ABSTRACT – OVERALL COMPONENT Benign prostatic hyperplasia (BPH) is the most common cause of urinary symptoms in older men, yet we understand little about its origins, drivers of growth, and how it causes lower urinary tract symptoms. Since BPH-caused Lower Urinary Tracts Symptoms (LUTS) appears unique to man, we propose a highly integrated project to create an atlas encompassing the molecular, cellular, microenvironmental, histological and macroscopic dimensions of human BPH. Definition of the features responsible for growth and progression of BPH could ultimately lead to new therapeutic approaches to treat or prevent BPH. Our overall goal is to expand research in benign urology to improve our understanding and treatment of urological diseases. The components of the Stanford O’Brien Urology Research Center include: The Administrative Core is based in the Department of Urology and directed by Dr. James Brooks, an experienced clinician and translational scientist in prostate disease who will administer the Center to ensure the scientific and training goals are realized and interface with the NIDDK and Urology Research Consortia. He will be advised by an Internal and External Advisory Board, to ensure progress is made and to provide scientific advice to ensure success. He will meet with the Investigator Committee to formulate plans, integrate findings between projects and allocate Project and Core resources to ensure projects succeed. The Biospecimen/Bioimaging Core, directed by Dr. Robert West provides critical support to projects of the Center by providing human BPH tissues with deidentified data, generates histological images and manages these and the MRI images and provides Multiplexed Ion Beam Imaging (MIBI) and data analysis for Projects 1, 2 & 3. The Core also provides this service to the O’Brien Urology Centers and Urology Disease Centers. Project 1 seeks to define the role of fibroblast subtypes in the development and progression of BPH. Project 2 characterizes the immune microenvironment and investigates how it is shaped by the stromal cells and how it influences the stromal and epithelial compartments of BPH. Project 3 uses MR Images with associated International Prostate Symptom Scores (IPSS) and Bothersome Indices (BI) to construct 3D models of BPH overlayed with histology. These models serve as an atlas for integrating stromal and immune microenvironment data and gene expression subtypes and will provide a means to test how molecular, cellular, microenvironment, histological and radiologic features and their heterogeneity relate BPH to LUTS. These projects serve as the nucleus for training of undergraduate, graduate, and post graduate students to become the next generation of leaders in urological science.