This Mentored Clinical Scientist Development award could give the candidate financial freedom to devote a vast percentage of his time to basic science research. It is his ultimate goal to become an independent investigator in pediatric urology based on the skills, knowledge, and personal interactions he will acquire during this initial investigate period. He has a proven inclination toward research originality and performance and combined with excellent leadership and guidance of Dr. Iekuni Ichikawa his goals of attaining career as an independent researcher can be attained. The first two years of this award will be largely devoted to didactic and bench education of the candidate. The final years will be devoted to learning more advanced laboratory skills as well as to gaining financial and investigative independence. This will be done in the context of investigating the role of the renin-angiotensin system in the development of the kidney and urinary tract. The scientific portion of this application is summarized as follows: When perfusion pressure to the kidney falls as a result of mechanical hindrance to the renal arterial blood flow, the renal synthesis of angiotensin (Ang) surges. Ang continues to increased until sufficient Ang effectively raises systematic blood pressure so that the perfusion pressure to the kidney returns to a near baseline level. In this context, the kidney as a high efficient feedback mechanism to preserve it sown environment. A surge of renal Ang synthesis also occurs when there is a mechanical hindrance to urine outflow. This phenomenon of ureteral pressure- sensitive activation of Ang has been heretofore viewed merely as an error of nature. Studies on mutant mice (lacking the gene involving the synthesis or action of Ang) generated in the PI's laboratory drastically revise this traditional view. The results indicate RAS as a mechanism to protect kidneys from obstructive injury during organogenesis. Further studies are underway to pursue these findings.
