Microbiome and Proteome As Predictive Biomarkers of UCPPS

描述（由申请人提供）：这是 Cedars-Sinai 医疗中心成为 MAPP 网络发现站点的提案。我们组建了一支出色的多学科团队，其中包括在 NIH 资助的泌尿学研究中心领导方面拥有 20 多年经验的人；在良性泌尿系统疾病方面的发现和假设驱动研究以及 NIH 资助的长期记录； NIH 资助的人类受试者研究记录；基于最先进的基于质谱的蛋白质组学和相关技术的实施，在临床生物标志物发现方面取得了杰出的记录；在复杂微生物群落的研究和发现方面处于领先地位；以及转化病理学和生物样本库。雪松西奈医疗中心 (CSMC) 是美国西部最大的学术医疗中心之一。我们的总体目标是使用最先进的方法来开发表型分析的新策略，并最终改善泌尿科慢性盆腔疼痛综合征 (UCPPS) 患者的临床护理。该项目的总体假设是，未培养的共生微生物群落及其与宿主的相互作用与 UCPPS 的发展有关，并且尿液和血液中产生的蛋白质模式创建了 UCPPS 的标志性诊断。我们将使用两种互补的方法来检验这一假设：（1）我们将采用最先进的微生物组基因组测序和表征资源（其中一些是 Cedars-Sinai 所独有的）来定义 UCPPS 患者与正常受试者相比的微生物组/真菌组，（2）我们假设 UCPPS 是由某些蛋白质在表达和翻译后修饰水平的变化引起的，并且可以使用以下方法以公正的方式快速识别这些变化：先进的蛋白质组学技术。具体目标是： 目标 1. 通过对患有 UCPPS 的 MAPP 患者和对照受试者尿液中的核糖体 DNA 进行新一代测序，确定膀胱共生细菌和真菌群落的疾病特异性变化。目标 2：通过对 MAPP 患者的尿液和血液进行深度蛋白质组学分析，鉴定临床相关的 UCPPS 非侵入性尿液生物标志物。 CSMC 团队的成果以及该提案促进的多学科互动将为 MAPP 网络内 UCPPS 的创新合作研究奠定基础。

DESCRIPTION (provided by applicant): This is a proposal for Cedars-Sinai Medical Center to become a Discovery Site for the MAPP Network. We have assembled an exceptional multidisciplinary team, which includes over 20 years of experience in NIH-funded urology research center leadership; a long track record of discovery and hypothesis-driven research and NIH funding in benign urologic conditions; an NIH-funded track record in studies of human subjects; a distinguished record in clinical biomarker discovery based on implementation of state-of-the-art mass spectrometry-based proteomics and related technologies; leadership in research and discovery of complex microbial communities; and translational pathology and biobanking. Cedars-Sinai Medical Center (CSMC) is one of the largest academic medical centers in the western US. Our overall objective is to use state-of-the-art approaches to develop novel strategies for phenotyping and ultimately improving the clinical care of patients with urologic chronic pelvic pain syndromes (UCPPS). The overall hypothesis of this project is that uncultivated commensal microbial communities and their interactions with the host are associated with the development of UCPPS and that the resultant protein patterns in the urine and blood create a signature diagnostic of UCPPS. We will use two complementary approaches to test this hypothesis: (1) We will employ state-of-the-art resources in microbiome genomic sequencing and characterization, some of which are unique to Cedars-Sinai, to define the microbiome/mycobiome of UCPPS patients in comparison to normal subjects, (2) We hypothesize that UCPPS is caused by the changes of some proteins at the expression and post-translational modification levels and that these changes can be rapidly identified in an unbiased manner using advanced proteomics technologies. The Specific Aims are: Aim 1. To identify disease-specific changes in bladder commensal bacterial and fungal communities by next generation sequencing of ribosomal DNA in urine from MAPP patients with UCPPS and control subjects. Aim 2: To identify clinically relevant non-invasive urinary biomarkers of UCPPS through deep proteomics analysis of urine and blood from MAPP patients. Results from the CSMC team and the multidisciplinary interactions promoted by this proposal will lay the groundwork for innovative collaborative studies on UCPPS within the MAPP network.