATES WITH PAIN. AIM 2 WILL ELUCIDATE WHETHER THE BENEFICIAL EFFECTS OF INTERVENTIONS, SUCH AS EXERCISE AND ENVIRONMENTAL ENRICHMENT, ARE MEDIATED BY PPAR. RATIONALE: COMPLEMENTARY INTERVENTIONS WILL IMPACT THE ENTERIC GLIA VIA PARASYMPATHETIC ACTIVATION, SHIFTING IT FROM THE ENDOMETRIOSIS-INDUCED, PRO-INFLAMMATORY PHENOTYPE TO AN ANTI-INFLAMMATORY ONE, DECREASING PROINFLAMMATORY CYTOKINE RELEASE AND OXIDATIVE STRESS. SUCCESSFUL OUTCOMES COULD EXPLAIN CHRONIC PELVIC INFLAMMATION AND GASTROINTESTINAL SYMPTOMS AND PROVIDE A NOVEL TARGET. THIS STUDY WILL CONTRIBUTE TO THE GOALS OF THE SURE PROGRAM BY SUSTAINING THE RESEARCH EXCELLENCE OF THE PI AND STRENGTHENING THE INSTITUTIONAL RESEARCH ENVIRONMENT. THIS STUDY WILL PROVIDE GRADUATE AND UNDERGRADUATE STUDENTS AT VARIOUS LEVELS WITH OPPORTUNITIES IN MULTIDISCIPLINARY RESEARCH AREAS TO ENCOURAGE THEIR CONTINUED INVOLVEMENT IN BIOMEDICAL SCIENCES RESEARCH AND STIMULATE THEIR INTEREST IN NOVEL INTEGRATIVE INTERVENTIONS.

EVALUATION OF DENGUE EPIDEMIOLOGY, OUTCOMES AND PREVENTION IN SENTINEL SURVEILLAN

BEHAVIORAL HEALTH WORKFORCE EDUCATION AND TRAINING (BHWET) PROGRAM

BEHAVIORAL HEALTH WORKFORCE EDUCATION AND TRAINING (BHWET) PROGRAM

STRESS: POTENTIAL IMPACT ON AN ANIMAL MODEL OF ENDOMETRIOSIS

ENRICHED ENVIRONMENTS: A MULTI-LEVEL INTEGRATIVE MEDICINE INTERVENTION FOR ENDOMETRIOSIS

ADRENERGIC SIGNALING INHIBITION TO ENHANCE THE IMMUNOGENICITY OF THE OVARIAN TUMOR MICROENVIRONMENT PRIOR TO PD-1 CHECKPOINT THERAPY

FEAR MODULATION OF IL EXCITABILITY

SUPPRESSION OF MUTAGENESIS WITH ANTIOXIDANTS

PHYSICAL ACTIVITY AS A THERAPEUTIC INTERVENTION IN ENDOMETRIOSIS

FKBP5 MODULATION OF PREFRONTAL FUNCTION.

