BIMS Affiliated Research Faculty

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Thomas  J.  Braciale
Degree(s): M.D., Ph.D.
Graduate School: University of Pennsylvania
Primary Appointment: Professor, Pathology
Research Interests:
T Lymphocyte Responses To Virus Infection

Email Address: tjb2r@virginia.edu


Biomedical Sciences Graduate Program(s)
  • Microbiology, Immunology and Infectious Diseases
  • Molecular Medicine
  • Molecular Cell and Developmental Biology

  • Research Description

    My laboratory is interested in the host immune response to virus infection - specifically, we study the role of the adaptive immune response in the clearance of both virus and virus-infected cells from the body, and the contribution of the immune response in producing injury during virus infection. Much of our work focuses on infection of the respiratory tract (the lungs) by two viruses: Influenza virus and Respiratory Syncytial Virus (RSV).

    Our research on Influenza focuses on the response of CD8+ T lymphocytes -- Cytolytic T Lymphocytes (CTL) or killer T cells -- to Influenza infection. We want to understand three main things: 1) how CTL are generated during infection; 2) how CD8+ T cells interact with the principal antigen presenting cells of the body (i.e. dendritic cells) to produce those CTL; and 3) how the interplay between Influenza virus and the CTL response contributes to lung injury during infection. We use modern techniques of cell and molecular biology -- including T cell receptor transgenic murine models and virus reverse genetics (to alter the structure of the Influenza genome) in order to understand how specific virus genes (and their products), as well as CTL products (e.g. cytokines) operate to clear infection and/or produce disease. Recently, we have extended this work to include avian influenza virus ("Bird Flu") infection in order to define the mechanisms of lethal infection produced by this virus.

    The second virus that we study, RSV, is a major cause of severe lung infection in young infants; and there is currently no safe vaccine for this virus. Immunization with conventional RSV vaccines (e.g. killed virus) results in more severe injury after subsequent natural RSV infection (when compared to natural infection alone). Thus, RSV can induce immune-mediated disease, and can inhibit the normal immune response. Our research in this area is aimed at understanding how this virus can dysregulate the immune response; so safe and effective vaccines can be developed.

    In addition to our work in Influenza and RSV, our laboratory has also become involved in Bio-Defense research. Our current project is aimed at the development of new vaccines against the small pox virus when delivered as a weapon of bio-terrorism. We are employing a murine model of small pox infection using the murine equivalent of the virus (i.e. ectromelia or mouse pox virus). We are using innovative methods to clone and express genes from vaccinia virus (the pox virus used to vaccinate humans against small pox) to identify candidate proteins which could serve as the basis for vaccines directed against small pox infection.


    Selected Publications
  • Legge KL, Braciale TJ: Lymph node dendritic cells control CD8+ T cell responses through regulated FasL expression. Immunity, 23: 649-659. 2005.
  • Galkina E, Thatte J, Dabak D, Williams MB, Ley K, Braciale TJ: Preferential migration of activated effector CD8+ T-cells into the interstitium of the normal lungs. J Clin Inv, 115: 3473-3483. 2005.
  • Lawrence CW, Braciale TJ: Activation, differentiation and migration of naïve, virus-specific CD8+ T cells during pulmonary Influenza virus infection. J Immunol, 173:1209-1218. 2004.
  • Legge KL, Braciale TJ: Accelerated Migration of Respiratory Dendritic Cells to the Regional Lymph Nodes is Limited to the Early Phase of Pulmonary Infection. Immunity, 18: 265-277. 2003.
  • PubMed Listings for this Faculty Member

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    Contact Information
      Office Address: PO Box 801386, MR-6, 3709A, MR-6 3525, 
      Office Phone: +1 434-924-9233
      Fax Phone: +1 434-924-1221

    Other Web sites for this mentor:
    http://www.healthsystem.virginia.edu/internet/pathology/Faculty/braciale.cfm

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