- West Virginia University School of Medicine
Leader Mechanisms of Metastasis & Therapeutic Response Program (MMTR)
- PhD, McMaster University, Hamilton, 1990
Frisch SM, Schaller MD, "The wind god promotes lung cancer", Cancer Cell. 2014 May 12;25(5):551-2. doi: 10.1016/j.ccr.2014.04.022.
Reynolds AB, Kanner SB, Bouton AH, Schaller MD, Weed SA, Flynn DC, Parsons JT, "SRChing for the substrates of Src", Oncogene. 2014 Sep 11;33(37):4537-4547. doi: 10.1038/onc.2013.416. Epub 2013 Oct 14. Review.
Hartman ZR, Schaller MD, Agazie YM, "The tyrosine phosphatase SHP2 regulates focal adhesion kinase to promote EGF-induced lamellipodia persistence and cell migration", Mol Cancer Res. 2013 Jun;11(6):651-64. doi: 10.1158/1541-7786.MCR-12-0578. Epub 2013 Mar 19.
Frisch SM, Schaller M, Cieply B, "Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis", J Cell Sci. 2013 Jan 1;126(Pt 1):21-9. doi: 10.1242/jcs.120907. Review.
Cable J, Prutzman K, Gunawardena HP, Schaller MD, Chen X, Campbell SL. (2012) "In vitro phosphorylation of the focal adhesion targeting domain of focal adhesion kinase by Src kinase". Biochemistry. 51:2213- 23.
Hall JE, Fu W, Schaller MD, "Focal adhesion kinase: exploring Fak structure to gain insight into function", Int Rev Cell Mol Biol. 2011;288:185-225. doi: 10.1016/B978-0-12-386041-5.00005-4. Review.
Mechanisms of Metastasis & Therapeutic Response
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.