# Cellular and molecular mediators of fibrosis in the development of urinary tract dysfunction

> **NIH NIH U54** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $3,177

## Abstract

PROJECT SUMMARY- OVERALL
No consequential advances in medical treatment of prostate-related lower urinary tract symptoms (LUTS) have
emerged in decades. Existing medical therapies improve LUTS but robustness of these effects are marginal.
Not all men respond to existing therapies, some respond with adverse effects requiring discontinuation of
therapy, and most experience a progressive worsening of symptoms pursuant to initial relief. Multiple
mechanisms drive development and progression of prostate-related LUTS. The overarching goal of the O’Brien
Center for Benign Urology Research is to identify mechanisms that result in lower urinary tract dysfunction and
prostate-related LUTS. The overarching hypothesis of the center is that fibrosis is a cause of male LUTS. In
contrast to benign prostatic enlargement and smooth muscle dysfunction, prostatic fibrosis remains untargeted
by existing therapies. In order to advance the scientific understanding and medical management of prostatic
fibrosis, it will be necessary to: (1) identify cellular and molecular mediators of fibrosis and therapeutically-
susceptible pathways using clinical specimens, (2) develop and validate preclinical mouse models of prostatic
fibrosis and strategies for granular assessment of voiding function, (3) test new therapies in these preclinical
models with the long term goal of treating fibrosis in men, and (4) develop new non-invasive radiologic imaging
strategies with the long-term goal of diagnosing prostatic fibrosis in men. Two additional goals will advance the
urologic research community: (1) develop and publicly disseminate resources to increase research efficiency,
reproducibility, and rigor, and (2) cultivate an outstanding educational enrichment program to attract and retain
young basic- and physician-scientists into the benign urologic research field. The Center will apply state of the
art molecular and histological methods to visualize and characterize fibrosis in a range of human and animal
prostatic tissues and examine how prostatic fibrosis develops, progresses, and responds to treatment.
Interactions and engagement with the O’Brien Centers’ Interaction Core, the UW O’Brien Centers Website, and
GUDMAP will accelerate the dissemination of data, software, methods, and tissue resources to the greater
biomedical community. The leadership and experience within the Center will allow for the promotion of
interactions among Center Projects, the Biomedical Research Core, and other Centers (U54, P20, K12) through
communication, collaboration, and coordination. The larger vision is that O’Brien Centers will be a nidus for
ideas, research, resources, training, and a unified voice across the urologic research community. To realize this
vision, the Centers must become more than the sum of their parts. The UW O’Brien Center and its affiliates will
contribute to this synergism by leveraging existing Center assets and relationships, conducting rigorous
investigation, fostering teachin...

## Key facts

- **NIH application ID:** 10487693
- **Project number:** 3U54DK104310-08S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** WILLIAM A RICKE
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,177
- **Award type:** 3
- **Project period:** 2014-08-01 → 2021-08-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487693

## Citation

> US National Institutes of Health, RePORTER application 10487693, Cellular and molecular mediators of fibrosis in the development of urinary tract dysfunction (3U54DK104310-08S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10487693. Licensed CC0.

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