Sheila A. Lukehart, PhD
Professor, Department of Medicine
Assistant Dean for Research and Graduate Education-HMC
This laboratory focuses on the pathogenesis of syphilis and the immune response Treponema pallidum in humans and in animal models. 1) Our current major interest is the newly-identified polymorphic tpr gene family of T. pallidum. This gene family comprises 2% of the T. pallidum genome and is hypothesized to encode surface-exposed antigens that are important in syphilis pathogenesis, are major targets of the protective immune response, and are promising vaccine candidates. We have recently demonstrated that one member of the family, TprK, undergoes rapid sequence variation during infection in a host, thus likely contributing to persistence of the organism in immunocompetent hosts. Antibody responses during infection are focused on the variable regions of TprK and are highly specific for TprK variants. These studies are conducted in collaboration with Drs. Arturo Centurion and Wes Van Voorhis. 2.) Studies to date have indicated that the protective immune response to Treponema pallidum is mediated by Th1-type CD4+ lymphocytes and infiltrating macrophages. Ongoing projects in the laboratory include the cloning and characterization of major T cell antigens of T. pallidum, including the above Tpr antigens, and investigation of cytokine induction by these antigens. 3). Bacterial clearance in vivo results from ingestion and killing of opsonized treponemes by macrophages. The laboratory is currently working to identify the surface molecules that are targets of opsonization, and to define the kinetics of and requirements for bactericidal activity by macrophages. 4). Invasion of the central nervous system by T. pallidum occurs in the early weeks of infection. With Dr. Christina Marra, the laboratory is exploring the immunologic response to T. pallidum within the CNS, and the efficacy of recommended therapy for CNS syphilis in immunocompetent and HIV-infected patients.