Sheila A.
Lukehart
PhD
Related links
Bio
The Lukehart laboratory studies the pathogenesis of syphilis and the immune response to Treponema pallidum in humans and in animal models. Our current major interest is the 12-membered tpr gene family of T. pallidum, which is hypothesized to encode surface-exposed antigens that are major targets of the protective immune response, may be involved in immune evasion, and are promising vaccine candidates. We have demonstrated that one member of the Tpr family, TprK, undergoes antigenic variation; studies related to the immunological relevance and molecular mechanism of this variation are ongoing. New studies are focused on TprC and TprD, which are also surface exposed, and which differ in sequence among T. pallidum strains and subspecies. The laboratory is also working to identify surface molecules that are targets of opsonization and to define the kinetics of and requirements for bactericidal activity by macrophages. Many of the projects described above involve collaborations with Drs. Arturo Centurion-Lara and Lorenzo Giacani.
Additionally, our laboratory is involved in studies of clinical aspects of syphilis and other trponematoses. With Dr. Christina Marra (Neurology), the laboratory is exploring the molecular basis for neuroinvasion, the immunologic response to T. pallidum within the CNS, and the efficacy of recommended therapy for CNS syphilis in immunocompetent and HIV-infected patients. Other ongoing studies involve the investigation of emerging macrolide resistance, application of a molecular typing method for T. pallidum to epidemiological studies of syphilis, and studies of yaws in Papua New Guinea.
Research interests
- Treponema pallidum
- Syphilis, Yaws, Bejel
- Bacterial pathogenesis
- Vaccine development
Clinical interests
- Syphilis
- yaws
Education & training
BA, Biology, University of California, San Diego, CA (1973)
PhD, Microbiology and Immunology, University of California, Los Angeles, CA (1978)
Senior Postdoctoral Fellow, Department of Medicine/Infectious Diseases, School of Medicine, University of Washington (King K. Holmes, M.D., Ph.D.), University of Washington, Seattle, WA (1979-1980)
Postdoctoral Research Fellow, Department of Pathology, School of Medicine, University of California, San Diego (Stewart Sell, M.D.), University of Washington, Seattle, WA (1978-1979)
Honors
Distinguished Career Award, American Sexually Transmitted Diseases Association, 2007
Seattle Association for Women in Science Award for Scientific Advancement, 2013
American Venereal Disease Association Achievement Award, 1991
Gordon Research Conference on Biology of Spirochetes: Vice Chair, 1996-1998
Keynote Lecture Gordon Conference on Biology of Spirochetes, 2018
Publications
Giacani L, Brandt SL, Ke W, Reid TB, Molini BJ, Iverson-Cabral S, Ciccarese G, Drago F, Lukehart SA, Centurion-Lara A. Transcription of TP0126, Treponema pallidum putative OmpW homolog, is regulated by the length of a homopolymeric guanosine repeat. Infect Immun. 2015 Jun; 83(6): 2275–2289.
• PubMed Abstract
Ke W, Molini BJ, Lukehart SA, Giacani L, Treponema pallidum subsp. pallidum TP0136 protein Is heterogeneous among isolates and binds cellular and plasma fibronectin via its NH2-terminal end. PLoS Negl. Trop. Dis. 2015; 9:e0003662.
• PubMed Abstract
Mitjà O, Houinei W, Moses P, Kapa A, Paru R, Hays R, Godornes C, Vivaldo Bieb S, Grice T, Siba P, Mabey D, Sanz S, Alonso PL, Asiedu K, Lukehart SA, Bassat Q. Mass treatment with single-dose Azithromycin for yaws. New Eng J Med. 2015; 372:703-710.
• PubMed Abstract
Reid TB, Molini BJ, Fernandez MC, Lukehart SA. Antigenic variation of TprK facilitates development of secondary syphilis. Infect Immun. 2014 Dec; 82: :4959-67. (Selected for Spotlight)
• PubMed Abstract
Mitja O, Lukehart SA, Pokowas G, Moses P, Kapa A, Paru R, Godornes C, Robson J, Cherian S, Houinei W, Kazadi W, Siba P, de Lazzari E, Bassat Q. Haemophilus ducreyi is major cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: A prospective cohort study. Lancet Glob Hlth. 2014;2:e235–241.
• The Lancet
Centurion-Lara A, Giacani L, Godornes C, Molini BJ, Brinck Reid T, Lukehart SA. Fine analysis of genetic diversity of the tpr gene family among treponemal species, subspecies and strains. PLoS Negl Trop Dis. 2013; 7(5):e2222.
• PubMed Abstract