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
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.
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.
Meghan O’Donoghue Altman, Ph.D.; Matthew Angel, Ph.D.; Davide Angeletti, Ph.D.; Devin Dersh, Ph.D.; Ivan Kosik, PhD.; John Shannon; Mina Seedhom, Ph.D.; Jiajie Wei, Ph.D.
James Gibbs, Ph.D.; Heather Hickman, Ph.D.; Glennys Reynoso
Angeletti D, Gibbs JS, Angel M, Kosik I, Hickman H, Frank GM, Das SR, Wheatley AK, Andrews SF, Chambers M, McDermott AB, Yewdell JW. Defining B-cell immunodominance to influenza A virus. Nature Immunol. 2017. In press.
Seedhom MO, Hickman HD, Wei J, David A, Yewdell JW. Protein translation activity: a new measure of host immune cell activation. J Immunol. 2016 Aug 15;197(4):1498-506.
Cush SS, Reynoso GV, Kamenyeva O, Bennink JR, Yewdell JW, Hickman HD. Locally produced IL-10 limits cutaneous vaccinia virus spread. PLoS Pathog. 2016 Mar 18;12(3):e1005493.
Hickman HD, Reynoso GV, Ngudiankama BF, Cush SS, Gibbs J, Bennink JR, Yewdell JW. CXCR3 chemokine receptor enables local CD8(+) T-cell migration for the destruction of virus-infected cells. Immunity. 2015 Mar 17;42(3):524-37.
Altman MO, Bennink JR, Yewdell JW, Herrin BR. Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity. Elife. 2015 Aug 7;4.
Brooke CB, Ince WL, Wei J, Bennink JR, Yewdell JW. Influenza A virus nucleoprotein selectively decreases neuraminidase gene-segment packaging while enhancing viral fitness and transmissibility. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16854-9.