Mark Mamula, Ph.D. Associate Professor of Medicine S-515, The Anlyan Center Phone: 203-737-2840 Fax: 203-785-7053 e-mail: mark.mamula@yale.edu

Research Activities

The immune system maintains a delicate balance in its ability to recognize and eliminate foreign pathogens versus its ability to be tolerant of self tissues. Studies in the Mamula laboratory are directed at understanding the mechanisms that may shift this balance toward the initiation of autoimmune responses. In particular, Dr. Mamula’s efforts are centered on the molecular interactions of autoimmune B and T cell responses to intracellular autoantigens in systemic lupus erythematosus (SLE). The laboratory has identified novel forms of autoantigens capable of breaking immunologic tolerance in animal models of human SLE. We are also examining the processing of these autoantigens and in understanding the role of autoreactive T cells in autoimmune disease. We have also delineated the importance of cell surface proteins in the co-stimulation of T cell responses in SLE and their role in the development of disease. Our studies are intended to identify potential targets for the immunotherapeutic intervention of autoimmune disease. Finally, the lab is applying the features of autoimmunity in attempts to better elicit “autoimmune” responses to tumor cells. Dr. Mamula has utilized posttranslationally modified tumor peptides in the induction of CTLs and anti-tumor antibody responses. In the context of these studies, Dr. Mamula’s work will rely heavily on all three core technologies. The work from the laboratory in understanding the trafficking of self antigens into processing cells will utilize the imaging core, with emphasis on labeling of self antigens and determining their appearance, both in time and location, within immune tissues. Second, the T cell biology studied in the laboratory will utilize multi-parameter analysis of both cytokine secretion by autoreactive T cells, as well as signaling analysis performed by Luminex technology. Finally, the use of novel mouse strains for studies in lupus autoimmunity will fully utilize the animal resource core.

Selected Recent Publications

1. Shlomchik, M.S., J.C. Craft, and M.J. Mamula. 2001. From T to B and back again: Positive feedback in systemic autoimmune disease. Nature Immunol. Rev. 1:147-154.
2. Doyle, H.A. and M.J. Mamula. 2001. Post translational protein modifications in antigen recognition and autoimmunity. Trends in Immunol. 22:443-449.
3. Yan, J. and M.J. Mamula. 2002. Autoreactive T cells revealed in the normal repertoire: Escape from negative selection and peripheral tolerance. J. Immunol. 168:3188-3194.
4. Doyle, H.A., R.J. Gee, and M.J. Mamula. 2003. A failure to repair self proteins leads to T cell hyperproliferation and autoantibody production. J. Immunol. 171:2840-2847.