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

摘要 Cravatt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 技术来解剖和靶向癌症的生化途径。我们一直得到 NCI已经超过15年，目前有计划资助到2020年。本研究的基础是 基于质谱（MS）的尖端技术，不断开发和应用于 阐明癌症致病性的关键蛋白质调节剂。癌症必需介质的鉴定 生长将使得能够开发有效的和选择性的新型癌症治疗剂。我们的癌症相关 研究可以分为三个主要项目：1）创新的化学蛋白质组学的发展 在癌症中定位致癌途径和靶向这些途径的药物的方法（CA 087660）; 2） 鉴定癌症中失调的代谢途径和这些途径中的蛋白质， 代表癌症治疗的新靶点（CA 132630）;和3）我们基于活性的蛋白质组学的应用 鉴定负责调节致癌N-Ras棕榈酰化状态的丝氨酸水解酶的方法 癌症（CA 193994）。这些研究项目依赖于各种蛋白质组学和代谢组学 以MS为基础的方法来成功完成。作为克拉瓦特实验室唯一的高级职员， 在所有基于MS的项目的规划和执行中发挥重要作用，无论是直接执行高度 专业技术，或通过培训实验室成员和/或合作者。我们也有一些 严重依赖MS仪器的合作。我负责管理这些合作， 要么执行实验并传达结果，要么管理执行实验的人员。 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 Cravatt实验室的MS仪器的性能处于最佳水平，这对于实现 我们所有的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.