This proposal describes a 4-year training program for the development of an academic career in Pediatric Nephrology. Through the scientific work and training proposed herein the principal investigator will expand upon his scientific skills through a carefully mentored training program and develop an independent scientific project to start his own research laboratory. Dr. Keith Mostov is a leader in the field of epithelial cell biology and will mentor the Pl's scientific development. Dr. Mostov is Vice-Chair of the Department of Anatomy and has trained numerous postdoctoral fellows who are now independently funded researchers. Dr. Hiep T. Nguyen will provide technical training in animal surgery, as well as scientific expertise in the field of congenital obstructive nephropathy. In addition, an advisory committee consisting of highly regarded biomedical scientists and clinician scientists will provide scientific and career advice. The proposed research will focus on the role of the protein nectin in renal epithelial cell cystogenesis and obstructive nephropathy. Recent work in Dr. Mostov's laboratory and in collaboration with Dr. Nguyen has demonstrated that over-expression of nectin inhibits apoptosis during cystogenesis as well as following mechanical stretch, an vitro model for obstructive nephropathy.
The specific aims i nclude 1) Determining the effect of over-expression of nectin on apoptosis due to various stimuli in MDCK cells. 2) Characterizing signaling molecules affected by nectin over-expression. 3) Evaluating the effect of disruption of nectin-1 on apoptosis in the unilateral ureteral obstruction model of congenital obstructive nephropathy. The departments of Anatomy and Pediatrics at the University of California, San Francisco provide an ideal setting for training clinician-scientists by providing diverse scientific resources, outstanding senior scientists and a structured mentoring. This environment maximizes the likelihood that the principal investigator will establish an independent scientific niche from which an academic career can be forged.
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