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Molecular
Mechanisms of Autoimmunity/Structure, Cell Biology, and
Immunopathology of Autoantigens
The research focuses on mechanisms of autoimmunity that result in destruction
of pancreatic b-cells and development of insulin dependent diabetes mellitus
(IDDM). There are three main target 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 ¤-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) and mechanisms
of transplantation tolerance, and development of methods to prevent allo-
as well as autoimmune destruction of islet cell transplants.
Selected Publications:
Kang, S.-M., Schneider, D.B., Lin, Z., Hanahan, D., Dichek, D.A., Stock,
P.G., and Baekkeskov, S. Fas ligand expression in islets of Langerhans
does not confer immune privilege and instead targets them for rapid destruction.
Nature Med. 3:738-743 (1997).
Kash, S. F., Johnson, R.S., Tecott, L.H., Noebels, J.L., Mayfield, R.D.,
Hanahan, D., and Baekkeskov, S. Epilepsy in mice deficient in the 65 kDa
isoform of glutamic acid decarboxylase. Proc, Natl. Acad. Sci. USA 94,
14060-14065 (1997).
Hensch, T. K., Fagiolini, M., Mataga, N., Stryker, M. P., Baekkeskov,
S., and S. Kash, S. Local GABA circuit control of experience-dependent
plasticity in developing visual cortex. Science 282, 1504-1508 (1998).
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).
Contact Information:
Email: s baekkeskov@biochem.ucsf.edu
Phone: 415/476-6267
Address: Box 0534, Room HSW 1090
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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