The goal of this project is to bring together an interdisciplinary team of researchers to test the hypothesis that urine metabolic and proteomic biomarkers can predict the response to therapy for human lower urinary tract symptoms (LUTS) and identify the most appropriate animal models for mechanistic studies of LUTS. Current data are most consistent with the idea that human LUTS has multiple etiologies and multiple manifestations. Plausible etiologies for LUTS include, but are not limited to, benign prostatic hyperplasia, inflammation in the prostate and bladder neck, changes in smooth muscle tone in the prostate and bladder neck, and neurologic changes in the lower urinary tract. Ideally, treatment for LUTS would take into account the different manifestations of disease to achieve more rapid and effective therapy for individual patients. Barriers to achieving this goal include the lack of adequate biomarkers to stratify the different manifestations of human LUTS and a lack of clarity regarding the most appropriate animal models for mechanistic studies of the different manifestations of LUTS. To address these barriers to progress in the field, this project will conduct experiments organized into three Specific Aims.
Aim 1 will identify urine biomarkers of human LUTS using proteomic and metabolomic approaches.
Aim 2 will identify changes in biomarker expression that correlate with effective treatment of LUTS symptoms.
Aim 3 will conduct interspecies comparative studies to identify biomarker similarities among human LUTS patients, mice with bacterial prostatitis, and mice with hormone-induced urinary obstruction. It is anticipated that completion of these Aims will identify biomarkers that can stratify LUTS into different disease sub-types, predict response to therapy, and identify animal models that are most appropriate for investigating the underlying mechanisms associated with different sub-types of LUTS. Completion of these Aims will also create a base of knowledge needed to support a more comprehensive interdisciplinary project to determine the underlying cause(s) of LUTS using human patient data and data from animal models with different manifestations of urinary tract disease.

Public Health Relevance

This project relevant for public health because it will identify new biomarkers that stratify patients with lower urinary tract symptoms (LUTS) into distinct groups, and biomarkers for LUTS that are predictive for treatment efficacy. This information will facilitate future efforts to achieve better patient outcomes through individualized treatment choices. This project will also identify animal models that are best suited to particular.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory Grants (P20)
Project #
3P20DK097826-02S2
Application #
8848292
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Hoshizaki, Deborah K
Project Start
2012-09-29
Project End
2015-08-31
Budget Start
2014-07-01
Budget End
2015-08-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Urology
Type
Schools of Medicine
DUNS #
City
Madison
State
WI
Country
United States
Zip Code
53715
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