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Dr Toni M Antalis
Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, D.C. and
Holland Laboratory, American Red Cross
15601 Crabbs Branch Way, Rockville, MD 20855
Email: antalist@usa.redcross.org
Tel: 301 738 0658
Fax: 301 738 0465
Homepage:
| Research |
We are interested in the biological functions of membrane-associated serine proteases and serine protease inhibitors in normal and disease processes. We have applied homology cloning approaches, database mining, and transcription profiling to identify and characterize serine proteases involved in cancer and endothelial cell morphogenesis. Our particular focus is a new subfamily of membrane-associated serine proteases which appear to have diverse functions in development and hemostasis. These proteases represent unique molecular targets for diagnostic assays and possible drug therapies. One of these proteases, Testisin, is attached to the plasma membrane through a glycosylphosphatidylinositol (GPI) anchor, and plays a role in sperm maturation. Testsin has been associated with advanced stage disease in ovarian cancers and also functions as a tumor suppressor for testicular cancers in an animal model.
We are also interested in the role of the interacellular serine protease inhibitor (serpin), plasminogen activator inhibitor type 2 (PAI-2) in macrophage biology and keratinocyte differentiation. We have shown that PAI-2 binds the retinoblastoma tumor suppressor protein through a unique ‘PENF’ motif. This interaction is likely responsible for the diverse phenotypes described for cells and tissues expressing PAI-2 and also suggests the potential for PAI-2-based therapeutics for modulation of Rb-activities.
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| Collaborations |
Andreas Suhrbier, Ph.D. Queensland Institute of Medical Research, Brisbane, 4029, Australia
Thomas Bugge, Ph.D. NIDCR, National Institutes of Health, USA
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| Publications |
Hooper, J.D., Clements, J.A., Quigley, J.P., Antalis, T.M. (2000) Type II Transmembrane Serine Proteases - Insights into an emerging class of cell surface proteolytic enzymes. J Biol Chem. 276(2), 857-860.
Aimes, R.T., Zijlstra, A., Hooper, J.D., Ogbourne, S., Sit, M.-L., Fuchs, S., Gotley, D.C., Quigley, J.P., Antalis, T.M.. Serine protease gene expression by human endothelial cells during vascular morphogenesis and angiogenesis. Thrombosis and Haemostasis 89(3), 561-72.
Netzel-Arnett, S., Hooper, J.D., Szabo, R., Madison, E.L., Quigley, J.P., Bugge, T.H., and Antalis, T.M. (2003) Membrane Associated Serine Proteases: A rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer and Metastasis Reviews 22:237-258.
Darnell, G.A., Antalis, T.M., Johnstone, R.W., Stringer, B.W., Ogbourne, S.M., Harrich, D., Suhrbier, A. (2003) Plasminogen activator inhibitor-2 is an intracellular retinoblastoma binding protein. Mol. Cell. Biol. 23, 6520-6532.
Antalis, T.M., and Lawrence, D.A. (2004) Serpin Mutagenesis. Methods 32(2),130-140.
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