Prostate inflammation increases collagen and voiding dysfunction

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Project Summary/Abstract Few veterinary clinicians pursue a career in urologic research despite working with patients that develop spontaneous voiding dysfunction. The applicant is a uniquely qualified candidate, having a veterinarian’s understanding of animal models, access to patients prone to spontaneous urinary dysfunction, and the basic urologic research training few veterinarians receive. The goal of this fellowship is to provide the applicant with training for a successful career as a veterinary pathologist and translational researcher. The training plan accomplishes this goal by building research study design skills, a strong background in the primary literature, proficiency in basic histopathology, and foundational veterinary knowledge and clinical skills. In addition, the training plan fosters key professional development opportunities by building proficiency in laboratory business skills, mentorship, collaboration, communication, and grantsmanship. The plan includes specific activities for each segment of the applicant’s training and progress will be evaluated by the applicant’s sponsor and thesis committee. The proposed research focuses on prostatic collagen accumulation, which is linked to bothersome lower urinary tract symptoms (LUTS) in aging men. Men with LUTS often have increased frequency and urgency to urinate, difficulty initiating urination, incomplete bladder emptying, decreased urine stream force, and interruption of stream, symptoms that decrease quality of life and for which health care is costly. Mechanisms for prostatic collagen accumulation in humans and canines remain unknown but inflammation has been linked to collagen accumulation. In particular, prostatic interleukin-1-beta (IL-1β) abundance has been correlated with LUTS in men. IL-1β is a mediator of inflammatory responses, and prostatic expression of IL-1β can be manipulated in genetically engineered mice. This training plan will use these genetically engineered mice to test the overarching hypothesis that prostatic IL-1β drives inflammation, fibrosis and voiding dysfunction. The University of Wisconsin-Madison is the ideal environment to conduct these studies because it is the home of an NIH-designated O’Brien Center for Excellence in Benign Urologic Research, one of only three focused on prostate-related disease. The UW-Madison O’Brien Center provides an unparalleled rodent urinary function testing core facility, bimonthly speakers, and numerous opportunities for collaboration. The sponsor of this work, Dr. Vezina, is also a longstanding contributor to the NIDDK-sponsored Genitourinary Development Molecular Anatomy Project (GUDMAP), bringing expertise on detailed molecular mapping, training that will be needed to complete the research aims and throughout the applicant’s career. UW-Madison also has a Veterinary, Pharmacy, and School of Medicine on the same campus, providing access to clinically relevant species, unique resources and further collaborations.