Molecular and neuro-inflammatory biology of aging bladder in normal and disease states

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PROJECT SUMMARY Nearly 50% of post-menopausal women suffer from urinary tract infections (UTIs), and over 25% of post- menopausal women experience burdensome lower urinary tract symptoms (LUTS), including urinary urgency, incontinence, and painful urination. Given that nearly 1.5 billion people will be ≥65 years old worldwide by 2050, we must determine the pathophysiologic basis of these disorders so as to treat and prevent them. Solving this challenge will require an interdisciplinary approach. Thus, this is a proposal to establish an Interdisciplinary Research Center in Benign Urology focused on “Molecular and neuroinflammatory biology of aging bladder in normal and disease states”. The overarching, long-term goal of the Center is to catalyze the rapid translation of breakthroughs in our understanding of chronic inflammation in the aged bladder from the preclinical to the clinical setting. The Center will accomplish this by bringing together an interdisciplinary team of physicians and scientists with diverse areas of expertise to systematically investigate markers and mechanisms driving chronic inflammation and its effects in mouse models and in human patients. The team includes practicing urogynecologists and basic and translational scientists interested in infections, age-associated immune dysfunction, and neurobiology of the bladder. The scientific research project proposes that the culprit behind many recurrent UTI and LUTS cases is a chronic neuro-inflammatory process of the bladder mucosa that can present as cystitis cystica, characterized as aggregates of lymphocytes that appear raised on cystoscopy. The Project has three Aims to define the cellular, molecular, immunological, and neurobiological changes that accompany infection and chronic inflammation in the aged bladder in mice and humans. The Center will include an Administrative Core responsible for fostering synergistic collaborations, integrating with existing NIH- sponsored O'Brien Centers in Urological diseases and urology training programs, and overseeing an Educational Enrichment Program. This Program will arrange visits to Washington University by outside speakers to present seminars relevant to the goals of the Center. The Program will also initiate didactic and practical Summer Scholar Research Experiences in Urogynecology-relevant labs for high school, college, and medical students. Together, the research and educational activities supported by the Center will allow the Team to increase interest in urology research and make substantial inroads into understanding the pathophysiology of recurrent UTIs and LUTS.