Edward J. Usherwood, Ph.D.
Professor of Microbiology and Immunology
Microbiology and Immunology
University of Cambridge, U.K., Ph.D., 1997
University of Cambridge, U.K., BA 1994
Dr. Usherwood received his B.A. in 1990 in Natural Sciences from the University of Cambridge, U.K. He continued his studies at the University of Cambridge and was awarded his Ph.D. from the Department of Pathology in 1994. From 1994 to 1997 Dr. Usherwood undertook postdoctoral research at the University of Edinburgh, U.K. then he moved to Memphis, TN for further postdoctoral work in the Department of Immunology at St. Jude's Children's Research Hospital. From 1999 to 2001 he held a position as a Research Assistant Member at The Trudeau Institute, NY. He came to Dartmouth in 2001 as an Assistant Professor, then was promoted to Associate Professor in 2007.
Molecular and Cellular Biology Graduate Programs
Molecular Pathogenesis Program
Norris Cotton Cancer Center
Dartmouth Medical School
Borwell Research Building - HB7556
1 Medical Center Drive
Lebanon NH 03756
Dr Usherwood studies the generation and maintenance of T cell memory. T cells recognized and destroy cells infected with intracellular pathogens such as viruses and are also important in protection against tumor development . A large expansion in the number of virus-specific T cells occurs shortly after virus infection, however most of these cells die after virus clearance has been accomplished. A small residual population of T cells then persists lifelong and forms the basis of immunological memory. Using techniques such as MHC/peptide tetramer staining we can identify these memory cells and interrogate their functional capabilities under different conditions. Our work has shown that costimulation and CD4 T cell help have dramatic effects both on the resting memory population and their ability to mount secondary immune response. We have devised several methods to restore the functional defects present in these cells, and these may represent important new immunotherapies.
Another major area of interest in the lab is the impact upon the memory response of a persistent virus infection. We use the murine gammaherpesvirus model system, which represents a low-load persistent virus infection. This virus is also a model for the human gammaherpesviruses, which are significant causes of malignancy and other disease in immunosuppressed patients. Therefore this work has significance both for our understanding of the memory T cell response in general and more specifically how the gammaherpesviruses are controlled, in addition to how and why this control breaks down. Our research has shown several distinct changes occur in the memory response during persistent infection. In models where immune surveillance breaks down we are studying the underlying mechanisms for this breakdown, and developing immune therapies to restore immune surveillance to the virus.
NCI R01 "Immune surveillance in murine gammaherpesvirus infection"
NIAID R01 "T cell function in murine gammaherpesvirus infection"
Medical Virology (Medical School)
Immune Therapy Advanced Course (MCB graduate program)
MCB graduate program core course
Functional heterogeneity in the CD4+ T cell response to murine γ-herpesvirus 68.
MCL1 enhances the survival of CD8+ memory T Cells after viral infection.
Immune escape of γ-herpesviruses from adaptive immunity.
CX3CR1 delineates temporally and functionally distinct subsets of myeloid-derived suppressor cells in a mouse model of ovarian cancer.
Dissecting the role of retinoic acid receptor isoforms in the CD8 response to infection.
Regulatory CD8+ T cells associated with erosion of immune surveillance in persistent virus infection suppress in vitro and have a reversible proliferative defect.
Critical role for all-trans retinoic acid for optimal effector and effector memory CD8 T cell differentiation.
MicroRNA miR-155 affects antiviral effector and effector Memory CD8 T cell differentiation.
Strain-dependent requirement for IFN-γ for respiratory control and immunotherapy in murine gammaherpesvirus infection.
Autoimmune melanocyte destruction is required for robust CD8+ memory T cell responses to mouse melanoma.