|Department Affiliations||Department of Anesthesiology and Critical Care Medicine, Department of Cell Biology, Department of Pediatrics|
|SOM Address||Room 370 Ross Research Building|
Endothelial cells modulate vasculogenesis, maintain the patency of the microcirculation and regulate vascular permeability. FAK, or the focal adhesion kinase, is a cytoplasmic tyrosine kinase that localizes to sites of cell adhesion to extracellular matrix.
We are using cultured human endothelial cells, and fibroblasts from mice that lack expression of the FAK or Src family kinases to study the following issues: Inflammatory cytokine effects on cell adhesion to extracellular matrix; The role of FAK and Src family kinases in cell-matrix interactions during adhesion and motility; Mechanisms of FAK signaling that prevent apoptosis; and The shaping of the endothelial cell’s cytoskeleton and matrix environment by FAK.
Kinase mutants with altered kinase activity and/or scaffolding functions are introduced into cells by transfection and viral infection (that is harmless to the investigators). Cells are studied using biochemical assays of kinase and adhesion functions, and by epifluorescence microscopy. Fluorescent protein chimeras of cytoskeletal proteins and kinases are used to study adhesion and matrix assembly in living cells in real time using state-of-the-art microscopy in our laboratory.
- Gilmore, A., and Romer, LH. Inhibition of FAK Signalling in Focal Adhesions Decreases Cell Motility and Proliferation. Molecular Biology of the Cell 7:1209-1224, 1996.
- Gilmore, A.P., Metcalfe, A.D., Romer. L.H., Streuli, C.H. Integrin-mediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization. Journal of Cell Biology, 149: 431-446, 2000.
- Cooley, M., Broome, J., Ohngemach, C., Romer. L.H., Schaller, M.D. Paxillin binding is not the sole determinant of focal adhesion localization or dominant negative activity of FAK/FRNK. Molecular Biology of the Cell, 11:3247-3263, 2000.
- Volberg, T., Romer, L.H., Zamir, E., and Geiger, B. pp60c-src and related tyrosine kinases: a role in the assembly and reorganization of matrix adhesions. Journal of Cell Science, 114:2279-2289, 2001.
- Rajfur, Z., Roy, P., Otey, C., Romer, L.H., and Jacobson, K.A. Chromophore-assisted laser inactivation (CALI) of EGFP fusion proteins: probing the connection between the stress fiber and the focal adhesion. Nature Cell Biology, in press, 2002.
- Doutova, E. Gabarra-Niecko, V., Arthur, W.T., Schaller, M.D., and Romer, L.H. FAK regulates fibronectin matrix assembly. Molecular Biology of the Cell, S12:323a, 2001