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Targeting bone morphogenetic protein 5 (BMP5) and its synergistic growth factors in benign prostatic hyperplasia

Award Number: K01DK146250
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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Targeting bone morphogenetic protein 5 (BMP5) and its synergistic growth factors in benign prostatic hyperplasia - PROJECT SUMMARY/ABSTRACT The goal of my proposal is to gain technical and professional skills that position me to become an independent investigator at a leading academic institution where I will develop a research program elucidating the molecular mechanisms driving benign prostatic hyperplasia (BPH), a condition affecting a significant portion of men and imposing an economic burden of over $4 billion annually. Through this project, I will determine the effects of bone morphogenetic protein 5 (BMP5) activation and inhibition on BPH growth as well as identify BMP5- mediated cell changes via spatial RNA sequencing, patient-derived xenografts (PDXs), and spheroid models. My training is focused on three key areas: 1). Gain hands-on training in spatial transcriptomic technology including sample preparation and data processing to identify BMP5-mediated changes using BPH PDXs 2). Develop an in vitro spheroid model to test growth factors alone or in combination with BMP5 that modulate BPH growth for therapeutic targeting. 3). Further characterizing the PDX model I developed for pre-clinical testing of BMP inhibitors. Benign urology research provides an ideal environment for interdisciplinary research and career development, supported by an advisory team specializing in spatial RNA sequencing, 3D-culture models, and BPH pathology, along with Stanford resources such as courses in translational genomics, departmental grand rounds/seminars, benign urology conferences, clinical training, and AUA courses. My hypothesis is that BMP5 promotes epithelial proliferation and survival, contributing to BPH progression, and that BMP5 inhibition will suppress these processes, offering a targeted therapeutic approach. I will test this hypothesis through three specific aims: 1. Determine the effects of BMP5 inhibition and exogenous BMP5 treatment on BPH PDX growth and survival; 2. Elucidate the molecular mechanisms underlying BMP5- mediated prostate epithelial growth and survival; 3: Identify additional growth factors alone or in combination with BMP5 that modulate BPH growth and survival for therapeutic targeting. To strengthen the clinical relevance of our findings, we will validate BMP5-related changes observed in pre-clinical models using human tissue microarrays (TMAs). This validation strategy fortifies the translational potential of BMP5 inhibitors and provides strong rationale for the clinical testing of potent and selective BMP5 inhibitors in BPH patients. This proposal will support my own unique research direction that will be independent of my mentors (e.g. focus on growth factor combinations and pre-clinical testing of inhibitors in vivo and in vitro) and integrate my prior training in molecular biology and engineering as well as expand my capabilities in prostate physiology, molecular profiling, and 3D cellular models. By targeting BMP5, this research addresses limitations of current nonspecific treatments and establishes a robust platform for advancing therapeutic strategies and understanding BPH pathogenesis. This study will not only generate real-world impact in patient care but also broaden the understanding of BPH biology and provide rich resources for the BPH research community.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $138,272 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/23/2026	NEW	$138,272
														Subtotal = $138,272

Grand Total All Awards = $138,272

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Targeting bone morphogenetic protein 5 (BMP5) and its synergistic growth factors in benign prostatic hyperplasia

Award Number: K01DK146250

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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