Biography
Contact:
Department of Microbiology and Immunology
Weill Medical College of Cornell University
1300 York Avenue
New York, NY 10021
Tel: (212) 746-4404
Fax: (212) 746-4427
Email: xim2002@med.cornell.edu
Research Interests: MOLECULAR MECHANISMS OF INTERLEUKIN-12 AND INTERLEUKIN-10 GENE EXPRESSION IN INNATE AND ADAPTIVE IMMUNITY
Interleukin-12 (IL-12) is a heterodimeric, proinflammatory cytokine produced by phagocytic cells and plays a critical role in the activation and function of antigen-presenting cells and effector lymphocytes during microbial infection. Interleukin-10 (IL-10) is a homodimeric cytokine produced mainly by monocytes/macrophages, activated T and B lymphocytes. IL-10 has potent anti-inflammatory and immunosuppressive activities on myeloid cell functions while it also exerts immune stimulatory effects on B cells for proliferation, differentiation and antibody production. It is a pivotal homeostatic regulator of immune reactivity. The production of IL-12 and IL-10 by phagocytic and antigen-presenting cells is regulated in opposite manners during innate and adaptive immune responses. The understanding of the molecular mechanisms controlling the gene expression of IL-12 and IL-10 in interactions between pathogens and the immune system is essential to efforts to develop therapeutic strategies for infectious and malignant diseases. We are currently investigating in the following areas:
I. Molecular mechanisms of pathogen/antigen-mediated regulation of IL-12 and IL-10 gene expression in macrophages and dendritic cells.
II. Molecular mechanisms of the regulation of IL-12 and IL-10 gene expression during phagocytosis of apoptotic cells by macrophages and dendritic cells.
III. Molecular basis of the antitumor effect and immunity conferred by IL-12 in mouse mammary tumor models.
PUBLICATIONS
Kim, S., Elkon, K.B., and Ma, X. 2004. A Novel Transcription Factor Suppresses Interleukin-12 Following Phagocytosis of Apoptotic Cells. IMMUNITY (in press).
Liu, J., Xiang, Z., and Ma, X. 2004. Role of Interferon Regulatory Factor-1 and Interleukin-12 in Immunological Resistance to Pathogenesis of N-methyl-N-nitrosourea-induced T Lymphoma. J. Immunol. 173(2):1184-93.
Mitsuhashi, M., Liu, J., Shi, X., Cao, S., and Ma, X. 2004. Regulation of Interleukin-12 Gene Expression and Its Anti-tumor Activities by Prostaglandin E2 Derived from Mammary Carcinomas. J Leukoc Biol. 76:322-332.
Luo, Q., Ma, X., Wahl, S.M., Bieker, J.J., Crossley, M. and Montaner, L.J. 2004. Activation and Repression of IL-12 p40 Transcription by Erythroid Kruppel-Like Factor (EKLF) in Macrophages. J. Biol. Chem. 279: 18451-18456.
Shi, X., Liu, J., Xiang Z., Mitsuhashi, M., Wu, R., and Ma, X. 2004. Gene Expression Analysis in Interleukin-12-induced Suppression of Mouse Mammary Carcinoma. Int. J. Cancer. 110: 570-578.
Shi, X., Cao, S., Mitsuhashi, M., Xiang Z., and Ma, X. 2004. Genome-wide Analysis of Molecular Changes in Interleukin-12-induced Control of Mammary Carcinoma via Interferon-gamma-independent Mechanisms. J. Immunol. 172: 4111-4122.
Liu, J., Cao, S., Herman, L.M., and Ma. X. 2003. Differential Regulation of IL-12 p35 and p40 Gene Expression and Interferon-gamma-primed IL-12 production by Interferon Regulatory Factor-1. J. Exp. Med. 198(8): 1265-1276.
Xiang, Z., Yang, Y., Ma, X., and Ding, W. 2003. Microarray Expression Profiling: Analysis and Applications. Current Opinions in Drug Discovery and Development. 6(3):384-395.
Kim, S.J., Gershov, D., Ma, X., Brot, N., Elkon, E.L. 2003. Opsonization of Apoptotic Cells and its Effect on Macrophage and T cell Immune Responses. Ann N Y Acad Sci. 987:68-78.
Murray, H.W., Moreira, A.L., Lu, C.M., DeVecchio, J., Mitsuhashi, M., Ma, X., and Heinzel, F.P. 2003. Determinants of response to interleukin-10 receptor blockade immunotherapy in experimental visceral leishmaniasis. J. Infectious Diseases. 188(3):458-64.
Kim, S.J., Gershov, D., Ma, X., Brot, N., Elkon, E.L. 2002. IPLA2 activation during apoptosis exposes membrane lysophosphatidylcholine and leads to binding by natural IgM antibodies and complement activation. J. Exp. Med. 196 (5): 655-665.
Cao, S., Liu, J., Chesi, M., Bergsagel, P.L., Ho, I.C., Donnelly, R.P. and Ma, X. 2002. Differential regulation of IL-12 and IL-10 gene expression in macrophages by the bZIP transcription factor c-Maf. J. Immunol. 169:5715?5725.
Ma. X. and Trinchieri G. 2001. Regulation of Interleukin-12 production in antigen-presenting cells. Advances in Immunology. 79:55-92.
Ma, X. 2001. TNF-alpha and IL-12: a balancing act in macrophage functioning. Microbes and Infection. Forum in Immunology: inhibitory receptors of mononuclear phagocytes. Institut Pasteur. 3(2):121-9.
Becker, C., Wirtz, S., Ma, X., Blessing, M., Galle, P.R., and Neurath, M. 2001. Regulation of IL-12 p40 promoter activity in primary hu,man monocytes: roles of NF-kappaB, CCAAT/Enhancer-binding protein beta and PU.1 and identification of a novel repressor element (GA-12) that responds to IL-4 and prostaglandin E2. J. Immunol. 167:2608-2618.
Byrnes, A.A., Ma, X., Cuomo, P., Park, K., Wahl, L., Wolf, S.F., Zhou, H., Trinchieri, G., and Karp, C.L. 2001. Type I interferons, Interleukin-12, and Interferon gamma: convergence and cross-regulation among mediators of cellular immunity. European Journal of Immunology. 31:2026-2034.
Cappiello, M.G., Sutterwala, F.S., Trinchieri, G., Mosser, D.M., and Ma, X. 2001. Suppression of Macrophage IL 12 Transcription Following Fcgamma Receptor Ligation. J. Immunol. 166:4498-4506.
Ma, X., and Montaner, L.J. 2000. Proinflammatory response and IL-12 expression in HIV-1 infection. J Leukoc Biol. 68(3):383-90.
Wang, I.M., Contursi, C., Masumi, A., Ma, X., Trinchieri, G., Ozato, K. 2000. ICSBP is an interferon-gamma inducible activator of IL-12 p40 transcription. J. Immunol. 165:271-279.
Ma, X., Sun, J., Riemann, H., Bailer, R.T., Robertson, S., Papasavvas, E., Moore, A., Marshall, J., Donnelly, R., Trinchieri, G., and Montaner, L.J. 2000. Inhibition of Interleukin-12 production in human monocyte-derived macrophages by TNF-alpha. J. Immunol. 164:1722-1729.
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