Loyola University

LOYOLA_CARES_INSTITUTIONAL

LOYOLA CARES

TCR GENE MODIFIED T CELLS FOR ADOPTIVE IMMUNOTHERAPY

STRUCTURAL DETERMINANTS OF CALCIUM PUMP REGULATION

INSTITUTIONAL PORTION OF HIGHER EDUCATION EMERGENCY RELIEF FUND FORMULA GRANTS

COLLABORATIVE INTEGRATION OF HCV MOLECULAR VIROLOGY AND MATHEMATICAL MODELING

LOYOLA UNIVERSITY MARYLAND CARES CERTIFICATION AGREEMENT 2

EMERGENCY FINANCIAL AID GRANTS TO STUDENTS UNDER THE CORONAVIRUS AID, RELIEF, AND ECONOMIC SECURITY (CARES) ACT

MECHANISMS OF VIRAL PROTEASES IN CORONAVIRUS REPLICATION AND PATHOGENESIS

LOYOLA UNIVERSITY MARYLAND CARES CERTIFICATION AGREEMENT

PARADOXICAL EFFECTS OF NF-KB IN ISCHEMIA; NOVEL POLYMERIC GENE SILENCING IN VIVO

IDO1 AND IMMUNOTOLERANCE IN GLIOBLASTOMA

PLUS LOYOLA CLINICAL CENTER

INVESTIGATING INTERFERON ANTAGONISTS IN DELAYING INNATE IMMUNE RESPONSES TO SARS-COV-2 - TITLE: INVESTIGATING INTERFERON ANTAGONISTS IN DELAYING INNATE IMMUNE RESPONSES TO SARS-COV-2 PI: SUSAN C. BAKER, PHD, LOYOLA UNIVERSITY CHICAGO STRITCH SCHOOL OF MEDICINE THE GOAL OF THIS PROPOSAL IS TO DETERMINE HOW VIRAL INTERFERON ANTAGONISTS FUNCTION IN THE REPLICATION AND PATHOGENESIS OF CORONAVIRUSES, PARTICULARLY DURING REPLICATION OF SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2). CORONAVIRUSES (COVS) ARE A DIVERSE FAMILY OF POSITIVE-SENSE RNA VIRUSES THAT INCLUDE PATHOGENIC STRAINS INFECTING HUMAN AND ANIMAL HOSTS. COVS HAVE REPEATEDLY JUMPED FROM ANIMAL RESERVOIRS INTO HUMAN CIRCULATION, CAUSING SEVERE DISEASE AND PANDEMICS, AS WE ARE CURRENTLY EXPERIENCING WITH SARS-COV-2. DEVELOPING APPROPRIATE PROTECTIVE MEASURES AGAINST EMERGING COVS, INCLUDING SARS-COV- 2, WILL DEPEND UPON GAINING AN UNDERSTANDING OF CORONAVIRUS-HOST INTERACTIONS. WE DISCOVERED THAT THE ENDORIBONUCLEASE (ENDOU), A HIGHLY CONSERVED COMPONENT OF THE COV REPLICASE COMPLEX, REDUCES DSRNA SPECIES RECOGNIZED BY HOST PATTERN RECOGNITION RECEPTOR MDA5, DELAYING THE INDUCTION OF INTERFERON. WE REPORTED THAT VIRUSES EXPRESSING AN INACTIVE FORM OF ENDOU REPLICATE AS EFFICIENTLY AS WILD TYPE VIRUS IN IFN NON- RESPONSIVE CELLS. IMPORTANTLY, REPLICATION OF ENDOU MUTANT COVS IN INTERFERON-RESPONSIVE CELLS ACTIVATE ROBUST IMMUNE RESPONSES, WHICH EXTINGUISHES VIRUS REPLICATION AND REDUCES PATHOGENESIS IN ANIMALS. RECENTLY, WE IDENTIFIED THE TARGET OF ENDOU ACTIVITY TO BE POLY-URIDINE CONTAINING NEGATIVE SENSE RNA, WHICH WE TERM PUN RNA. THIS REMOVAL OF THE PUN RNA DELAYS THE GENERATION OF DSRNA SPECIES THAT ARE RECOGNIZED BY HOST PATTERN RECOGNITION RECEPTOR MDA5. WE HYPOTHESIZE THAT ENDOU ACTIVITY CONTRIBUTES TO THE DELAY IN THE INNATE IMMUNE RESPONSE TO SARS-COV-2 REPLICATION. HERE, WE PROPOSE TO INVESTIGATE THE MECHANISM OF HOW ENDOU ACTS IN SARS-COV-2, HOW ENDOU ASSOCIATES WITH THE REPLICASE COMPLEX, AND HOW PUN RNA CONTRIBUTES TO ACTIVATING MDA5. IN AIM 1, WE WILL EVALUATE ENDOU AND OTHER IFN ANTAGONISTS FOR THEIR ROLE AS MODULATORS OF TYPE I AND TYPE III IFN RESPONSES TO SARS-COV-2 INFECTION IN PRIMARY HUMAN AIRWAY CELLS AND IN ENTEROCYTES. WE WILL USE REVERSE GENETICS TO GENERATE VIRUSES WITH INACTIVE IFN ANTAGONISTS AND EVALUATE THE EFFECTS OF COMBINING INACTIVATION OF ENDOU WITH INACTIVATING MUTATIONS OF OTHER VIRAL PROTEIN IFN ANTAGONISTS. IN AIM 2 WE WILL DELINEATE AND DISRUPT ENDOU INTERACTIONS WITHIN THE CORONAVIRUS REPLICASE COMPLEX. THE RESULTS OF THESE STUDIES WILL GUIDE STRATEGIES FOR DISRUPTION OF ENDOU FROM THE COV REPLICASE COMPLEX, WHICH WOULD ACTIVATE PROTECTIVE IMMUNE RESPONSES TO COV INFECTIONS. IN AIM 3, WE WILL IDENTIFY REGIONS OF POLY-URIDINE NEGATIVE-SENSE RNA, TERMED PUN RNA, REQUIRED FOR RECOGNITION BY ENDOU AND MDA5. THESE STUDIES WILL PROVIDE NEW INFORMATION ON HOW PUN RNAS ARE RECOGNIZED BY ENDOU AND MDA5. OVERALL, THESE STUDIES WILL DEFINE A NEW MECHANISM FOR HOW AN ENDORIBONUCLEASE ACTS AS A VIRULENCE FACTOR. THIS NEW INFORMATION CAN BE USED TO DEVELOP ANTIVIRAL THERAPIES AND VACCINES AGAINST EXISTING AND EMERGING CORONAVIRUSES.

GENETICS OF HYPERTENSION IN BLACKS

LIGAND-INDEPENDENT SIGNALING OF ESTROGEN RECEPTOR BETA AND THE AGING BRAIN

MOLECULAR MECHANISMS OF FOCAL ADHESION KINASE IN PROMOTING HEPATOCARCINOGENESIS

NEUROMOLECULAR CONSEQUENCES OF ADOLESCENT BINGE DRINKING

NEW MECHANISMS OF SERCA REGULATION: DIMERIZATION AND MICROPEPTIDES

METS-SLEEP: SLEEP TIMING, GUT MICROBIOTA AND CARDIOMETABOLIC RISK ACROSS THE EPIDEMIOLOGIC TRANSITION

COMPUTATIONAL MODELING FOR HCV VACCINE TRIAL DESIGN AND OPTIMAL VACCINE-BASED COMBINATION INTERVENTIONS - PROJECT SUMMARY/ABSTRACT DESPITE REMARKABLE PROGRESS WITH DIRECT-ACTING ANTIVIRALS (DAAS), HEPATITIS C VIRUS (HCV) INFECTION REMAINS A SERIOUS GLOBAL PUBLIC HEALTH PROBLEM WITH OVER 1% OF THE WORLD’S POPULATION AND ABOUT 3 MILLION IN THE UNITED STATES (U.S.) INFECTED. THE U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES RECENTLY RENEWED THE ACTION PLAN TO PREVENT, CARE AND TREAT VIRAL HEPATITIS TO ELIMINATE VIRAL HEPATITIS INFECTION AS A PUBLIC HEALTH THREAT AND THE WHO INTRODUCED GLOBAL TARGETS FOR THE CARE AND MANAGEMENT OF HCV. WHILE THE HIGHEST UPTAKE OF HCV TREATMENT OCCURRED IN 2017 AND 1.5 MILLION PEOPLE WERE CURED, 1.6 MILLION NEW INFECTIONS OCCURRED. DUE TO MANY TREATMENT BARRIERS, ONLY AN ESTIMATED 21% OF INFECTED PATIENTS ARE DIAGNOSED AND ONLY 2% OF TOTAL INFECTED PATIENTS ARE BEING TREATED FOR THE DISEASE ANNUALLY. DAAS ALONE ARE UNLIKELY TO ACHIEVE HCV ELIMINATION; AS SUCH, THE DEVELOPMENT OF A VACCINE TO PREVENT HCV INFECTION IS AN IMPORTANT FOCUS OF ONGOING RESEARCH. VACCINE CLINICAL TRIALS FOR HCV INFECTION WILL NEED TO RECRUIT FROM HIGH-RISK POPULATIONS, SUCH AS PERSONS WHO INJECT DRUGS (PWID), WHO CONTRIBUTE AN ESTIMATED 60% OF ALL NEW HCV INFECTIONS IN THE U.S. AND HAVE AN INCREASING INCIDENCE OF HCV, ESPECIALLY AMONG YOUNG PWID. ADDITIONALLY, LIMITED ACCESS TO DAA TREATMENT, SYRINGE SERVICE PROGRAMS (SSP), AND CONTINUED INJECTION DRUG USE POSES CHALLENGES AMONG PWID EVEN AS TREATMENT WITH MEDICATION FOR OPIOID USE DISORDER (MOUD) IS EXPANDING. FACTORS CONTRIBUTING TO TRANSMISSION AND SUCCESSFUL INTERVENTION (DAAS, MOUD, SSP) AMONG PWID ARE DYNAMIC AND COMPLEX AND OCCUR AT THE INDIVIDUAL (E.G., PATHOGEN-HOST INTERPLAY, RISK BEHAVIORS), SOCIAL (E.G., INJECTION NETWORK, SOCIAL NORMS), STRUCTURAL (E.G., ACCESS TO SSP AND MOUD), AND GEOGRAPHIC (E.G., INTERACTION LOCATIONS) LEVELS. AS SUCH, PERFORMING HCV VACCINE RANDOMIZED CLINICAL TRIALS (RCT) IN THE PWID POPULATION PRESENTS MAJOR CHALLENGES. WE PROPOSE TO DEVELOP AN INTEGRATED COMPREHENSIVE COMPUTATIONAL MODELING APPROACH TO EXAMINE THESE CHALLENGES SYSTEMATICALLY AND ASSESS THE IMPACT OF SPECIFIC RCT MODIFICATIONS ON CLINICAL TRIAL SUCCESS. TO EXPLORE VACCINE TRIAL DESIGN AND OUTCOMES, OUR INTERDISCIPLINARY TEAM WILL: (1) DESIGN AND EVALUATE CLINICAL TRIALS IN LOW INCIDENCE PWID SITES, USING METROPOLITAN CHICAGO AS THE MODEL, WHICH REDUCES THE CHANCE OF SOMEONE BECOMING EXPOSED BEFORE BEING FULLY PROTECTED; (2) DESIGN AND EVALUATE CLINICAL TRIALS IN HIGH INCIDENCE PWID SITES, USING SAN FRANCISCO AS THE MODEL, WHICH INCREASES THE CHANCE OF SOMEONE BECOMING EXPOSED BEFORE BEING FULLY PROTECTED; AND (3) DISCOVER EFFECTIVE HCV VACCINE-BASED INTERVENTION STRATEGIES TO ACHIEVE WHO ELIMINATION GOALS IN THE CONTEXT OF A LICENSED VACCINE. THE LITERATURE SUPPORTS THAT NON-STERILIZING VACCINES ARE EXPECTED TO BE THE FOCUS OF FUTURE TRIALS, REMINISCENT OF RECENT COVID-19 VACCINES, THEREFORE WE WILL SIMULATE THEIR EFFECT ON TRANSMISSION TO REACH ELIMINATION. WE WILL ACCOUNT FOR SSP AND MOUD AND THEIR EFFECT ON OUTCOMES IN TWO CITIES WITH DISPARATE HCV EPIDEMIC PROFILE AMONG PWID—CHICAGO AND SAN FRANCISCO.

