Proteogenomic studies aimed at understanding ovarian tumor responses to agents targeting the DNA damage response and translating this knowledge into clinical benefit

蛋白质组学研究旨在了解卵巢肿瘤对针对 DNA 损伤反应的药物的反应，并将这些知识转化为临床益处

• 批准号: 10287121
• 负责人: Michael Birrer
• 金额: --
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10287121
• 关键词: Alzheimer' s Disease; Alzheimer' s disease brain; Biological Assay; Clinical; Communities; Complement; Complex; DNA Damage; Data; Diagnosis; Drug resistance; Functional disorder; Immune; Immune system; Immunoassay; Inflammation; Innate Immune Response; Knowledge; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Mass Spectrum Analysis; Methodology; Natural Immunity; Operative Surgical Procedures; Parents; Proteins; Protocols documentation; Research; Resistance; Resistance development; Resources; Signal Transduction; Standardization; Time; Translating; Translational Research; Validation; Woman; Work; base; behavioral study; brain tissue; cancer cell; chemotherapy; immunoregulation; multiple reaction monitoring; multiplex assay; novel; novel strategies; novel therapeutics; open source; ovarian neoplasm; proteogenomics; response; targeted agent; therapeutic target; tumor progression

ABSTRACT We will provide the Alzheimer’s disease (AD) community with a novel assay resource based on advanced methodology that enables precise, highly specific, standardizable, multiplex quantification of the innate immunity- complement protein network in AD brain tissues. The innate immune response and its ties to inflammation are important to the pathophysiology of AD and represents a viable therapeutic target. Regulation of the immune system is the result of interplay amongst many 100s of proteins, and conventional protein quantification approaches (e.g. immunoassays) typically target one analyte at a time, which is not adequate for studying the behavior of a complex and robust signaling network such as innate immunity. We will develop multiplex assays to quantify proteins in the innate immune network, using a NextGen protein quantification platform based on a targeted form of mass spectrometry called multiple reaction monitoring (MRM). All assay protocols and validation data will be made publicly available as a novel resource to the community via the established, open-source NCI Assay Portal (assays.cancer.gov). We believe that this work is likely to stimulate additional work leading to progress on AD by providing the AD community with a novel assay resource based on advanced methodology that enables precise, highly specific, standardizable, multiplex quantification of the inflammation / innate immunity protein network in AD brains.

摘要 我们将为阿尔茨海默病(AD)社区提供一种基于高级 能够对先天免疫进行精确、高度特异、标准化、多重量化的方法- 阿尔茨海默病脑组织中的补体蛋白网络先天免疫反应及其与炎症的联系是 对阿尔茨海默病的病理生理学很重要，是一个可行的治疗靶点。免疫调节 系统是许多100种蛋白质相互作用的结果，以及传统的蛋白质定量 方法(例如免疫分析)通常一次只针对一种分析物，这不足以研究 复杂而强大的信号网络的行为，如先天免疫。我们将开发多种检测方法 为了量化先天免疫网络中的蛋白质，使用基于 靶向形式的质谱学称为多反应监测(MRM)。所有分析方案和验证 数据将通过建立的、开源的NCI作为一种新的资源向社区公开提供 分析门户网站(assays.ancer.gov)。我们认为，这项工作可能会刺激额外的工作，从而导致 基于先进方法学为AD社区提供新的检测资源的AD研究进展 这使炎症/先天炎症的精确、高度特异、可标准化、多重量化成为可能 阿尔茨海默病脑内的免疫蛋白网络。