Research Interests
My research interests are in oncogenic transformation and cell signaling via cellular focal adhesions. Several components of focal adhesions, including the focal adhesion kinase (FAK) and paxillin, were originally isolated as substrates for the Src protein tyrosine kinase in cells transformed by the v-src oncogene. FAK can also be amplified in some human tumors suggesting it might also play a role in human disease. My research efforts have focused upon signaling via FAK and the related tyrosine kinase CAK?/Pyk2/CadTK. Three main aspects of FAK/CAK ? signaling are under investigation in the laboratory. First, experiments are being performed to elucidate the basic mechanisms by which FAK and CAK? function. These include studies exploring interactions between FAK/CAK? and other proteins. These analyses will provide insight into the mechanisms of regulation by upstream signals, engagement of components of downstream signaling pathways and targeting of FAK/CAK? to discrete cellular locations. Second, the role of FAK in human disease, specifically breast cancer, is being explored. Initial experiments are utilizing human breast epithelial and cancer cell lines. FAK signaling has been perturbed by overexpression of wild type FAK, activated or dominant negative mutants of FAK and the consequences of altering FAK signaling assessed. Third, negative regulation of FAK/CAK? signaling by a protein tyrosine phosphatase is being explored. Paxillin, a FAK and CAK? substrate, binds and is dephosphorylated by the phosphatase, PTP-PEST. Recent evidence suggests that CAK? may also be a PTP-PEST substrate. Currently, biochemical and biological approaches are being used to determine the consequences of dephosphorylation of CAK? and paxillin by PTP-PEST.

Publications
Richardson, Shannon, J.D., Adams, R.B., Schaller, M.D., & Parsons, J.T. (1997). Identification of integrin stimulated sites of serine phoshorylation in FRNK, the separately expressed C-terminal domain of focal adhesion kinase: a potential role for protein kinase A. Biochem. J, 324, 141-149.

Lin, Aplin, A.E., Shen, Y., Chen, Q., Schaller, M., Romer, L., Aukhil, I., & Juliano, R.L. (1997). Integrin-mediated activation of MAP kinase is independent of FAK: Evidence for dual integrin signaling pathways in fibroblasts. J Cell Biol, 136, 1385-1395

Schaller, M., & Sasaki, T. (1997). Differential signaling by the focal adhesion kinase and cell adhesion kinase b. J Biol Chem, 272, 25319-25325.

Schaller, M. (1997). Signaling through the focal adhesion kinase. In S.C. Froehner & V. Bennett (Eds.), Cytoskeletal Regulation of Membrane Function (pp. 241-255). The Rockefeller University Press.

Thomas, Ellis, B., Boerner, R.J., Knight, W.B., White III, G.C., & Schaller, M.D. (1998). SH2 and SH3 mediated interactions between FAK and Src. J Biol Chem, 273, 577-583.

Y. Shen, G. Schneider, J-F. Cloutier, A. Veillette and M.D. Schaller. (1998). Direct association of protein-tyrosine phosphatase PTP-PEST with paxillin. J Biol Chem 273, 6474-6481.

Y. Shen and M.D. Schaller. (1999). Focal adhesion targeting: the critical determinant of FAK regulation and substrate phosphorylation. Mol Biol Cell 10, 2507-2518.

J.W. Thomas, M.A. Cooley, J.M. Broome, R. Salgia, J.D. Griffin, C.R. Lombardo and M.D. Schaller. (1999). The role of FAK binding in the regulation of tyrosine phosphorylation of paxillin. J Biol Chem 274, 36684-36692.

Y. Shen, P. Lyons, M.A. Cooley, D. Davidson, A. Veillette, R. Salgia, J.D. Griffin and M.D. Schaller. (2000). The noncatalytic domain of PTP-PEST targets paxillin for dephosphorylation in vivo. J Biol Chem 275, 1405-1413.

E-mail: crispy4@med.unc.edu
Telephone: (919) 966-0391
FAX: (919) 966-1856
Address: 534 Taylor Hall, CB# 7090 Chapel Hill, NC

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