ASTROCYTIC HIV NEF CAUSES LEARNING IMPAIRMENT VIA INFLAMMATION AND TGF SIGNALING

DEFINING BREAST CANCER RISK: THE ROLE OF GENETIC VARIATIONS IN DNA REPAIR GENES

APPLYING IN VITRO RECORDING TECHNIQUES TO EXTINCTION OF CONDITIONED FEAR

THE ROLE OF TRANSGENDER EMBODIMENT ON BREAST AND UTERINE CERVIX CANCER SCREENING

CAREGIVERS-PATIENTS SUPPORT TO LATINX COPING WITH ADVANCED-CANCER - PROJECT SUMMARY THE GOAL OF THIS K08 IS TO PREPARE THE PI, TO RECEIVE HANDS-ON EXPERIENCE IN IMPLEMENTATION AND DISSEMINATION, DESIGNING AND LEADING RANDOMIZED CONTROLLED TRIALS (RCTS) IN PALLIATIVE CARE, AND IMPROVE GRANT WRITING SKILLS TO BECOME AN INDEPENDENT R01-FUNDED INVESTIGATOR. HISPANIC/LATINX (H/L) COMMUNITIES EXPERIENCE DISPARATE GENERAL HEALTH OUTCOMES AND ARE MORE LIKELY TO BE DIAGNOSED WITH ADVANCED CANCER WHEN COMPARED TO NON-H/L POPULATIONS. H/L PATIENTS EXPERIENCING ADVANCED CANCER AND THEIR CAREGIVERS ARE AT AN INCREASED RISK FOR UNMET PSYCHOSOCIAL NEEDS; THIS K08 WILL ALLOW THE PI TO FOCUS ON THIS IMPORTANT GAP IN MINORITY HEALTH CARE. THE RESEARCH GOAL OF THIS PROPOSAL IS TO REFINE AND PILOT AN INTERVENTION TITLED: CAREGIVERS PATIENTS SUPPORT TO LATINX COPING WITH ADVANCED CANCER (CASA), A FIVE-SESSION, 60-MINUTE EACH TELEHEALTH SERIES FOR PATIENT-CAREGIVER DYADS. THE LONG-TERM TRAINING GOAL OF THIS APPLICATION IS TO ENABLE THE APPLICANT (PI) TO BECOME AN INDEPENDENT INVESTIGATOR AS A CULTURAL ADAPTATION EXPERT ON PSYCHOSOCIAL INTERVENTIONS IN HEALTH DISPARITY RESEARCH. THE RATIONALE FOR THIS PROJECT IS THAT IT WILL LAY THE GROUNDWORK FOR A RANDOMIZED CONTROL TRIAL (RCT) TESTING THE EFFICACY OF CASA. IT WILL ALSO ASSESS THE IMPLEMENTATION OF AN INNOVATIVE METHOD TO DELIVER THE CASA INTERVENTION. THIS STUDY AIMS TO USE THE COLLABORATIVE INTERVENTION PLANNING FRAMEWORK AND ORBIT MODEL TO MODIFY AND ASSESS THE FEASIBILITY AND PRELIMINARY EFFECT OF THE CASA INTERVENTION. THE OVERALL IMPACT OF THIS STUDY IS TO IMPROVE ACCESS TO PSYCHOSOCIAL, CULTURALLY ADAPTED INTERVENTIONS AMONG H/L PATIENTS AND CAREGIVERS COPING WITH ADVANCED CANCER. THE SPECIFIC AIMS ARE AS FOLLOWS: AIM 1. USE A COLLABORATIVE INTERVENTION PLANNING FRAMEWORK WITH PROVIDERS AND COMMUNITY STAKEHOLDERS TO REFINE STUDY PROCEDURES PRIOR TO THE IMPLEMENTATION OF A PILOT RANDOMIZED CONTROLLED TRIAL. AIM 2: TO TRAIN COMMUNITY MEMBERS AS PATIENT RECRUITERS AND CLINICAL PSYCHOLOGY DOCTORAL STUDENTS AS INTERVENTIONISTS OF THE CASA INTERVENTION. AIM 3: TO IMPLEMENT A PILOT RANDOMIZED CONTROLLED TRIAL TO EVALUATE THE FEASIBILITY, ACCEPTABILITY, AND POTENTIAL EFFICACY OF THE CASA INTERVENTION WITH HISPANIC/LATINX DYADS COPING WITH CANCER.

