About

Kevan Shokat is a Professor of Chemistry and Co-Chair of the Department of Cellular and Molecular Pharmacology at UCSF. Born in 1964, he completed his B.A. at Reed College in 1986 and earned his Ph.D. from UC Berkeley in 1991. His research focuses on bio-organic chemistry, specifically using organic chemistry to probe fundamental signal transduction pathways in cells and organisms. His laboratory develops novel chemical tools to decipher these pathways on a genome-wide scale, with a particular emphasis on protein kinases, which are enzymes responsible for protein phosphorylation and act as on/off switches in cellular signaling. Shokat's work aims to understand the role of individual kinases in the body and identify candidates for drug development to treat diseases such as asthma, various cancers, neurological disorders, bacterial infections, drug addiction, and chronic pain. His approach involves engineering mutations into kinase active sites and designing small molecules that selectively inhibit mutated kinases, thereby enabling precise dissection of kinase functions within complex biological systems. His lab has developed a chemical genetic system that allows for the study of protein kinases across multiple model organisms, including yeast, mice, C. elegans, and flies. His contributions have advanced the understanding of kinase signaling and provided new avenues for therapeutic intervention.

Research topics

• Biology
• Medicine
• Genetics
• Virology
• Cancer research
• Bioinformatics
• Computational biology
• Cell biology
• Internal medicine
• Pharmacology

Selected publications

• Drugging the “Undruggable” MYCN Oncogenic Transcription Factor: Overcoming Previous Obstacles to Impact Childhood Cancers

  Cancer Research · 2021 · 64 citations

  • Biology
  • Cancer research
  • Bioinformatics

  , the inability to obtain structural information on MYCN protein complexes, and the challenges of using traditional small molecules to inhibit protein-protein or protein-DNA interactions. However, there is now promise for directly targeting MYCN based on scientific and technological advances on all of these fronts. Here, we discuss prior challenges and the reasons for renewed optimism in directly targeting this "undruggable" transcription factor, which we hope will lead to improved outcomes for patients with pediatric cancer and create a framework for targeting driver oncoproteins regulating gene transcription.

  DOI

• A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

  Nature · 2020 · 4839 citations

  • Virology
  • Biology
  • Pharmacology
  DOI

• Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

  Science · 2020 · 806 citations

  • Virology
  • Biology
  • Medicine

  The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.

  DOI

• The Global Phosphorylation Landscape of SARS-CoV-2 Infection

  Cell · 2020 · 1142 citations

  • Biology
  • Virology
  • Cell biology
  DOI

• PI4KIIIβ is a therapeutic target in chromosome 1q–amplified lung adenocarcinoma

  Science Translational Medicine · 2020 · 66 citations

  • Cancer research
  • Biology
  • Medicine

  Heightened secretion of protumorigenic effector proteins is a feature of malignant cells. Yet, the molecular underpinnings and therapeutic implications of this feature remain unclear. Here, we identify a chromosome 1q region that is frequently amplified in diverse cancer types and encodes multiple regulators of secretory vesicle biogenesis and trafficking, including the Golgi-dedicated enzyme phosphatidylinositol (PI)-4-kinase IIIβ (PI4KIIIβ). Molecular, biochemical, and cell biological studies show that PI4KIIIβ-derived PI-4-phosphate (PI4P) synthesis enhances secretion and accelerates lung adenocarcinoma progression by activating Golgi phosphoprotein 3 (GOLPH3)-dependent vesicular release from the Golgi. PI4KIIIβ-dependent secreted factors maintain 1q-amplified cancer cell survival and influence prometastatic processes in the tumor microenvironment. Disruption of this functional circuitry in 1q-amplified cancer cells with selective PI4KIIIβ antagonists induces apoptosis and suppresses tumor growth and metastasis. These results support a model in which chromosome 1q amplifications create a dependency on PI4KIIIβ-dependent secretion for cancer cell survival and tumor progression.

  DOI

Recent grants

• Inhibitors of the G protein GNAS which drives pancreatic tumorigenesis

  NIH · $2.0M · 2020–2026

• Determination of c-Scr's Direct Substrates Following PDGF-BB Stimulation of Fibroblasts

  NSF · $270k · 1999–2003

• NIH Grant R01CA190408

  NIH · $1.5M · 2020

• NIH Grant R01CA070331

  NIH · $1.7M · 2003

• NIH Grant R01EB001987

  NIH · $2.9M · 2013

Frequent coauthors

• William A. Weiss

  324 shared

• Nevan J. Krogan

  Gladstone Institutes

  163 shared

• Zachary A. Knight

  Howard Hughes Medical Institute

  158 shared

• German G. Gomez

  Private University of the North

  147 shared

• W. Cavenee

  Ludwig Cancer Research

  147 shared

• Ziyang Zhang

  Tsinghua University

  130 shared

• Gelareh Zadeh

  Princess Margaret Cancer Centre

  128 shared

• C. Hawkins

  University of Portsmouth

  120 shared

Education

• Ph.D., Chemistry

  UC Berkeley College of Chemistry

  1991

• B.A., Chemistry

  Reed College

  1986

Awards & honors

• Life Sciences Research Foundation Fellow, Stanford Universit…
• NSF Early Career Development Award (1995-97)
• Pew Scholar in the Biomedical Sciences (1996-00)
• Searle Scholar (1997-00)
• Cottrell Scholar (1997-00)

Similar researchers at University of California, Berkeley

• Peidong Yangh-262
• Jennifer A. Doudnah-230
• Jeffrey R. Longh-189
• John F. Hartwigh-180
• Rasmus Nielsenh-180