Laurence Buxbaum, M.D., Ph.D.
Assistant Professor, Dept of Medicine, Division of Infectious Diseases

Microbiology, Virology and Parasitology Program

Address

VA Medical Center
Research 151 (A505) (Lab)
3900 Woodland Ave
Philadelphia, PA 19104

Office tel.: 215 823-5800 x3426
Fax: 215 823-5171
E-mail: buxbaum@mail.med.upenn.edu

Link(s)

Dr. Buxbaum's at the Division of Infectious Diseases

Education

Massachusetts Institute of Technology, S.B, S.B, (Mathematics, Biology) 1987

Johns Hopkins School of Medicine, Ph.D., (Biochemistry, Cellular, and Molecular Biology) 1995

Johns Hopkins School of Medicine, M.D., 1995

Hospital of the University of Pennsylvania, Residency and Fellowship (Residency in Internal Medicine, Fellowship in Infectious Diseases) 1995-2000

Research Interests

• Immunology of Chronic Leishmania Infection

Key words: immunology, immunoparasitology, Leishmania, parasite, IL-10, Fcgamma R, cysteine proteinase

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Description of Research

Worldwide there are 12 million people infected with the single-celled parasite Leishmania, with 2 million new infections a year. Spread by sandfly bites, this parasite causes fatal disease of the internal organs as well as non-healing and potentially disfiguring diseases of the skin and mucous membranes. Thirteen Gulf War veterans contracted an unusual version of leishmaniasis that affected the internal organs, even though this strain exclusively causes skin disease in local populations. Over 1200 cases of cutaneous leishmaniasis have occurred in the US troops stationed in Iraq and Afghanistan.

We have been studying infection of mice by Leishmania mexicana, attempting to understand why this parasite causes non-healing disease, whereas a related parasite, L. major, causes lesions that heal. We have found that the cytokine IL-10 suppresses a protective T cell-mediated IFN-gamma response and that IL-10 is therefore required for chronic infection. IL-10 production is triggered by antibodies on the surface of parasites. FcgammaR, likely on macrophages, are also required for chronic disease to occur. We are trying to determine the IgG isotypes and FcgR types involved in this IL-10 process as well as the cellular source of IL-10 (macrophages, T cells, B cells, other?) in order to better understand the mechanism of this suppressive response and to help guide vaccine development.  More recently we began new investigations into the role of glycolipids as parasite surface targets of IgG.

A better understanding of the immune mechanisms of Leishmania infection may give insights into many other diseases that involve cell-mediated immunity, especially those caused by pathogens that live inside host cells such as tuberculosis, toxoplasmosis, and HIV.

Recent Publications

Buxbaum, L.U., Milne, K.G., Werbovetz, K.A. and Englund, P.T. Myristate exchange on the Trypanosoma brucei variant surface glycoprotein. Proc. Natl. Acad. Sci. USA. 93:1178-1183, 1996.

Jones, D.E., Buxbaum, L.U., and Scott, P. IL-4 independent inhibition of IL-12 responsiveness during Leishmania amazonensis infection. J. Immunol. 165:364-372, 2000.

Buxbaum, L.U., Uzonna, J.E., Goldschmidt, M.H., and Scott, P. Control of New World cutaneous leishmaniasis is interleukin-12 independent but STAT4 dependent. Euro. J. Immunol. 32:3206-3215. 2002.

Buxbaum, L.U., Denise, H., Coombs, G.H., Alexander, J., Mottram, J.C., and Scott, P. Cysteine protease B of Leishmania mexicana inhibits host Th1 responses and protective immunity. J. Immunol. 171:3711-3717, 2003.

Buxbaum, L.U. and Scott, P. Interleukin 10- and Fcgamma receptor-deficient mice resolve Leishmania mexicana lesions. Infect. Immun. 73:2101-8, 2005.

Lab

Rotation Projects

We are studying the immunology of chronic cutaneous Leishmaniasis. In particular I am concentrating on the role of FcgammaR on macrophages and their role in inducing IL-10, which suppresses the protective immune response. One project involves the effects of passive transfer of antibodies on parasite load. Another project would include developing real-time PCR assessment of IL-10 from lesions.

We have also recently begun to study the role of glycolipids as antigens, possibly presented by CD-1, an MHC-like molecule that presents glycolipid antigens rather than peptides. These glycolipids may be responsible for IgG responses that in turn generate the suppressive IL-10 response. This project involves glycolipid biochemistry as well as immunology. A rotation project could involve testing human serum samples from L. mexicana infected people to see if the antibody responses seen in mice to glycolipids occur in humans as well. Analysis of the epitopes on the glycolpids that are recognized by antibodies is also a feasible project.

Lab personnel:

Dr. Niansheng Chu- Research Specialist
Dr. Bolaji Thomas- Postdoctoral Fellow