SYNERGISTIC NEUROTOXICITY OF SPEEDBALL AND HIV TOXINS

PREFRONTAL MODULATORS OF STRESS-INDUCED EXTINCTION IMPAIRMENT IN FEMALE RATS - PROJECT SUMMARY ABSTRACT: ALTHOUGH WOMEN HAVE TWICE THE INCIDENCE OF DEVELOPING POST-TRAUMATIC STRESS DISORDER (PTSD), THE IDENTIFIED NEUROBIOLOGICAL MECHANISMS THAT INCREASE THE SUSCEPTIBILITY OF FEMALE ANIMALS TO STRESS-INDUCED FEAR EXTINCTION IMPAIRMENT ARE LIMITED. ABUNDANT STUDIES SHOW THAT THE INFRALIMBIC CORTEX (IL) IS CRITICAL FOR PROPER FEAR EXTINCTION RECALL. TO BEGIN TO ADDRESS THIS GAP, ADULT FEMALE RATS WERE EXPOSED TO SINGLE PROLONGED STRESS (SPS) AND THE ANIMALS THAT SHOWED IMPAIRED EXTINCTION RECALL WERE IDENTIFIED. THE RATS THAT WERE SUSCEPTIBLE TO STRESS-INDUCED EXTINCTION IMPAIRMENT EXHIBITED DISTINCT PROTEOMIC CHANGES IN IL COMPARED TO RATS THAT SHOWED GOOD EXTINCTION RECALL. ALTHOUGH MANY OF THE IDENTIFIED PROTEINS, INCLUDING NEUROGRANIN AND MICROTUBULE ASSOCIATED PROTEIN TAU (MAPT), ARE INVOLVED IN NEURONAL FUNCTION AND SYNAPTIC PLASTICITY, THEIR ROLE IN STRESS-INDUCED EXTINCTION IMPAIRMENT IS UNKNOWN. IN THIS PROPOSAL, WE WILL BUILD ON OUR PRELIMINARY FINDINGS TO FURTHER VALIDATE THE PROTEOMIC FINDINGS AND EXAMINE THE ROLE OF IL NEUROGRANIN AND MAPT IN SUSCEPTIBILITY TO IMPAIRED EXTINCTION RECALL AFTER EXPOSURE TO TRAUMATIC STRESS IN FEMALE RATS. THE GOAL OF THIS PROPOSAL IS TO COMPARE, THROUGH ROBUST EXPERIMENTATION, THE MECHANISMS BY WHICH PREFRONTAL NEUROGRANIN AND MAPT EXPRESSION CONTRIBUTE TO IMPAIRED FEAR EXTINCTION AFTER TRAUMATIC STRESS IN FEMALE RATS AS AN IMPORTANT STEP TOWARD UNDERSTANDING PREFRONTAL MECHANISMS THAT ALTER SUSCEPTIBILITY TO IMPAIRED EXTINCTION AFTER EXPOSURE TO TRAUMATIC STRESS IN FEMALES. OUR CENTRAL HYPOTHESIS IS THAT EXPOSURE TO TRAUMATIC STRESS ALTERS NEUROGRANIN OR MAPT EXPRESSION IN THE IL OF SUSCEPTIBLE RATS LEADING TO REDUCED EXCITABILITY OF IL NEURONS AND IMPAIRED FEAR EXTINCTION RECALL IN FEMALES. TO ADDRESS THIS HYPOTHESIS, THE TEAM WILL EXAMINE THE RELATIONSHIP BETWEEN IL NEUROGRANIN AND MAPT EXPRESSION AND IMPAIRED FEAR EXTINCTION AFTER SPS EXPOSURE IN AIM 1. IN AIM 2, THEY WILL DETERMINE IF REDUCING THE EXPRESSION OF NEUROGRANIN OR MAPT IN IL ENHANCES FEAR EXTINCTION AND ALTERS IL NEURONAL EXCITABILITY. THE OVERALL IMPACT OF THESE AIMS WILL GREATLY INCREASE THE UNDERSTANDING OF THE MECHANISMS BY WHICH EXPOSURE TO TRAUMATIC STRESS CAN HINDER FEAR EXTINCTION AND HIGHLIGHT THE ROLE OF CHANGES IN NEUROGRANIN, MAPT, AND THE IL PROTEOME IN THIS PROCESS. THIS DATA WILL ENHANCE NIH’S MISSION TO IDENTIFY THE NEUROBIOLOGICAL BASIS FOR COMPLEX BEHAVIORAL RESPONSES TO TRAUMA AND POTENTIALLY LEAD TO NOVEL TREATMENTS.

