Research Expertise and Interest

chemistry, bio-organic chemistry, diabetes, protein phosphorylation, fundamental signal transduction pathways in cells and whole organisms, kinase, drug development, asthma, multiple forms of cancer, neurological disorders, drug addiction

Research Description

Research in the Shokat laboratory is focused on the discovery of new small molecule tools and drug candidates targeting protein/lipid kinases, GTPases, and RNA helicases. They utilize the tools of synthetic organic chemistry, protein engineering, structural biology, biochemistry and cell biology. In oncology and neurodegenerative diseases they focus primarily on targets in pathways which have been validated by human genetics such as the lipid kinase PIK3CA mutants (20% of human tumors), the first human oncogene—the GTPase--KRAS, the metabolic and growth factor sensitive kinase mTOR, the mitochondrial kinase, PINK1 (Parkinson’s Disease), the kinase Lrrk2 (Parkinson’s Disease).

In addition to a focus on early drug discovery, they seek to uncover fundamental principles of cell signaling that require the development of new chemical tools. Pharmacology allows rapid, reversible and dose dependent inactivation of single components in intact cells or organisms. The challenge is that highly selective pharmacological probes (agonists, antagonists, traceable substrates, etc.) of members of large enzyme families (protein kinases & RNA helicases) are difficult to develop because every family member shares a highly homologous ATP binding pocket. Their laboratory has solved this fundamental problem for the largest family of enzymes in the human genome, protein kinases, by using protein engineering to create a unique ATP binding pocket which does not exist naturally and then to create a matched chemical inhibitor or substrate which exploits that pocket to selectively target one member of the family at a time. We have termed this approach chemical genetics. It has been widely applied in yeast, plants, mammalian cells and animals.

In the News

International group of researchers race to find treatment for COVID-19

The international team of researchers is testing an unusual new approach to identify potential antiviral drugs with proven efficacy to treat SARS-Cov-2 infections. Given the world crisis, the strategy of testing known/approved drugs could help reduce the numbers of deaths in the near term while the world health community battles the epidemic.

Featured in the Media

Please note: The views and opinions expressed in these articles are those of the authors and do not necessarily reflect the official policy or positions of UC Berkeley.
January 9, 2020
Linda Wang
Chemical engineering professor Enrique Iglesia, chemistry and molecular and cell biology professor Alanna Schepartz, chemistry professor Kevan Shokat, and postdoctoral chemistry scholar Anna Wuttig are among this year's American Chemical Society National Award winners. The honor recognizes contributions of major significance to the chemistry field. Professor Iglesia is cited for "outstanding contributions to chemistry and engineering concepts with broad impact on the practice of catalytic transformations." Professor Schepartz is cited for "pioneering and creative development and application of alpha- and beta-peptides to explore and expand the chemistry in biology." Professor Shokat is cited for the "development of chemical tools and drug candidates that precisely regulate individual kinases and GTPases to re-wire signaling pathways in cancer." And Anna Wuttig is cited for "contributions to energy conversion chemistry by developing comprehensive mechanistic models for the catalytic conversion of carbon dioxide to chemical fuels driven by renewable electricity."
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