Lukehart, Sheila, Ph.D.

Lukehart, Sheila, Ph.D.
Research Professor of Medicine,
Adjunct Research Professor of Pathobiology,
Microbiology

CONTACT INFORMATION
Department of Medicine
Box 359779
Harborview Medical Center
325 Ninth Avenue
Seattle, WA 98104

Phone: (206) 341-5362
Fax: (206) 341-5363
lukehart@u.washington.edu

LINK TO THE SHEILA LUKEHART'S COMMUNITY OF SCIENCE WEB PAGE

This laboratory focuses on several aspects of the pathogenesis and immune response to syphilis and other treponemal infections in humans and in animal models. (1) 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, and investigation of cytokine induction by these antigens. (2) 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. (3) In collaboration with Drs. Arturo Centurion and Wesley Van Voorhis, the lab is investigating the hypothesis that there is phase variation or antigenic variation of important surface molecules (e.g., opsonic targets) that allows immune evasion leading to chronic infection. (4) Comparative genetic and antigenic studies are being conducted on the various pathogenic treponemes, with the goal of identifying protective antigens and important virulence factors. (5) 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. In addition, mechanisms of neuroinvasion by T. pallidum are being investigated in the rabbit model. (6) Treponemes comprise 40% of bacteria in periodontal lesions. The laboratory is examining the interaction of oral treponemes with the innate immune response of the gingival epithelium.

Marra CM, Maxwell CL, Smith SL, Lukehart SA, Rompalo AM, Eaton M, Stoner BP, Augenbraun M, Barker DE, Corbett JJ, Zajackowski M, Raines C, Nerad J, Kee R, Barnett SH. Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis, in press.

Brissette CA, Lukehart SA. Treponema denticola is resistant to human ß-defensins. Infect Immun 70:3982-4, 2002.

Morgan CA, Molini BJ, Lukehart SA, Van Voorhis WC. Segregation of B and T cell epitopes of Treponema pallidum TprK to variable and conserved regions during experimental syphilis infection. J Immunol 169:952-7, 2002.

Centurion-Lara A, Castro C, Barrett L, Cameron C, Mostowfi M, Van Voorhis WC, Lukehart SA. Treponema pallidum major sheath protein homologue TprK is a target of opsonic antibody and the protective immune response. J Exp Med 189:647-56, 1999.
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