Advancing Cancer Research through Comprehensive Proteomics and Metabolomics Analyses

通过全面的蛋白质组学和代谢组学分析推进癌症研究

• 批准号: 10516914
• 负责人: Hsin Yao Tang
• 金额: $ 23.71万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10516914
• 关键词: Advanced Malignant Neoplasm; Biological; Biological Assay; Cancer Center; Cancer Research Project; Cells; Chemicals; Computer software; Consultations; Data; Data Analyses; Development; Diagnosis; Disease; Ensure; Experimental Designs; Fatty Acids; Fox Chase Cancer Center; Funding; Future; Goals; Institution; Ions; Isotopes; Kimmel Cancer Center at the Thomas Jefferson University; Label; Lipids; Liquid substance; Malignant Neoplasms; Methodology; Methods; Modification; Ovarian; Pathway interactions; Peptides; Performance; Post-Translational Protein Processing; Prostate; Proteins; Proteomics; Research Personnel; Research Project Grants; Research Support; Resource Sharing; Resources; Role; Sampling; Site; Technology; The Wistar Institute; Tissues; Tracer; Universities; Update; anticancer research; cancer prevention; cancer type; cost; crosslink; exosome; improved; insight; instrumentation; melanoma; metabolomics; palmitoylation; protein complex; stable isotope; success

Project Summary The Proteomics and Metabolomics Shared Resource (PMSR) provides a comprehensive set of proteomics and metabolomics assays to the Wistar Cancer Center, Fox Chase Cancer Center at Temple University, and Sidney Kimmel Cancer Center at Thomas Jefferson University as a primary goal. Resources of the PMSR are also available to investigators in other Cancer Centers and academic institutions as a secondary goal. Dr. Tang’s role as the PMSR Managing Director is to support NCI-funded cancer research projects by providing expert consultation and state-of-the-art technologies that operate at maximum performance at affordable costs to cancer investigators and other biomedical researchers. The Managing Director will assist in experimental design, perform MS data analyses as needed, and assist in the biological interpretation of results. The Managing Director will also devote substantial effort to optimizing and implementing new methods, update analytical and data analyses methods, and update instrumentation to ensure each project is performed using state-of-the-art methodologies. This is critical because instrumentation, software, and analytical strategies continue to evolve rapidly, and most current and anticipated future projects involve very challenging proteomics and metabolomics problems. Proteomics projects will include: 1) in-depth, global quantitative comparisons of exosomes, secretomes, cell lysates, tissues and biological fluids; 2) quantitative comparisons of post-translational modifications; and 3) LC-MS/MS analysis of isolated protein complexes with and without chemical crosslinking. Quantitative data will be obtained either using label-free quantitation of integrated MS ion currents, or using stable isotopes such as SILAC or TMT isobaric tag labeling. Metabolomics projects will include quantifying the steady state levels of polar metabolites, lipids and fatty acids, and 13C isotope tracer analysis. Representative specific plans for future development of new analytical approaches include: 1) improving characterization of protein palmitoylation with identification of specific modification sites; 2) de novo peptide sequencing for identification of HLA peptides; 3) an alternate approach to ubiquitome enrichment; and 4) absolute quantitation of gut metabolites. In addition, Dr. Tang will implement additional new or improved methods that are likely to be needed in future cancer projects. These proteomics and metabolomics analyses will contribute to critical data required to identify biomolecular targets, as well as generate hypotheses that are vital for the success of the cancer-related projects described in this application.

项目摘要 蛋白质组学和代谢组学共享资源(PMSR)提供了一套全面的蛋白质组学和 代谢组学分析对维斯塔尔癌症中心、坦普尔大学的福克斯·蔡斯癌症中心和西德尼进行 托马斯·杰斐逊大学的坎摩尔癌症中心作为主要目标。PMSR的资源还包括 可供其他癌症中心和学术机构的研究人员作为次要目标。唐医生的 PMSR常务董事的角色是通过提供专家来支持NCI资助的癌症研究项目 咨询和最先进的技术，以经济实惠的成本实现最高性能 癌症研究人员和其他生物医学研究人员。常务董事将协助进行试验 根据需要设计、执行MS数据分析，并协助对结果进行生物学解释。《管理学》 主任还将投入大量精力来优化和实施新方法，更新分析和 数据分析方法，并更新工具，以确保使用最先进的技术执行每个项目 方法论。这一点至关重要，因为仪器、软件和分析策略在不断发展 快速、最当前和最预期的未来项目涉及极具挑战性的蛋白质组学和代谢组学 有问题。蛋白质组学项目将包括：1)深入的、全球范围内的外切体定量比较， 分泌体、细胞裂解物、组织和生物液；2)翻译后的定量比较 3)化学交联型和不交联型分离蛋白复合体的LC-MS/MS分析。 定量数据将使用积分MS离子电流的无标记量化，或使用 稳定的同位素，如SILAC或TMT等压标记。代谢组学项目将包括量化 极性代谢物、脂类和脂肪酸的稳态水平，以及13C同位素示踪分析。代表 未来发展新的分析方法的具体计划包括：1)改进对 蛋白质棕榈酰化与特定修饰位点的鉴定；2)从头测序 人类白细胞抗原多肽的鉴定；3)泛素组浓缩的替代方法；以及4)绝对定量 肠道代谢物。此外，唐博士还将实施其他新的或改进的方法，这些方法很可能是 在未来的癌症项目中需要。这些蛋白质组学和代谢组学分析将有助于关键数据 识别生物分子靶标以及产生对成功至关重要的假设所需的 本申请中描述的癌症相关项目。