Sheila A. Lukehart

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University of Washington
School of Medicine
Medicine
Allergy and Infectious Diseases
Research ProfessorAppointed: 1980
University of Washington
School of Public Health and Community Medicine
Pathobiology
Adjunct Research ProfessorAppointed: 1998
University of Washington
School of Dentistry
Periodontics
Adjunct Research ProfessorAppointed: 1995
University of Washington
School of Medicine
Microbiology
Adjunct Research ProfessorAppointed: 1993
Professional Headshot of Sheila A. Lukehart

Mailing Address

University of Washington, Harborview Medical Center
Department of Medicine
325 Ninth Avenue Box 359779
Seattle, Washington 98104
United States

Contact Information

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

Qualifications

Ph.D., University of California, Los Angeles, 1978.

Expertise and Research Interests

This laboratory focuses on the pathogenesis of syphilis and the immune response of 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 familycomprises 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 are exploring the possibility that these genes confer antigenic variation in T. pallidum, thus permitting persistence of the organism in immunocompetent hosts. 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.

Other Expertise

Journal Responsibilities:
1987-1991, Journal of Immunology, Associate Editor;
1990-present, Sexually Transmitted Diseases, Editorial Board;
1985-present, J Immunol, Infect Immun, J infect Dis, Ann Intern Med, Sex Trans Dis, Eur J Clin Micro, Clin Infect Dis,

Grant Review Responsibilities;
1990-95, University of California Task Force on AIDS Study Section;
1985-present, Multiple NIH Site Visit Teams; Ad Hoc Review Committees;
Special Review Committee for Lyme Disease, Chair
1985-present, Veterans Administration, Ad Hoc Merit Review Committees.
1997-present Microbiology and Infectious Diseases Research Committee, NIAID, NIH, Chair, 1999-present

Special Responsibilities:
1998 Chair, Gordon Research Conference on Biology of Spirochetes
1996Vice-Chair, Gordon Research Conference on Biology of Spirochetes

Keywords

COS Keywords:

Immunology, Medical Microbiology, Microbiology, Sexually Transmitted Diseases, Venereal Diseases.

Additional Terms:

Immunology/immunobiology, Immunology/immunobiology: Blood/blood Cells: Lymphocytes, Immunology/immunobiology: Blood/blood Cells: White Cells, Immunology/immunobiology: Inflammation, Immunology/immunobiology: Inflammation: Macrophages, Infectious Diseases, Microbiology, Microbiology: Bacteria/bacterial Disease, Sexually Transmitted Diseases, Spirochetes, Syphilis, Treponema Pallidum.

Memberships

American Association of Immunologists
American Sexually Transmitted Diseases Association
American Society for Microbiology
Association for Women in Science
Infectious Diseases Society of America
International Union Against Sexually Transmitted Infections

Honors and Awards

1999-2002, Chair, Microbiology and Infectious Diseases Research Committee, National Institutes of Health
1996-1998, Vice Chair, 1996; Chair, 1998, Gordon Research Conference on Biology of Spirochetes
1993, Science in Medicine Lecture, University of Washington
1991, American Venereal Disease Association Achievement Award,

Funding Received

  • NIAID: Molecular immunology of syphilis, $413,941 annual, Sep 30, 1993 to Jul 31, 2004.
  • NIAID: University of Washington STD Cooperative Reserach Center, $68,834 annual, Sep 16, 1999 to Sep 15, 2003.
  • NIAID: Surface antigens of T. pallidum: Identification by function, $188,051 annual, Oct 1, 1999 to Sep 30, 2003.
  • Cerus Corporation: Inactivation of Treponema pallidum in human platelets and plasma, $128,286 annual, Jul 1, 2000 to Jun 30, 2003.
  • NINDS: Persistence of CNS T. pallidum in HIV infection, $209,750 annual, Jul 1, 1996 to Jun 30, 2002.
  • NINDS: Role of T. pallidum Msp-homologues in CNS invasion, $150,000 annual, Dec 1, 2000 to Nov 30, 2005.
  • NIAID: Treponema pallidum: Pathogenesis-associated molecules, $157,595 annual, Dec 1, 1997 to Nov 30, 2002.
  • NIAID: Impact of social networks on syphilis transmission, $219,526 annual, Apr 1, 2000 to Mar 31, 2004.
  • NIAID: Impact of social networks on syphilis transmission, $219,526 annual, Apr 1, 2000 to Mar 31, 2004.

