Kevan Shokat

Last updated
Kevan Michael Shokat
Born (1964-08-26) August 26, 1964 (age 59)
Alma mater Reed College
University of California, Berkeley
Known for Kinase signaling
Scientific career
Fields Chemical biology
Institutions Princeton University
University of California, San Francisco
Doctoral advisor Peter G. Schultz
Other academic advisors Christopher Goodnow

Kevan Michael Shokat (born August 26, 1964) [1] is an American chemical biologist. He is a Professor and chair in the Department of Cellular and Molecular Pharmacology at University of California, San Francisco, a professor in the Department of Chemistry at University of California, Berkeley, and an Investigator with the Howard Hughes Medical Institute.

Contents

Biography

Shokat received his B.A, in chemistry from Reed College in 1986, completing his thesis, "Synthesis of a precursor of PRCPCP, a non-hydrolyzable analog of phosphoribosylpyrophosphate (PRPP)," with Ron McClard, and his Ph.D. from University of California, Berkeley in 1991, under Peter G. Schultz.

Research

Shokat is one of the leading figures in the field of chemical genetics. [2] He uses methods of bioorganic chemistry to elucidate signal transduction pathways at the single cell and whole organism levels, and is particularly interested in protein kinases, and developing methods to elucidate the particular targets of each kinase, such as the Bump and hole method.

In 2013 Shokat published the first covalent inhibitors of KRAS G12C using a tethering screen. [3] Following this strategy many pharma companies have developed KRAS programs leading to phase I/II clinical trials in this space, a landmark for what was once thought to be an undruggable oncogene.

Honors and awards

Related Research Articles

<span class="mw-page-title-main">Carolyn Bertozzi</span> American chemist (born 1966)

Carolyn Ruth Bertozzi is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. She coined the term "bioorthogonal chemistry" for chemical reactions compatible with living systems. Her recent efforts include synthesis of chemical tools to study cell surface sugars called glycans and how they affect diseases such as cancer, inflammation, and viral infections like COVID-19. At Stanford University, she holds the Anne T. and Robert M. Bass Professorship in the School of Humanities and Sciences. Bertozzi is also an Investigator at the Howard Hughes Medical Institute (HHMI) and is the former director of the Molecular Foundry, a nanoscience research center at Lawrence Berkeley National Laboratory.

<span class="mw-page-title-main">François Diederich</span> Luxembourgian chemist (1952–2020)

François Diederich was a Luxembourgian chemist specializing in organic chemistry.

<span class="mw-page-title-main">KRAS</span> Protein-coding gene in humans

KRAS is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell to grow and divide (proliferate) or to mature and take on specialized functions (differentiate). It is called KRAS because it was first identified as a viral oncogene in the KirstenRAt Sarcoma virus. The oncogene identified was derived from a cellular genome, so KRAS, when found in a cellular genome, is called a proto-oncogene.

<span class="mw-page-title-main">Peter Dervan</span> American chemist (born 1945)

Peter B. Dervan is the Bren Professor of Chemistry at the California Institute of Technology. The primary focus of his research is the development and study of small organic molecules that can sequence-specifically recognize DNA, a field in which he is an internationally recognized authority. The most important of these small molecules are pyrrole–imidazole polyamides. Dervan is credited with influencing "the course of research in organic chemistry through his studies at the interface of chemistry and biology" as a result of his work on "the chemical principles involved in sequence-specific recognition of double helical DNA". He is the recipient of many awards, including the National Medal of Science (2006).

<span class="mw-page-title-main">JoAnne Stubbe</span> American chemist

JoAnne Stubbe is an American chemist best known for her work on ribonucleotide reductases, for which she was awarded the National Medal of Science in 2009. In 2017, she retired as a Professor of Chemistry and Biology at the Massachusetts Institute of Technology.

<span class="mw-page-title-main">Brian Druker</span> American physician-scientist

Brian J. Druker is a physician-scientist at Oregon Health & Science University (OHSU), in Portland, Oregon. He is the director of OHSU's Knight Cancer Institute, JELD-WEN Chair of Leukemia Research, Associate Dean for Oncology in the OHSU School of Medicine, and professor of medicine.

