Project 1-Vanderbilt Developmental Center for Translational Research in Benign Urologic Diseases

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Project Summary – Project 01 The complexity of lower urinary tract symptoms (LUTS) leading to benign prostatic hyperplasia (BPH) can coincide with a number of conditions, some of which may be causal to the disease state while others may be a consequence of shared pathophysiologic changes. This complex etiology complicates treatment, with many patients non-responsive or developing resistance to standard therapies including 5α-reductase inhibitors (5ARI) or alpha-adrenergic blockers (alpha-blockers). The overarching goal of this Center is to develop a new resource for research and training for the research community to investigate BPH pathophysiology and drug therapy failure. This Resource Development Project will utilize tissue and data from the Medical Therapy of Prostatic Symptoms (MTOPS) to develop and disseminate gene expression data for extended BPH research. MTOPS randomized men with LUTS to a 5ARI, alpha-blocker, combined 5ARI+alpha blocker, or placebo, and prospectively followed participants for BPH progression. In Aim 1, we conduct RNA-Seq on transitional zone prostate tissue collected at baseline and follow-up among those men with BPH progression (n=98) and a blocked random sample of participants without BPH progression after treatment (n=98). This new resource will provide the community with the data necessary to identify genes, gene sets, and pathways associated with LUTS severity, change in LUTS severity, and resistance to treatment. In Aim 2: we create a web-interface such that investigators may learn about the data resource, conduct initial queries, and obtain gene expression data to test new hypotheses of BPH. This Resource Development Project will utilize our experience in laboratory analyses, data management, and biostatistical and bioinformatic analyses to create the RNA-Seq gene expression library and dissemination platform from the MTOPS human BPH tissue repository. No comparable resource exists with prospectively repeated tissue collection within BPH/LUTS patients before and after treatment. Our vision for this Center is that the resources developed will open the doors for investigators, including junior investigators, to efficiently test new ideas and accelerate the exploration of novel hypotheses of BPH pathophysiology and treatment response/failure.