Publications

  • Centurion-Lara A, Sun ES, Barrett LK, Castro C, Lukehart SA, Van Voorhis WC, Multiple alleles of Treponema pallidum repeat gene D in Treponema pallidum isolates, Journal of Bacteriology, 182(8), 2332-5, April 2000 Abstract
  • Cameron CE, Lukehart SA, Castro C, Molini B, Godornes C, Van Voorhis WC, Opsonic potential, protective capacity, and sequence conservation of the Treponema pallidum subspecies pallidum Tp92, Journal of Infectious Diseases, 181(4), 1401-13, April 2000 Abstract
  • Centurion-Lara A, Godornes C, Castro C, Van Voorhis WC, Lukehart SA, The tprK gene is heterogeneous among Treponema pallidum strains and has multiple alleles, Infection and Immunity, 68(2), 824-31, February 2000 Abstract
  • Kolman CJ, Centurion-Lara A, Lukehart SA, Owsley DW, Tuross N, Identification of Treponema pallidum subspecies pallidum in a 200-year-old skeletal specimen, Journal of Infectious Diseases, 180(6), 2060-3, December 1999 Abstract
  • Arroll TW, Centurion-Lara A, Lukehart SA, Van Voorhis WC, T-Cell responses to Treponema pallidum subsp. pallidum antigens during the course of experimental syphilis infection., Infection and Immunity, 67(9), 4757-63, September 1999 Abstract
  • Cameron CE, Castro C, Lukehart SA, Van Voorhis WC, Sequence conservation of glycerophosphodiester phosphodiesterase among Treponema pallidum strains., Infection and Immunity, 67(6), 3168-70, June 1999 Abstract
  • Centurion-Lara A, Castro C, Barrett L, Cameron C, Mostowfi M, Van Voorhis WC, Lukehart SA, Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response., Journal of Experimental Medicine, 189(4), 647-56, 15 Feb 1999 Abstract
  • Kolman CJ, Centurion-Lara A, Lukehart SA, Owsley DW, Tuross N., Identification of Treponema pallidum subsp. pallidum in a 200-year-old skeletal specimen, Journal of Infectious Diseases, 180, 2060-3, 1999
  • Cameron CE, Castro C, Lukehart SA, Van Voorhis WC, Function and protective capacity of Treponema pallidum subsp. pallidum glycerophosphodiester phosphodiesterase., Infection and Immunity, 66(12), 5763-70, December 1998 Abstract
  • Centurion-Lara A, Castro C, Castillo R, Shaffer JM, Van Voorhis WC, Lukehart SA, The flanking region sequences of the 15-kDa lipoprotein gene differentiate pathogenic treponemes, Journal of Infectious Diseases, 177(4), 1036-40, April 1998 Abstract
  • Centurion-Lara A, Castro C, Castillo R, Shaffer JM, Van Voorhis WC, Lukehart SA, The flanking region sequences of the 15-kDa lipoprotein gene differentiate pathogenic treponemes., Journal of Infectious Diseases, 177(4), 1036-40, 1998 Abstract
  • Stebeck CE, Shaffer JM, Arroll TW, Lukehart SA, Van Voorhis WC, Identification of the Treponema pallidum subsp. pallidum glycerophosphodiester phosphodiesterase homologue, Fems Microbiology Letters, 154(2), 303-10, September 1997 Abstract
  • Centurion-Lara A, Castro C, Shaffer JM, Van Voorhis WC, Marra CM, Lukehart SA, Detection of Treponema pallidum by a sensitive reverse transcriptase PCR, Journal of Clinical Microbiology, 35(6), 1348-52, June 1997 Abstract
