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

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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.