Application of (chemo)proteomic methods to map cancer biochemical pathways

摘要 克拉瓦特实验室在开发和应用先进的化学蛋白质组学和代谢组学方面有着悠久的历史。 在癌症中解剖和定位生化途径的技术。我们一直由 NCI已有超过15年的时间，目前有资助到2020年的计划。这项研究的基础是 基于尖端质谱学(MS)的技术不断开发和应用于 阐明癌症致病的关键蛋白质调节因子。癌症基本介体的鉴定 增长将使有效和有选择性的新癌症疗法的开发成为可能。我们与癌症相关的 研究可分为三个主要项目：1)开发创新的化学蛋白质组 绘制致癌途径的方法和针对癌症中这些途径的药物(CA087660)； 确定癌症中非调控的代谢途径以及这些途径中可能存在的蛋白质 代表癌症治疗的新靶点(CA132630)；以及3)我们基于活性的蛋白质组的应用 方法鉴定负责调节致癌N-RAS棕榈酰化状态的丝氨酸水解酶 癌症(CA193994)。这些研究计划依赖于各种蛋白质组和代谢组 基于MS的方法，为他们的成功完成。作为克拉瓦特实验室唯一的高级职员，我扮演 在所有基于MS的项目的计划和执行中扮演重要角色，无论是通过直接执行 专业技术，或通过培训实验室成员和/或合作者。我们还有一些 严重依赖MS仪器的协作。我负责管理这些协作，并且 要么执行实验并交流结果，要么管理执行 实验。我还在故障排除和仪器维护方面发挥着不可或缺的作用，确保所有 克拉瓦特实验室的MS-仪器的性能处于最佳水平，这对实现 我们所有NCI资助的研究项目的目标。

ABSTRACT The Cravatt lab has a long history of developing and applying advanced chemical proteomic and metabolomic techniques to dissect and target biochemical pathways in cancer. We have continuously been funded by the NCI for over 15 years, and currently have programs funded through 2020. The foundation of this research is cutting-edge mass spectrometry (MS)-based techniques that are continually developed and applied to elucidate critical protein modulators of cancer pathogenicity. Identification of essential mediators of cancer growth will enable development of potent and selective novel cancer therapeutics. Our cancer-related research can be broken up into three main programs: 1) development of innovative chemical proteomic methods for mapping oncogenic pathways and drugs that target these pathways in cancer (CA087660); 2) identification of deregulated metabolic pathways in cancer and proteins within these pathways that may represent novel targets for cancer treatment (CA132630); and 3) application of our activity-based proteomic methods to identify serine hydrolases responsible for regulation of the palmitoylation state of oncogenic N-Ras in cancer (CA193994). These research programs are dependent on a variety of proteomic and metabolomic MS-based methods for their successful completion. As the only senior staff member in the Cravatt lab, I play an essential role in the planning and execution of all MS based projects, either by directly performing the highly specialized techniques, or by training lab members and/or collaborators. We also have a number of collaborations that rely heavily on MS instruments. I am responsible for managing these collaborations and either performing the experiments and communicating the results, or managing the people that perform the experiments. I also play an indispensible role in troubleshooting and instrument maintenance, ensuring that all of the Cravatt lab's MS-instruments are performing at optimal levels, which is essential to achievement of the goals for all of our NCI-funded research programs.