DATA-DRIVEN MATHEMATICAL AND COMPUTATIONAL MODELING OF HEPATITIS D INFECTION AND TREATMENT RESPONSE

ALCOHOL INTOXICATION AND POSTBURN INTESTINAL IMMUNITY

HOST-ASSOCIATED BIOFILM FORMATION AND DISPERSAL MECHANISMS

WEIGHTING LONGITUDINAL DATA TO ACCESS OPIOID ANALGESIA TAPERING OUTCOMES AMONG PATIENTS WITH CO-OCCURRING CHRONIC PAIN AND SUBSTANCE USE DISORDER - PROJECT SUMMARY/ABSTRACT IN 2016, THE CENTERS FOR DISEASE CONTROL (CDC) RELEASED GUIDELINES RECOMMENDING NON-PHARMACOLOGIC TREATMENT FOR CHRONIC PAIN OVER USE OF OPIOID ANALGESIA IN RESPONSE TO RISING OVERDOSE DEATHS AND BASED ON STUDIES SHOWING NONOPIOID AND MULTIDISCIPLINARY APPROACHES TO PAIN CONTRIBUTE TO FUNCTIONAL AND PAIN SEVERITY IMPROVEMENTS. CDC GUIDELINES ALSO RECOMMENDED OPIOID TAPERING FOR CHRONIC PAIN PATIENTS WITH SUBSTANCE USE DISORDER (SUD) AND TRANSITION TO MEDICATIONS FOR OPIOID USE DISORDER (MOUD) FOR PATIENTS WITH CO-OCCURRING OPIOID USE DISORDER (OUD). WHILE OPIOID TAPERING HAS BEEN WIDELY IMPLEMENTED, FEW STUDIES ASSESS TRANSITIONS TO MOUD OR MULTIDISCIPLINARY MEDICINE USE SPECIFICALLY AMONG PATIENTS WITH CHRONIC PAIN AND CO-OCCURRING SUD. A PRIMARY REASON FOR THIS LIMITED KNOWLEDGE IS THE POPULATION WITH CHRONIC PAIN AND CO-OCCURRING SUD IS OFTEN RELATIVELY SMALL IN ANY GIVEN HEALTHCARE FACILITY OR SYSTEM, AND OUTCOMES OF INTEREST MAY OCCUR IN LOW TOTAL NUMBERS. THUS, A LARGE DATABASE IS REQUIRED TO CONDUCT MULTIFACTORIAL RESEARCH ON OUTCOMES ASSOCIATED WITH DIFFERENT APPROACHES TO OPIOID TAPERING, ESPECIALLY WHEN EVALUATING WHETHER TRENDS HOLD AMONG SMALLER DEMOGRAPHIC GROUPS. TO ADDRESS THIS CRITICAL GAP, OUR GOAL IS TO CREATE WEIGHTS FOR THE CERNER REAL-WORLD© DATABASE, WHICH INCLUDES ELECTRONIC HEALTH RECORDS (EHR) DATA FROM OVER 100 MILLION UNIQUE U.S. PATIENTS AT 600 PARTICIPATING HOSPITALS AND CLINICS. OUR HYPOTHESIS IS THAT WEIGHTING THE DATABASE WILL SIGNIFICANTLY ENHANCE ITS REPRESENTATIVENESS IN ORDER TO LONGITUDINALLY ASSESS THE RELATIONSHIP BETWEEN OPIOID TAPERING, MULTIDISCIPLINARY MEDICINE, MOUD, AND OUTCOMES FOR CHRONIC PAIN PATIENTS WITH CO-OCCURRING SUD. OUR AIMS ARE TO USE AMERICAN HOSPITAL ASSOCIATION AND U.S. CENSUS DATA TO CREATE WEIGHTS, STRATIFIED BY HOSPITAL CHARACTERISTICS AND ADJUSTED BY DEMOGRAPHIC VARIABLES, FOR ANALYZING THE CERNER DATABASE (AIM 1); VALIDATE THE WEIGHTING SCHEME IN AIM 1 BY COMPARING WEIGHTED ESTIMATES FROM THE CERNER DATABASE TO ESTIMATES FROM A WELL-ESTABLISHED POPULATION (THE NATIONWIDE INPATIENT SAMPLE) FOR CHRONIC PAIN, SUD, AND OVERDOSE DIAGNOSES AND RELEVANT MULTIDISCIPLINARY PAIN INTERVENTIONS FOR THE YEARS 2000-2025 (AIM 2); AMONG PATIENTS WITH CHRONIC PAIN AND CO-OCCURRING OUD, EXAMINE HOW TAPERING OPIOID ANALGESICS AND TRANSITIONING TO MOUD AFFECTS RISK FOR OVERDOSE, SUICIDE, AND OTHER HOSPITALIZATIONS, AND ASSESS HOW SEX AND RACE/ETHNICITY OPERATE AS EFFECT MODIFIERS IN THESE RELATIONSHIPS (AIM 3); AND AMONG PATIENTS WITH CHRONIC PAIN AND CO-OCCURRING SUD, EXAMINE HOW TAPERING OPIOID ANALGESICS WHILE USING MULTIDISCIPLINARY PAIN TREATMENT AFFECTS RISK FOR OVERDOSE, SUICIDE, AND OTHER HOSPITALIZATIONS, AND ASSESS HOW SEX AND RACE/ETHNICITY OPERATE AS EFFECT MODIFIERS IN THESE RELATIONSHIPS (AIM 4). THIS PROJECT WILL CREATE A NATIONAL DATABASE WITH VALIDATED WEIGHTING THAT WILL ENABLE RIGOROUS EXAMINATION OF OPIOID TAPERING APPROACHES AMONG PATIENTS WITH CHRONIC PAIN AND CO-OCCURRING SUD, WHICH WILL SUBSEQUENTLY IMPROVE KNOWLEDGE OF HOW MULTIDISCIPLINARY PAIN TREATMENT AND MOUD AFFECT RISKS, WHILE CONSIDERING TAPERING-RELATED INEQUITIES AMONG DEMOGRAPHIC SUBPOPULATIONS.

NOVEL PARACRINE MECHANISMS FOR CELL-BASED THERAPY OF INJURED LUNGS

A NOVEL ANTI-SPORE NASAL VACCINE FOR PROTECTION FROM ANTHRAX

TRAINING IN NEUROIMMUNOENDOCRINE EFFECTS OF ALCOHOL

THE FEMALE URINARY MICROBIOME AND URINARY INCONTINENCE

MAINTAINING B CELL IMMUNITY WITH AGED B LYMPHOCYTES

DETERMINANTS AND CONSEQUENCES OF LOW VITAMIN D IN POPULATIONS OF AFRICAN DESCENT

GUT MICROBIOTA, SHORT CHAIN FATTY ACIDS, AND ADIPOSITY ACROSS THE EPIDEMIOLOGIC TRANSITION

SOMATIC DIVERSIFICATION OF IMMUNOGLOBULIN GENES IN GALT

DEFINING THE NUCLEAR IMPORT PATHWAYS OF HIV-1 - ABSTRACT HUMAN IMMUNODEFICIENCY VIRUS (HIV-1), LIKE ALL PRIMATE LENTIVIRUSES POSSESSES THE ABILITY TO INFECT NON-DIVIDING CELLS BY ENGAGING WITH COMPONENTS OF THE NUCLEAR PORE COMPLEX AND MEDIATING THE NUCLEAR TRANSLOCATION OF THE VIRAL RIBONUCLEOPROTEIN COMPLEX (RNP) FOR SUBSEQUENTLY INTEGRATION INTO THE HOST CELL GENOME. THE VIRAL CAPSID PROTEIN (CA) INTERACTS WITH NUMEROUS HOST FACTORS INVOLVING CONSTITUENTS OF THE NUCLEAR PORE COMPLEX (NPC) TO ACCOMPLISH THE PROCESS OF NUCLEAR IMPORT. UNFORTUNATELY, THE EXACT MECHANISM BY WHICH HIV-1 TRANSLOCATES THROUGH THE NUCLEAR PORE COMPLEX REMAINS ONE OF THE LEAST UNDERSTOOD STEPS OF THE VIRAL LIFE CYCLE. IN ADDITION, RECENT EVIDENCES SUPPORTING THE NOTION OF NPCS BEING MORE HETEROGENEOUS THAN PREVIOUSLY THOUGHT FURTHER CONFOUNDS THIS SITUATION. WE HAVE DEVELOPED AN INDUCIBLE NUCLEAR PORE BLOCKADE THAT ALLOWS THE RATE OF NUCLEAR IMPORT OF FUNCTIONAL, INFECTIOUS VIRAL GENOMES TO BE MONITORED IN ANY RELEVANT CELLS TYPES. USING THIS TECHNIQUE, WE OBSERVE THAT CERTAIN CA MUTANTS ARE INSENSITIVE TO A NUP62 MEDIATED NUCLEAR PORE BLOCKADE IN CELLS WHICH POTENTLY BLOCK INFECTION BY WILD TYPE CA, DEMONSTRATING THAT HIV-1 CAN UTILIZE DISTINCT NUCLEAR IMPORT PATHWAYS DURING INFECTION. IN THIS APPLICATION, WE WILL DETERMINE THE DEGREE TO WHICH NPC ARE HETEROGENEOUS AND MAP THE SPECIFIC NUCLEAR PORE CONSTITUENTS THAT MAKEUP THE NPCS UTILIZED BY HIV-1 DURING NUCLEAR ENTRY. WITH OUR NUCLEAR PORE BLOCKADE, WE NOW HAVE THE CAPABILITY TO BLOCK NPCS USING DIFFERENT NUCLEAR PORE CONSTITUENTS. AS SUCH, THIS APPLICATION AIMS TO DEFINE AND VISUALIZE THE SPECIFIC NUCLEAR PORE CONSTITUENTS THAT INTERACT AND MEDIATE THE NUCLEAR IMPORT OF HIV-1 AND HOW SPECIFIC NPC USAGE AFFECTS VIRAL INTEGRATION IN TARGET CELLS. COLLECTIVELY THIS APPLICATION WOULD CLOSE CRITICAL GAPS TO OUR UNDERSTANDING IN TO THE NUCLEAR IMPORT OF HIV-1.

