# Interstitial fibroblasts drive prostate branching morphogenesis

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $341,444

## Abstract

Interstitial fibroblasts drive prostate branching morphogenesis
Douglas W. Strand, PI
Chad Vezina, Co-I
UT Southwestern Medical Center, Dallas, TX
Summary
The paracrine factors that drive prostate development and disease are still unknown. We recently discovered a
population of interstitial fibroblasts that surround the prostatic urethra of the normal prostate and are sparse in
the transition zone. We showed that the characteristic nodules that form in human benign prostatic hyperplasia
(BPH) are an expansion of interstitial fibroblasts in the transition zone. Key preliminary spatial transcriptomic
analysis of interstitial fibroblasts inside BPH nodules revealed the enrichment of mitogens and morphogens that
are normally only expressed during organogenesis. These data represent a breakthrough in our understanding
of stromal-epithelial interactions in human BPH and could help solve the long-held hypothesis that BPH is a
reawakening of the embryonic signaling that induces prostate development.
We will test the hypothesis that paracrine signaling from interstitial fibroblasts drives prostate branching
morphogenesis in development and disease with three critical lines of inquiry: 1) spatial transcriptomics analysis
of interstitial fibroblasts in human prostate development and BPH; 2) mechanistic analysis of paracrine
morphogens and mitogens on adult prostate epithelial proliferation and branching ex vivo; and 3) in vivo analysis
of autocrine regulation of prostate epithelial proliferation by the receptors of interstitial fibroblast ligands.
Successful completion of our aims will establish a new mechanism of prostate growth that is actionable in clinical
trials.
Relevance
Establishing the paracrine factors responsible for prostate growth holds great promise for identifying novel
approaches to medical therapy for the reversal or prevention of hyperplasia.

## Key facts

- **NIH application ID:** 10833588
- **Project number:** 5R01DK135535-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Douglas William Strand
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $341,444
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833588

## Citation

> US National Institutes of Health, RePORTER application 10833588, Interstitial fibroblasts drive prostate branching morphogenesis (5R01DK135535-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10833588. Licensed CC0.

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