Vasa Inc

AC5 INHIBITOR FOR HEART FAILURE

ADENYLYL CYCLASE TYPE 5 INHIBITION TO TREAT MYOCARDIAL INFARCTION

TRANSLATING A NOVEL THERAPEUTIC APPROACH TO THE TREATMENT FOR IDIOPATHIC PULMONARY FIBROSIS - PROJECT ABSTRACT THE GOAL OF THIS FAST-TRACK SBIR APPLICATION IS TO DEVELOP A NOVEL DRUG CANDIDATE TO TREAT IDIOPATHIC PULMONARY FIBROSIS (IPF). IPF IS A FATAL DISEASE THAT REMAINS UNCURABLE AND CARRIES A MEDIAN SURVIVAL OF 2-3 YEARS POST DIAGNOSIS. THE TWO CURRENT FDA-APPROVED DRUGS NINTEDANIB AND PIRFENIDONE MARGINALLY EXTEND QUALITY-ADJUSTED LIFE YEARS WHILE PRESENTING SEVERE LIFE-ALTERING SIDE EFFECTS, RESULTING IN EXTREMELY POOR COMPLIANCE. CURRENT PIPELINE THERAPEUTICS ARE FOCUSED ON MORE EFFECTIVE TARGETS TO IMPROVE FUNCTIONAL OUTCOMES BUT MANY, IF NOT ALL, PRESENT SIGNIFICANT SAFETY CONCERNS BY TARGETING CRITICAL, SYSTEMICALLY ACTIVE RECEPTORS AND INTRACELLULAR SIGNALING PROTEINS. OUR TOOL COMPOUND, VSR-H5, HAS DEMONSTRATED AN ABILITY TO 1) SPECIFICALLY TARGET ONLY REGIONS OF ONGOING FIBROSIS WITHIN DIAGNOSED IPF PATIENT LUNG TISSUES WHILE NOT BINDING HEALTHY TISSUES/REGIONS; 2) SELECTIVELY INHIBIT ACTIVATION OF PATIENT-DERIVED FIBROBLASTS’ ON PRO-FIBROTIC MIMETIC EXTRACELLULAR MATRIX (ECM) IN VITRO; AND 3) MITIGATE FIBROSIS PROGRESSION IN MULTIPLE IN VIVO MOUSE MODELS OF LUNG FIBROSIS AND A CLEAN TOX PROFILE. OUR APPROACH SPECIFICALLY AVOIDS SYSTEMIC DISRUPTION OF CRITICAL, NORMAL RECEPTOR ENGAGEMENT BY TARGETING A UNIQUE, CRYPTIC EPITOPE THAT IS ONLY EXPOSED IN TISSUES UNDERGOING ACTIVE FIBROSIS. IN THIS PROPOSAL WE WILL FIRST (PHASE I) PERFORM AFFINITY MATURATION AND LIABILITY ASSESSMENT AND REMOVAL TO CREATE A POOL OF CANDIDATE ANTIBODY DRUGS. THEN IN PHASE II WE WILL PERFORM SUCCESSIVE SELECTION ASSAYS TO ESTABLISH OUR PRIMARY DRUG CANDIDATE FROM THE POOL GENERATED IN PHASE I AND THEN FURTHER ESTABLISH ITS TRANSLATABILITY THROUGH A SERIES OF PK/PD, TOXICITY/SAFETY, AND EFFICACY ANALYSES IN ESTABLISHED ANIMAL MODELS, WHILE EXPLORING POTENTIAL FORMULATIONS FOR FUTURE PROCESS DEVELOPMENT AND MANUFACTURING. AT THE SUCCESSFUL CONCLUSION OF THIS PROJECT, WE WILL BE POISED TO DESIGN AND INITIATE IND-ENABLING STUDIES.