COMPREHENSIVE PREPARATION OF SCHOOL PSYCHOLOGISTS TO SUPPORT THE MENTAL HEALTH OF STUDENTS THAT ARE CULTURALLY AND LINGUISTICALLY DIVERSE IN THE CICERO COMMUNITY

MOLECULAR GENETICS OF MLL-ASSOCIATED LEUKEMIA

SUPPORT FOR NURSING EDUCATION AT LOYOLA UNIVERSITY NEW ORLEANS' COLLEGE OF NURSING & HEALTH

MECHANISMS OF CONTRACTILE NETWORK ASSEMBLY

ADVANCED NURSING EDUCATION WORKFORCE

THE NKA INTERACTOME IN HEALTH AND DISEASE - PROJECT SUMMARY/ABSTRACT: THE NA/K-ATPASE (NKA), OR “SODIUM PUMP”, IS AN ENZYME THAT TRANSPORTS IONS ACROSS CELL MEMBRANES. BETWEEN 30-70% OF THE CELL’S ATP BUDGET IS SPENT BY THE NKA TO CREATE STRONG CHEMICAL GRADIENTS FOR SODIUM AND POTASSIUM. THESE GRADIENTS CONTROL CELL VOLUME, SUPPORT ELECTRICAL SIGNALING (ACTION POTENTIALS) AND ENERGIZE MANY OTHER TRANSPORT PROCESSES. DISRUPTION OF SODIUM HANDLING IS ASSOCIATED WITH DISEASES INCLUDING CARDIAC HYPERTROPHY/FAILURE, PARKINSON’S DISEASE, SCHIZOPHRENIA, AND ALZHEIMER’S DISEASE. VARIOUS CELL TYPES IN DIVERSE TISSUES OF THE BODY HAVE VERY DIFFERENT REQUIREMENTS FOR NA/K TRANSPORT, AND TRANSPORT RATES MUST RESPOND TO PHYSIOLOGICAL CHALLENGES (E.G. EXERCISE). TO ADAPT NKA TO THESE DIFFERENT CONDITIONS, THE PUMP IS REGULATED BY TISSUE-SPECIFIC TRANSMEMBRANE PEPTIDES THAT INCREASE OR DECREASE THE PUMP’S ENZYMATIC ACTIVITY. IN AIM 1 OF THE PROJECT WE WILL FOCUS ON THE NORMAL PHYSIOLOGICAL REGULATION OF NKA BY FXYDS, TESTING HOW FXYD PROTEINS BIND AND STABILIZE SPECIFIC NKA CONFORMATIONS TO ALTER NKA TRANSPORT KINETICS. WE WILL USE NOVEL SPECTROSCOPIC ASSAYS TO INVESTIGATE THE STRUCTURE AND STABILITY OF DIFFERENT NKA-FXYD REGULATORY COMPLEXES. WE WILL INVESTIGATE HOW PHYSICAL COUPLING OF TWO PUMPS INTO A SINGLE FUNCTIONAL UNIT CAN ALLOW FASTER OVERALL CYCLING. AIM 2 IS THE TRANSLATIONAL ARM OF THE RESEARCH PROJECT. THE RESEARCH TEAM WILL INVESTIGATE HOW NKA REGULATION BY FXYDS BECOMES DISORDERED IN DISEASE, USING PROTEOMIC ANALYSIS TO COMPARE THE NKA-FXYD INTERACTOME IN HEALTHY AND FAILING HUMAN HEART TISSUE. WE WILL DETERMINE WHETHER FRAGMENTS OF DIGESTED MEMBRANE PROTEINS MAY DISRUPT NKA FUNCTION IN DISEASE. WE WILL ALSO TEST THE FEASIBILITY OF USING GENE DELIVERY OF AN INHIBITORY SPECIES (FXYD1) AS A THERAPY TO IMPROVE THE CONTRACTION STRENGTH OF A FAILING HEART. FINALLY, WE WILL COMPARE FXYDS THAT ACTIVATE NKA AND FXYDS THAT INHIBIT NKA. THE PROJECT BRINGS TOGETHER 6 DIFFERENT INVESTIGATORS THAT SPECIALIZE IN DIFFERENT COMPLEMENTARY APPROACHES. THE LABORATORY OF THE PROJECT PI, PROF. SETH ROBIA, USES FLUORESCENCE SPECTROSCOPY AND CELL PHYSIOLOGY TO INVESTIGATE THE STRUCTURE, AFFINITY, AND FUNCTION OF NKA-FXYD COMPLEXES IN CARDIAC MYOCYTES AND HETEROLOGOUS CELLS. HE WORKS CLOSELY WITH TWO LOYOLA UNIVERSITY CHICAGO COLLEAGUES: JONATHAN KIRK (CO-I) AND PETE KEKENES-HUSKEY (CO-I). PROF. KIRK WILL USE PROTEOMICS APPROACHES SUCH AS MASS SPECTROMETRY TO DISCOVER POST- TRANSLATIONAL MODIFICATIONS AND NOVEL NKA REGULATORS. PROF. KEKENES-HUSKEY WILL ASSIST WITH COMPUTATIONAL MODELING OF THE PROTEIN COMPLEXES. PROF. JULIE BOSSUYT (MPI) WILL INVESTIGATE A-A COUPLING, CONDUCTING MICROSCOPY AND BIOCHEMISTRY EXPERIMENTS TO IDENTIFY THE INTERACTION INTERFACE. PROF. ARTIGAS (CO-I) AT TEXAS TECH WILL PERFORM DETAILED ELECTROPHYSIOLOGICAL ANALYSES OF FXYD PROTEINS AND MEMBRANE PROTEIN FRAGMENTS. PROF. RAZVAN CORNEA (CONSULTANT) IS AN EXPERT IN MEMBRANE PROTEIN BIOPHYSICS. HE WILL ADVISE THE TEAM ON ALL ASPECTS OF THE PROJECT. TOGETHER, THE COLLABORATORS WILL UNCOVER IMPORTANT NEW INFORMATION ABOUT NKA-FXYD STRUCTURE/FUNCTION RELATIONSHIPS, AND LEARN HOW THESE MECHANISMS BECOME DISORDERED IN DISEASE.

LOYOLA RESEARCH COMPUTING CORE

PATHOLOGICAL RESPONSES TO MITOCHONDRIAL ROS IN SEPSIS-INDUCED CARDIAC DYSFUNCTION

BINGE ALCOHOL-INDUCED NEURODEGENERATION AND OMEGA-3 DHA PROTECTION

EXPERIMENTAL IMMUNOLOGY TRAINING GRANT

UNCOVERING AND HARNESSING CONNECTED METABOLIC PATHWAYS ESSENTIAL TO VIRUS INFECTION.

MINDFULNESS BASED STRESS REDUCTION FOR PSYCHO-IMMUNE DYSREGULATION IN CANCER

IMMUNE DYSREGULATION BY PSYCHOSOCIAL DISTRESS

SUPPORT OF THE UPWARD BOUND PROGRAM AT LOYOLA UNIVERSITY NEW ORLEANS

THE IMPACT OF A RACE-BASED STRESS REDUCTION INTERVENTION ON WELL-BEING, INFLAMMATION, AND DNA METHYLATION IN OLDER AFRICAN AMERICAN WOMEN AT RISK FOR CARDIOMETABOLIC DISEASE - PROJECT SUMMARY THIS RANDOMIZED CONTROLLED TRIAL WILL EVALUATE THE IMPACT OF A NOVEL RACE-BASED STRESS REDUCTION PROGRAM ON WELL-BEING, INFLAMMATORY BURDEN, AND DNA METHYLATION (DNAM) IN OLDER AFRICAN AMERICAN (AA) WOMEN AT RISK FOR CARDIOMETABOLIC DISEASE (CMD). ALTHOUGH THE NUMBER OF DEATHS RELATED TO CMD CONTINUES TO DECLINE, THAT DECLINE HAS SLOWED RECENTLY WITH AAS BEARING A DISPROPORTIONATE BURDEN. FURTHERMORE, WOMEN FACE MORE SEX- SPECIFIC RISK FACTORS FOR INCREASED ADIPOSITY AND AA WOMEN HAVE THE HIGHEST PREVALENCE OF OBESITY, HYPERTENSION, AND PREDIABETES COMPARED TO ALL OTHER RACIAL AND ETHNIC GROUPS. CHRONIC STRESS IS ASSOCIATED WITH LOW-GRADE INFLAMMATION AND INCREASED CMD RISK. GROWING EVIDENCE DEMONSTRATES THAT STRESSORS SUCH AS RACISM AND DISCRIMINATION ARE SIGNIFICANT CONTRIBUTING FACTORS TO PSYCHOLOGICAL DISTRESS, LOW-GRADE CHRONIC INFLAMMATION, AND CMD HEALTH DISPARITIES AMONG MINORITIES, PARTICULARLY AMONG OLDER AA WOMEN WHO ENDURE THE INTERSECTION OF BOTH RACISM AND SEXISM ACROSS THEIR LIFESPAN. RESILIENCE, STRESS, AND ETHNICITY (RISE) IS A GROUP-BASED, 8-WEEK INTERVENTION THAT INTEGRATES COGNITIVE-BEHAVIORAL STRATEGIES FOCUSED ON THE BIOPSYCHOSOCIAL IMPACT OF RACISM, RACIAL IDENTITY DEVELOPMENT, AND EMPOWERMENT. BASED ON OUR PRELIMINARY WORK, WE ANTICIPATE THAT PARTICIPATION IN RISE WILL REDUCE PSYCHOLOGICAL DISTRESS AND INFLAMMATION. FURTHER, OUR PREVIOUS WORK DEMONSTRATED THAT WOMEN WITH HIGH LEVELS OF PERCEIVED DISCRIMINATION HAVE A GREATER PROINFLAMMATORY CYTOKINE RESPONSE TO ACUTE STRESS AND DECREASED DNAM OF GENES RELATED TO INFLAMMATION AND HYPERTENSION. DNAM IS ONE TYPE OF EPIGENETIC PROCESS THAT MODULATES GENE EXPRESSION BY ADDING OR REMOVING METHYL GROUPS TO DNA IN RESPONSE TO THE ENVIRONMENT. STUDIES DEMONSTRATE THAT HYPER OR HYPO METHYLATION OF GENES DUE CHRONIC STRESSORS, INCLUDING RACISM AND DISCRIMINATION ARE SIGNIFICANTLY ASSOCIATED WITH CMD RISK. EMERGING EVIDENCE DEMONSTRATES THAT PSYCHOBEHAVIORAL INTERVENTIONS MAY MODIFY METHYLATION OF STRESS RESPONSE-RELATED GENES POTENTIALLY BUFFERING THE IMPACT OF PSYCHOLOGICAL STRESS AT THE MOLECULAR LEVEL. HOWEVER, FEW STUDIES HAVE EXAMINED THE IMPACT OF A PSYCHOBEHAVIORAL INTERVENTION ON CHANGES IN DNAM AND NONE HAVE ADDRESSED CHRONIC STRESS IN OLDER AA WOMEN.THEREFORE, THE SPECIFIC AIMS ARE: (1) DETERMINE THE EXTENT TO WHICH PARTICIPATION IN RISE DECREASES STRESS-RELATED SYMPTOMS AND INFLAMMATORY BURDEN IN OLDER AA WOMEN AT RISK FOR CMD; (2) EVALUATE THE EXTENT TO WHICH RISE INCREASES THE USE OF ADAPTIVE COPING VERSUS MALADAPTIVE COPING STRATEGIES IN OLDER AA WOMEN AT RISK FOR CMD; AND (3) DETERMINE THE EXTENT TO WHICH PARTICIPATION IN RISE MODIFIES DNAM OF STRESS RESPONSE- RELATED CANDIDATE GENES IN OLDER AA WOMEN AT RISK FOR CMD FROM BASELINE TO POST RISE INTERVENTION. AA WOMEN 50 TO 70 YEARS OF AGE WHO ARE AT RISK FOR CMD WILL BE RANDOMIZED INTO EITHER AN 8-WEEK RISE PROGRAM OR A HEALTH EDUCATION PROGRAM. RISE IS AN INNOVATIVE INTERVENTION THAT ADDRESSES PERCEIVED RACISM AND DISCRIMINATION AT THE INDIVIDUAL LEVEL. FURTHER, RISE HAS THE POTENTIAL TO IMPROVE THE HEALTH OF MINORITY WOMEN IMPACTED BY RACISM AND DISCRIMINATION.

