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.

Public Health Relevance

The UW-Madison O'Brien Research Center will provide a complete spectrum of basic science and clinical research activities dedicated towards identifying underlying molecular, cellular, and physiological causes of symptomatic benign prostatic hyperplasia entailing prostatic fibrosis, informing patient treatment decisions, identifying new targets for future treatment, and training the next generation of urologic researchers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54DK104310-01
Application #
8824991
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (O2))
Program Officer
Hoshizaki, Deborah K
Project Start
2014-09-24
Project End
2019-07-31
Budget Start
2014-09-24
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$1,671,757
Indirect Cost
$511,976
Name
University of Wisconsin Madison
Department
Urology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Wegner, Kyle A; Abler, Lisa L; Oakes, Steven R et al. (2018) Void spot assay procedural optimization and software for rapid and objective quantification of rodent voiding function, including overlapping urine spots. Am J Physiol Renal Physiol 315:F1067-F1080
Patalano, Susan; Rodríguez-Nieves, José; Colaneri, Cory et al. (2018) CXCL12/CXCR4-Mediated Procollagen Secretion Is Coupled To Cullin-RING Ubiquitin Ligase Activation. Sci Rep 8:3499
Ruetten, Hannah; Wegner, Kyle A; Romero, Michael F et al. (2018) Prostatic collagen architecture in neutered and intact canines. Prostate 78:839-848
Shea, Michael P; O'Leary, Kathleen A; Wegner, Kyle A et al. (2018) High collagen density augments mTOR-dependent cancer stem cells in ER?+ mammary carcinomas, and increases mTOR-independent lung metastases. Cancer Lett 433:1-9
Joseph, Diya B; Chandrashekar, Anoop S; Abler, Lisa L et al. (2018) In vivo replacement of damaged bladder urothelium by Wolffian duct epithelial cells. Proc Natl Acad Sci U S A 115:8394-8399
Hao, Ling; Wang, Jingxin; Page, David et al. (2018) Comparative Evaluation of MS-based Metabolomics Software and Its Application to Preclinical Alzheimer's Disease. Sci Rep 8:9291
Weaver, Samantha R; Fricke, Hannah P; Xie, Cynthia et al. (2018) Peripartum Fluoxetine Reduces Maternal Trabecular Bone After Weaning and Elevates Mammary Gland Serotonin and PTHrP. Endocrinology 159:2850-2862
Abler, Lisa L; Vezina, Chad M (2018) Links between lower urinary tract symptoms, intermittent hypoxia and diabetes: Causes or cures? Respir Physiol Neurobiol 256:87-96
Cunha, Gerald R; Vezina, Chad M; Isaacson, Dylan et al. (2018) Development of the human prostate. Differentiation 103:24-45
Coriano, Carlos G; Liu, Fabao; Sievers, Chelsie K et al. (2018) A Computational-Based Approach to Identify Estrogen Receptor ?/? Heterodimer Selective Ligands. Mol Pharmacol 93:197-207

Showing the most recent 10 out of 54 publications