Thomas J. Braciale
Primary AppointmentProfessor, Pathology
- BS, Biology, St. Joseph's College, Philadelphia, PA
- MD, Medicine and Immunology, Univ. of Pennsylvania, Philadelphia, PA
- PhD, Medicine and Immunology, Univ. of Pennsylvania, Philadelphia, PA
- Residency, Pathology, Barnes Hospital (Washington Univ.) St. Louis, MO
- Postdoc, Immunology and Virology, Australian National University, Canberra, Australia
T Lymphocyte Responses To Virus Infection
Our research on Influenza focuses on the response of CD8+ T lymphocytes -- Cytolytic T Lymphocytes (CTL) or killer T cells -- to Influenza infection. Wewant 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 interplaybetween Influenza virus and the CTL response contributes to lung injury duringinfection. 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.