Lewis C. Cantley is an American cell biologist and biochemist who has made significant advances to the understanding of cancer metabolism. Among his most notable contributions are the discovery and study of the enzyme PI-3-kinase, now known to be important to understanding cancer and diabetes mellitus. He is currently Meyer Director and Professor of Cancer Biology at the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine in New York City. He was formerly a professor in the Departments of Systems Biology and Medicine at Harvard Medical School, and the Director of Cancer Research at the Beth Israel Deaconess Medical Center, in Boston, Massachusetts. In 2016, he was elected Chairman of the Board for the Hope Funds for Cancer Research.

<span class="mw-page-title-main">Stephen J. Lippard</span> American chemist

Stephen James Lippard is the Arthur Amos Noyes Emeritus Professor of Chemistry at the Massachusetts Institute of Technology. He is considered one of the founders of bioinorganic chemistry, studying the interactions of nonliving substances such as metals with biological systems. He is also considered a founder of metalloneurochemistry, the study of metal ions and their effects in the brain and nervous system. He has done pioneering work in understanding protein structure and synthesis, the enzymatic functions of methane monooxygenase (MMO), and the mechanisms of cisplatin anticancer drugs. His work has applications for the treatment of cancer, for bioremediation of the environment, and for the development of synthetic methanol-based fuels.

Alanna Schepartz is an American professor and scientist. She is currently the T.Z. and Irmgard Chu Distinguished Chair in Chemistry at University of California, Berkeley. She was formerly the Sterling Professor of Chemistry at Yale University.

K-Ras(G12C) inhibitor 6 is an irreversible inhibitor of oncogenic K-Ras(G12C), subverting the native nucleotide preference to favour GDP over GTP. Its family of inhibitors allosterically control GTP affinity and effector interactions by fitting inside a "pocket", or binding site, of mutant K-Ras. It is the most frequently mutated oncogene.

<span class="mw-page-title-main">Anthony R. Hunter</span> British-American biologist (born 1943)

Anthony Rex Hunter is a British-American biologist who is a professor of biology at the Salk Institute for Biological Studies and the University of California San Diego. His research publications list his name as Tony Hunter.

<span class="mw-page-title-main">Targeted covalent inhibitors</span>

Targeted covalent inhibitors (TCIs) or Targeted covalent drugs are rationally designed inhibitors that bind and then bond to their target proteins. These inhibitors possess a bond-forming functional group of low chemical reactivity that, following binding to the target protein, is positioned to react rapidly with a proximate nucleophilic residue at the target site to form a bond.

Owen Witte is an American physician-scientist at the University of California, Los Angeles. He is a University Professor of microbiology, immunology and molecular genetics in the David Geffen School of Medicine at UCLA, founding director emeritus of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and the UC Regents’ David Saxon Presidential Chair in developmental immunology (1989–present). Witte is also a Howard Hughes Medical Institute investigator (1986–2016) and a member of the President's Cancer Panel, the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and the Cancer Research Academy of the AACR. He serves on numerous editorial boards and scientific advisory boards for academic centers and biotechnology companies.

<span class="mw-page-title-main">William Kaelin Jr.</span> American Nobel Laureate, Professor of Medicine at Harvard University

William G. Kaelin Jr. is an American Nobel laureate physician-scientist. He is a professor of medicine at Harvard University and the Dana–Farber Cancer Institute. His laboratory studies tumor suppressor proteins. In 2016, Kaelin received the Albert Lasker Award for Basic Medical Research and the AACR Princess Takamatsu Award. He also won the Nobel Prize in Physiology or Medicine in 2019 along with Peter J. Ratcliffe and Gregg L. Semenza.

Nikola Panayot Pavletich is the former chair of structural biology at Memorial Sloan Kettering Cancer Center.