  • Centurion-Lara A, Arroll T, Castillo R, Shaffer JM, Castro C, Van Voorhis WC, Lukehart SA, Conservation of the 15-kilodalton lipoprotein among Treponema pallidum subspecies and strains and other pathogenic treponemes: genetic and antigenic analyses, Infection and Immunity, 65(4), 1440-4, April 1997 Abstract
  • Buchwald D, Collier AC, Lukehart SA, Kith P, Goldstein E, Hooton TM, Evaluation of cerebrospinal fluid in Southeast Asian refugees with reactive serologic tests for syphilis, Western Journal of Medicine, 165(5), 289-93, November 1996 Abstract
  • Centurion-Lara A, Castro C, van Voorhis WC, Lukehart SA, Two 16S-23S ribosomal DNA intergenic regions in different Treponema pallidum subspecies contain tRNA genes, Fems Microbiology Letters, 143(2-3), 235-40, October 1996 Abstract
  • Van Voorhis WC, Barrett LK, Nasio JM, Plummer FA, Lukehart SA, Lesions of primary and secondary syphilis contain activated cytolytic T cells, Infection and Immunity, 64(3), 1048-50, March 1996 Abstract
  • Van Voorhis WC, Barrett LK, Koelle DM, Nasio JM, Plummer FA, Lukehart SA, Primary and secondary syphilis lesions contain mRNA for Th1 cytokines, Journal of Infectious Diseases, 173(2), 491-5, February 1996 Abstract
  • Cummings MC, Lukehart SA, Marra C, Smith BL, Shaffer J, Demeo LR, Castro C, McCormack WM, Comparison of methods for the detection of treponema pallidum in lesions of early syphilis, Sexually Transmitted Diseases, 23(5), 366-9, 1996 Abstract
  • Marra CM, Longstreth WT Jr, Maxwell CL, Lukehart SA, Resolution of serum and cerebrospinal fluid abnormalities after treatment of neurosyphilis. Influence of concomitant human immunodeficiency virus infection, Sexually Transmitted Diseases, 23(3), 184-9, 1996 Abstract
  • Lukehart SA, Modern syphilis--still a shadow on the land, Western Journal of Medicine, 163(6), 587-8, December 1995 Abstract
  • Marra CM, Critchlow CW, Hook EW 3rd, Collier AC, Lukehart SA, Cerebrospinal fluid treponemal antibodies in untreated early syphilis, Archives of Neurology, 52(1), 68-72, January 1995 Abstract
  • Gordon SM, Eaton ME, George R, Larsen S, Lukehart SA, Kuypers J, Marra CM, Thompson S, The response of symptomatic neurosyphilis to high-dose intravenous penicillin G in patients with human immunodeficiency virus infection, New England Journal of Medicine, 331(22), 1469-73, December 1994 Abstract
  • Garcia Monco JC, Wheeler CM, Benach JL, Furie RA, Lukehart SA, Stanek G, Steere AC, Reactivity of neuroborreliosis patients (Lyme disease) to cardiolipin and gangliosides, Journal of the Neurological Sciences, 117(1-2), 206-14, July 1993 Abstract
  • Baker-Zander SA, Shaffer JM, Lukehart SA, VDRL antibodies enhance phagocytosis of Treponema pallidum by macrophages, Journal of Infectious Diseases, 167(5), 1100-5, May 1993 Abstract
  • Baker-Zander SA, Shaffer JM, Lukehart SA, Characterization of the serum requirement for macrophage-mediated killing of Treponema pallidum ssp. pallidum: relationship to the development of opsonizing antibodies, Fems Immunology and Medical Microbiology, 6(4), 273-9, April 1993 Abstract
  • Shaffer JM, Baker-Zander SA, Lukehart SA, Opsonization of Treponema pallidum is mediated by immunoglobulin G antibodies induced only by pathogenic treponemes, Infection and Immunity, 61(2), 781-4, February 1993 Abstract
