Jonathan C.R. Jones, PhD Professor Cell and Molecular Biology Functional analyses of cell-matrix interactions Curricula: Cancer Biology Cell Biology E-mail:   j-jones3@northwestern.edu

To isit the Jones Lab website click here.

The major research interest in the my laboratory centers on the structure and assembly of hemidesmosomes, junctions which act to tether certain epithelial cells to extracellular matrix elements and which act to transduce signals from the connective tissue to the epithelium and vice versa. The lab has identified a number of the molecular links between hemidesmosome proteins that stabilize the structure of the hemidesmosome and ensure that the keratin cytoskeleton adheres to the cells surface at the site of each hemidesmosome.

Recently the lab has focused on studying matrix signaling in normal and tumor cells and the role of matrix degradative enzymes in modifying the function of matrix proteins associated with hemidesmosomes. The lab has shown that the hemidesmosome matrix protein laminin-5 can regulate cell proliferation by a signal transduction cascade mediated by integrins and MAP kinase. In other studies, the lab has provided evidence that cancer cells produce a form of laminin-5 that drives cell migration and has identified a mechanism by which normal cells process their laminin-5 such that it becomes competent to induce hemidesmosome assembly. This has lead to new insights into why cancer cells fail to do so.

The lab has also developed an interest in angiogenesis, an essential component of tumor development. The lab has characterized a novel matrix connector in endothelial cells that links laminins to the vimentin cytoskeleton of these cells and which appears to play an important role in endothelial cell migration and their morphogenesis into blood vessels.

Publications:

Tsuruta, D., Gonzales, M., Hopkinson, S.B., Otey, C., Khuon, S., Goldman, R.D. and Jones, J.C.R. (2002). Microfilament-dependent movement of the b3 integrin subunit within focal contacts of endothelial cells. FASEB J., 16: 866-868 (full text at http://www.fasebj.org/cgi/doi/10.1096/fj.01-0878fje).

Weaver, V.M., Lelievre, S., Lakins, J.N., Chrenek, M.A., Jones, J.C.R., Giancotti, F., Werb, Z and Bissell, M.J. (2002). b4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2: 205-216.

Gonzalez, A.M., Gonzales, M., Herron, G.S., Nagavarapu, U., Hopkinson, S.B., Tsuruta, D and Jones, J.C.R. (2002). Complex interactions between the laminin a4 subunit and integrins regulate endothelial cell behavior in vitro and angiogenesis in vivo. P.N.A.S. 99: 16075-16080.

Tsuruta, D., Hopkinson, S.B. and Jones, J.C.R. (2003). Hemidesmosome protein dynamics in live epithelial cells. Cell Motil. Cytoskel. 54:122-134.

Tsuruta, D.* Hopkinson, S.B.* Lane, K. Werner, M.E., Cryns, V.L. and Jones, J.C.R. Crucial role of the specificity-determining loop of the integrin b4 subunit in the binding of cells to laminin-5 and outside-in signal transduction. J. Biol. Chem. In press. * Co-first authors.

Tsuruta, D. and Jones, J.C.R. The vimentin cytoskeleton regulates focal contact size and adhesion of endothelial cells subjected to shear stress. J. Cell Sci. In press.