PILOT STUDY TO PREVENT TRANSITION FROM OVERWEIGHT TO OBESITY AMONG YOUNG OVERWEIGHT COLLEGE STUDENTS IN PONCE, PUERTO RICO

THE ROLE OF LOX AND LOXL1 IN THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS

COMBINED ROLE OF HIV-1 TAT AND OPIOID IN NEUROPATHOGENESIS

MOLECLAR REGULATION OF HIV-1 NEF NEUROPATHOGENESIS BY TRANSFORMING GROWTH FACTOR BETA

THE EFFECTS OF STRESS ON THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS

THE ROLE OF RELIGION ON HIV/AIDS STIGMA MANIFESTATIONS AMONG PUERTO RICANS NURSES

HIPPOCAMPAL ROLE IN EXTINCTION INDUCED PREFRONTAL PLASTICITY

INTERACTION OF HIV-1 NEF AND GLUTAMATE HOMEOSTASIS IN THE NUCLEUS ACCUMBENS DURING COCAINE ADDICTION - SUMMARY THE RECREATIONAL USE OF COCAINE CAN LEAD TO AN ADDICTION THAT INCREASES THE RISK OF ACQUIRING THE HUMAN IMMUNODEFICIENCY VIRUS (HIV) THROUGH HIGH-RISK BEHAVIORS SUCH AS AN INCREASE IN UNPROTECTED SEXUAL ACTIVITY, AND A MORE RAPID PROGRESSION TO AIDS. APPROXIMATELY 33% OF THE 1.2 MILLION PEOPLE IN THE UNITED STATES (US) LIVING WITH HIV USE ILLICIT SUBSTANCES, AND APPROXIMATELY 1 IN 10 NEW HIV DIAGNOSES ARE ATTRIBUTED TO INJECTION DRUG USERS EVERY YEAR. PEOPLE LIVING WITH HIV WHO TAKE COMBINATION ANTIRETROVIRAL THERAPY (CART) AND MAINTAIN VIRAL LOADS BELOW DETECTABLE LEVELS LIVE A NEAR-NORMAL LIFESPAN. HOWEVER, DESPITE THE ADVANCES IN EFFICACIOUS MEDICATION, THERE ARE STILL NO MEDICATIONS THAT PREVENT THE VIRAL INVASION TO THE CENTRAL NERVOUS SYSTEM (CNS) SOLIDIFYING THAT THE RISK OF DEVELOPING HIV-1 ASSOCIATED NEUROCOGNITIVE DISORDERS (HAND) HAS NOT DECREASED. THEREFORE, TO PROTECT CHRONICALLY INFECTED PEOPLE FROM THE RAVAGES OF HIV-1 INFECTION IN THE BRAIN, PARTICULARLY WHEN COMBINED WITH SUBSTANCE USE DISORDER (SUD), IT IS NECESSARY TO ADVANCE THE UNDERSTANDING OF THE INTERSECTION OF HIV-1 AND ADDICTION TO IDENTIFY NOVEL THERAPEUTIC TARGETS. BOTH COCAINE AND HIV PROTEINS CONTRIBUTE TO NEURONAL DAMAGE DURING