Microbiome and Proteome As Predictive Biomarkers of UCPPS

微生物组和蛋白质组作为 UCPPS 的预测生物标志物

• 批准号: 9113661
• 负责人: Jennifer Tash Anger
• 金额: $ 23.33万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-10 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9113661
• 关键词: Academic Medical Centers; Affect; Autoimmune Process; Basic Science; Benign; Biological Markers; Bladder; Blood; Body Surface; Body cavities; Chronic Prostatitis; Clinical; Code; Communities; Complex; DNA Sequence; Data Set; Development; Diagnosis; Diagnostic; Disease; Ecosystem; Funding; Gastrointestinal tract structure; Genes; Genetic Markers; Genetic Variation; Genomics; Goals; Health; Human; Internet; Interstitial Cystitis; Intervention; Lead; Leadership; Life; Mass Spectrum Analysis; Medical center; Methods; Molecular; Nature; Organ; Pain; Pathogenesis; Pathology; Patients; Pattern; Pelvic Pain; Phenotype; Population; Post-Translational Protein Processing; Prevention strategy; Process; Proteins; Proteome; Proteomics; Reaction; Reporting; Research; Research Personnel; Resources; Ribosomal DNA; Ribosomal RNA; Role; Severity of illness; Signal Transduction; Site; Sterility; Symptoms; Technology; Testing; Translational Research; United States National Institutes of Health; Urinary tract; Urinary tract infection; Urine; Urology; Variant; Woman; base; biobank; biomarker discovery; body cavity; chronic pelvic pain; clinical biomarkers; clinical care; clinically relevant; diagnostic biomarker; disease phenotype; drug discovery; experience; genomic data; human subject; improved; innovation; insight; men; microbial; microbial community; microbiome; microorganism; multidisciplinary; next generation; next generation sequencing; novel; novel marker; novel strategies; predictive marker; urinary; urologic

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.

描述（由申请人提供）：这是Cedars-Sinai医疗中心成为MAPP网络的发现地点的建议。我们组建了一个杰出的多学科团队，其中包括20多年的NIH资助泌尿外科研究中心领导层的经验；在良性泌尿科条件下发现和假设驱动的研究和NIH资金的长期记录； 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中的杰出记录；研究和发现复杂微生物社区的领导；以及翻译病理和生物群。 Cedars-Sinai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制定表型的新型策略，并最终改善泌尿科慢性骨盆疼痛综合征（UCPP）患者的临床护理。该项目的总体假设是，未经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，并且尿液中所得的蛋白质模式和血液在UCPP中产生了签名诊断。 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修改水平，可以使用高级蛋白质组学技术以公正的方式快速识别这些变化。具体目的是：目标1。通过下一代核糖体DNA测序在尿液中，来自UCPPS和对照组受试者的MAPP患者的核糖体DNA测序，以确定膀胱共生细菌和真菌群落中的疾病特异性变化。目的2：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临床相关的非侵入性尿生物标志物。 CSMC团队的结果以及该提案促进的多学科互动将为MMAPP网络中UCPPS的创新协作研究奠定基础。