Jonathan Wilson Yewdell, M.D., Ph.D.

Jonathan Wilson Yewdell, M.D., Ph.D.

Chief, Cellular Biology Section

Major Areas of Research

  • Generation of MHC class I peptide ligands from defective ribosomal products (DRiPs) and other endogenous antigens
  • Cell biology of specialized and non-canonical protein translation
  • Defining mechanisms of influenza A virus evolution and antigenic variation in viral glycoproteins
  • Understanding immunodominance in B-cell and antibody responses to influenza A virus
  • Real-time imaging of virus-host interactions using multiphoton microscopy

Program Description

Viruses pose a constant danger to living organisms. An astounding variety of viruses are recognized as human pathogens. The roster lengthens as humans come into more intimate contact with animal reservoirs harboring novel viruses and new technologies reveal human viruses that previously escaped detection.

The vertebrate immune system evolved in response to the threat posed by viruses. The importance of the immune system in protecting against lethal viral infections becomes obvious in innate or acquired immunodeficiencies, where depression of one or more elements of the system results in death from a typically “self-limited” viral infection, or in the success of vaccines in preventing dangerous viral infections. The immune system (like every biological system) is not perfect, and overzealous anti-viral responses frequently contribute to viral diseases.

The mission of the Cellular Biology Section is to extend basic understanding of the interaction between the host and viruses and to use viruses as tools to better understand cell biology.

Biography

Dr. Yewdell received an A.B. in biochemistry magna cum laude from Princeton University in 1975, working with Dr. Arnold Levine for his undergraduate thesis on immune recognition of virus-transformed cells. He received an M.D. and a Ph.D. in immunology from the University of Pennsylvania in 1981, working with Dr. Walter Gerhard on using monoclonal antibodies to understand influenza A virus hemagglutinin antigenicity and function. As a postdoctoral fellow, he worked with Dr. David Lane at the Imperial College in London, studying the newly discovered p53 protein. From 1983 to 1987, he was an assistant professor at the Wistar Institute in Philadelphia. In 1987, Dr. Yewdell joined the Laboratory of Viral Diseases and in 1993 was appointed to lead its Cellular Biology Section.

Research Group

Lab Members

Postbaccalaureate Fellows

  • Neetij Krishnan, B.A.
  • Nicholas Usher, B.Sc.

Visiting Fellows

  • Nathan Fridlyand, Ph.D.
  • Jaroslav Holly, Ph.D.
  • Tiansheng Li, Ph.D.
  •  Alberto López-Muñoz, Ph.D.
  • Jefferson Santos, Ph.D.
  • Zhe Hu, Ph.D.

Research Fellows

  • Devin Dersh, Ph.D.
  • Ivan Kosik, Ph.D.

Research Staff

James Gibbs, Ph.D. – Biologist

Selected Publications

Wei J, Kishton RJ, Angel M, Conn CS, Dalla-Venezia N, Marcel V, Vincent A, Catez F, Ferré S, Ayadi L, Marchand V, Dersh D, Gibbs JS, Ivanov IP, Fridlyand N, Couté Y, Diaz JJ, Qian SB, Staudt LM, Restifo NP, Yewdell JW. Ribosomal Proteins Regulate MHC Class I Peptide Generation for Immunosurveillance. Mol Cell. 2019 Mar 2173(6).

Kosik I, Angeletti D, Gibbs JS, Angel M, Takeda K, Kosikova M, Nair V, Hickman HD, Xie H, Brooke CB, Yewdell JW. Neuraminidase inhibition contributes to influenza A virus neutralization by anti-hemagglutinin stem antibodies. J Exp Med. 2019 Feb 4 216(2).

Angeletti D, Kosik I, Santos JJS, Yewdell WT, Boudreau CM, Mallajosyula VVA, Mankowski MC, Chambers M, Prabhakaran M, Hickman HD, McDermott AB, Alter G, Chaudhuri J, Yewdell JW. Outflanking immunodominance to target subdominant broadly neutralizing epitopes. Proc Natl Acad Sci U S A. 2019 Jul 2 116(27).

Angeletti D, Gibbs JS, Angel M, Kosik I, Hickman HD, Frank GM, Das SR, Wheatley AK, Prabhakaran M, Leggat DJ, McDermott AB, Yewdell JW. 2017. Defining B cell immunodominance to viruses. Nat Immunol. 2017 Apr 18(4):.

Altman MO, Bennink JR, Yewdell JW, Herrin BR. 2015. Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity. Elife. 2015 Aug 7 4.

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