Fred Wang, M.D.

Professor of Medicine

Harvard Medical School
Brigham & Women's Hospital
Channing Laboratory
181 Longwood Avenue
Boston, MA 02115
Tel: 617-525-4258
Fax: 617-525-4257
e-mail: fwang@rics.bwh.harvard.edu 
3 postdoctoral fellows, 1 pre-doctoral students

Our research focuses on the molecular biology, pathogenesis, and therapy of
Epstein-Barr virus infection and associated malignancies.  We use
experimental animal model systems and translational human studies to better
understand the virology and immunology of EBV infection in the context of
an intact organism and to develop new approaches for immunotherapy.

We have pioneered the use of non-human primates as the most authentic
animal model for EBV infection in humans. Old World primates were known to
be naturally infected with B lymphotropic herpesviruses, or
lymphocryptoviruses (LCV) closely related to Epstein-Barr virus.  Like EBV
in humans, these simian LCV infect nearly all individuals by adulthood and
cause persistent asymptomatic infection for the life of the host.  Simian
LCV-induced B cell tumors can develop when the animals are immunosuppressed
by SIV infection analogous to the EBV-induced tumors occurring in AIDS and
transplant patients. LCV-naive macaques can be experimentally infected by
the natural route of infection to reproduce EBV infection in humans. We
have cloned and sequenced the entire rhesus LCV genome and have developed a
genetic system for making mutant rhesus LCV.  Ongoing projects focus on how
specific viral genes contribute to persistent infection, what immune
responses are critical for control of persistent infection, and how
potential viral immune evasion mechanisms contribute to successful
infection in the context of the natural host.

A better understanding of EBV virology and immunology is also being applied
to translational studies in humans with EBV-associated nasopharyngeal
carcinoma to develop more effective immunotherapy for EBV-induced
malignancies.  In EBV-induced cancers, virus proteins act as foreign tumor
markers that can be successfully attacked by the administration of
EBV-specific T cells expanded in vitro.  Ongoing clinical and laboratory
studies are focused on dissecting which EBV-specific T cells are most
important for clinical efficacy and developing improved strategies for
generating more active EBV-specific T cells for immunotherapy.

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