PREVENTION OF CARDIAC CELL DEATH BY MST1 INHIBITOR

THE LEGAL ASSISTANCE FOR VICTIMS (LAV) GRANT PROGRAM, AUTHORIZED BY AUTHORIZED BY 34 U.S.C. 20121, IS INTENDED TO INCREASE THE AVAILABILITY OF CIVIL AND CRIMINAL LEGAL ASSISTANCE NEEDED TO EFFECTIVELY AID ADULT AND YOUTH (AGES 11 TO 24) VICTIMS OF DOMESTIC VIOLENCE, DATING VIOLENCE, STALKING, OR SEXUAL ASSAULT, BY PROVIDING FUNDS FOR COMPREHENSIVE DIRECT LEGAL SERVICES TO VICTIMS IN LEGAL MATTERS RELATING TO OR ARISING OUT OF THAT ABUSE OR VIOLENCE. LEGAL ASSISTANCE IS ASSISTANCE IN: A) DIVORCE, PARENTAL RIGHTS, CHILD SUPPORT, TRIBAL, TERRITORIAL, IMMIGRATION, EMPLOYMENT, ADMINISTRATIVE AGENCY, HOUSING, CAMPUS, EDUCATION, HEALTHCARE, PRIVACY, CONTRACT, CONSUMER, CIVIL RIGHTS, PROTECTION OR OTHER INJUNCTIVE PROCEEDINGS, RELATED ENFORCEMENT PROCEEDINGS, AND OTHER SIMILAR MATTERS; B) CRIMINAL JUSTICE INVESTIGATIONS, PROSECUTIONS, AND POST-CONVICTION MATTERS (INCLUDING SENTENCING, PAROLE, AND PROBATION) THAT IMPACT THE VICTIMS SAFETY, PRIVACY, OR OTHER INTERESTS AS A VICTIM; C) ALTERNATIVE DISPUTE RESOLUTION, RESTORATIVE PRACTICES, OR OTHER PROCESSES INTENDED TO PROMOTE VICTIM SAFETY, PRIVACY, AND AUTONOMY, AND OFFENDER ACCOUNTABILITY, REGARDLESS OF COURT INVOLVEMENT; OR D) POST-CONVICTION RELIEF PROCEEDINGS IN STATE, LOCAL, TRIBAL, OR TERRITORIAL COURT, WITH RESPECT TO A CONVICTION OF A VICTIM RELATING TO OR ARISING FROM DOMESTIC VIOLENCE, DATING VIOLENCE, SEXUAL ASSAULT, STALKING, OR SEX TRAFFICKING VICTIMIZATION OF THE VICTIM. THROUGH THIS CONTINUATION LEGAL ASSISTANCE FOR VICTIMS PROJECT, SOUTH CAROLINA COALITION AGAINST DOMESTIC VIOLENCE & SEXUAL ASSAULT, IN PARTNERSHIP WITH ITS 22 MEMBER ORGANIZATIONS, WILL PROVIDE HOLISTIC LEGAL SERVICES TO VICTIMS OF DOMESTIC VIOLENCE, SEXUAL ASSAULT, DATING VIOLENCE, AND STALKING IN SOUTH CAROLINA. THE PROJECT WILL ADDRESS PRIORITY AREA 3: UNDERSERVED COMMUNITIES.

THE OVW STATE AND TERRITORY DOMESTIC VIOLENCE AND SEXUAL ASSAULT COALITIONS PROGRAM, AUTHORIZED BY 34 U.S.C. § 10441(C), SUPPORTS THE CRITICAL WORK OF STATE AND TERRITORY DOMESTIC VIOLENCE AND SEXUAL ASSAULT COALITIONS AND IS A SET-ASIDE PROGRAM UNDER THE OVW STOP VIOLENCE AGAINST WOMEN FORMULA GRANT PROGRAM STATUTE. THESE ORGANIZATIONS PLAY AN IMPORTANT ROLE IN ADVANCING THE GOAL OF ENDING DOMESTIC VIOLENCE, DATING VIOLENCE, SEXUAL ASSAULT, AND STALKING. GRANT FUNDS MAY BE USED FOR THE FOLLOWING ACTIVITIES: PROVIDING TRAINING AND TECHNICAL ASSISTANCE TO MEMBER ORGANIZATIONS, EXPANDING THE TECHNOLOGICAL CAPACITY OF COALITIONS AND/OR MEMBER ORGANIZATIONS, DEVELOPING OR ENHANCING APPROPRIATE STANDARDS OF SERVICES FOR MEMBER PROGRAMS, INCLUDING CULTURALLY APPROPRIATE SERVICES FOR UNDERSERVED POPULATIONS, CONDUCTING STATEWIDE, REGIONAL AND/OR COMMUNITY-BASED MEETINGS OR WORKSHOPS FOR VICTIM ADVOCATES, SURVIVORS, LEGAL SERVICE PROVIDERS, AND CRIMINAL JUSTICE REPRESENTATIVES, BRINGING LOCAL PROGRAMS TOGETHER TO IDENTIFY GAPS IN SERVICES AND TO COORDINATE ACTIVITIES, INCREASING THE REPRESENTATION OF UNDERSERVED POPULATIONS IN COORDINATION ACTIVITIES, ENGAGING IN ACTIVITIES THAT PROMOTE COALITION-BUILDING AT THE LOCAL AND/OR STATE LEVEL, OR COORDINATING AT THE FEDERAL, STATE AND TERRITORY LEVEL WITH JUDICIAL OR LOCAL LAW ENFORCEMENT AGENCIES TO DEVELOP OR ENHANCE STRATEGIES. THIS PROGRAM ALSO INCLUDES A STATUTORY SET ASIDE FROM THE SEXUAL ASSAULT SERVICES PROGRAM (SASP) STATUTE, SPECIFICALLY FOR STATE AND TERRITORY SEXUAL ASSAULT COALITIONS (34 U.S.C. § 12511(D)).

