Jesse Bloom

About

Jesse Bloom is a professor affiliated with the Fred Hutch Cancer Center and the University of Washington. His research focuses on rapid evolution in viral diseases, including influenza. His group employs a combination of experimental and computational techniques to study questions in virology, immunology, and protein biochemistry from an evolutionary perspective. Bloom's work aims to understand the mechanisms and implications of viral evolution, which has significant relevance for public health and the development of medical interventions.

Research topics

• Virology
• Biology
• Medicine
• Genetics
• Internal medicine
• Immunology
• Computer Science
• Computational biology
• Pharmacology
• Chemistry

Selected publications

• Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding

  Cell · 2020 · 2221 citations

  Senior authorCorresponding

  The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD's surface that may be desirable targets for v…

  DOI

• Protocol and Reagents for Pseudotyping Lentiviral Particles with SARS-CoV-2 Spike Protein for Neutralization Assays

  Viruses · 2020 · 888 citations

  Senior authorCorresponding

  SARS-CoV-2 enters cells using its Spike protein, which is also the main target of neutralizing antibodies. Therefore, assays to measure how antibodies and sera affect Spike-mediated viral infection are important for studying immunity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. Such pseudotyping has now been described for single-cycle lentiviral, retroviral, and vesicular stomatitis virus (VSV) pa…

  DOI

• Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

  Science · 2021 · 856 citations

  Senior authorCorresponding

  Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targe…

  DOI

• Compensatory epistasis maintains ACE2 affinity in SARS-CoV-2 Omicron BA.1

  Nature Communications · 2022 · 171 citations

  = 32,768 genotypes), spanning all possible evolutionary intermediates from the ancestral Wuhan Hu-1 strain to BA.1. We find that immune escape mutations in BA.1 individually reduce ACE2 affinity but are compensated by epistatic interactions with other affinity-enhancing mutations, including Q498R and N501Y. Thus, the ability of BA.1 to evade immunity while maintaining ACE2 affinity is contingent on acquiring multiple interacting mutations. Our results implicate compensatory epistasis as a key fa…

  DOI

• Replaying germinal center evolution on a quantified affinity landscape

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-05 · 23 citations

  preprintOpen access

  Darwinian evolution of immunoglobulin genes within germinal centers (GC) underlies the progressive increase in antibody affinity following antigen exposure. Whereas the mechanics of how competition between GC B cells drives increased affinity are well established, the dynamical evolutionary features of this process remain poorly characterized. We devised an experimental evolution model in which we "replay" over one hundred instances of a clonally homogenous GC reaction and follow the selective p…

  PublisherOA PDFDOI

Recent grants

• Viral Pathogenesis and Evolution Training Program (VPETP)

  NIH · $2.7M · 2009–2024

• Complete mapping of immune selection from antibodies to HIV

  NIH · $2.4M · 2018–2025

• High-throughput experiments to guide influenza vaccine strain selection

  NIH · $2.1M · 2016–2022

Frequent coauthors

• Allison J. Greaney

  Fred Hutch Cancer Center

  352 shared

• Tyler N. Starr

  University of Utah

  272 shared

• Katharine H. D. Crawford

  University of Washington

  252 shared

• Adam S. Dingens

  Fred Hutch Cancer Center

  193 shared

• Andrea N. Loes

  Howard Hughes Medical Institute

  192 shared

• Rachel Eguia

  Fred Hutch Cancer Center

  154 shared

• David Veesler

  University of Washington

  118 shared

• Sarah K. Hilton

  University of Wisconsin–Madison

  100 shared

Labs

• UW Biological Physics, Structure and DesignPI

Education

• Ph.D., Virology

  University of California, San Francisco

  2001

• M.S., Virology

  University of California, San Francisco

  1997

• B.A., Molecular and Cell Biology

  University of California, Berkeley

  1994

Similar researchers at University of Washington

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• Valerie Daggetth-81
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