DISEASE PROGRESSION THROUGH DYSREGULATION OF GLUTAMATE HOMEOSTASIS IN THE BRAIN. IT HAS BEEN DOCUMENTED THAT AS HIGH AS 19% OF ASTROCYTES IN THE BRAINS OF PATIENTS WITH SEVERE HAND ARE INFECTED WITH HIV-1. NEF IS ONE OF THE EARLIEST EXPRESSED VIRAL PROTEINS IN APPROXIMATELY 1% OF INFECTED ASTROCYTES. EVEN WITHOUT MEASURABLE VIRAL REPLICATION, NEF COULD CONTRIBUTE TO CONTINUED NEURONAL DEGENERATION EVEN IN PATIENTS ON CART. EXTRACELLULAR GLUTAMATE IS NORMALLY TAKEN UP BY ASTROCYTES THROUGH A GLUTAMATE TRANSPORTER (GLT-1) AND EXCHANGED FOR CYSTEINE THROUGH THE CYSTINE/GLUTAMATE EXCHANGER. SS -CATENIN, A DUAL FUNCTION PROTEIN, REGULATES THE EXPRESSION OF GLUTAMATE TRANSPORTERS PREVENTING NEUROTOXICITY CAUSED BY EXCESS NMDA RECEPTOR ACTIVATION IN NEURONS. HOWEVER, COCAINE DOWNREGULATES GLT-1 AND THE CYSTINE/GLUTAMATE EXCHANGER. DURING WITHDRAWAL OF COCAINE EXPOSURE, THE AMPA/NMDA RATIO INCREASES IN THE NUCLEUS ACCUMBENS (NAC). THE NAC IS AN IMPORTANT BRAIN STRUCTURE INVOLVED IN THE DEVELOPMENT OF COCAINE ADDICTION. THE OVERALL OBJECTIVE IS TO STUDY THE INTERACTION BETWEEN HIV-1 NEF AND COCAINE RELATED TO GLUTAMATE HOMEOSTASIS AND DRUG-SEEKING BEHAVIOR. THE CENTRAL HYPOTHESIS IS THAT COMBINED COCAINE EXPOSURE AND ASTROCYTIC NEF EXPRESSION WILL EXACERBATE GLUTAMATE EXCITATION INDUCING NEUROPHYSIOLOGICAL CHANGES THAT STRENGTHEN SYNAPTIC TRANSMISSION AND REINFORCE THE COCAINE-SEEKING BEHAVIOR. TO ADDRESS THIS HYPOTHESIS, THE TEAM WILL DEVELOP THE FOLLOWING TWO SPECIFIC AIMS. AIM 1: DETERMINE THE IMPACT OF HIV-1 NEF AND COCAINE ON GLUTAMATERGIC NEUROTRANSMISSION. AIM 2: DETERMINE THE IMPACT OF HIV-1 NEF ON COCAINE-SEEKING BEHAVIOR IN RATS. WITH THE COMBINATION OF IN VIVO SELF-ADMINISTRATION, ELECTROPHYSIOLOGY, AND MOLECULAR STUDIES USING BRAIN TISSUE, THE TEAM WILL ELUCIDATE THE ROLE OF HIV-1 NEF ON COCAINE-SEEKING AND CONSUMPTION ESSENTIAL TO DEVELOPING NEW THERAPIES TO TREAT PEOPLE WITH HIV AND SUD.

