Mediators of fibrosis in the development of lower urinary tract dysfunction

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DESCRIPTION (provided by applicant): The Specific Aims of the UW-Madison George M. O'Brien Urology Cooperative Research Center are: 1. To investigate molecular and cellular biological mechanisms driving fibrosis in the prostates of mice and men; and 2. To investigate the relationship of hormonal, developmental, metabolic, and inflammatory processes in development of fibrosis associated with lower urinary tract dysfunction tract using functional urological testing. Fibrosis is commonly observed in the prostates of men with Benign Prostatic Hyperplasia (BPH) and Lower Urinary Tract Symptoms (LUTS). Fundamental causes of prostatic fibrosis and the relationship of prostatic fibrosis to LUTS remain unclear. The overall goals of this Center are to critically investigate fundamental mechanisms that underlie development of prostatic fibrosis and to determine the relationship between benign prostatic disease and lower urinary tract dysfunction. Our center consists of four research projects, and each incorporates unique models of benign prostatic disease in mice and analysis of tissues from BPH patients to address the objectives of the Center. The Administrative Core will provide oversight and alignment of projects. The Administrative Core will also manage the Educational Enrichment Program and Opportunity Pool. The Biomedical Research Core will provide project leaders and other investigators with the resources in mouse urinary function testing and histology to achieve the goals of the research. The Biomedical Core, in cooperation with the NIDDK and other groups, will also develop a robust database to make results and pertinent information generated by the Center and elsewhere readily accessible. This is a new venture and one that is of substantial importance to the urological research community. The long-range goal is to achieve an individualized and mechanistic understanding of LUTS pathophysiology and thereby refine patient selection for existing therapies. We will leverage our extensive institutional resources to develop an outstanding educational enrichment program that incorporates new researchers from all levels into urologic research. By meeting these objectives, this Center will make significant progress toward understanding mechanisms underlying LUTS, resulting in new mechanistically-targeted therapeutic options.