Distinguished McKnight Professor

Research Interests   Membrane Receptors and Autoimmunity

Most of our research efforts seek to understand the mechanisms that trigger and modulate undesirable antibody responses related to autoimmune diseases and hemophilia. These antibodies are directed to protein components of our body: they either cause diseases or do not allow successful treatment of diseases.

Currently, we are studying the function of the CD4+ T cells that control those antibody responses. These studies include the mechanisms by which the CD4+ T cells become activated, the structures they recognize, and the cytokines they use to either stimulate or downregulate the synthesis of antibodies. The model systems that we are studying are the human autoimmune disease myasthenia gravis and the immune response to coagulation factor VIII that occurs in congenital hemophilia A and in acquired (autoimmune) hemophilia. We study also the mouse models of those diseases.

The ultimate goal of these studies is to devise specific treatments, targeted on those T cells, to specifically turn off the undesirable antibody response while leaving all the other functions of the immune system intact.

A second branch of the research ongoing in our laboratory seeks to understand the structure and function of novel acetylcholine receptors sensitive to nicotine, that are expressed by the cells that line external and internal surfaces of our bodies (tegumental cells). Such cells include the keratinocytes that cover the skin, the epithelial cells that line the bronchi, and the endothelial cells that line the blood vessels.

The presence of receptors sensitive to nicotine that control important cellular functions in organs that are primary targets of tobacco toxicity strongly suggests that nicotine may be directly responsible for some ill effects of tobacco usage and a facilitator of the carcinogenic effects of tobacco smoke.

For all projects, we employ a multidisciplinary experimental approach, that includes cellular and molecular biology techniques, as well as peptide chemistry and structural biology methods.

Recent Publications
Milani M, Ostlie N, Wu H, Wang W, Conti-Fine BM (2006). CD4+ T and B cells cooperate in the immunoregulation of Experimental Autoimmune Myasthenia Gravis. J. Neuroimmunol 179:152-62.

Pratt KP, Qian J, Ellaban E, Okita DK, Diethelm-Okita BM, Conti-Fine B, Scott DW. (2004) Immunodominant T-cell epitopes in the factor VIII C2 domain are located within an inhibitory antibody binding site. Thromb Haemost. 92(3):522-8.

Yang H, Goluszko E, David C, Okita DK, Conti-Fine B, Chan TS, Poussin MA, Christadoss P. (2003). Induction of myasthenia gravis in HLA transgenic mice by immunization with human acetylcholine receptors. Ann N Y Acad Sci. 998:375-8.

Yang H, Goluszko E, David C, Okita DK, Conti-Fine B, Chan TS, Poussin MA, Christadoss P. (2002). Mapping myasthenia gravis-associated T cell epitopes on human acetylcholine receptors in HLA transgenic mice. J Clin Invest. 109(8):1111-20.

Raju R, Zhan WZ, Karachunski P, Conti-Fine B, Sieck GC, David C. (2002). Cryptic determinants and promiscuous sequences on human acetylcholine receptor. HLA dependent dichotomy in T cell function. Human Immunology, 63(4):237-47.