DISSECTING THE ROLE OF AMYGDALO-STRIATAL CIRCUITS IN THE REGULATION OF STRESS AND COCAINE COMORBIDITY IN RATS - SUMMARY/ABSTRACT GENERALLY, POST TRAUMATIC STRESS DISORDER (PTSD) AND SUBSTANCE USE DISORDER (SUD) ARE EXAMINED SEPERATELY IN PRECLINICAL STUDIES, ALTHOUGH THEY CAN OCCUR SIMULTANEOUSLY IN PATIENTS. THEREFORE, IT IS NECESSARY TO OBSERVE THESE TWO DISORDERS CLOSELY TOGETHER TO BETTER UNDERSTAND THE MECHANISMS THAT UNDERLIE THIS COMORBIDITY AND THE EFFECTS ON THE NEUROPHYSIOLOGY. ONE OF THE MAIN PROBLEMS IN ADDICTION IS THE HIGH RELAPSE RATE WHEN THE PATIENT IS EXPOSED TO ENVIRONMENTAL CUES OR OTHER FACTORS THAT CAN TRIGGER MEMORIES ASSOCIATED WITH ADDICTION. PRESENTLY, ONE OF THE FACTORS ASSOCIATED WITH A HIGH RELAPSE STATE IS STRESS. EXPOSURE TO A STRESSFUL OR TRAUMATIC EVENTS CAN LEAD TO THE DEVELOPMENT OF PTSD. MOREOVER, PTSD PATIENTS EXHIBIT HIGHER RATES OF SUD. TWO IMPORTANT BRAIN STRUCTURES INVOLVED IN THE DEVELOPMENT OF THESE DISORDERS ARE THE BASOLATERAL AMYGDALA (BLA) AND THE NUCLEUS ACCUMBENS ( NAC). THE BLA CONCERNS THE DEVELOPMENT OF FEAR MEMORIES AND PTSD, WHILE THE NAC IS PART OF THE REWARD CIRCUITRY AND PLAYS AN IMPORTANT ROLE IN THE PROGRESSION OF SUD. THIS NAC IS SUB-DIVIDED IN TWO MAIN REGIONS: THE CORE AND THE SHELL. STUDIES HAVE SHOWN THAT THE CORE DRIVES COCAINE-SEEKING BEHAVIOR WHILE THE SHELL MODULATES EXTINCTION, DECREASING COCAINE-SEEKING BEHAVIOR. IMPORTANTLY, THE INHIBITION OF BLA-NAC SYNAPSES LEADS TO A DECREASE IN OVERALL DRUG SEEKING BEHAVIOR, BUT THE EFFECTS OF CHRONIC STRESS ON THESE SYNAPSES ARE STILL UNKNOWN. THE OBJECTIVE IS TO DISSECT THE MECHANISM BY WHICH BLA MODULATES THE NAC IN A COMBINED ANIMAL MODEL OF PTSD AND SUD. THIS WILL HELP TO BETTER UNDERSTAND HOW ONE DISORDER INFLUENCES THE OTHER. THE CENTRAL HYPOTHESIS IS THAT CHRONIC STRESS WILL INDUCE NEUROPHYSIOLOGICAL CHANGES TO THE BLA-NAC CORE AND SHELL SYNAPSES, WHICH WILL CORRELATE WITH INCREASED COCAINE-SEEKING BEHAVIORS. TO ADDRESS THIS, THE TEAM PROPOSED THE FOLLOWING AIMS: AIM 1: DETERMINE THE EFFECTS OF CHRONIC STRESS ON THE NEUROPHYSIOLOGY OF SYNAPSES OF THE BASOLATERAL AMYGDALA AND NUCLEUS ACCUMBENS PRIOR TO COCAINE EXPOSURE. AIM 2: DETERMINE THE EFFECTS OF OPTICAL ACTIVATION OF BLA-NAC SHELL AND CORE SYNAPSES INDEPENDENTLY ON COCAINE-SEEKING BEHAVIOR IN RATS WITH CHRONIC STRESS PRIOR TO COCAINE EXPOSURE. THE OVERALL GOAL IS TO UNDERSTAND HOW THE CHRONIC STRESS INDUCED NEUROPHYSIOLOGICAL CHANGES IN A RODENT CORRELATE WITH COCAINE SEEKING-BEHAVIOR CHANGES PRIOR TO COCAINE EXPOSURE. THE LONG-TERM GOAL IS TO UNDERSTAND THE MECHANISMS AND ADAPTATIONS OF THE BRAIN CAUSED BY A TRAUMATIC EVENT THAT LEADS TO THE DEVELOPMENT OF PTSD AND THE SUSCEPTIBILITY OF ACQUIRING SUD.

