Pallen, Catherine J
Associate Member, Dept of Pathology and Laboratory Medicine
Professor, Dept of Pediatrics
BSc, University of Western Ontario (1982)
PhD, University of Calgary (1986)
Postdoctoral Fellowship, Imperial Cancer Research Fund, U.K. (1986-87)
Postdoctoral Fellowship, Ludwig Institute for Cancer Research, U.K (1987-88)
RESEARCH INTERESTS
Protein tyrosine phosphatases (PTPs): Signal transduction, structure/function, regulation, and roles in human disease: Defective or dysregulated protein tyrosine phosphatases (PTPs) are proving to be critical factors in the development and progression of a variety of human disorders and disease states such as cancer and diabetes. However, there is still a far from complete understanding of the cellular and physiological actions of many PTPs. The ongoing characterization of PTP substrates, pathways of action, regulation, localization, and structure will determine the specific roles of PTPs in cells and whole organisms, reveal linkages with human pathophysiologies, and facilitate the development of PTP-directed molecular and chemical therapeutics for disease intervention. Studies in my lab are focused on elucidating the molecular actions and signaling pathways of two members of the PTP superfamily, PTPa and PRL-3.
PTPa: We are utilizing PTPa-/- (knockout) mice, and cells derived from these animals, to investigate PTPa function in several defective signaling processes/events that we have identified in these systems. These include integrin signaling (migration , invasion, cancer cell biology), T cell receptor signaling and proliferation (immune cell function), and in neuronal function and development (synaptic transmission, excitotoxicity, myelination). Current research in the lab is directed in the above areas to precisely elucidate the molecular actions of PTPa in these fundamental cellular and biological processes.
PRL-3: PRL-3 belongs to a subclass (PRL-1, -2, -3) of non-receptor PTPs that are implicated in cell proliferation and transformation. Remarkably, PRL-3 expression is specifically upregulated in metastases of colorectal and some other cancers. Our current research is elucidating the molecular action(s) of PRL-3 and the PRL-3-modulated signaling pathways that affect the gain of metastatic ability by a tumor cell, determining the mechanisms controlling PRL-3 upregulation, and investigating the correlation between PRL-3 expression and clinical outcome in cancer patients.
SELECTED PUBLICATIONS
Maksumova, L., Le, H.T., Muratkhodjaev, F., Davidson, D., Veillette, A., and Pallen, C.J. (2005) Protein tyrosine phosphatase alpha regulates fyn activity and Cbp/PAG phosphorylation in thymocyte lipid rafts. J. Immunol. 175: 7947-7956.
Le, H.T., Ponniah, S., and Pallen, C.J. (2004) Insulin signaling and glucose homeostasis in mice lacking protein tyrosine phosphatase alpha (PTPa). Biochem. Biophys. Res. Commun. 314: 321-329.
Pallen, C.J. (2003) Protein tyrosine phosphatase a (PTPa): A src family kinase activator and mediator of multiple biological effects. Curr. Top. Med. Chem. 7: 821-835.
Zeng, L., Si, X., Yu, W.-P., Le, T.H., Ng, K.P., Teng, R.M.H., Ryan, K., Wang, D. Z.-M., Ponniah, S., and Pallen, C.J. (2003) PTPa regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration. J. Cell Biol. 160: 137-146.
Hu, Q.-D., Ang, B.-T., Karsak, M., Hu, W.-P., Cui, X.-Y., Duka, T., Takeda, Y., Chia, W., Natesar, S., Ng, Y.-K., Ling, E.-A., Maciag, T., Small, D., Trifonova, R., Kopan, R., Okano, H., Nakafuku, M., Chiba, S., Hirai, H., Aster, J.C., Schachner, M., Pallen, C.J., Watanabe, K., and Xiao, Z.-C. (2003) F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation. Cell 115: 163-175.
Skelton, M.R., Ponniah, S., Wang, D. Z.-M., Doetschman, T., Vorhees, C.V., and Pallen, C.J. (2003) Protein tyrosine phosphatase alpha (PTPa) knockout mice show deficits in Morris water maze learning, decreased locomotor activity, and decreased anxiety. Brain Res. 984: 1-10.
Zeng, Q., Dong, J.-M., Guo, K., Li, J., Tan, H.-X., Koh, V., Pallen, C.J., Manser, E., and Hong, W. (2003) PRL-3 and PRL-1 promote cell migration, invasion, and metastasis. Canc. Res. 63: 2716-2722.