LAV PROJECT

GRANTS TO STATE DOMESTIC VIOLENCE AND SEXUAL ASSAULT COALITIONS

2019 STATE AND TERRITORIAL SEXUAL ASSAULT AND DOMESTIC VIOLENCE COALITIONS PROGRAM

FY 2015 GRANTS TO STATE SEXUAL ASSAULT AND DOMESTIC VIOLENCE COALITIONS PROGRAM

SCCADVSA COALITION GRANT

GRANT TO STATE SEXUAL ASSAULT AND DOMESTIC VIOLENCE COALITIONS

SOUTH CAROLINA COALITION AGAINST DOMESTIC VIOLENCE AND SEXUAL ASSAULT

SDVC-2025 - STATEWIDE DOMESTIC VIOLENCE COALITION

THE OVW STATE AND TERRITORY DOMESTIC VIOLENCE AND SEXUAL ASSAULT COALITIONS PROGRAM, (COALITIONS PROGRAM, CFDA 16.556) IS AUTHORIZED BY 34 U.S.C. 10441(C) AND 34 U.S.C. 12511(D). THIS GRANT PROGRAM SUPPORTS THE CRITICAL WORK OF STATE AND TERRITORY DOMESTIC VIOLENCE AND SEXUAL ASSAULT COALITIONS. IT IS A SET-ASIDE PROGRAM UNDER THE OVW STOP VIOLENCE AGAINST WOMEN FORMULA GRANT PROGRAM STATUTE AND ALSO INCLUDES A STATUTORY SET ASIDE FROM THE SEXUAL ASSAULT SERVICES PROGRAM (SASP) STATUTE, SPECIFICALLY FOR STATE AND TERRITORY SEXUAL ASSAULT COALITIONS. GRANT FUNDS AUTHORIZED UNDER THE STOP SET-ASIDE MAY BE USED FOR ONE OR MORE OF THE FOLLOWING PURPOSES: 1. COORDINATING STATE AND TERRITORY VICTIM SERVICES ACTIVITIES. 2. COLLABORATING AND COORDINATING WITH FEDERAL, STATE, TERRITORY, AND LOCAL ENTITIES ENGAGED IN VIOLENCE AGAINST WOMEN ACTIVITIES. GRANT FUNDS AUTHORIZED UNDER THE SASP SET-ASIDE MAY BE USED FOR ONE OR MORE OF THE FOLLOWING PURPOSES: A) WORKING WITH LOCAL SEXUAL ASSAULT PROGRAMS AND OTHER PROVIDERS OF DIRECT SERVICES TO ENCOURAGE APPROPRIATE RESPONSES TO SEXUAL ASSAULT WITHIN THE STATE OR TERRITORY. B) WORKING WITH JUDICIAL OR LAW ENFORCEMENT AGENCIES TO ENCOURAGE APPROPRIATE RESPONSES TO SEXUAL ASSAULT CASES. C) WORKING WITH COURTS, CHILD PROTECTIVE SERVICES AGENCIES, AND CHILDRENS ADVOCATES TO DEVELOP APPROPRIATE RESPONSES TO CHILD CUSTODY AND VISITATION ISSUES WHEN SEXUAL ASSAULT HAS BEEN DETERMINED TO BE A FACTOR. D) DESIGNING AND CONDUCTING PUBLIC EDUCATION CAMPAIGNS. E) PLANNING AND MONITORING THE DISTRIBUTION OF GRANTS AND GRANT FUNDS TO THEIR STATE OR TERRITORY. F) COLLABORATING WITH AND INFORMING FEDERAL, STATE, OR LOCAL PUBLIC OFFICIALS AND AGENCIES TO DEVELOP AND IMPLEMENT POLICIES TO REDUCE OR ELIMINATE SEXUAL ASSAULT.

