Veterans Medical Research Foundation Of Sd

TO ENHANCE THE HEALTH OF VETERANS OF ALL GENERATIONS THROUGH RESEARCH AND EDUCATION.

DR. IX - KIDNEY TUBLAR DAMAGE AND DYSFUNCTION IDENTIFY A NOVEL AXIS OF CHRONIC KIDNEY: PATHOLOGIC STUDIES DEMONSTRATE THAT KIDNEY TUBULE INJURY, ATROPHY, AND FIBROSIS ARE COMMON FEATURES OF CHRONIC KIDNEY DISEASE (CKD) AND ARE HIGHLY PREDICTIVE OF PROGRESSION TO DIALYSIS. ESTABLISHED CKD RISK FACTORS INCLUDING HYPERTENSION AND ADVANCED AGE ARE ASSOCIATED WITH TUBULAR INJURY AND FIBROSIS ON BIOPSY. HOWEVER, CURRENT CLINICAL ASSESSMENT OF CKD EVALUATES ONLY GLOMERULAR FUNCTION (GFR) AND GLOMERULAR INJURY (ALBUMINURIA), BUT NOT KIDNEY TUBULAR DYSFUNCTION OR INJURY. THE OVERALL HYPOTHESIS OF THIS APPLICATION IS THAT KIDNEY TUBULAR DYSFUNCTION AND INJURY ARE MEASURABLE CONTRIBUTORS TO CKD PATHOGENESIS AND PROGNOSIS.DYSFUNCTION OF THE KIDNEY TUBULES WILL BE ASSESSED BY THREE INDICES: (1) RENAL TUBULE RESISTANCE TO HORMONE ACTIONS OF FGF23 AND PTH; (2) ACID/BASE HOMEOSTASIS; AND (3) URINE RE-ABSORPTIVE CAPACITY.WE WILL: (1) DETERMINE THE ASSOCIATION OF KIDNEY TUBULAR DYSFUNCTION AND INJURY WITH RISK OF CVD EVENTS, (2) DETERMINE THE ASSOCIATION OF KIDNEY TUBULAR DYSFUNCTION AND INJURY WITH CKD PROGRESSION, AND (3) DETERMINE WHETHER RANDOMIZATION TO INTENSIVE BLOOD PRESSURE MANAGEMENT ARM OF THE TRIAL SLOWS PROGRESSION OF KIDNEY TUBULAR DYSFUNCTION AND INJURY OVER TIME COMPARED WITH STANDARD BLOOD PRESSURE MANAGEMENT.

DR. GUATELLI-ENHANCEMENT OF INFECTIVITY BY HIV-1 VIA ANTAGONISM OF SERINC PROTEINS.THE PURPOSE OF THIS PROJECT IS TO 1) COMBINE OUR BIOCHEMICAL, CELL BIOLOGIC, AND VIROLOGIC ASSAYS TO VALIDATE AND ELABORATE THESE MECHANISMS 2) DETERMINE THE STRUCTURAL BASIS OF SERINC ANTAGONISM BY NEF. WE AIM TO PROVIDE HIGH-RESOLUTION STRUCTURES OF THE INTERACTION OF NEF WITH SERING PROTEINS AND CLATHRIN ADAPTORS. 3) DETERMINE HOW SERING PROTEINS AFFECT INFECTIVITY IN AN ENV-DEPENDENT MANNER. TO FACILITATE AN UNDERSTANDING OF SERINC FUNCTION, WE WILL CHARACTERIZE A FULL-LENGTH PROTEIN BIOPHYSICALLY AND AIM TO PROVIDE A HIGH-RESOLUTION STRUCTURE. WE WILL TEST THE HYPOTHESIS THAT SERINC PROTEINS INTERACT WITH ENV TO INHIBIT INFECTIVITY AND MAP THE INTERACTION. WE WILL DETERMINE WHETHER SERINC PROTEINS AFFECT THE CONFORMATION OF ENV TRIMERS AS DISPLAYED ON THE CELL SURFACE AND ON VIRIONS. LASTLY, WE WILL ELABORATE A MODEL IN WHICH THE CYTOPLASMIC DOMAIN OF ENV CONTRIBUTES TO COUNTERACTION OF SERING PROTEINS. WHEN THE PROPOSED EXPERIMENTS ARE COMPLETE, WE SHOULD HAVE A HIGH RESOLUTION MECHANISTIC UNDERSTANDING OF HOW NEF COUNTERACTS THE INHIBITORY INFLUENCE OF THE SERINC PROTEINS ON VIRAL INFECTIVITY, AND A MODEL FOR HOW THE ACTIVITY OF ENV IS INHIBITED BY THESE PROTEINS

DR. GUPTA POST-POLYPECTOMY SURVEILLANCE FOR REDUCING COLON CANCER INCIDENCE AND MORTALITY - OUR SPECIFIC AIMS ARE TO DETERMINE WHETHER POST-POLYPECTOMY SURVEILLANCE COLONOSCOPY REDUCES COLORECTAL CANCER (CRC) INCIDENCE (AIM 1) AND MORTALITY (AIM 2). WE HYPOTHESIZE THAT GUIDELINE-RECOMMENDED SURVEILLANCE REDUCES CRC INCIDENCE AND MORTALITY. TO ACCOMPLISH THESE GOALS, WE PLAN TO CONDUCT A CASE-COHORT STUDY. THE STUDY BASE CONSISTS OF VETERANS WHO HAD A BASELINE COLONOSCOPY WITH POLYPECTOMY. FROM THE STUDY BASE, WE WILL IDENTIFY ALL INDIVIDUALS WITH INCIDENT AND/OR FATAL CRC SUBSEQUENT TO BASELINE POLYPECTOMY. INCIDENT AND FATAL CRC WILL BE ASCERTAINED BY THE ONCOLOGY DOMAIN AND THE NATIONAL DEATH INDEX (NDI), RESPECTIVELY. ELECTRONIC HEALTH RECORDS (EHRS) FOR CANDIDATE CASES AND SUB COHORT MEMBERS WILL BE REVIEWED TO ASSESS INCLUSION AND EXCLUSION CRITERIA. WE WILL INCLUDE ALL INDIVIDUALS CONFIRMED TO HAVE HAD BASELINE POLYPECTOMY OF AN ADENOMA OR SESSILE SERRATED ADENOMA/POLYP (SSA/P) WITH EXAM COMPLETE TO THE CECUM. WE WILL EXCLUDE INDIVIDUALS THAT HAD POOR BOWEL PREP, AS WELL AS THOSE WITH INCREASED RISK FOR CRC (DEFINED AS PRIOR OR BASELINE CRC, PRIOR OR BASELINE INFLAMMATORY BOWEL DISEASE, FAMILY HISTORY OF CRC, AND/OR ANY KNOWN HEREDITARY CANCER SYNDROMES).

VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO, WHERE WE HONOR SERVICE WITH SCIENCE, IS THE REGION'S ONLY MEDICAL RESEARCH INSTITUTE DEDICATED TO VETERANS. WE FACILITATE WORLD-CLASS RESEARCH AT THE VA SAN DIEGO HEALTHCARE SYSTEM THAT PROVIDES IMPROVEMENTS FOR VETERANS' HEALTHCARE. WHILE FOCUSED ON VETERANS, OUR MEDICAL ADVANCES EXTEND TO THE ENTIRE POPULATION AND RAISE THE STANDARD OF CARE FOR EVERYONE.