[R.L. Modlin's picture]
Robert L. Modlin, M.D. 
Professor, Chief, Med/Derm. 
536 MBI 
Mail Code: 175018 
310-825-6214 
Fax: 310-206-9878

Administrative Support 
Juliana Galindo
52-121 CHS
Mail Code: 175018 
310-825-5420 
Fax: 310-206-9878

Office: 52-121 CHS
Lab: 536 MBI


Research Interests
Research Title: Mechanisms of T-cell responsiveness to microbial pathogens
 Research Summary
 
The major focus of our research has been to investigate mechanisms of host resistance and susceptibility to infection, with an emphasis on the immunobiology of antigen presentation, T-cell recognition and cytokine responses. Leprosy provides an extraordinary window onto immune regulation in humans, because the disease presents as a spectrum, in which the ability of the host to control the infection correlates with the level of the T-cell response to the pathogen, Mycobacterium leprae. Our approach has been to focus on the investigation of T lymphocytes at the site of disease activity in order to define cellular subsets and cytokine patterns which may contribute to resistance versus susceptibility to infection. Our lab is currently interested in the role of interleukin-10 and interleukin-12 in microbial immunity, analyzing the transcriptional regulation of mycobacterial induced IL-10 and IL-12 production and the signal transduction pathways leading to their release.

 For more than a decade, a central paradigm in immunology has been that T-cells recognize peptide antigen presented in the context of MHC molecules. Recent work in our laboratory has identified a pathway for non-MHC restricted presentation of nonpeptide antigens to T cells, thus substantially enlarging this central paradigm of T-cell recognition. This novel pathway involves the presentation of lipid and lipoglycan antigens by a family of MHC-related molecules, known collectively as CD1. Our studies show that T cells activated by this pathway can contribute functionally to the elimination of intracellular pathogens. Work is underway to study this unique antigen presentation pathway and to identify mechanisms by which CD1-restricted T cells kill microbial invaders. It is anticipated that such studies will lead to novel immunotherapeutic approaches against human infectious disease.

 
 
Selected Publications
Representative Publications
 
  • Yamamura M, Uyemura K, Deans RJ, Weinberg K, Rea TH, Bloom BR, Modlin RL. Defining protective responses to pathogens: Cytokine profiles in leprosy lesions. Science 254:277-279, 1991.
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  • Sieling PA, Wang X-H, Gately MK, Oliveros JL, McHugh T, Barnes PF, Wolf SF, Golkar L, Yamamura M, Yogi Y, Uyemura K, Rea TH, Modlin RL. IL-12 regulates T-helper Type 1 cytokine responses in human infectious disease. J Immunol. 153:3639-3647, 1994.
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  • Sieling PA, Chatterjee D, Porcelli SA, Prigozy TI, Mazzaccaro RJ, Soriano T, Bloom BR, Brenner MB, Kronenberg M, Brennan PJ, Modlin RL. CD1-restricted T-cell recognition of microbial lipoglycan antigens. Science 269:227-230, 1995.
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  • Stenger S, Mazzaccaro RJ, Uyemura K, Cho S, Barnes P, Rosat JP, Sette A, Brenner MB, Porcelli SA, Bloom BR, Modlin RL. Differential effects of cytolytic T cell subsets on intracellular infection. Science 276:1684-1687, 1997.
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