ROLE OF IKBKE IN STRESS-INDUCED OVARIAN CANCER PROGRESSION

THE ROLE OF THE CXCR4/CXCL12 AXIS IN ENDOMETRIOSIS

ROLES OF E2F3 AND SGO1 IN THE EPITHELIAL-TO-MESENCHYMAL TRANSITION AND METASTASIS OF BREAST CANCER

ROLE OF INFRALIMBIC EPHB2 IN FEAR EXTINCTION

THE ROLE OF SEMINAL AMYLOID FIBRILS IN HIV-1 TRANSMISSION ON CERVICAL MUCOSA

MODULATION OF INTESTINAL INFLAMMATION IN COLITIS BY MANIPULATING DENDRITIC CELLS

MODULATION OF INTRINSIC EXCITABILITY IN MPFC NEURONS

TARGETING SP-NK1R-EGFR INTERACTIONS IN COLITIS ASSOCIATED DYSPLASIA

THE ROLE OF THE HISTONE EPIGENOME IN THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS

INFLUENCE OF FEAR CONDITIONING PRIOR TO COCAINE SELF-ADMINISTRATION ON COCAINE SEEKING IN ADULT RATS: ASSESSING THE ROLE OF THE FRONTOSTRIATAL CIRCUITS IN TRAUMA AND COCAINE USE CO-OCCURRENCE - PROJECT SUMMARY RESEARCH HAS SHOWN A HIGH PREVALENCE OF TRAUMA-RELATED DISORDERS AND SUBSTANCE USE DISORDER (SUD) CO- OCCURRENCE. HOWEVER, THE MECHANISMS BY WHICH A TRAUMATIC EVENT INCREASES THE VULNERABILITY TO SUD DEVELOPMENT AND RELAPSE ARE UNKNOWN. IT IS KNOWN THAT THE PRELIMBIC CORTEX (PL) AND NUCLEUS ACCUMBENS (NAC) CORE PLAY CRITICAL ROLES IN TRAUMA-RELATED DISORDERS AND SUD, BUT THE NEUROPHYSIOLOGICAL CHANGES CAUSED IN THESE STRUCTURES BY TRAUMA AND COCAINE EXPOSURE ARE NOT FULLY UNDERSTOOD. THIS PROPOSAL AIMS TO DISSECT THE MECHANISM BY WHICH A TRAUMATIC EXPERIENCE AND COCAINE EXPOSURE ALTER PL AND NAC CORE COMMUNICATION IN WAYS THAT MAY INCREASE VULNERABILITY TO COCAINE USE DISORDER DEVELOPMENT. THE HYPOTHESIS IS THAT A TRAUMATIC EVENT AND COCAINE EXPOSURE WILL CAUSE NEUROPHYSIOLOGICAL CHANGES IN PL-NAC CORE SYNAPSES, RESULTING IN INCREASED DRUG-SEEKING BEHAVIOR. TO TEST THE HYPOTHESIS, WE WILL ASSESS THE EFFECTS OF FEAR CONDITIONING (FC) AS A TRAUMATIC EVENT, AND COCAINE EXPOSURE ON COCAINE-SEEKING BEHAVIOR IN MALE AND FEMALE RATS. ALSO, WE WILL ANALYZE THE SYNAPTIC CHANGES OF THE PL-PROJECTING NEURONS TO THE NAC CORE, USING WHOLE CELL PATCH-CLAMP ELECTROPHYSIOLOGICAL RECORDINGS WITH OPTOGENETIC MANIPULATION (AIM 1), AS WELL AS THE INFLUENCE OF PL INACTIVATION ON COCAINE SEEKING (AIM 2) FROM COCAINE-EXPOSED RATS WITH OR WITHOUT FC. PRELIMINARY BEHAVIORAL DATA SHOW THAT FC PRIOR TO COCAINE EXPOSURE INCREASES CUE-PRIMED REINSTATEMENT AND COCAINE-PRIMED REINSTATEMENT IN MALE RATS, PROVIDING A SUITABLE BEHAVIORAL PARADIGM FOR INVESTIGATING THE NEUROPHYSIOLOGICAL CHANGES THAT OCCUR IN THIS COMORBIDITY. THE FINDINGS OF THE PROPOSED STUDY WILL PROVIDE INSIGHT INTO HOW PL MODULATES THE NAC CORE NEURONS IN THE PRESENCE OF A TRAUMATIC EXPERIENCE AND DRUG EXPOSURE, TO INFLUENCE DRUG-SEEKING BEHAVIOR.

THE ROLE OF FKBP5 IN ANXIETY LIKE BEHAVIORS

PLASTICITY OF THALAMIC INPUTS OF INHIBITORY NEURONS

MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

PILOT STUDY TO PREVENT TRANSITION FROM OVERWEIGHT TO OBESITY AMONG YOUNG OVERWEIGHT COLLEGE STUDENTS IN PONCE, PUERTO RICO

PILOT STUDY TO PREVENT TRANSITION FROM OVERWEIGHT TO OBESITY AMONG YOUNG OVERWEIGHT COLLEGE STUDENTS IN PONCE, PUERTO RICO