SDVC-2024

STC6-2022

THE OVW STATE AND TERRITORY DOMESTIC VIOLENCE AND SEXUAL ASSAULT COALITIONS PROGRAM, (COALITIONS PROGRAM, CFDA 16.556) IS AUTHORIZED BY 34 U.S.C. 10441(C) AND 34 U.S.C. 12511(D). THIS GRANT PROGRAM SUPPORTS THE CRITICAL WORK OF STATE AND TERRITORY DOMESTIC VIOLENCE AND SEXUAL ASSAULT COALITIONS. IT IS A SET-ASIDE PROGRAM UNDER THE OVW STOP VIOLENCE AGAINST WOMEN FORMULA GRANT PROGRAM STATUTE AND ALSO INCLUDES A STATUTORY SET ASIDE FROM THE SEXUAL ASSAULT SERVICES PROGRAM (SASP) STATUTE, SPECIFICALLY FOR STATE AND TERRITORY SEXUAL ASSAULT COALITIONS. GRANT FUNDS AUTHORIZED UNDER THE STOP SET-ASIDE MAY BE USED FOR ONE OR MORE OF THE FOLLOWING PURPOSES: 1. COORDINATING STATE AND TERRITORY VICTIM SERVICES ACTIVITIES. 2. COLLABORATING AND COORDINATING WITH FEDERAL, STATE, TERRITORY, AND LOCAL ENTITIES ENGAGED IN VIOLENCE AGAINST WOMEN ACTIVITIES. GRANT FUNDS AUTHORIZED UNDER THE SASP SET-ASIDE MAY BE USED FOR ONE OR MORE OF THE FOLLOWING PURPOSES: A) WORKING WITH LOCAL SEXUAL ASSAULT PROGRAMS AND OTHER PROVIDERS OF DIRECT SERVICES TO ENCOURAGE APPROPRIATE RESPONSES TO SEXUAL ASSAULT WITHIN THE STATE OR TERRITORY. B) WORKING WITH JUDICIAL OR LAW ENFORCEMENT AGENCIES TO ENCOURAGE APPROPRIATE RESPONSES TO SEXUAL ASSAULT CASES. C) WORKING WITH COURTS, CHILD PROTECTIVE SERVICES AGENCIES, AND CHILDRENS ADVOCATES TO DEVELOP APPROPRIATE RESPONSES TO CHILD CUSTODY AND VISITATION ISSUES WHEN SEXUAL ASSAULT HAS BEEN DETERMINED TO BE A FACTOR. D) DESIGNING AND CONDUCTING PUBLIC EDUCATION CAMPAIGNS. E) PLANNING AND MONITORING THE DISTRIBUTION OF GRANTS AND GRANT FUNDS TO THEIR STATE OR TERRITORY. F) COLLABORATING WITH AND INFORMING FEDERAL, STATE, OR LOCAL PUBLIC OFFICIALS AND AGENCIES TO DEVELOP AND IMPLEMENT POLICIES TO REDUCE OR ELIMINATE SEXUAL ASSAULT.

