Leukocytic Phenotypes Associated with BPH Progression

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OVERALL: SUMMARY The goals of this Center for Benign Urological Diseases are: 1) to create and maintain an environment that supports important and innovative research in the field of benign urology by focusing on a Scientific Research Project examining “Leukocyte phenotypes associated with BPH progression,” 2) to educate and inform young scientists and physicians about BPH, and 3) to develop new interactive projects and collaborations involving other groups in the benign urology research community. The program brings together expertise in basic science, bioinformatics, and clinical urology to apply new technologies in the field of benign urologic research. The research team includes members from the benign and malignant urology fields as well as from non- urologic cancers. Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are highly prevalent and will become increasingly more frequent with an aging demographic. Approximately one- third of BPH patients are resistant to current medical therapy, and a further third of initial responders (around 10% of the total patient population) subsequently develop therapy resistance after an initial positive response. So, for around 40% of the patient population there is no effective medical therapy, leaving surgery as the sole treatment option. Approximately 120,000 surgeries are performed annually in the United States to treat men who are resistant to the available medical interventions. Many of these are elderly patients often with significant co-morbidities who are often not ideal surgical candidates. BPH is closely associated with pro- inflammatory co-morbidities. However, the characteristics and pathways linking immune/inflammatory changes to BPH progression are unclear. We show in preliminary data that TNFα antagonists can reduce the incidence of BPH in patients with autoimmune inflammatory conditions suggesting that a more complete understanding of the leukocyte signaling network in the prostate could elucidate new therapeutic targets. This proposal will utilize single-cell (sc)RNA-seq to fully characterize the leukocyte population in patients with small prostates and low IPSS scores vs. those with large prostates, high symptom scores, and progression to surgery specifically for a BPH indication. This will provide a comprehensive picture of the cells that are present and will allow for the application of bioinformatics approaches to define the extracellular signaling pathways that are activated in these inflammatory cells as disease progresses. The Administrative Core coordinates all Center activities, maintains financial and administrative oversight, manages the Educational Enrichment Program charged with the education of the next generation of scientists, and informs scientists and clinicians of our work. The Administrative Core also coordinates with the NIDDK and the other IR-BU Centers and integrates our approaches with the wider benign urologic research community.