<span class="mw-page-title-main">Cynthia Wolberger</span> American structural biologist

Cynthia Wolberger is an American structural biologist currently at Johns Hopkins University School of Medicine and an Elected Fellow of the American Association for the Advancement of Science. On April 19, 2019, she was elected as a member of the National Academy of Science among 100 new members and 25 foreign associates. She received her undergraduate degree in Physics from Cornell University in 1979 and her Ph.D. in Biophysics at Harvard University in 1987. She completed postdoctoral work at the University of California, San Francisco (1987-1989) and the Johns Hopkins School of Medicine (1989-1991). Her research concentrations include structural biology, ubiquitin signaling, and transcription regulation. Significant progress has been made by Wohlberger in understanding the structural biology of gene and protein control.

Barbara Imperiali is a Professor of Biology and Chemistry at Massachusetts Institute of Technology and Affiliate Member of the Broad Institute. She is an elected member of the National Academy of Sciences and a Fellow of the Royal Society of Chemistry.

<span class="mw-page-title-main">Bump and hole</span> Tool in chemical genetics

The bump-and-hole method is a tool in chemical genetics for studying a specific isoform in a protein family without perturbing the other members of the family. The unattainability of isoform-selective inhibition due to structural homology in protein families is a major challenge of chemical genetics. With the bump-and-hole approach, a protein–ligand interface is engineered to achieve selectivity through steric complementarity while maintaining biochemical competence and orthogonality to the wild type pair. Typically, a "bumped" ligand/inhibitor analog is designed to bind a corresponding "hole-modified" protein. Bumped ligands are commonly bulkier derivatives of a cofactor of the target protein. Hole-modified proteins are recombinantly expressed with an amino acid substitution from a larger to smaller residue, e.g. glycine or alanine, at the cofactor binding site. The designed ligand/inhibitor has specificity for the engineered protein due to steric complementarity, but not the native counterpart due to steric interference.

T Govindaraju is a professor in the Bioorganic Chemistry Laboratory at Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru. The researchers in the Bioorganic Chemistry Laboratory work in areas which lie at the intersection of chemistry, biology and biomaterials science, and in particular, on problems related to Alzheimer's disease, peptide chemistry, molecular probes, molecular architectonics, nanoarchitectonics and biomimetics.

References

  1. "Oral history interview with Kevan M. Shokat". Science History Institute Digital Collections. Retrieved 2022-08-21.
  2. "Kevan Shokat at the Michael j. Fox foundation" . Retrieved 1 February 2017.
  3. Ostrem, Jonathan M.; Peters, Ulf; Sos, Martin L.; Wells, James A.; Shokat, Kevan M. (November 2013). "K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions". Nature. 503 (7477): 548–551. Bibcode:2013Natur.503..548O. doi:10.1038/nature12796. PMC   4274051 . PMID   24256730.
  4. "Kevan M. Shokat, Ph.D."
  5. "The Protein Society : Protein Society Awards". proteinsociety.org. 2019-12-03. Archived 2019-12-03 at the Wayback Machine
  6. Eli Lilly Award in Biological Chemistry Archived 2020-10-09 at the Wayback Machine , Prizewinners 1935 - 2017, retrieved 1/26/2017
  7. Kevan M. Shokat, at National Academy of Sciences (nasonline.org), retrieved 1/26/2017
  8. Book of Members 1780–present , Members of the American Academy of Arts & Sciences, 1780-2016, retrieved 1/26/2017
  9. "Ronald Breslow Award for Achievement in Biomimetic Chemistry".
  10. "Kraft Prize Symposium".
  11. "Frank H. Westheimer Prize".
  12. "Priming Cancer Cells for Detection by the Immune System". July 2019.
  13. "Past Recipients".
  14. "Kevan Shokat Ph.D. To be Awarded the First SWCRF Breakthrough Science Award".
  15. "AACR Announces Recipients of its 2022 Scientific Achievement Awards and Lectureships".
  16. "NAS Award for Scientific Discovery".
  17. "Dr. Kevan Shokat '86 Receives Vollum Award for Cancer Research". 17 February 2023.
  18. "Sjöberg Laureate brings new hope to people with lung cancer".