SDC6-2021

TARGETING A DISEASE-SPECIFIC CONFORMATION OF FIBRONECTIN AS A NOVEL APPROACH FOR LIVER FIBROSIS TREATMENT - PROJECT ABSTRACT THE OVERARCHING GOAL OF THIS PHASE I STTR APPLICATION IS TO EVALUATE THE IN VIVO EFFICACY OF A NOVEL APPROACH TO HEPATIC FIBROSIS TREATMENT AND TO EXPLORE ITS CLINICAL TRANSLATABILITY. HEPATIC FIBROSIS IS A PROGRESSIVE LIVER DISEASE CAUSED BY MULTIPLE ETIOLOGIES AND CAN BE SEEN IN MOST PATIENTS WITH CHRONIC LIVER INJURY. WHILE INITIALLY REVERSIBLE, HEPATIC FIBROSIS IS OFTEN LEFT UNTREATED DUE TO ITS ASYMPTOMATIC NATURE AND THUS CAN PROGRESS INTO AN IRREVERSIBLE LATE STAGE RESULTING IN LIVER CIRRHOSIS, PORTAL HYPERTENSION, LIVER FAILURE, AND EVENTUALLY, DEATH. UNFORTUNATELY, THERE ARE CURRENTLY NO FDA-APPROVED DRUGS AVAILABLE TO TREAT LIVER FIBROSIS. VSR-H5 IS A NOVEL THERAPEUTIC THAT SPECIFICALLY TARGETS A UNIQUE EPITOPE WITHIN THE EXTRACELLULAR MATRIX (ECM) ONLY IN AREAS OF UNDERGOING ACTIVE ECM REMODELING AND FIBROGENESIS, DISRUPTING PRO-FIBROTIC MYOFIBROBLAST ACTIVATION. THIS NOVEL APPROACH SPECIFICALLY AVOIDS SYSTEMIC DISRUPTION OF CRITICAL, NORMAL INTEGRIN RECEPTOR ENGAGEMENT, THUS REPRESENTS AN APPROACH THAT CAN ACHIEVE BOTH HIGH POTENCY AND STRONG SAFETY. IN THIS PROPOSAL WE WILL EXPLORE TWO AIMS: 1) ESTABLISH THE IN VIVO EFFICACY OF VSR- H5 IN TREATING LIVER FIBROSIS USING A WELL-ESTABLISHED CARBON TETRACHLORIDE (CCL4)-INDUCED MOUSE LIVER FIBROSIS MODEL; AND 2) DETERMINE THE CLINICAL TRANSLATABILITY OF VSR-H5 BY CONFIRMING THE PRESENCE OF THE TARGET EPITOPE IN HUMAN CIRRHOTIC LIVER TISSUE AND EVALUATING THE ANTIBODY'S ABILITY TO REVERSE FIBROTIC CELLULAR PHENOTYPES IN PRIMARY HUMAN LIVER STELLATE CELLS OUR ESTABLISHED AND VALIDATED HUMAN IN VITRO FIBROSIS MODEL. SUCCESSFUL COMPLETION OF THIS PHASE I STTR WILL PROVIDE THE DATA NECESSARY TO JUSTIFY FURTHER INVESTMENT IN THIS STRATEGY TOWARD TREATING LIVER FIBROSIS.

SDVC-2020

SDVC-2023

SDVC-2021

FY 2021 OVW STATE AND TERRITORY COALITIONS GRANT PROGRAM

RAPE PREVENTION AND EDUCATION: ENHANCING CAPACITY FOR SEXUAL VIOLENCE PREVENTION IN RURAL COUNTIES OF SOUTH CAROLINA.

