Location: Low Library 313
Inflammation is the mammalian response to infection. Normally it is defensive and thwarts pathogenic assaults but occasionally it runs amok, leading to physiological chaos and death. We are interested in the regulation of the inflammatory pathway as mediated by various cytokines. We focus on the regulation of interleukin-1 by the interleukin-1 receptor antagonist, determine its interactions with other cytokines and assay the cellular and molecular consequences when interleukin expression is altered. Transgenic mice and mice deleted for genes encoding these regulatory molecules have been generated and we utilize them as tools for deciphering these inflammatory pathways.
Cells use receptor mediated endocytosis to take up proteins from their environment, be it for antigen processing, polypeptide hormone signaling, nutrient supplementation, growth factor stimulation or receptor modulation. We are studying the endocytic pathway and receptor recycling using a molecular genetic analysis in the model organism, C. elegans. Our purpose is to identify new key molecular components in the pathway and to elucidate their structures and functions.
Hirsch, E., Irikura, V., Paul, S.M. and Hirsh, D. (1996) Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice. Proc. Natl. Acad. Sci. U.S.A. 93, 11008-11013.
Xie, H. and Hirsh, D. (1998). In vivo function of mutated spliced leader RNAs in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. 95, 4235-4240.
Ma, Y., Thorton, S., Boivin, G.P., Hirsh, D., Hirsch, R., and Hirsch, E. (1998). Altered susceptibility to collagen induced arthiritis in transgenic mice with aberrant expression of IL-1 receptor antagonist. Arthritis Rheum. 10, 1798-1805.
Irikura, V. M., Hirsch, E. and Hirsh, D. (1999). Effects of Interleukin-1 receptor antagonist overexpression on infection by Listeria monocytogenes. Infect Immun. 67, 1901-1909.
Grant, B. and Hirsh, D. (1999). Receptor-mediated endocytosis in the C. elegans oocyte. Mol. Biol. Cell. Vol 10, 4311-4326.
Josephs, M.D., Solorzano, C.C., Ksontini, R., Taylor, M., Topping, D., Abouhamze, A., Mackay, S.L.D., Hirsch, E., Hirsh, D., LaBow, M. and Moldawer, L.L. (2000). Modulation of the acute phase response to a turpentine abscess by altered expression of the IL-1 p80 receptor or IL-1 receptor antagonist. Am. J. Physiol. 278: R824-R830.
Greener, T., Grant, B., Zhang,Y., Wu, X., Greene, L.E., Hirsh, D., Eisenberg, E. (2001). Caenorhabditis elegans auxilin: a J-domain protein essential for clathrin-mediated endocytosis in vivo. Nature Cell Biol. 3, 215-219.
Lin, S.X., Grant, B., Hirsh, D., and Maxfield, F. (2001). Rme-1 Regulates the Distribution and Function of the Endocytic Recycling Compartment in Mammalian Cells. Nature Cell Biol. 3, 657-572.
Grant, B., Zhang, Y., Paupard, M.C., Lin, S.X., Hall, D.H., and Hirsh, D. (2001). Evidence that RME-1, a conserved C. elegans EH domain protein, functions in endocytic recycling. Nature Cell Biol. 3, 573-579.
Zhang, Y., Grant, B., and Hirsh, D. (2001). RME-8 a Conserved J-Domain Protein, Is Required in Endocytosis in C. elegans. Mol. Biol. Cell 12, 2011-2021.