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超过20年的经验;在良性泌尿系统疾病的发现和假设驱动的研究以及NIH资助方面的长期记录; NIH资助的人类受试者研究的记录;基于最先进的质谱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;领导复杂微生物群落的研究和发现;以及转化病理学和生物库。Cedars-Sinai医学中心（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新的表型分析策略，并最终改善泌尿系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，未培养的肠道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产生了UCPPS的特征诊断。我们将使用两种互补的方法来检验这一假设：（1）我们将采用微生物组基因组测序和表征方面的最先进资源，其中一些是Cedars-Sinai独有的，以定义UCPPS患者与正常受试者相比的微生物组/真菌组，（2）我们推测UCPPS是由表达时和表达后的某些蛋白质的变化引起的。翻译修饰水平，并且这些变化可以使用先进的蛋白质组学技术以无偏倚的方式快速鉴定。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进行下一代测序，确定膀胱粘膜细菌和真菌群落的疾病特异性变化。目标二：通过对MAPP患者的尿液和血液进行深度蛋白质组学分析，确定UCPPS的临床相关非侵入性尿液生物标志物。CSMC团队的成果和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.