CELL PERMEANT PEPTIDOMIMETICS TO PREVENT DELAYED VASOSPASM AND NEUROLOGICAL DEFICITS AFTER SUBARACHNOID HEMORRHAGE - PROJECT SUMMARY SUBARACHNOID HEMORRHAGE (SAH) DUE TO RUPTURE OF AN INTRACRANIAL ANEURYSM LEADS TO DELAYED VASOSPASM RESULTING IN NEUROISCHEMIA (STROKE). THE OVERALL MORBIDITY (PROFOUND NEUROLOGIC DEFICIT IN 10-20% OF SURVIVORS) AND MORTALITY (50%) ARE HIGH, AND THE DISEASE AFFECTS A RELATIVELY YOUNG ADULT POPULATION. THERAPEUTIC OPTIONS TO PREVENT DELAYED VASOSPASM AND NEUROISCHEMIA AFTER SAH ARE CURRENTLY LIMITED TO HEMODYNAMIC OPTIMIZATION AND NIMODIPINE, WHICH HAVE MARGINAL CLINICAL EFFICACY. THUS, TREATMENT OF DELAYED VASOSPASM AFTER SAH REPRESENTS AN UNMET CLINICAL NEED IN AN ORPHAN POPULATION WITH SEVERE CLINICAL CONSEQUENCES. ATTEMPTS TO TREAT SAH-INDUCED VASOSPASM WITH EXISTING VASODILATORS OFTEN FAIL BECAUSE OF SYSTEMIC HYPOTENSION (LEADING TO DECREASED CEREBRAL PERFUSION) AND A CEREBRAL VASCULATURE THAT IS REFRACTORY TO ACTIVATION OF NITRIC OXIDE (NO)-DEPENDENT SIGNALING PATHWAYS.5 NO SIGNALING MODULATES VASCULAR SMOOTH MUSCLE (VSM) RELAXATION AND REGULATION OF CEREBRAL BLOOD FLOW. THE IMPAIRED RESPONSE OF CEREBRAL VESSELS TO VASODILATORS, I.E. IMPAIRED VASORELAXATION AFTER SAH, IS LIKELY DUE TO DOWN REGULATION OF THE SIGNALING ELEMENTS IN THE NO PATHWAY AFTER SAH. THE HYPOTHESIS OF THIS INVESTIGATION IS THAT TREATMENT WITH A RATIONALLY DESIGNED, CELL PERMEANT PHOSPHOPEPTIDE MIMETIC OF A DOWNSTREAM EFFECTOR PROTEIN OF THE NO PATHWAY WILL BYPASS DOWNREGULATED SIGNALING ELEMENTS, RESTORE VASORELAXATION, AND PREVENT DELAYED VASOSPASM AFTER SAH. THIS APPROACH IS MORE TARGETED AND STOICHIOMETRIC THAN APPROACHES THAT ACTIVATE OR INHIBIT RECEPTORS OR ENZYMES. IN ADDITION, THIS APPROACH IS PARTICULARLY USEFUL IN SAH WHERE PREVENTING SYSTEMIC HYPOTENSION AND OPTIMIZING CEREBRAL VASODILATION IS PARAMOUNT. A FAMILY OF CELL PERMEANT PHOSPHOPEPTIDE ANALOGUES OF A SUBSTRATE OF CGMP-DEPENDENT PROTEIN KINASE (PKG), AND AN ACTIN-ASSOCIATED PROTEIN THAT MODULATES VSM RELAXATION, WERE RATIONALLY DESIGNED AND SYNTHESIZED. THREE CANDIDATE PEPTIDES WERE DEMONSTRATED TO DIRECTLY RELAX INTACT VSM IN EX VIVO BIOACTIVITY ASSAYS. THE PEPTIDE WITH THE SHORTEST SEQUENCE (DENOTED AS VP3) AND STRONGEST BIOACTIVITY WAS CHOSEN AS THE OPTIMAL PEPTIDE FOR USE TO DETERMINE IN VIVO EFFICACY.