SEX-SPECIFIC REGULATION OF MICRORNAS IN ALZHEIMER DISEASE - PROJECT SUMMARY ALZHEIMER’S DISEASE IS MORE PREVALENT IN WOMEN THAN MEN, YET A BIOLOGICAL BASIS FOR THIS SEX DIFFERENCE IS NOT UNDERSTOOD. THE PRIMARY OBJECTIVE OF THIS PROPOSAL IS TO UNDERSTAND HOW 17SS-ESTRADIOL (E2) REGULATES MICRORNA (MIR) BIOGENESIS AND STABILITY ACROSS THE LIFESPAN AND IN ALZHEIMER’S DISEASE (AD). WE HYPOTHESIZE THAT DYSREGULATION OF E2-MEDIATED MIR EXPRESSION IN THE AGED BRAIN LEADS TO GREATER ALZHEIMER DISEASE RISK IN WOMEN. THE STUDIES PROPOSED ARE FOCUSED ON UNDERSTANDING HOW ESTROGENS REGULATE THESE MIRS TO GET A BETTER UNDERSTANDING OF THEIR DYSREGULATION IN AD - SPECIFICALLY IN WOMEN. THIS WILL ADDRESS A MAJOR GAP IN OUR UNDERSTANDING BECAUSE HOW E2 INFLUENCES THE COMPONENTS OF THE MIR BIOGENESIS PATHWAY TO REGULATE MATURE MIR EXPRESSION LEVELS IN A CELL- AND/OR AGE-SPECIFIC MANNER IS UNKNOWN, DESPITE SEVERAL STUDIES DEMONSTRATING TEMPORAL AND CELL-SPECIFIC EFFECTS OF E2 ON MIR EXPRESSION IN A VARIETY OF ORGAN SYSTEMS. OUR PRIOR STUDIES DEMONSTRATED THAT E2 TREATMENT ALTERED THE EXPRESSION LEVELS OF A SUBSET OF MIRS IN THE FEMALE BRAIN, AND THE ABILITY TO REGULATE THESE MIRS DEPENDED ON AGE, BRAIN REGION, AND LENGTH OF E2 DEPRIVATION (I.E., TIME POST- MENOPAUSE). COLLECTIVELY THE EXPERIMENTS IN AIM 1 WILL TEST THE HYPOTHESIS THAT E2 DIFFERENTIALLY MEDIATES MATURE MIR STABILITY DEPENDING ON AGE AND IN ALZHEIMER’S DISEASE. WE WILL USE MIR DEGRADATION ASSAYS TO DETERMINE WHETHER AGE AND/OR E2 AFFECT THE RATE OF MIR DEGRADATION AND, USING A PROTEOMICS APPROACH, IDENTIFY THE CIS- AND TRANS-ACTING FACTORS THAT REGULATE MIR STABILITY. AIM 2 WILL ADDRESSES MECHANISTICALLY HOW A SELECT SUBSET OF MIRS COULD BE SPECIFICALLY REGULATED BY E2 POST-TRANSCRIPTION. WE WILL TEST THE HYPOTHESIS THAT HNRNP H BINDING TO ERSS REDUCES ITS ASSOCIATION WITH PRI-MIR TRANSCRIPTS, ERSS INTERACTS WITH BRCA1 TO DIFFERENTIALLY FACILITATE DROSHA COMPLEX ASSEMBLY, AND THAT THESE INTERACTIONS ARE DEPENDENT ON AGE AND E2 TREATMENT. AIM 3 WILL DETERMINE THE EFFECTS OF AGE AND E2 ON MIR SUBCELLULAR LOCALIZATION AND ASSESS DISRUPTION OF E2- MEDIATED MIR SUBCELLULAR LOCALIZATION IN ALZHEIMER’S DISEASE. THIS AIM WILL TEST THE HYPOTHESIS THAT E2 FACILITATES SUBCELLULAR TRAFFICKING OF MIRS, THEREBY IMPACTING MIR FUNCTION. MOREOVER, WE WILL TEST THE HYPOTHESIS THAT MIR SUBCELLULAR LOCALIZATION CHANGES ACROSS THE LIFESPAN AND THAT NORMAL AGE-RELATED SUBCELLULAR LOCALIZATION IS DISRUPTED IN ALZHEIMER’S DISEASE. IMPACT: UNDERSTANDING THE BASIC MOLECULAR SIGNALING PATHWAYS OF E2 IN THE AGING BRAIN WILL HELP DRIVE THERAPEUTIC ADVANCES AND INFORM TREATMENT STRATEGIES FOR WOMEN WITH ALZHEIMER’S DISEASE.

INTESTINAL BACTERIA AND EPITHELIAL BARRIER DISRUPTION AFTER ALCOHOL AND BURN INJURY

NATIONAL INSTITUTE FOR MENTORING EARLY MINORITY FACULTY IN NEUROSCIENCE

DEVELOPMENT OF B CELL MEMORY IN ALLERGIC ASTHMA - PROJECT SUMMARY/ABSTRACT ALLERGIC ASTHMA IS A CHRONIC INFLAMMATORY DISEASE OF THE LUNGS WITHOUT CURE. REPETITIVE ALLERGEN EXPOSURE IN THE AIRWAY LEADS TO THE GENERATION OF PATHOGENIC IMMUNE MEMORY AND THE EXCESSIVE PRODUCTION OF ALLERGEN SPECIFIC IGE ANTIBODIES THAT MEDIATE INFLAMMATION, AIRWAY CONSTRICTION AND RESPIRATORY DISTRESS IN PATIENTS WITH ALLERGIC ASTHMA. MEMORY B CELLS ARE A KEY COMPONENT OF IMMUNE MEMORY. THE PHENOTYPIC AND FUNCTIONAL HETEROGENEITY OF MBCS AFFORDS THEIR DIFFERENTIAL ANTIBODY RESPONSES AS WELL AS IMPACT THEIR TRAFFICKING, TISSUE RETENTION AND ABILITY TO DISSEMINATE SYSTEMICALLY. IN A MOUSE MODEL OF ALLERGIC LUNG INFLAMMATION, WE HAVE OBSERVED STABLE LUNG- LOCALIZED MBCS AND EVIDENCE FOR THE GENERATION OF PATHOGENIC ANTIBODY RESPONSES IN SENSITIZED LUNGS. WE HYPOTHESIZE THAT AFTER LOCAL ANTIGEN SENSITIZATION, THE LUNG ACQUIRES IMMUNE FUNCTIONS REMINISCENT OF THOSE IN SECONDARY LYMPHOID TISSUES, CAPABLE OF MAINTAINING LONG-LIVED MEMORY B CELLS AS WELL AS GENERATING NEW MBCS THAT CAN RECIRCULATE AND DISSEMINATE IN OTHER TISSUES TO MEDIATE SYSTEMIC ALLERGIC INFLAMMATION. IN THIS STUDY, WE WILL 1) PROBE THE DEVELOPMENT OF MEMORY B CELLS (MBCS) IN ALLERGIC LUNGS INCLUDING IN-DEPTH CHARACTERIZATION OF THE CRITICAL MBC SUBSET THAT CONTRIBUTES TO ALLERGEN SPECIFIC IGE RESPONSE, AND 2) HOW THESE MBCS DISSEMINATE SYSTEMICALLY. WE WILL ALSO 3) EXPLORE STRATEGIES TO INTERCEPT THE SYSTEMIC DISSEMINATION OF PATHOGENIC MBCS TO HALT THE PROGRESSION OF ALLERGIC INFLAMMATION. THESE STUDIES WILL ADVANCE OUR FUNDAMENTAL UNDERSTANDING OF MEMORY B CELLS AS WELL AS HELP DEVISE NEW THERAPEUTIC STRATEGIES FOR ALLERGIC ASTHMA.

USING THE FITBIT FOR EARLY DETECTION OF INFECTION AND REDUCTION OF HEALTHCARE UTILIZATION AFTER DISCHARGE IN PEDIATRIC SURGICAL PATIENTS - PROJECT SUMMARY PEDIATRIC APPENDECTOMY, THE MOST PREVALENT INPATIENT PROCEDURE IN CHILDREN, IS ASSOCIATED WITH SIGNIFICANT BURDEN TO THE PATIENT, THEIR PARENTS, HEALTHCARE SYSTEMS AND THIRD PARTY PAYORS. AFTER DISCHARGE, MONITORING BY PARENTS CONSISTS ONLY OF SUCH “PROXY” SUBJECTIVE ASSESSMENTS, WHICH HAVE BEEN REPORTED AS INACCURATE, AND RESULTED IN BOTH INCREASED COMPLICATIONS (E.G., READMISSIONS), AND WASTED HEALTHCARE RESOURCES (E.G., POTENTIALLY AVOIDABLE EMERGENCY DEPARTMENT (ED) VISITS AFTER SURGERY). ADVANCES IN CONSUMER WEARABLE DEVICES (“CWDS”) THAT PASSIVELY AND NON-INVASIVELY MONITOR PHYSICAL ACTIVITY (PA), HEART RATE (HR), AND SLEEP ARE USHERING IN A NEW ERA OF SYMPTOMS SCIENCE, PARTICULARLY AFTER SURGERY. THEIR EXPANDING CAPABILITY TO GENERATE CONTINUOUS, VALID, OBJECTIVE, AND ACTIONABLE MEASURES IN NEAR-REAL TIME IN CHILDREN, PROVIDE OPPORTUNITIES TO DETECT ALTERED POST-OPERATIVE RECOVERY PATTERNS EARLY, AND THEREFORE IMPROVE THE PRECISION AND TIMELINESS OF ANY NECESSARY CLINICAL INTERVENTIONS. THE PROPOSED STUDY WILL USE A CWD, THE FITBIT INSPIRE 2, AND WILL APPLY MACHINE LEARNING METHODS TO THE FITBIT DATA (PHYSICAL ACTIVITY, HR, AND SLEEP) TO CREATE CLINICALLY MEANINGFUL ALERTS FOR EARLY DETECTION OF POSTOPERATIVE INFECTION. DURING HOSPITALIZATION AND CONTINUING AFTER DISCHARGE, A FITBIT INSPIRE 2, A WIDELY-USED, COMMERCIALLY WEARABLE DEVICE WELL-TOLERATED BY YOUNG CHILDREN (3- 18 YEARS OLD) WILL BE USED TO MEASURE STEP COUNTS, SLEEP, AND HR. THE PROPOSAL HAS 2 AIMS. AIM 1 DEVELOPS AND VALIDATES MACHINE LEARNING ALGORITHM FOR INFECTION USING THE FITBIT. AIM 2 PROSPECTIVELY FEEDS NEAR-REAL TIME FITBIT DATA ON POSTOPERATIVE APPENDECTOMY PATIENTS TO CLINICIANS, AND EXAMINES THEIR EFFECT ON CLINICAL DECISION MAKING, TIME TO FIRST CONTACT WITH THE HEALTHCARE SYSTEM, AND ON OVERALL HEALTHCARE USE PATTERNS. THE PROPOSAL IS ALIGNED WITH NINR’S RESEARCH PRIORITIES. METHODS DEVELOPED FROM THIS WORK WILL PAVE THE WAY TO DEVELOP SIMILAR ALGORITHMS FOR OTHER PATIENT POPULATIONS NEEDING A PROXY, AS WELL AS TO CHARACTERIZE OTHER SURGERIES AND, SHOULD IMPROVE OVERALL POSTOPERATIVE MANAGEMENT FOR ALL SURGICAL PATIENTS.

