The Assoian Laboratory at the University of Pennsylvania School of Medicine

About Our Lab

Principal Investigator

Richard K. Assoian [ Brief CV: PDF (7k) ] [ Bibliography ]
Professor of Pharmacology, School of Medicine

Research Interests

Our research is centered at the interface of signal transduction, gene expression, and G1 phase cell cycle progression. There are presently three areas of focus.

Signal transduction mechanisms regulating G1 phase cyclin-cdks. We study cooperative signal transduction by receptor tyrosine kinases, integrins, and the actin cytoskeleton in fibroblasts, focusing on the mechanisms that regulate expression of cyclin D1 and the cyclin-dependent kinase inhibitors, p27and p21. These studies involve an analysis of MAP kinases, AKT, and the Rho family GTPases. The overall goal is to determine how the cell integrates external and internal cues and how this integrated signaling ultimately leads to control of G1 phase.
Vascular remodeling. We are studying the signaling and cell cycle regulatory mechanisms that maintain normal vascular smooth muscle cells in a quiescent state, and how insults such as vascular injury or atherosclerosis lead to smooth muscle cell proliferation. Using wild-type and knock-out mice, these studies combine mechanistic analyses in primary smooth muscle cells with in vivo models of smooth muscle cell proliferation.
Growth regulation in mammary epithelial cells. Genetic analysis in mice indicates that cyclin D1 is essential for mammary cell proliferation. Similarly, overexpression of cyclin D1 is a common feature of the early (premalignant) stages of human breast cancer. We are studying the pathways regulating the expression of cyclin D1 in mammary epithelial cells and comparing them to those used in mesenchymal cells. We are also beginning to determine if the signal transduction pathways to cyclin D1 are differentially employed during mammary epithelial cell proliferation and differentiation.

Selected Recent Publications

Welsh, C.F., Roovers, K., Villanueva, J., Zhao, X., Schwartz, M.A, and Assoian, R.K. (2001) Timing of cyclin D1 expression within G1 phase is controlled by Rho. Nature Cell Biology 3: 950-957.
Kothapalli, D., Fuki, I., Ali, K., Stewart, S.A., Zhao, L., Yahil, R., Kwiatkowski, D., Hawthorne, E.A., FitzGerald, G.A., Phillips, M.C., Lund-Katz, S., Pure, E., Rader, D.J. and Assoian, R.K. (2004) Antimitogenic effects of HDL and apolipoprotein E mediated by cyclooxygenase-2-dependent IP activation. J. Clin. Invest, 609-618.
Kothapalli, D, Zhao, L., Hawthorne, E.A., Lee, E., Puré, E., and Assoian, R.K. (2007) Hyaluronan and CD44. antagonize mitogen-dependent cyclin D1 expression in mesenchymal cells. J. Cell Biol. 176: 535-544.
Yung, Y., Walker, J.L., Roberts, J.M., and Assoian, R.K. (2007) A Skp2 autoinduction loop and restriction point control. J. Cell Biol., 178: 741-747.
Assoian, R.K. and Yung, Y. (2008) A reciprocal relationship between Rb and Skp2: implications for restriction point control, signal transduction to the cell cycle, and cancer. Cell Cycle 7: 24-27.
Fournier, A.K., Campbell, L.E., Castagnino, P.. Liu, W.F., Chung, B.M., Weaver, V.M., Chen, C.S., and Assoian, R.K. (2008) Rac-dependent cyclin D1 gene expression regulated by cadherin- and integrin-mediated adhesion, J. Cell Science 121:226-233.

Commercial Antibodies (presently in use in our lab)