SDVC-2019

2017 SDVC

2016 SDVC

A NOVEL PHARMACOLOGICAL INHIBITOR OF ADENYLYL CYCLASE TYPE 5 TO TREAT ALZHEIMER'S DISEASE - PROJECT SUMMARY: ALZHEIMER’S DISEASE IS ASSOCIATED WITH METABOLIC DYSFUNCTION, GLUCOSE AND INSULIN RESISTANCE, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, AND REDUCED EXERCISE CAPACITY. OXIDATIVE STRESS AND MITOCHONDRIAL DYSFUNCTION CORRELATE WITH THE DEVELOPMENT OF BETA-AMYLOID (ASS) DEPOSITS, ONE OF THE HALLMARKS OF AD THAT BEGIN YEARS BEFORE THE ONSET OF MEMORY AND COGNITIVE DECLINE. MOREOVER, PATIENTS WITH AD HAVE A REDUCED LIFESPAN. ACCORDINGLY, IT WOULD BE BENEFICIAL TO EXAMINE NOVEL MODELS OF HEALTHFUL LONGEVITY WITH ENHANCED METABOLISM, GLUCOSE AND INSULIN TOLERANCE, EXERCISE CAPACITY, AND PROTECTION AGAINST OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, AND APOPTOSIS. ALL THESE FEATURES ARE PRESENT IN THE ADENYLYL CYCLASE TYPE 5 (AC5) KNOCK OUT (KO) MOUSE, WHICH EXHIBITS HEALTHFUL LONGEVITY, ASSOCIATED WITH ALL MAJOR MOLECULAR FACTORS THAT PROTECT AGAINST AD. ADENYLYL CYCLASE (AC) INDUCES CYCLIC AMP (CAMP) AND, THEREFORE, REGULATES SYMPATHETIC CONTROL AND SS-ADRENERGIC RECEPTOR (SS- AR) SIGNALING, AND IS THUS A KEY REGULATOR OF HEALTH AND LONGEVITY IN ORGANISMS RANGING FROM YEAST TO MAMMALS. AC5 IS ONE OF TEN AC ISOFORMS AND IS EXPRESSED IN VIRTUALLY EVERY ORGAN IN THE BODY, INCLUDING THE BRAIN. IN SUPPORT OF ITS ROLE IN AGING, WE HAVE FOUND THAT DISRUPTION OF AC5 (AC5 KO) PROMOTES HEALTHFUL LONGEVITY, ENHANCES EXERCISE PERFORMANCE AND PROTECTS AGAINST DIABETES AND HEART FAILURE, ALL OF WHICH SHOULD BE HELPFUL IN PROTECTING AGAINST ALZHEIMER’S DISEASE. OUR PRELIMINARY DATA ALSO SHOW THAT AC5 KO MICE PERFORM BETTER ON MEMORY AND MOTOR TASKS COMPARED TO WILD-TYPE MICE. IN CONTRAST, THE ALZHEIMER MODEL J20 MICE, A TRANSGENIC ANIMAL THAT OVEREXPRESSES MUTANT HUMAN AMYLOID PRECURSOR PROTEIN (APP), EXHIBITS MEMORY LOSS AS EXPECTED. A PHARMACOLOGICAL INHIBITOR OF AC5 IS THE GOAL FOR CLINICAL TRANSLATION. WE HAVE DEVELOPED A PHARMACOLOGICAL INHIBITOR OF AC5, WHICH IS KNOWN AS C90, AS THE LEAD CANDIDATE FOR THE INHIBITION OF AC5 TARGETING MYOCARDIAL ISCHEMIA. C90 LEADS TO ROBUST INHIBITION OF AC5, HAS HIGH SOLUBILITY AND READILY ABSORBED ORALLY. IT SHOWED EFFICACY IN ANIMAL MODELS OF EXERCISE AND MYOCARDIAL ISCHEMIA. THE MAIN DRAWBACK WITH C90 IS THE PRESENCE OF A HYDROXAMIC ACID GROUP. HYDROXAMATES ARE ASSOCIATED WITH ADVERSE EFFECTS AND ARE OFTEN MUTAGENIC. THE MUTAGENICITY OF THE HYDROXAMATE GROUP IS PROPOSED BE DUE TO ITS REARRANGEMENT TO ISOCYANATE WHICH ACT AS ALKYLATING AGENTS OF DNA. THE GOAL OF THIS APPLICATION IS TO DESIGN AND SYNTHESIZE A NOVEL C90 THAT WOULD RETAIN THE BIOLOGICAL ACTIVITY OF C90, BUT DEVOID OF THE TOXIC LIABILITY OF A HYDROXAMIC ACID GROUP.

2010 SDVC

2009 SDVC

2015 SDVC

SDVC-2018

2014 SDVC

SDVC-2022

2011 SDVC

2012 SDVC

2008 SDVC

2013 SDVC

SOUTH CAROLINA SEXUAL ASSAULT AND DOMESTIC VIOLENCE COALITION GRANT

FLUID MEDICAL (BIOLOGICAL & PHARMACOLOGICAL)WASTE TREATMENT SYSTEM FOR INFECTIOUS DISEASE PREVENTION AND ENVIRONMENTAL PROTECTION

