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Edward J. Usherwood, Ph.D.

Title(s):
Professor of Microbiology and Immunology

Department(s):
Microbiology and Immunology

Education:
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.

Programs:
Immunology Program
Molecular and Cellular Biology Graduate Programs
Molecular Pathogenesis Program
Norris Cotton Cancer Center

Curriculum Vitae:
Usherwood_E_CV_2009-02-02.pdf

NIH Biosketch:
Usherwood_E_BIO_2009-02-02.pdf

Websites:
Usherwood lab website:
http://dms.dartmouth.edu/usherwood/

http://dms.dartmouth.edu/microbio/
http://dms.dartmouth.edu/immuno/

Contact Information:

Dartmouth Medical School
Borwell Research Building - HB7556
1 Medical Center Drive
Lebanon NH 03756

Phone: 603-650-7730
Fax: 603-650-6223
Email: Edward.J.Usherwood@Dartmouth.Edu


Professional Interests:

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.

Grant Information:

NCI R01 "Immune surveillance in murine gammaherpesvirus infection"
NIAID R01 "T cell function in murine gammaherpesvirus infection"

Courses Taught:

Medical Virology (Medical School)
Immune Therapy Advanced Course (MCB graduate program)
MCB graduate program core course


Selected Publications:

 

Hu Z, Usherwood EJ
Immune escape of γ-herpesviruses from adaptive immunity.
Rev Med Virol 2014 Apr 15;
PMID: 24733560

Hart KM, Usherwood EJ, Berwin BL
CX3CR1 delineates temporally and functionally distinct subsets of myeloid-derived suppressor cells in a mouse model of ovarian cancer.
Immunol Cell Biol 2014 Mar 11;
PMID: 24613975

Guo Y, Lee YC, Brown C, Zhang W, Usherwood E, Noelle RJ
Dissecting the role of retinoic Acid receptor isoforms in the CD8 response to infection.
J Immunol 2014 Apr 1; 192(7):3336-44
PMID: 24610012

Hu Z, Zhang W, Usherwood EJ
Regulatory CD8+ T cells associated with erosion of immune surveillance in persistent virus infection suppress in vitro and have a reversible proliferative defect.
J Immunol 2013 Jul 1; 191(1):312-22
PMID: 23733872

Allie SR, Zhang W, Tsai CY, Noelle RJ, Usherwood EJ
Critical role for all-trans retinoic acid for optimal effector and effector memory CD8 T cell differentiation.
J Immunol 2013 Mar 1; 190(5):2178-87
PMID: 23338237

Tsai CY, Allie SR, Zhang W, Usherwood EJ
MicroRNA miR-155 affects antiviral effector and effector Memory CD8 T cell differentiation.
J Virol 2013 Feb; 87(4):2348-51
PMID: 23221547

Tsai CY, Hu Z, Zhang W, Usherwood EJ
Strain-dependent requirement for IFN-γ for respiratory control and immunotherapy in murine gammaherpesvirus infection.
Viral Immunol 2011 Aug; 24(4):273-80
PMID: 21830899

Byrne KT, Cote AL, Zhang P, Steinberg SM, Guo Y, Allie R, Zhang W, Ernstoff MS, Usherwood EJ, Turk MJ
Autoimmune melanocyte destruction is required for robust CD8+ memory T cell responses to mouse melanoma.
J Clin Invest 2011 May; 121(5):1797-809
PMID: 21540555

Molloy MJ, Zhang W, Usherwood EJ
Suppressive CD8+ T cells arise in the absence of CD4 help and compromise control of persistent virus.
J Immunol 2011 Jun 1; 186(11):6218-26
PMID: 21531895

Allie SR, Zhang W, Fuse S, Usherwood EJ
Programmed death 1 regulates development of central memory CD8 T cells after acute viral infection.
J Immunol 2011 Jun 1; 186(11):6280-6
PMID: 21525385