Carl Hashimoto, Ph.D.

Associate Professor, Cell Biology Director of Graduate Studies
Phone: (203) 737-2746 Fax: (203) 785-7446 e-mail: carl.hashimoto@yale.edu		Department of Cell Biology Yale University School of Medicine 333 Cedar Street PO Box 208002 New Haven, CT 06520-8002 <Courier Address> 333 Cedar Street, SHM C-223 New Haven, CT 06510-3206

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Proteolysis drives a wide range of biological processes from the cell cycle to embryonic patterning, and is thought to mediate complex brain functions such as learning and memory. Not surprisingly, then, dysfunction in proteolysis is associated with many human disorders, including cancer and dementia. My laboratory is generally interested in cellular and developmental processes that are regulated by proteolysis.

A major current focus is the discovery of new biological processes involving regulation by proteolytic pathways.  We have been investigating, using genetic and molecular methods, the biological functions of protease inhibitors called serpins, which inhibit their targets by a unique “suicide-substrate” mechanism.  Serpins are found in a wide range of animals, plants, and viruses, but the biological function for most serpins is still unknown.  We have identified several serpins apparently involved in immunity and in development, so studies are underway to decipher the specific biological processes and underlying molecular pathways involving these serpins.

We are also interested in the role played by proteolysis in human diseases, in particular neurodegenerative disorders such as Alzheimer’s disease.  Our strategy is to study the basic biology of proteolysis implicated in disease, with the ultimate goal of uncovering new insights into the molecular basis of disease as well as therapeutic leads.

Drosophila embryo lacking protease inhibitor (spn27A-) fails to develop normal dorsoventral polarity, as defined by region-specific expression of the marker genes zen, rho, and twi seen in wild type.

Selected Publications

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Hashimoto, C., Kim, D.R., Weiss, L.A., Miller, J.W. and Morisato, D. (2003) Spatial regulation of developmental signaling by a serpin. Dev. Cell 5, 945-950.

Richer, M. J., Keays, C. A., Waterhouse, J., Minhas, J., Hashimoto, C. and Jean, F. (2004) The Spn4 gene of Drosophila encodes a potent furin-directed secretory pathway serpin. Proc. Natl. Acad. Sci. USA 101, 10560-10565.

Jang, I. H., Chosa, N., Kim, S. H., Nam, H. J., Lemaitre, B., Ochiai, M., Kambris, Z., Brun, S., Hashimoto, C., Ashida, M., Brey, P. T. and Lee, W. J. (2006) A Spatzle-processing enzyme required for Toll signaling activation in Drosophila innate immunity.  Dev. Cell 10, 45-55.

Tang, H., Kambris, Z., Lemaitre, B. and Hashimoto, C. (2006) Two proteases defining a melanization cascade in the immune system of Drosophila. J. Biol. Chem. 281, 28097-28104.