Vanberbilt Biomarker Developmental Laboratory

描述(由申请人提供)：本申请建议建立一个Vanderbilt Biomarker开发实验室(Vanderbilt BDL)，该实验室将作为NCI早期检测研究网络(EDRN)的组成部分。范德比尔特癌症研究所将在位于范德比尔特-英格拉姆癌症中心的吉姆·艾尔斯癌症前检测和诊断研究所内建立，该研究所提供致力于生物标记物开发问题的杰出资源、仪器和工作人员。Vanderbilt BDL将使用标准化的液相色谱-串联质谱仪(LC-MS/MS)和液相色谱-多反应监测质谱仪(LC-MRM-MS)分析平台，以无偏见地发现蛋白质生物标志物并进行有针对性的定量。这些分析平台与艾尔斯研究所和范德比尔特-英格拉姆癌症中心的胸腔肿瘤学项目的广泛的信息学支持基础设施和正在进行的生物样品收集相结合。Vanderbilt BDL将通过三个具体目标实现EDRN BDL计划的目标：1)开发和应用新的信息学工具和方法，以确定突变、变异和修饰蛋白质为候选癌症生物标记物。这项工作将强调应用新的序列标签和信号分析算法和软件来识别区分癌症表型的新的蛋白质形式，2)发现和验证基于血浆的结直肠癌和肺癌检测的蛋白质生物标记物候选。这项工作将应用标准化的鸟枪式蛋白质组学分析在组织中发现生物标记候选，并应用标准化的LC-MRM-MS平台来量化血浆中的生物标记候选。Vanderbilt BDL将与范德比尔特拟建的EDRN Biomarker参考实验室(William Pao，PI)和拟建的EDRN临床验证中心(皮埃尔·马塞斯，PI)以及EDRN网络合作伙伴密切互动，广泛部署用于生物标记物开发的标准化蛋白质组技术。

DESCRIPTION (provided by applicant): This application proposes a Vanderbilt Biomarker Developmental Laboratory (Vanderbilt BDL), which will serve as a component of the NCI Early Detection Research Network (EDRN). The Vanderbilt BDL will be established within the Jim Ayers Institute for Precancer Detection and Diagnosis in the Vanderbilt-lngram Cancer Center which provides outstanding resources, instrumentation and staff dedicated to the problem of biomarker development. The Vanderbilt BDL will employ standardized liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM-MS) analysis platforms for unbiased discovery and targeted quantitation of protein biomarkers. These analysis platforms are coupled to extensive informatics support infrastructure and ongoing biospecimen collections of the Ayers Institute and the Thoracic Oncology Program in the Vanderbilt-lngram Cancer Center. The Vanderbilt BDL will address the goals of the EDRN BDL program through three specific aims, 1) Develop and apply new informatics tools and approaches to identify mutant, variant and modified proteins as candidate cancer biomarkers. This work will emphasize application of new sequence tagging and signal analysis algorithms and software to identify novel protein forms that distinguish cancer phenotypes, 2) Discover and verify protein biomarker candidates for plasma-based detection of colorectal and lung cancers. This work will apply standardized shotgun proteomics analyses for biomarker candidate discovery in tissues and a standardized LC- MRM-MS platform for quantitation of biomarker candidates in plasma. The Vanderbilt BDL will interact closely with a proposed EDRN Biomarker Reference Laboratory (William Pao, PI) and a proposed EDRN Clinical Validation Center (Pierre Massion, PI) at Vanderbilt as well as with EDRN network partners to broadly deploy standardized proteomic technologies for biomarker development.