MODELING THE EPIDEMIOLOGIC TRANSITION: ENERGY EXPENDITURE, OBESITY AND DIABETES

LOYOLA UNIVERSITY MARYLAND SCHOOL COUNSELING SCHOLARSHIP PROGRAM: CULTURALLY RESPONSIVE AND INCLUSIVE SCHOOL-COUNSELOR PREPARATION (CRISP)

CYBERCORPS SCHOLARSHIP FOR SERVICE: CYBERRAMBLERS BOLSTER NATIONAL SECURITY -CYBERSECURITY IS CRITICAL TO ALL ASPECTS OF MODERN LIFE, FROM ENERGY, COMMERCE, FINANCE, EDUCATION, AND HEALTHCARE TO MANUFACTURING AND AGRICULTURE. WELL-TRAINED CYBERSECURITY PROFESSIONALS SERVING IN THE GOVERNMENT WORKFORCE ARE CRITICAL TO NATIONAL SECURITY. THIS PROJECT WILL ESTABLISH THE CYBERRAMBLERS ? LOYOLA UNIVERSITY CHICAGO CYBERCORPS? SCHOLARSHIP FOR SERVICE PROGRAM TO IMPROVE THE UNITED STATES' NATIONAL SECURITY. SCHOLARS WILL BE TRAINED IN TECHNICAL KNOWLEDGE FROM COMPUTER SCIENCE AND CYBERSECURITY, AND SOCIAL AND BEHAVIORAL KNOWLEDGE OF CYBERCRIME FROM PSYCHOLOGY, AND CRIMINAL JUSTICE AND CRIMINOLOGY. THIS LEADS TO SCHOLARS RECEIVING A WELL-ROUNDED CYBERSECURITY EDUCATION AND TRAINING. FOUR COHORTS OF UNDERGRADUATE STUDENTS MAJORING IN THE B.S. FOR CYBERSECURITY PROGRAM WILL BE RECRUITED FOR A TOTAL OF 20 STUDENTS OVER FIVE YEARS. THE STUDENT RECRUITMENT PROCESS EMPHASIZES RECRUITING AND RETAINING MEMBERS OF UNDERREPRESENTED AND UNDERSERVED GROUPS. THE OUTCOME OF THIS PROJECT WILL BE A WELL-PREPARED COHORT OF CYBERSECURITY PROFESSIONALS AND LEADERS READY TO MEET THE NATION?S CYBERSECURITY WORKFORCE NEEDS. THE PROJECT WILL BUILD ON THE EXISTING INTERDISCIPLINARY CYBERSECURITY PROGRAM TO RECRUIT STUDENTS FROM COMPUTER SCIENCE, CYBERSECURITY, PSYCHOLOGY, AND CRIMINAL JUSTICE AND CRIMINOLOGY. EACH CYBERRAMBLER SCHOLAR WILL RECEIVE TWO YEARS OF SCHOLARSHIP SUPPORT AND ADVISING AND MENTORING SUPPORT TO ENSURE ADEQUATE PROGRESS TOWARD GRADUATION AND SUCCESSFUL JOB PLACEMENT. SCHOLARS WILL BE INVOLVED IN INTERDISCIPLINARY RESEARCH AND EDUCATION AND RECEIVE TRAINING TO DEVELOP THE CRITICAL THINKING, INDEPENDENCE, TEAMWORK, AND TECHNICAL KNOWLEDGE REQUIRED IN A CYBERSECURITY CAREER. THESE SCHOLARSHIPS FOR SERVICE WILL PROVIDE THE NECESSARY HANDS-ON TRAINING AND EDUCATION FOR SCHOLARS TO START A SUCCESSFUL CYBERSECURITY CAREER AS PART OF THE GOVERNMENT WORKFORCE. TO ENSURE THE EFFECTIVENESS AND SUSTAINABILITY OF THE PROGRAM, COMPREHENSIVE FORMATIVE AND SUMMATIVE EVALUATION MECHANISMS WILL BE USED TO ASSESS THE PROGRESS AND ACHIEVEMENTS OF THE STUDENT SCHOLARS. THESE WILL SPECIFICALLY FOCUS ON SCHOLARS? SKILL DEVELOPMENT, KNOWLEDGE ACQUISITION, AND READINESS TO MEET THE NATION'S CYBERSECURITY WORKFORCE NEEDS. THIS PROJECT AIMS TO CREATE CYBERSECURITY PROFESSIONALS WHO WILL POSITIVELY IMPACT NATIONAL SECURITY AND MEET THE EVOLVING CHALLENGES OF THE CYBER LANDSCAPE THROUGH STRATEGIC RECRUITMENT, INTERDISCIPLINARY CYBERSECURITY-FOCUSED CURRICULUM, RIGOROUS EVALUATION, AND GOVERNMENT PARTNERSHIPS. THIS PROJECT IS SUPPORTED BY THE CYBERCORPS? SCHOLARSHIP FOR SERVICE (SFS) PROGRAM, WHICH FUNDS PROPOSALS ESTABLISHING OR CONTINUING SCHOLARSHIP PROGRAMS IN CYBERSECURITY AND ALIGNS WITH THE U.S. NATIONAL CYBER STRATEGY TO DEVELOP A SUPERIOR CYBERSECURITY WORKFORCE. FOLLOWING GRADUATION, SCHOLARSHIP RECIPIENTS ARE REQUIRED TO WORK IN CYBERSECURITY FOR A FEDERAL, STATE, LOCAL, OR TRIBAL GOVERNMENT ORGANIZATION FOR THE SAME DURATION AS THEIR SCHOLARSHIP SUPPORT. 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.

MICROBE-DRIVEN DEVELOPMENT OF GALT

LOYOLA UNIVERSITY NEW ORLEANS UPWARD BOUND PROJECT

SELENOF IS A NOVEL TUMOR SUPPRESSOR AND A NEW TARGET TO OVERCOME RACIAL DISPARITY IN BREAST CANCER. - PROJECT SUMMARY / ABSTRACT THIS PROPOSAL ADDRESSES THE CHALLENGE OF CLOSING THE RACIAL DISPARITY GAP IN BREAST CANCER MORTALITY BY IDENTIFYING A CONTRIBUTING BIOLOGICAL FACTOR AND DEVELOPING THERAPEUTIC STRATEGIES TO OVERCOME ITS IMPACT. THE SELENOPROTEIN, SELENOF, WAS RECENTLY IDENTIFIED AS A NEW TUMOR SUPPRESSOR IN BREAST CANCER. THE BROAD HYPOTHESIS IS THAT LOWER SELENOF LEVELS IN AFRICAN AMERICAN PATIENTS CONTRIBUTE TO THE RACIAL DISPARITY IN BREAST CANCER MORTALITY BY DRIVING TUMOR PROGRESSION AND POOR PATIENT OUTCOME. THEREFORE, THERAPEUTIC STRATEGIES TO MITIGATE ITS LOSS ARE NEEDED TO HELP CLOSE THE DISPARITY GAP. THE SCIENTIFIC PREMISE FOR THE HYPOTHESIS IS BASED ON THE FOLLOWING: 1) THE GENOMES OF BREAST TUMORS FROM AFRICAN AMERICANS HAVE A 5-10 FOLD HIGHER FREQUENCY OF SELENOF SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS), WHICH ACCOUNT FOR LOWER SELENOF PROTEIN LEVELS, 2) SELENOF MRNA EXPRESSION IS SIGNIFICANTLY LOWER IN BREAST TUMORS FROM AFRICAN AMERICAN PATIENTS COMPARED TO CAUCASIANS, AND LOWER SELENOF LEVELS PREDICT SHORTER SURVIVAL IN THESE PATIENTS, 3) LOSS OF SELENOF IN NORMAL BREAST EPITHELIAL CELLS RESULTED IN INCREASED PROLIFERATION AND ABROGATED CELL DEATH, FEATURES OF CELLULAR TRANSFORMATION, AND 4) OVEREXPRESSION OF SELENOF IN BREAST CANCER CELLS INDUCED CELL DEATH, BLOCKED PROLIFERATION AND SURVIVAL, ENHANCED RESPONSE TO THERAPIES, AND INHIBITED TUMOR GROWTH IN VIVO. THE EUKARYOTIC INITIATION FACTOR 4A3 (EIF4A3) WAS IDENTIFIED AS A TRANSLATIONAL REPRESSOR OF SELENOF. THE SELENOF LOCUS SNPS ARE PREDICTED TO ENHANCE EIF4A3’S BINDING AFFINITY RESULTING IN STRONGER REPRESSION OF SELENOF TRANSLATION. PRELIMINARY DATA SHOWED THAT PHARMACOLOGIC INHIBITION OF EIF4A3 RESULTS IN INCREASED SELENOF PROTEIN LEVELS AND REDUCED BREAST CANCER CELL VIABILITY IN A SELENOF-DEPENDENT MANNER. LOSS OF SELENOF ALSO RESULTED IN HYPERACTIVATION OF THE KINASE/RNASE INOSITOL-REQUIRING ENZYME 1 (IRE1), A MASTER REGULATOR OF THE UNFOLDED PROTEIN RESPONSE. THIS RENDERED CELLS HIGHLY SUSCEPTIBLE TO IRE1 INHIBITION, THUS IDENTIFYING A NEW VULNERABILITY IN THESE CELLS. FOUR AIMS ARE PROPOSED: 1) DETERMINE THE MECHANISMS UNDERLYING SELENOF-INDUCED CELL FATE IN BREAST CANCER, 2) DETERMINE WHETHER LOSS OF SELENOF DRIVES TUMORIGENESIS BY USING AFRICAN AMERICAN DERIVED XENOGRAFTS AND A MURINE MODEL OF BREAST CANCER, 3) DETERMINE THE IMPACT OF SNPS ON THE REGULATION OF SELENOF TRANSLATION BY EIF4A3, AND 4) DETERMINE WHETHER EIF4A3 OVEREXPRESSION AND THE SNPS CONTRIBUTE TO REDUCED SELENOF TUMOR LEVELS AND POOR OUTCOME IN AFRICAN AMERICAN BREAST CANCER PATIENTS. OUR WORK WILL ESTABLISH SELENOF AS A NEW TARGET TO REDUCE RACIAL DISPARITY IN BREAST CANCER, AND THUS SUPPORT THE DEVELOPMENT OF SELENOF-BASED THERAPIES. IN THE CLINIC, SELENOF’S SNPS AND LEVELS CAN ALSO SERVE AS CANDIDATE BIOMARKERS TO IDENTIFY AFRICAN AMERICAN PATIENTS AT RISK OF AGGRESSIVE DISEASE. THE DISTINCT THERAPEUTIC STRATEGIES INVESTIGATED HERE ARE LIKELY TO RESULT IN NOVEL AND MORE EFFECTIVE PERSONALIZED MEDICINE AND MAY HELP CLOSE THE DISPARITY GAP.

