Veterans Medical Research Foundation of San Diego

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. lang multi-site feasibility of compassion meditation for Veterans with ptsd he overall goal of this application is to leverage an existing compassion meditation (cm) protocol to develop the cognitively based compassion training (cbct-vet) for Veterans with ptsd. Specifically, this project aims to examine the feasibility of a multi-site trial of cbct-vet compared to a relaxation control (veteran.calm); develop procedures for therapist training and fidelity monitoring; and, pilot test multi-modal assessment procedures. If successful, this project could inform the study design of a future larger-scale rct multi- site efficacy study and contribute to the knowledge base of non-pharmacological behavioral approaches for ptsd in undertreated Veterans, a significant public health concern.

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

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.