Research Summary
Research in my laboratory is focused on the discovery of new chemical based tools to decipher cellular signaling networks with an emphasis on protein kinases and more recently, GTPases. The analysis of signal transduction pathways has proven challenging using the traditional tools of biochemistry, genetics, and chemistry. Biochemical approaches are often limited in utility because signaling networks span from the cell surface to the control of transcription and translation, confounding reconstitution efforts from purified proteins. Genetic approaches allow specific perturbation of single components in an intact cell or organism, yet are often confounded by the emergent properties of signaling cascades. Chemical and pharmacological approaches enable rapid, reversible, and graded (dose-dependent) inactivation of single components in intact cells or organisms. Unfortunately, highly selective chemical probes (agonists, antagonists, traceable substrates, etc.) of protein kinases are difficult to develop because the 500 protein kinases share highly homologous ATP binding pockets. My laboratory has solved this fundamental problem for the largest family of enzymes in the human genome, protein kinases, by development of a strategy based on a combination of protein engineering and organic synthesis. We have termed this approach chemical genetics.
Research Funding
March 1, 2020 - February 28, 2025 - Inhibitors of the G protein GNAS which drives pancreatic tumorigenesis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA244550
February 1, 2018 - January 31, 2023 - Improving the efficacy of mTOR inhibition , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA221969
August 15, 2021 - July 31, 2022 - Tissue-specific pharmacology to enhance healthspan , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R56AG071857
April 14, 2016 - March 31, 2021 - Modeling KRAS-Dependent Synthetic Lethality in Human Colon Organoids , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01CA199241
Education
Reed College (Portland, Oregon), B.A., 1986, Chemistry
UC Berkeley (Berkeley, California), Ph.D., 1991, Organic Chemistry