ACUTE CORONARY SYNDROME ANIMAL MODEL

AC5 INHIBITOR FOR OBESITY

ANTIMIR-199A FOR CARDIAC ISCHEMIA AND FAILURE

SDDR-2023

ASSESSING COALITION CAPACITY TO ADVANCE PRIMARY PREVENTION - THE SOUTH CAROLINA COALITION AGAINST DOMESTIC VIOLENCE AND SEXUAL ASSAULT IS NAMED ON THE CDC APPROVED STATE COALITIONS LIST FOR 2023. THIS ABSTRACT IS PROVIDED IN RESPONSE TO FUNDING OPPORTUNITY CDC-RFA-CE-23-0006. SOUTH CAROLINA HAS AMONG THE HIGHEST RATES OF SEXUAL AND INTIMATE PARTNER VIOLENCE IN THE NATION, CONSISTENTLY RANKING AS ONE OF THE MOST DANGEROUS STATES FOR WOMEN. THOSE LIVING IN RURAL AREAS ARE AT EVEN HIGHER RISK OF VICTIMIZATION. RURAL COMMUNITIES FURTHER FUNCTION AS A MULTIPLIER OF IMPACT FOR SUBGROUPS SUCH AS RACIAL AND ETHNIC MINORITY GROUPS, AND SEXUAL AND GENDER MINORITIES. NEARLY 50% (20 OF 46 COUNTIES) OF THE STATE IS CLASSIFIED AS RURAL/NON-METRO. THESE COUNTIES ARE HOME TO APPROXIMATELY 15% OF THE STATE’S POPULATION; MOST RESIDENTS LIVING IN POVERTY LIVE IN THESE RURAL/NON-METRO AREAS. THESE COUNTIES SUFFER SIGNIFICANT LACK OF ACCESS TO HEALTHCARE; INTERVENTION AND PREVENTION SERVICES, AND SOCIAL STRUCTURES THAT SUPPORT AND REINFORCE RISK FACTORS FOR SEXUAL VIOLENCE. THE PURPOSE OF THIS GRANT (PROJECT PERIOD) IS TO ASSESS THE COALITION’S CAPACITY TO ADDRESS THE HEALTH DISPARITIES THAT LEAD TO SEXUAL VIOLENCE IN RURAL AREAS WITH A FOCUS ON SUBGROUPS SUCH AS RACIAL AND ETHNIC MINORITY GROUPS, AND SEXUAL AND GENDER MINORITIES. THIS ASSESSMENT WILL IDENTIFY INFORMATION, RESOURCES, AND TOOLS NEEDED TO REDUCE THE DISPARITIES IN THE 20 RURAL/NONMETRO COUNTIES OF SOUTH CAROLINA. THE INTENDED OUTCOMES OF THIS CAPACITY ASSESSMENT REFLECT THE COALITION’S INTENTION TO INCREASE ITS CAPACITY TO SERVE SOUTH CAROLINA’S AT-RISK RURAL COMMUNITY. EXPECTED OUTCOMES INCLUDE INCREASED STAFF WORKFORCE, AND EXPERTISE IN WORKING WITH THIS POPULATION, INCREASED UNDERSTANDING OF AVAILABLE DATA SOURCES REGARDING HEALTH SERVICES AND CULTURAL RISK FACTORS, INCREASED UNDERSTANDING OF CURRENT AND FUTURE COMMUNITY PARTNERS TO ADDRESS RURAL HEALTH DISPARITIES, AND INCREASED UNDERSTANDING OF CURRENT COALITION TRAINING AND TECHNICAL ASSISTANCE AND EXISTING GAPS IN SERVICE.

SDC3-2020

TO CONDUCT A SERIES OF TWO-DAY WORKSHOPS TO EMPOWER YOUTH TO COMBAT GENDER-BASED VIOLENCE

THE PROJECT INTENDS TO FILL A CRITICAL GAP BY SUPPORTING LOCAL INTEGRATION AND EMPLOYMENT OF REFUGEES WHO CURRENTLY HOLD REFUGEE STATUS IN BIH.

PURPOSE OF THIS PROJECT IS TO CONTRIBUTE TO THE ELIMINATION OF MENSTRUATION (AND MENOPAUSE) STIGMA IN LITHUANIA BY USING CINEMA AS A TOOL FOR EDUCATION.

TO SUPPORT THE EXHIBITION "PAINTED PANORAMAS OF THE NEAR AND FAR EAST."

TO SUPPORT "AN EVENING OF KWUN AND YUEJU CHINESE OPERA," PERFORMANCES OF CHINESE OPERA WHICH WILL DEMONSTRATE TWO CHINESE OPERATIC TRADITIONS.

ASSISTING CROSS CULTURAL VICTIMS OF DOMESTIC AND SEXUAL VIOLENCE

TO SUPPORT A VISIT OF A MEMBER OF THE AMERICAN CINEMA FOUNDATION WHO WILL BE A PART OF AN INTERNATIONAL JURY AT VILNIUS INTERNATIONAL FILM FESTIVAL,

A SYSTEM OF TOOLS TO PROMOTE DEVELOPMENT, COMMUNICATION, AND EDUCATION OF OFF-LABEL MEDICATION USE POLICY