  • Lukehart SA, Shaffer JM, Baker-Zander SA, A subpopulation of Treponema pallidum is resistant to phagocytosis: possible mechanism of persistence, Journal of Infectious Diseases, 166(6), 1449-53, December 1992 Abstract
  • Marra C M, Handsfield H H, Kuller L, Morton W R, Lukehart S A, Alterations in the course of experimental syphilis associated with concurrent simian immunodeficiency virus infection., Journal of Infectious Diseases, 165(6), 1020-5, June 1992 Abstract
  • Riviere GR, Elliot KS, Adams DF, Simonson LG, Forgas LB, Nilius AM, Lukehart SA, Relative proportions of pathogen-related oral spirochetes (PROS) and Treponema denticola in supragingival and subgingival plaque from patients with periodontitis, Journal of Periodontology, 63(2), 131-6, February 1992 Abstract
  • Marra CM, Slatter V, Tartaglione TA, Baker-Zander SA, Lukehart SA, Evaluation of aqueous penicillin G and ceftriaxone for experimental neurosyphilis, Journal of Infectious Diseases, 165(2), 396-7, February 1992 Abstract
  • Baker-Zander SA, Lukehart SA, Macrophage-mediated killing of opsonized Treponema pallidum, Journal of Infectious Diseases, 165(1), 69-74, January 1992 Abstract
  • Schwebke JR, Lukehart SA, Roberts MC, Hillier SL, Identification of two new antigenic subgroups within the genus Mobiluncus, Journal of Clinical Microbiology, 29(10), 2204-8, October 1991 Abstract
  • Riviere GR, Weisz KS, Simonson LG, Lukehart SA, Pathogen-related spirochetes identified within gingival tissue from patients with acute necrotizing ulcerative gingivitis, Infection and Immunity, 59(8), 2653-7, August 1991 Abstract
  • Riviere GR, Wagoner MA, Baker-Zander SA, Weisz KS, Adams DF, Simonson L, Lukehart SA, Identification of spirochetes related to Treponema pallidum in necrotizing ulcerative gingivitis and chronic periodontitis, New England Journal of Medicine, 325(8), 539-43, August 1991 Abstract
  • Lukehart SA, Serologic testing after therapy for syphilis: is there a test for cure?, Annals of Internal Medicine, 114(12), 1057-8, June 1991 Abstract
  • Marra C, Baker-Zander SA, Hook EW 3d, Lukehart SA, An experimental model of early central nervous system syphilis, Journal of Infectious Diseases, 163(4), 825-9, April 1991 Abstract
  • Barron SL, Riviere GR, Simonson LG, Lukehart SA, Tira DE, O'Neil DW, Use of monoclonal antibodies to enumerate spirochetes and identify Treponema denticola in dental plaque of children, adolescents and young adults, Oral Microbiology and Immunology, 6(2), 97-101, April 1991 Abstract
  • Burstain JM, Grimprel E, Lukehart SA, Norgard MV, Radolf JD, Sensitive detection of Treponema pallidum by using the polymerase chain reaction, Journal of Clinical Microbiology, 29(1), 62-9, January 1991 Abstract
  • Schwebke JR, Hillier SL, Fohn MJ, Lukehart SA, Demonstration of heterogeneity among the antigenic proteins of Mobiluncus species, Journal of Clinical Microbiology, 28(3), 463-8, March 1990 Abstract
  • Lukehart SA, Fohn MJ, Baker-Zander SA, Efficacy of azithromycin for therapy of active syphilis in the rabbit model, Journal of Antimicrobial Chemotherapy, 25 Suppl A, 91-9, January 1990 Abstract

Profile Details

Last Updated: 1/7/2002

COS Expertise ID #135101
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