A REGULATORY CASCADE THAT CONTROLS PNEUMOCOCCAL CAPSULE BIOSYNTHESIS

MONOCYTE REGULATION OF INFANT IMMUNE RESPONSES

NURSING WORKFORCE DIVERSITY

SOUTHWEST ONCOLOGY GROUP

ETHANOL EFFECTS ON RECOVERY AFTER INJURY

MARKERLESS MOTION TRACKING OF LUNG TUMORS USING DUAL ENERGY IMAGING

COLLABORATIVE INTEGRATION OF HEPATITIS B MOLECULAR VIROLOGY AND MATHEMATICAL/COMPUTATIONAL MODELING

UPWARD BOUND

NURSE, EDUCATION, PRACTICE, QUALITY AND RETENTION - REGISTERED NURSES IN PRIMARY CARE

A NOVEL ANTI-INFLAMMATORY PROTEIN THERAPEUTIC THAT IMPROVES RESUSCITATION AND REDUCES TRAUMA, SHOCK AND ISCHEMIA INDUCES TISSUE DAMAGE

TRAINING IN TRAUMA AND BURN RESEARCH

CHROMATIN ORGANIZATION AS A PREDICTOR OF STRESS INDUCED IMMUNE DYSREGULATION

UPWARD BOUND PROGRAM

COMPUTATIONAL DISCOVERY OF EFFECTIVE HEPATITIS C INTERVENTION STRATEGIES

PURPOSE: THE PURPOSE OF THIS PROJECT IS TO PROCURE, INSTALL, AND PROVIDE LIFECYCLE SUPPORT FOR ADVANCED SCIENTIFIC, INSTRUCTIONAL, AND SAFETY EQUIPMENT TO MODERNIZE LABORATORIES INSIDE THE DONNELLY SCIENCE BUILDING. ACTIVITIES TO BE PERFORMED: THE RECIPIENT WILL EXECUTE A MULTI-PHASE EQUIPMENT ROLLOUT MANAGED BY THE UNIVERSITY'S DIRECTOR OF PROJECT MANAGEMENT AND THE CONSTRUCTION FIRM WHITING-TURNER. KEY ACTIVITIES INCLUDE THE PROCUREMENT AND INSTALLATION OF 70 LABCONCO FUME HOODS, A WALK-IN FUME HOOD, A LAERDAL NURSING SIMULATION SYSTEM WITH ASSOCIATED SOFTWARE, SIX STRETCHER CHAIRS, AND SPECIALIZED DEIONIZED WATER PURIFICATION NETWORKS. EXPECTED OUTCOMES: THE PROJECT WILL DELIVER FULLY OPERATIONAL, MODERNIZED TEACHING AND RESEARCH SPACES EQUIPPED WITH STATE-OF-THE-ART ANALYTICAL INSTRUMENTATION AND FLEXIBLE LABORATORY FURNITURE SYSTEMS. ANTICIPATED OUTCOMES INCLUDE A FUNCTIONAL NURSING SKILLS LAB AND EXAM ROOMS CONFIGURED TO REPLICATE ACTUAL HOSPITAL AND DOCTOR OFFICE CLINICAL ENVIRONMENTS. THE COMPLETED INSTALLATION WILL YIELD STANDARDIZED, HIGH-QUALITY DATA COLLECTION CAPABILITIES, SUSTAINED SUPPORT FOR STUDENT EXPERIMENTATION, AND IMMEDIATE RESOURCE ACCESS FOR MULTIPLE SCIENCE MAJORS.INTENDED BENEFICIARIES: THE PRIMARY BENEFICIARIES ARE UNDERGRADUATE AND GRADUATE STUDENTS, FACULTY MEMBERS, AND RESEARCHERS WHO GAIN DIRECT ACCESS TO ADVANCED, MULTI-DISCIPLINARY LABORATORY FACILITIES. STUDENTS ENROLLED IN NURSING, BIOLOGY, CHEMISTRY, COMPUTER SCIENCE, AND ENGINEERING PROGRAMS WILL BENEFIT FROM HANDS-ON TRAINING WITH INDUSTRY-ALIGNED TOOLS. THE UNIVERSITY'S ACADEMIC DIVISIONS WILL ALSO BENEFIT FROM ENHANCED INSTITUTIONAL CAPACITY TO SUPPORT DIVERSE STUDENT RESEARCH AND COLLABORATIVE PROJECTS.SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT INTEND TO SUBAWARD FUNDS.

EMPOWERING STEM SCHOLARS FOR SUCCESS -THIS PROJECT WILL CONTRIBUTE TO THE NATIONAL NEED FOR WELL-EDUCATED SCIENTISTS, MATHEMATICIANS, ENGINEERS, AND TECHNICIANS BY SUPPORTING THE RETENTION AND GRADUATION OF HIGH-ACHIEVING, LOW-INCOME STUDENTS WITH DEMONSTRATED FINANCIAL NEED AT LOYOLA UNIVERSITY MARYLAND. A TOTAL OF 24 SCHOLARS PURSUING BACHELOR'S DEGREES IN BIOLOGY, CHEMISTRY, BIOCHEMISTRY, ENGINEERING (WITH CONCENTRATIONS IN COMPUTER, MECHANICAL, MATERIALS, OR ELECTRICAL ENGINEERING), AND FORENSIC SCIENCE WILL RECEIVE SCHOLARSHIPS AVERAGING $15,000 PER YEAR FOR UP TO FOUR YEARS. SCHOLARS WILL RECEIVE FACULTY, PEER, AND INDUSTRY MENTORING, AND THE PROJECT WILL BUILD STRONG SCHOLAR COHORTS THROUGH PRE-COLLEGE ORIENTATION; MESSINA, A COMMON FIRST-YEAR STUDENT EXPERIENCE FOR ALL LOYOLA STUDENTS THAT WILL BE SPECIALIZED FOR STEM PROJECT STUDENTS; SMALL-GROUP TUTORING; AND REGULAR COHORT EVENTS. ADDITIONAL ACTIVITIES FOR SCHOLARS WILL INCLUDE SEMINARS AND NETWORKING WITH INDUSTRY PARTNERS, ON-SITE VISITS TO REGIONAL STEM ORGANIZATIONS AND BUSINESSES, AND ASSESSMENT AND WORKSHOPS FOR THE DEVELOPMENT OF EMOTIONAL INTELLIGENCE AND PROFESSIONAL SKILLS. THE OVERALL GOAL OF THIS TRACK 2 SCHOLARSHIPS IN STEM PROJECT IS TO INCREASE STEM DEGREE COMPLETION OF ACADEMICALLY TALENTED, LOW-INCOME UNDERGRADUATE STUDENTS WITH DEMONSTRATED FINANCIAL NEED. THERE IS A SIGNIFICANT NATIONAL NEED TO GROW THE STEM WORKFORCE AND NURTURE KEY TALENT THAT WILL ENSURE ECONOMIC COMPETITIVENESS AND PROVIDE DOMESTIC LEADERSHIP ACROSS CRITICAL SECTORS. THIS PROJECT DIRECTLY SPEAKS TO THIS NEED BY SUPPORTING STEM STUDENT SUCCESS, WHICH WILL STRENGTHEN THE WORKFORCE IN ENGINEERING, BIOLOGY, CHEMISTRY AND BIOCHEMISTRY, AND FORENSIC SCIENCE FIELDS AND OTHER KEY AREAS OF NEED. THE PROJECT WILL BE ASSESSED BY AN EXPERIENCED EVALUATOR THAT WILL PROVIDE FORMATIVE AND SUMMATIVE EVALUATIONS THROUGH A WIDE-RANGE OF DATA COLLECTION METHODS (E.G., SURVEYS, FOCUS GROUPS, INSTITUTIONAL RESEARCH DATA, PROFESSIONAL DEVELOPMENT SCALES, PARTICIPATION COUNTS, ETC.) TO DETERMINE THE STEM PROJECT'S SUCCESS IN ACHIEVING ITS OBJECTIVES IN RECRUITMENT, RETENTION AND GRADUATION, CAREER AND PROFESSIONAL DEVELOPMENT, COHORT BUILDING, AND EMPLOYMENT OUTCOMES. THE DATA GENERATED WILL CONTRIBUTE TO THE KNOWLEDGE BASE REGARDING EFFECTIVE STRATEGIES TO SUPPORT TALENTED, LOW-INCOME STUDENTS IN STEM. THIS PROJECT IS FUNDED BY NSF'S SCHOLARSHIPS IN SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS PROGRAM, WHICH SEEKS TO INCREASE THE NUMBER OF ACADEMICALLY TALENTED, LOW-INCOME STUDENTS WITH DEMONSTRATED FINANCIAL NEED WHO EARN DEGREES IN STEM FIELDS. IT ALSO AIMS TO IMPROVE THE EDUCATION OF FUTURE STEM WORKERS, AND TO GENERATE KNOWLEDGE ABOUT ACADEMIC SUCCESS, RETENTION, TRANSFER, GRADUATION, AND ACADEMIC/CAREER PATHWAYS OF LOW-INCOME STUDENTS. 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.

CUBA CIVIL SOCIETY PROGRAM - CNECT

LINKING NICOTINIC ACTIVATION WITH SKIN INNATE IMMUNITY AND ATOPIC DERMATITIS

INCREASING ACCESS FOR EARLY CHILDHOOD MENTAL HEALTH CARE SERVICES - THE LOYOLA CENTER FOR COUNSELING & EDUCATION (LCCE) IS APPLYING FOR FUNDING TO SUPPORT THE PROPOSED PROJECT INCREASING ACCESS FOR EARLY CHILDHOOD MENTAL HEALTH CARE SERVICES. THE LCCE IS HOUSED WITHIN THE COLLEGE OF NURSING & HEALTH AT LOYOLA UNIVERSITY NEW ORLEANS. SINCE ITS INCEPTION IN 2019, LCCE HAS BEEN COMMITTED TO PROVIDING EFFECTIVE MENTAL HEALTH COUNSELING SERVICES ON A SLIDING SCALE TO UNDERSERVED FAMILIES, COUPLES, GROUPS, AND INDIVIDUALS AT EVERY STAGE OF LIFE. IN TANDEM WITH CLINICAL SERVICES, LCCE SUPERVISES EXEMPLARY TRAINING FOR GRADUATE STUDENTS IN LOYOLA UNIVERSITY’S DEPARTMENT OF COUNSELING. WITH SUPPORT FROM THE INFANT AND EARLY CHILDHOOD MENTAL HEALTH PROGRAM, THE LCCE AIMS TO IMPROVE OUTCOMES FOR CHILDREN FROM BIRTH UP TO 12 YEARS OF AGE BY DEVELOPING, MAINTAINING, OR ENHANCING INFANT AND EARLY CHILDHOOD MENTAL HEALTH PROMOTION, INTERVENTION, AND TREATMENT SERVICES. PROVIDING ACCESS TO THESE SERVICES TO THIS TARGET POPULATION WILL BE ADDRESSING A SIGNIFICANT NEED IN OUR COMMUNITY. THE TARGET POPULATION FOR THIS PROJECT INCLUDES CHILDREN UP TO AGE 12 IN NEED OF ACCESS TO MENTAL HEALTH CARE WHO ARE UNABLE TO ACCESS THESE SERVICES WITH A PROVIDER THAT BILLS MEDICAID OR PRIVATE INSURANCE. THERE IS A SIGNIFICANT LACK OF AVAILABLE PROVIDERS IN THE EIGHT PARISHES OF THE GREATER NEW ORLEANS AREA AND THE MAJORITY ARE EITHER NOT TAKING NEW PATIENTS OR DO NOT ACCEPT MEDICAID CLIENTS. THE TARGET POPULATION WILL BE LOW-INCOME AND MIRROR THE DEMOGRAPHICS OF THE GREATER NEW ORLEANS AREA: WHITE ALONE NOT HISPANICE: 43%; AFRICAN AMERICAN: 33%; HISPANIC: 11%; ASIAN, PACIFIC ISLANDER NOT HISPANIC: 3%; AND TWO OR MORE RACES: 4%. WITH GRANT FUNDING, THE LCCE WILL ACCOMPLISH THE FOLLOWING GOALS AND MEASURABLE OBJECTIVES: PROGRAM GOALS: 1. PROVIDE AN ADDITIONAL ACCESS POINT FOR CHILDREN OF THE GREATER NEW ORLEANS AREA IN NEED OF MENTAL HEALTH CARE SERVICES WHO ARE UNABLE TO SECURE TREATMENT FROM OTHER SOURCES MEASURABLE OBJECTIVE: SERVE 220 CHILDREN UP TO AGE 12 OVER 5 YEARS 2.PROVIDE CHILDREN WITH ACCESS TO COMPREHENSIVE SCREENING AND EVIDENCE-BASED THERAPIES MEASURABLE OBJECTIVE:100% OF CLIENTS WILL RECEIVE A RISK & NEEDS ASSESSMENT AT IN-TAKE AND ACCESS TO EVIDENCE-BASED TRAUMA-INFORMED CARE AND CHILD CENTERED PLAY THERAPY 3.CREATE A COMMUNITY OF EARLY CHILDHOOD EDUCATORS AND CARE PROVIDERS EQUIPPED TO RECOGNIZE CHILDREN IN NEED OF MENTAL HEALTHCARE SERVICES MEASURABLE OBJECTIVE:ESTABLISH 20 PARTNERSHIPS WITH EARLY CARE AND EDUCATION PROGRAMS, CHILD AND FAMILY-SERVING PROFESSIONALS OVER FIVE YEARS TO PROVIDE EDUCATIONAL AND TRAINING OUTREACH SERVICES AND PROVIDE 2 WORKSHOPS PER YEAR 4. PROVIDE SPECIALIZED TRAINING FOR MENTAL HEALTH CLINICIANS IN INFANT AND EARLY CHILDHOOD MENTAL HEALTH, INCLUDING SPECIFIC TRAINING IN PROMISING AND EVIDENCE-BASED PRACTICES AND MODELS FOR PREVENTION, EARLY INTERVENTION, AND TREATMENT MEASURABLE OBJECTIVE: 52 GRADUATE STUDENTS WILL BE TRAINED AND CERTIFIED TO USE EVIDENCE-BASED TRAUMA-INFORMED CARE AND CHILD CENTERED PLAY THERAPY OVER FIVE YEARS THE PROPOSED PROJECT WILL ALSO COLLECT ALL SAMHSA REQUIRED DATA AND PROGRAM SPECIFIC DATA, CREATE A QI PLAN, AND WORK WITH A LEAD EVALUATOR WHO WILL MONITOR THE EFFECTIVENESS AND QUALITY OF THE SERVICES PROVIDED AND THE PROGRESS TOWARDS MEETING THE PROJECT GOALS AND DELIVERABLES.

