This application requests support to establish a Kidney and Urology Research Center at the University of Virginia. The central theme of the proposed P-50 Center is to investigate the neurovascular basis of renal and urogenital disorders in children. Novel model systems are exploited in single cells, isolated tissues, and/or whole animals to address the cellular and molecular mechanisms underlying clinically relevant disorders that affect renal and genitourinary function in children. The P-50 Center will have a synergistic impact on basic research programs in pediatric aspects of both nephrology and urology at the University of Virginia Medical Center. The administrative and investigative framework of the proposed center will unify three disparate resources available to basic and clinical scientists who study and treat diseases of the kidney and urogenital system. First, the P-50 award will supplement the university's investment in faculty, staff, and space by providing critical support for research projects and a core laboratory in immunocytochemistry. The center will promote technically sophisticated studies of vascular, smooth muscle or white blood cell function. Second, the P-50 award will extend NIH's investment in grants supporting basic studies in renal and urological disease at this institution by allowing us to develop a unique center where nephrologists and urologists can share a productive common ground in basic research at significant cost savings to NIH. Third, the proposed P-50 Center will provide a mechanism to integrate the advanced training of the next generation of academic urologists and pediatric nephrologists with our ongoing and proposed studies of the cellular and molecular aspects of renal and urologic disease. Six research projects are proposed under a common theme: neurovascular cell biology of the developing kidney and urogenital system. Specific topics include: 1) studies of atrial natriuretic peptide and the renin-angiotensin system in sodium homeostasis, 2) renin gene expression in smooth muscle cells of intrarenal arterioles, 3) studies of the mechanisms and treatments for testicular torsion, 4) cell and molecular physiology of microvessel failure in ischemic disorders of the developing testis, 5) the impact of congenital or accidental obstruction of the vas deferens/epididymis on testicular development, and 6) cellular and molecular mechanisms directing the innervation and function of developing bladder smooth muscle. Harnessing all six projects to the proposed P-50 Center will catalyze interdisciplinary approaches among project leaders who have the tradition, training, and commitment to develop and fully explore innovative questions about renal/urogenital performance in health and diseased states. The proposed integration of basic research in pediatric aspects of both nephrology and urology provides an exceptional opportunity to uncover the mechanisms of neurovascular complications in kidney and genitourinary disorders afflicting children.
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