Joined the faculty: 2008

Affiliations: MBR Cancer Center, Center for Cardiovascular and Respiratory Sciences

Teaching: BMS 705, BIOC 793L, BIOC 791, CCB 700, CCB 701

Office: 3124 HSN
Lab: 3111 HSN
Phone: (304) 293-9514
Fax: (304) 293-6846
Email: mschaller@hsc.wvu.edu

My major research interests are the signaling events regulated by integrin-dependent cell adhesion. These events regulate important processes like cell proliferation, cell survival and cell migration. We are specifically interested in FAK, the Focal Adhesion Kinase, a key enzyme regulated by integrin-dependent cell adhesion. FAK is important in controlling axonal guidance in response to netrins. It is critical for embryonic development including angiogenesis during embryogenesis and proper development of the heart. FAK also plays a role in the development of a number of cancers. FAK is overexpressed in human tumors and in experimental models has been linked to tumor growth and metastasis. Given the significance of this protein, we are very interested in its mechanism of regulation and how it controls downstream biochemical signaling events to regulate biological responses.

Recent structural studies suggest a conformational change is required for activation of FAK. One topic of current interest is the regulation of FAK conformation. Identification of FAK sequences required for regulation and FAK binding partners that function in regulating FAK activity are major goals. Biochemical, biophysical and cell based approaches using a novel conformational biosensor are being applied. We hope to elucidate the molecular mechanism(s) regulating FAK activity in fibroblasts, epithelial cells and endothelial cells under both normal and pathological conditions.

The long term goals of the lab are defining biochemical pathways utilized by FAK to elicit important biological responses. Biological areas of interest are cardiovascular and cancer biology. The role of FAK in controlling angiogenesis and endothelial cell responses to mechanical stimulation, which may be relevant to the development of atherosclerosis, are topics of interest in cardiovascular biology. In the area of cancer, the major focus is upon the role of FAK in controlling adhesions, cell morphology, migration and invasion, which are each important processes involved in metastasis.

  References:

• M.P. Playford, K. Vadali, X. Cai, K. Burridge and M.D. Schaller. 2008. Focal Adhesion Kinase regulates cell-cell contact formation in epithelial cells via modulation of Rho. Experimental Cell Research 314:3187-3194.
   
• D.M. Scheswohl, J.R. Harrell, Z. Rajfur, G. Gao, S.L. Campbell, M.D. Schaller. 2008. Multiple Paxillin Binding Sites Regulate FAK Function. J. Mol. Signaling 3:1.
   
• X. Cai, D. Lietha, D.F. Ceccarelli, A.V. Karginov, Z. Rajfur, K. Jacobson, K.M. Hahn, M.J. Eck, M.D. Schaller. 2008. Spatial and Temporal Regulation of FAK Activity in Living Cells. Mol. Cell. Biol. 28:201-214.
   
• K. Vadali, X. Cai and M.D. Schaller. 2007. Focal Adhesion Kinase: An Essential Kinase in the Regulation of Cardiovascular Functions. IUBMB Life 59:709-716.
   
• D. Lietha, X. Cai, Y. Li, M.D. Schaller, and M.J. Eck. 2007. Structure and regulation of Focal Adhesion Kinase. Cell 129:1177-1187.
   
• X. Cai, M. Li, J. Vrana and M.D. Schaller. 2006. GSK-3- and ERK-Dependent Phosphorylation of Paxillin Regulates Cytoskeletal Rearrangement. Mol. Cell. Biol. 26: 2857–2868.