The research focuses on mechanisms of autoimmunity that result in destruction of pancreatic beta-cells and development of insulin dependent diabetes mellitus (IDDM). There are three main tar-get antigens in this process, the smaller isoform of the GABA synthesizing enzyme glutamic acid decarboxylase, GAD65, a tyrosine phosphatase, IA-2, and a heavily glycosilated membrane protein named glima 38. Current research projects focus on four main areas:
i) structure, function, and cell biology of GAD65, IA-2 and glima 38;
ii) characterization of disease specific B-cell epitopes in GAD65, and IA2, and the temporal pattern of their recognition during early and late phases of beta-cell destruction;
iii) characterization of autoimmune T-cell epitopes in GAD65 and IA2, and how they can be used to induce apoptosis in autoimmune T-cells during the preclinical phase to prevent disease;
iv) mechanisms of transplantation tolerance, and development of methods to prevent allo- as well as autoimmune destruction of islet cell transplants.
|
Kang, S.-M., Schneider, D.B., Lin, X., Hanahan, D., Dichek, D., Stock, P.G., Baekkeskov, S. FAS ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction. Nature Medicine 3, 738-743, (1997).
Kash, S. Tecott, L. H., Hodge, C., and Baekkeskov, S. Increased anxiety and altered responses to anxiolytics in mice deficient in the 65 kDa isoform of glutamic acid decarboxylase. Proc. Natl. Acad. Sci. 96, 1698-1703 (1999).
Schwartz, H., Chandonia, J-M., Kash, S., Tunnel, E., Domingo, A., Cohen, F., Banga, J. P., Madec, A.-M., Richter W., and Baekkeskov, S. High resolution epitope mapping and structural modeling of human glutamic acid decarboxylase 65. J. Mol. Biol. 287, 983-999 (1999).
updated February 2004
|
Biomedical Sciences (BMS) Graduate Program
