International Protease Network

Assistant Professor of Pathology and Pathology, Microbiology and Immunology
Stanford University School of Medicine
Mail Code 5324, 300 Pasteur Drive, Stanford, CA 94305
Email: mbogyo@stanford.edu
Tel: 650-725-4132
Fax: 650-725-7424
Homepage: http://pathology.stanford.edu/people.html

Research

Our research group is interested in developing small molecule activity based probes (APBs) that can be use to profile and identify proteases from each of the major protease families. We have developed ABPs that target both the CA/CB as well as the CD clan of cysteine protease. These reagents can be used to label active proteases in crude cellular and tissue homogenates as well as in intact cells and whole animals. Furthermore, we have shown that ABPs can be used to screen for potent and selective inhibitors of proteases in complex mixtures, thereby allowing rapid identification of lead compounds without the need to express, clone and purify the desired protease target. Specifically, we have applied ABPs to study the role of papain family cysteine protease in the human malaria parasite Plasmodium falciparum and to image in vivo cathepsin protease activity in mouse models for cancer. The general cysteine protease ABP has also been used to identify and number of critical biological functions for papain family proteases in processes including production of peptide hormones, processing of transcription factors, and initiation of cataract formation. We are currently working to expand the APB technology to target additional protease families including serine and metallo proteases. These new reagents will be applied to the malaria and cancer projects but will also be made available to the greater protease community to help define the functional roles of proteases in a number of normal and pathological conditions.

Collaborations

Dr. Guy Salvesen, Burnham Institute, La Jolla, CA
Dr. Douglas Hanahan, University of California, San Francisco, CA
Dr. James McKerrow, University of California, San Francisco, CA
Dr. Chris Overall, University of British Columbia, Vancouver, British Columbia, Canada
Dr. Vivian Hook, University of California, San Diego, San Diego, CA
Dr. Vernon Carruthers, Johns Hopkins University, Baltimore, MD
Dr. Bonnie Sloane, Wayne State University, Detroit, MI
Dr. Johanna Joyce, Memorial Sloane Kettering Cancer Institute, New York, NY
Dr. Boris Turk, Jozef Stefan Institute, Ljubljana, Slovenia
Dr. Deiter Brömme, University of British Columbia, British Columbia, Canada
Dr. John Boothroyd, Stanford University Medical School, Stanford, CA
Dr. Helen Blau, Stanford University Medical School, Stanford, CA
Dr. José Villadangos, Walter & Eliza Hall Institute of Medical Research, Melbourne Australia
Dr. Brendan Crabb, Walter & Eliza Hall Institute of Medical Research, Melbourne Australia
Dr. Herman Overcleeft, University of Leiden, Leiden, The Netherlands
Dr. Hidde Ploegh, Harvard Medical School, Boston, MA
Dr. Benedikt Kessler, Harvard Medical School, Boston, MA

Publications

Joyce, J., Baruch, A., Chehade, K., Greenbaum, D., Meyer-Morse, N., Tsai, F-Y., Greenbaum, D., Hager, J., Bogyo, M., and Hanahan, D. (2004) Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell. 5, 443-453.

Goulet, B., Baruch, A., Greenbaum, D., Moon, N.-S., Poirier, M., Erickson, A., Bogyo, M., and Nepveu, A. (2004) A role for the lysosomal cysteine protease cathepsin L in transcriptional regulation in the nucleus. Molecular Cell. 14, 207-219.

Greenbaum, D., Baruch, A., Grainger, M., Bozdech, Z., Medzihradszky, K., Engel, J., Holder, T., DeRisi, J., and Bogyo, M. (2002) A role for the cysteine protease falcipain 1 in host cell invasion by the malaria parasite, Plasmodium falciparum. Science, 298, 2002-2006.

Greenbaum, D., Arnold, W., Lu, F., Hayrapetian, L., Baruch, A., Krumrine, J., Toba, S., Chehade, K., Bromme, D., Kuntz, I.D., and Bogyo, M. (2002) Small Molecule affinity fingerprinting: a tool for enzyme family sub-classification, target identification, and inhibitor design. Chemistry and Biology, 9, 1085-1094.

Greenbaum, D.C., Baruch, A., Hayrapetian, L., Medzihradszky, K.F., Darula, Z., Burlingame, A., and Bogyo, M. (2002) Chemical approaches for functionally probing the proteome. Mol. Cell. Proteomics, 1, 60-68.