ANALYZING THE SPREAD OF ANTHRAX IN FARMS IN PAKISTAN AND JORDAN

FRANK-STARLING'S LAW OF THE HEART: CELLULAR MECHANISMS

PS09-007, EVALUATING LOCALLY DEVELOPED HOMEGROWN HIV PREVENTION INTERVENTIONS

ENGLISH LANGUAGE ACQUISITION: NATIONAL PROFESSIONAL DEVELOPMENT PROGRAM

SCHOLARSHIPS FOR DISADVANTAGED STUDENTS

BEHAVIORAL HEALTH WORKFORCE EDUCATION AND TRAINING PROGRAM

COMMENSAL EXOPOLYSACCHARIDE PROTECTION FROM INFLAMMATION

PHOSPHODIESTERASE 1 (PDE1) REGULATION OF MYOCARDIAL CALCIUM AND FUNCTION - PROJECT SUMMARY THE CYCLIC NUCLEOTIDE CAMP SERVES AS A SECOND MESSENGER CRITICAL IN MULTIPLE CELLULAR PROCESSES. TWO PROTEINS HELP TO REGULATE THE LEVEL OF CAMP. G-PROTEIN COUPLED RECEPTORS (GPCRS) ARE TRANSMEMBRANE PROTEINS INVOLVED IN CAMP PRODUCTION. G PROTEINS ARE HETEROTRIMERIC, AND A SUBSET OF GPCRS CONSISTS OF A STIMULATORY, CATALYTIC G⍺ SUBUNIT (G⍺S) THAT UPON RECEPTOR LIGAND BINDING, INCREASE ADENYLYL CYCLASE (AC) PRODUCTION OF CAMP. PHOSPHODIESTERASES (PDES), ON THE OTHER HAND, HYDROLYZE CAMP INTO AMP. IN HEART FAILURE ANIMAL MODELS AND HUMAN PATIENTS, PDE1 INHIBITION HELPS TO IMPROVE CARDIAC FUNCTION BY INCREASING MYOCARDIAL CONTRACTILITY, IMPROVING RELAXATION, AND VASODILATING TO LOWER HEMODYNAMIC STRESS ON THE HEART. THESE EFFECTS ARE SIMILAR TO THOSE UPON PDE3 INHIBITION, BUT WHEREAS THE LATTER IS ASSOCIATED WITH FATAL ARRHYTHMIAS, NO ARRHYTHMIC EVENTS HAVE BEEN ASSOCIATED WITH PDE1 INHIBITOR USE. COMPARTMENTALIZED CAMP SIGNALING THAT IS UNIQUE TO PDE1 VS PDE3 MAY HELP TO EXPLAIN THIS IMPORTANT DIFFERENCE. IT IS KNOWN THAT SPECIFIC PDE-GPCR PAIRINGS WORK TOGETHER TO REGULATE DISTINCT POOLS OF CAMP. THE HEART EXPRESSES MORE THAN 200 GPCRS AND 3 CAMP-HYDROLYZING PDES (1, 3, AND 4). UNIQUE PAIRINGS HELP TO ESTABLISH COMPARTMENTALIZED GRADIENTS OF CAMP SIGNALING THAT ENABLE THE MODULATION OF SPECIFIC CELLULAR PROCESSES IN RESPONSE TO DIFFERENT STIMULI. WHILE MULTIPLE GPCR PAIRINGS WITH PDE3 OR PDE4 HAVE BEEN KNOWN, WHICH GPCR(S) PAIR WITH PDE1 REMAINS UNKNOWN. IN THIS DIVERSITY SUPPLEMENTAL PROJECT, WE WILL IDENTIFY THE GPCR(S) THAT FUNCTIONALLY ENHANCE(S) THE POSITIVE INOTROPIC EFFECTS OF PDE1 INHIBITION. WE WILL DO SO BY EMPLOYING CARDIOMYOCYTE CONTRACTILITY AND CALCIUM, AND FORSTER RESONANCE ENERGY TRANSFER (FRET) IMAGING EXPERIMENTS, AND CARDIAC SLICE PHYSIOLOGIC STUDIES. GUINEA PIG HEARTS, WHICH ARE MUCH MORE LIKE THE HUMAN HEART IN PDE BIOLOGY VERSUS THE COMMONLY USED RAT AND MOUSE MODELS WILL BE USED. OUR HYPOTHESIS IS THAT PDE1 WILL ESTABLISH A G⍺S- ASSOCIATED CAMP GRADIENT THAT IS DISTINCT FROM THAT REGULATED BY PDE3. THIS IS AN IMPORTANT QUESTION BECAUSE OF CLINICAL POTENTIALS OF PDE1 INHIBITION IN PATIENTS WITH PARKINSON’S DISEASE OR HEART FAILURE. THE COMPLETION OF OUR AIM WILL THUS CONTRIBUTE ORIGINAL FINDINGS WITH DIRECT CLINICAL RELEVANCE THAT CAN POTENTIALLY HELP IMPROVE THE HEALTH AND LIFE QUALITY OF PATIENTS.

INFLAMMASOME-MEDIATED CORNEAL EPITHELIAL CELL DEFENSES INHIBITED BY PATHOGENIC BACTERIA - PROJECT SUMMARY/ABSTRACT THE HEALTHY CORNEAL EPITHELIUM IS AN EFFECTIVE BARRIER TO PATHOGENIC AND ENVIRONMENTAL BACTERIA. BECAUSE OF THIS, CORNEAL INFECTION OR KERATITIS MODELS OFTEN RELY ON BYPASSING THE EPITHELIUM ALTOGETHER BY INTRODUCING MICROBES DIRECTLY INTO THE CORNEAL STROMA, WHERE THEY INITIATE IMMUNE CELL RESPONSES THAT CAN DAMAGE TISSUE AND CAUSE VISION-THREATENING SCARRING. A LIMITATION OF THIS EXPERIMENTAL APPROACH IS THAT EPITHELIAL DEFENSE MECHANISMS ARE UNABLE TO BE IDENTIFIED OR INVESTIGATED. THE BACTERIAL PATHOGEN PSEUDOMONAS AERUGINOSA IS THE MOST COMMON INFECTION ASSOCIATED WITH SOFT CONTACT LENS WEAR, SUGGESTING IT IS UNIQUELY CAPABLE OF CAUSING INFECTION IN THE STROMA EVEN WHEN THE EPITHELIUM REMAINS INTACT. ONE WAY IN WHICH P. AERUGINOSA COLONIZES THE EPITHELIUM IS BY INVADING AND REPLICATING INSIDE EPITHELIAL CELLS, WHICH HAS BEEN INVESTIGATED IN CULTURED CELLS, AND OBSERVED IN MOUSE CORNEAL INFECTION MODELS. PRELIMINARY DATA SHOW THAT THE TOXIN EXOS PRODUCED BY P. AERUGINOSA SUPPRESSES CASPASE-4 MEDIATED PYROPTOSIS OF INVADED CORNEAL EPITHELIAL CELLS, BUYING TIME FOR BACTERIA TO REPLICATE IN A PROTECTED NICHE. ADDITIONAL DATA INDICATE THAT A DIFFERENT INFLAMMASOME PATHWAY IS ALSO ACTIVE IN CORNEAL EPITHELIAL CELLS, AND LEADS TO PRODUCTION OF THE CYTOKINE IL-1SS, WHICH EXOS ALSO SUPPRESSES. THEREFORE, A NOVEL ROLE FOR EXOS IN CORNEAL INFECTION COULD BE TO PROLONG A NICHE FOR BACTERIA TO REPLICATE WITHIN CORNEAL EPITHELIAL CELLS, WHILE LIMITING SECRETION OF CYTOKINES THAT RECRUIT IMMUNE CELLS. USING IMAGING METHODS TO SELECTIVELY MONITOR INVADED CELLS, AND CRISPR-CAS9 TO MANIPULATE CORNEAL EPITHELIAL CELLS GENETICALLY, WE WILL ANSWER THREE OUTSTANDING QUESTIONS REGARDING BOTH CORNEAL EPITHELIAL DEFENSE, AND BACTERIAL SUBVERSION OF IT: 1. HOW DOES EXOS BLOCK CASPASE-4-MEDIATED PYROPTOSIS? 2. HOW DO CORNEAL EPITHELIAL CELLS DETECT AND RESPOND TO P. AERUGINOSA? 3. WHAT IS THE SIGNIFICANCE OF EPITHELIAL CELL INFLAMMASOME ACTIVATION AND PYROPTOSIS IN PROTECTING THE EYE FROM DEVELOPING KERATITIS IN THE STROMA? SUCCESSFUL COMPLETION OF THESE AIMS WILL IDENTIFY A NEW MECHANISM OF HOST DEFENSE AT THE OCULAR SURFACE, FURTHER OUR UNDERSTANDING OF INFLAMMASOMES IN EPITHELIAL CELLS, AND ELUCIDATE HOW A UNIQUELY DEVASTATING CORNEAL PATHOGEN IS ABLE TO OVERCOME HOST DEFENSES.

