Development and Implementation of Advanced Technologies for Cancer Metabolism Research

项目摘要 这份提案要求支持我作为桑福德癌症代谢中心主任的职位 Burnham Prebys医学发现研究所（SBP）核心是NCI指定癌症中心的一部分， 收缩压Ze'ev Ronai博士是癌症中心的主任，也是该部门的负责人，我和他一起工作了13年。 导演对此应用。Core通过提供基于GC-MS的稳定同位素支持癌症研究 (13C)代谢物追踪和定量服务。我在SBP研究稳定同位素示踪技术 自2008年以来，首先是在研究实验室，过去六年是在癌症代谢核心。I have developed 使用不同衍生化方案和MS电离方法测定极性代谢物、脂肪酸 （长链和短链）、胆固醇、糖和糖-磷酸盐，包括代谢物 量化和质量控制。在过去的五年里，核心已经贡献了至少18篇来自实验室的论文。 在NCI项目资助的支持下，我是其中13篇论文的合著者。我在这本书中描述了 应用于继续扩大稳定同位素示踪方法和代谢物定量 新收购的GC-MS/MS，将通过三重四重技术和 更容易与化学电离一起使用。我还计划研究癌症研究所需的特定方法， 包括用于胆汁酸、氧固醇、己糖胺途径中间体，以及用于分离细胞群的方法 和细胞器代谢组学。从这个R50奖的资金将进一步让我工作的发展， 针对无法使用GC-MS测量的代谢物的靶向LC-MS分析。 通过分析癌细胞和肿瘤内改变的代谢状态，该奖项将推动卓越的目标 在SBP癌症中心的转化多学科研究。

PROJECT SUMMARY This proposal requests support for my position as the Director of the Cancer Metabolism Core at Sanford Burnham Prebys Medical Discovery Institute (SBP). The Core is part of the NCI-designated Cancer Center at SBP. Dr. Ze’ev Ronai, with whom I have worked for thirteen years, is the Cancer Center Director and the Unit Director for this application. The Core supports cancer research by providing a GC-MS-based stable-isotope (13C) metabolite tracing and quantification service. I have worked at SBP on stable-isotope tracer technology since 2008, first in a research lab and for the last six years in the Cancer Metabolism Core. I have developed assays using differing derivatization protocols and MS ionization approaches for polar metabolites, fatty acids (long- and short-chain), cholesterol, sugars and sugar-phosphates, including methods for metabolite quantification and quality control. In the past five years, the Core has contributed to at least 18 papers from labs with NCI project grant support, and I have been a co-author on 13 of these papers. I describe plans in this application for continued expansion of stable isotope tracing methods and metabolite quantification using a newly-acquired GC-MS/MS that will improve detection sensitivity both through the triple quad technology and by being easier to use with chemical ionization. I also plan to work on specific methods needed for cancer research, including for bile acids, oxysterols, hexosamine pathway intermediates, and methods for isolated cell populations and organelle metabolomics. Funding from this R50 award will further allow me to work on the development of targeted LC-MS assays for metabolites that cannot be measured using GC-MS. By strengthening facilities for analysis of altered metabolic states within cancer cells and tumors, this award will advance the goal of excellence in translational multi-disciplinary research in the SBP Cancer Center.