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

尿路功能障碍发展过程中纤维化的细胞和分子介质

基本信息

批准号：
10331481
负责人：
WILLIAM A RICKE
金额：
$ 3.52万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-24 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10331481
关键词：
Adverse effects Affect Animals Benign Biomedical Research Bladder Boston Breeding Cell Lineage Cells Cheese Clinical Collaborations Collagen Communication Communities Computer software Consensus Consequentialism Data Databases Development Diagnosis Educational process of instructing Elderly Environment Estrogen Receptor alpha Etiology FDA approved Fibroblasts Fibrosis Financial Support Fostering Freezing Frozen Semen Functional Magnetic Resonance Imaging Functional disorder Funding Future Genetic Transcription Goals Health Care Costs Histologic Human Image Impairment Inflammation Inflammatory Infrastructure Insignia Institution Interleukin-13 Interleukin-4 Investigation Lead Leadership Learning Lobster Lower urinary tract Maps Mediator of activation protein Medical Metadata Methods Molecular Molecular Target Mouse Strains Mus Myofibroblast Pathway interactions Physicians Physiology Pre-Clinical Model Process Proliferating Prostate Prostatic Prostatic Tissue Protocols documentation Publications Quality of life Reproducibility Research Research Personnel Research Project Grants Resistance Resources SECTM1 gene SRD5A2 gene Sampling Scientific Advances and Accomplishments Scientist Smooth Muscle Solid Source Specimen Steroids Stream Stromal Cells Sum Symptoms Testing Testosterone 5-alpha-Reductase Therapeutic Tissues Training Ultrasonography Urethra Urinary tract Urination Urine Urology Vision Voice Work analytical method biobank connective tissue growth factor contrast enhanced data dissemination data sharing design experience imaging modality improved in vivo inhibitor/antagonist innovation lower urinary tract symptoms male member men mouse model novel therapeutics pre-clinical preclinical study programs radiological imaging searchable database single-cell RNA sequencing synergism tissue resource tool undergraduate research experience undergraduate student urinary urologic web site

项目摘要

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 teaching and learning, and through vigorous pursuit of innovation. With the solid financial support and “buy-in” from UW and its affiliates, Core A will lead this vision for this O’Brien Center.

项目总结-整体