KCNQ CHANNELS AND VASOCONSTRICTOR SIGNAL TRANSDUCTION

MECHANISMS UNDERLYING SEXUALLY DIFFERENTIATED BRAIN REMODELING DURING ADOLESCENCE

NURSE EDUCATION, PRACTICE, QUALITY AND RETENTION - WORKFORCE EXPANSION PROGRAM - FOUNDED IN 1935 AS THE FIRST BACCALAUREATE NURSING PROGRAM IN ILLINOIS, LOYOLA UNIVERSITY CHICAGO, MARCELLA NIEHOFF SCHOOL OF NURSING (LUC MNSON) HAS PREPARED OVER 10,000 NURSES TO ASSUME LEADERSHIP IN HEALTH CARE AND IN THE PROFESSION OF NURSING. WE PROPOSE TO CONTINUE OUR TRACK RECORD OF EXCELLENCE IN ACUTE AND LONG-TERM HEALTH CARE IN DESIGNATED RURAL AREAS THROUGH THE “NURSING – PROVIDING ACCESS TO RURAL ACUTE AND LONG-TERM HEALTHCARE (N-PARALTH)” PROJECT. THE N-PARALTH PROJECT WILL INCREASE THE NUMBER OF NURSING STUDENTS RETAINED AND GRADUATED FROM (LUC MNSON, INCREASE THE NUMBER OF NURSING STUDENTS RECEIVING ADDITIONAL SPECIALIZED TRAINING IN RURAL ACUTE AND LONG-TERM CARE SETTINGS, INCREASE THE NUMBER OF NEW GRADUATES FROM LUC MNSON EMPLOYED IN RURAL ACUTE AND LONG-TERM CARE SETTINGS AND INCREASE THE NUMBER OF PRECEPTORS AND CLINICAL FACULTY PREPARED TO EDUCATE LUC MNSON STUDENTS IN RURAL SETTINGS. THIS PROJECT WILL BE ACCOMPLISHED THROUGH THE FOLLOWING N-PARALTH OBJECTIVES: OBJECTIVE 1: CREATE A RURAL HEALTH CARE NURSING SCHOLAR (RHCNS) PROGRAM BEGINNING IN THE STUDENT’S FIRST YEAR OF NURSING EDUCATION AND LASTING THROUGHOUT THEIR BSN EDUCATION WHICH FOCUSES ON EVIDENCE-BASED KNOWLEDGE, SKILLS AND ATTITUDES FOR THE CARE OF RURAL RESIDENTS IN ACUTE AND LONG-TERM CARE FACILITIES. THE RHCNS PROGRAM WILL BE OPEN TO FOUR-YEAR NURSING STUDENTS, ACCELERATED NURSING STUDENTS, INCLUDING BOTH HYBRID AND FACE-TO-FACE NURSING STUDENTS. OBJECTIVE 2: ENHANCE AND EXPAND PARTNERSHIPS WITH NURSES IN RURAL LONG-TERM CARE AND ACUTE CARE SETTINGS PROVIDING CARE FOR RURAL, UNDERSERVED POPULATIONS INCLUDING BENNETT COUNTY CRITICAL ACCESS HOSPITAL, MARTIN, SOUTH DAKOTA, INDIAN HEALTH SERVICE HOSPITAL IN PINE RIDGE, SOUTH DAKOTA AND DESIGNATED CRITICAL ACCESS HOSPITALS AND LONG-TERM CARE FACILITIES IN DESIGNATED RURAL COUNTIES OF ILLINOIS, WISCONSIN, INDIANA, AND MICHIGAN THROUGH THE DELIVERY OF CONTINUED PROFESSIONAL DEVELOPMENT FOR PRACTICING RNS. AS STATED IN THE HRSA PUBLICATION “NURSE WORKFORCE PROJECTIONS, 2021-2036” MICHIGAN IS ONE OF THE TEN STATES WITH THE GREATEST SHORTAGES. OBJECTIVE 3: CREATE AND PILOT-TEST A RURAL, ACUTE CARE AND LONG-TERM CARE, ASYNCHRONOUS, MODULE-BASED EDUCATIONAL PROGRAM FOR BACCALAUREATE NURSING EDUCATION THAT CAN BE REPLICATED BY OTHER SCHOOLS OF NURSING INTERESTED IN EXPANDING THEIR EDUCATIONAL PROGRAMMING TO ADDRESS RURAL ACUTE CARE AND LONG-TERM CARE. MODULES DEVELOPED FOR THE N-PARALTH PROJECT WILL ADDRESS CURRENT RURAL HEALTH ISSUES EMPHASIZING SKILL BUILDING IN EVIDENCED–BASED INTERVENTIONS. IN ADDITION, STRATEGIES WILL BE USED TO ENCOURAGE GRADUATES TO SELECT RURAL HEALTH CARE AS A GEOGRAPHICAL LOCATION TO PROVIDE HEALTH CARE UPON GRADUATION WITH A FOCUS IN ACUTE AND LONG-TERM CARE NURSING AS A SPECIALTY. THE FOUR PATHS (PRE-PROFESSIONAL, PRECEPTOR, PATIENT, AND POPULATION) OF LOYOLA’S CURRENT PATH MODEL WILL ORGANIZE THE PROJECT ACTIVITIES. THE PRE-PROFESSIONAL PATH (I.E. STUDENT) WILL INCLUDE CURRICULUM INTEGRATING RURAL HEALTH CARE WITH ONLINE, HYBRID AND SIMULATED CONTENT, REFLECTIVE JOURNALING, SMALL GROUP AND FACE-TO-FACE CLASSROOM/WORKSHOP EDUCATION, AND SERVICE IMMERSION EXPERIENCES IN RURAL SITES. THE PRECEPTOR PATH WILL PROVIDE TRAINING FOR PRECEPTORS AND FACULTY IN RURAL HEALTH CARE, ACUTE AND LONG-TERM CARE ENSURING THAT REGISTERED NURSES HAVE THE KNOWLEDGE, SKILLS, AND ATTITUDES TO CARE FOR RURAL POPULATIONS. THE PATIENT PATH WILL FOCUS ON ASSESSING RURAL PATIENT NEEDS AND THE DEVELOPMENT OF EDUCATIONAL AND CULTURAL INTERVENTIONS TO SUPPORT PATIENTS IN MAINTAINING THEIR HIGHEST LEVEL OF FUNCTION. THE POPULATION PATH WILL INCORPORATE THEORY AND PRACTICE IN RURAL NURSING AND HEALTH CARE WITH PROPOSED INTERVENTIONS. A STATUTORY FUNDING PREFERENCE IS REQUESTED ON THE BASIS OF PROJECTS THAT SUBSTANTIALLY BENEFIT RURAL POPULATIONS AND THE STATE OF MICHIGAN.

ACETYL PHOSPHATE AS A GLOBAL STRESS SIGNAL

CONTRIBUTION OF CDIA TO PSEUDOMONAS AERUGINOSA PATHOBIOLOGY - PROJECT SUMMARY/ABSTRACT PSEUDOMONAS AERUGINOSA IS A LEADING CAUSE OF HEALTHCARE-ACQUIRED INFECTIONS WORLDWIDE. MANY GLOBALLY- DISTRIBUTED HIGH-RISK STRAINS ARE EMERGING DUE TO AN INCREASE IN ANTIBIOTIC RESISTANCE AND ACQUISITION OF NOVEL VIRULENCE TRAITS. WITH DIMINISHING TREATMENT OPTIONS FOR MANY OF THESE SEVERE P. AERUGINOSA INFECTIONS, STUDIES AIMED AT UNCOVERING THE VIRULENCE STRATEGIES USED BY THESE AGGRESSIVE CLINICAL STRAINS SHOULD HELP TO IDENTIFY NEW TARGETS FOR THERAPEUTIC INTERVENTION. OUR RESEARCH PROGRAM AIMS TO ELUCIDATE VIRULENCE STRATEGIES THAT ENHANCE THE PATHOGENICITY OF P. AERUGINOSA. WE RECENTLY EMPLOYED A COMPARATIVE GENOMICS APPROACH TO INTERROGATE THE ACCESSORY GENOMES OF 100 CLINICAL ISOLATES FOR POTENTIAL FACTORS THAT AUGMENT THE VIRULENCE OF P. AERUGINOSA. BY COMPARING VIRULENCE IN A MOUSE INFECTION MODEL WITH THE PRESENCE OR ABSENCE OF GENES IN THE ACCESSORY GENOME, WE IDENTIFIED SEVERAL VIRULENCE DETERMINANTS ENRICHED AMONG HIGHLY VIRULENT P. AERUGINOSA STRAINS THAT WERE ABSENT FROM LESS VIRULENT STRAINS. FROM THIS WORK WE IDENTIFIED AN ACCESSORY VIRULENCE FACTOR THAT SPANNED A PORTION OF TWO GENES ENCODING PRODUCTS INVOLVED IN CONTACT-DEPENDENT GROWTH INHIBITION (CDI). CDI IS ONE TYPE OF COMPETITIVE MECHANISM MICROORGANISMS USE TO ANTAGONIZE THEIR IMMEDIATE NEIGHBORS BY DELIVERING PROTEIN TOXINS DIRECTLY INTO TARGETED CELLS. THIS ANTAGONISM IS EXECUTED BY CDIA, A LARGE MULTIDOMAIN EXOPROTEIN THAT SITS AT THE SURFACE OF AN ATTACKING CELL AND DELIVERS A SELF-CONTAINED TOXIN DOMAIN INTO THE TARGETED CELL. THE IMPORTANCE OF THIS PROPOSAL STEMS FROM OUR DISCOVERY THAT: (I) CDIA CONTAINS A TOXIN DOMAIN THAT HAS TRNASE ACTIVITY AGAINST PROKARYOTIC AND EUKARYOTIC SUBSTRATES, (II) MUTATIONS THAT ABROGATE THE IN VITRO TRNASE ACTIVITY ATTENUATE BOTH CDI AND VIRULENCE IN MICE, (III) THE CDIA-TOXIN DOMAIN HAS CYTOPATHIC EFFECTS ON EUKARYOTIC CELLS DEPENDENT UPON ITS TRNASE ACTIVITY. TO OUR KNOWLEDGE THIS DULE ROLE FOR CDIA IN BOTH INTERBACTERIAL COMPLETION AND VIRULENCE WITHIN A MAMMALIAN HOST HAS NOT YET BEEN INVESTIGATED FOR P. AERUGINOSA. FROM THIS PRELIMINARY WORK WE HYPOTHESIZE THAT P. AERUGINOSA CAN UTILIZE CDIA TO INTOXICATE HOST CELLS FOR OVERCOMING BARRIERS TO INFECTION. OUR PROPOSAL SEEKS TO ANSWER A NUMBER OF OUTSTANDING QUESTIONS AT THE MOLECULAR (AIM 1), CELLULAR (AIM 2), AND ORGANISMAL (AIM 3) LEVEL. SUCCESSFUL COMPLETION OF THESE AIMS WILL PROVIDE DETAILED INSIGHT INTO HOW CDIA CONTRIBUTES TO P. AERUGINOSA PATHOBIOLOGY.

THE ROLE OF PTEN PHOSPHORYLATION REMODELING IN HEMATOPOIETIC STEM CELL REGULATION

PROBING CELLULAR INTRACELLULAR CALCIUM SIGNALING AND SENSING THROUGH COMPUTATION

LOYOLA-UKRAINIAN CATHOLIC UNIVERSITY INTERNATIONAL BIOETHICS RESEARCH TRAINING PROGRAM

NUCLEAR LIPID-SENSOR IN TYPE II DIABETIC NEUROPATHY

REQUIREMENTS FOR BACTERIAL COLONIZATION OF ANIMAL TISSUE

THE CELL BIOLOGY OF TRIM5ALPHA

SELF-MANAGEMENT IN ADOLESCENTS AND YOUNG ADULTS WITH SPINA BIFIDA