Jeffrey A. Greenwood
Associate Professor
541-737-4997
Education
Ph.D. 1995, University of Alabama, Birmingham
Research
Cell adhesion and migration is important for development, tissue morphogenesis, wound healing, and tumor invasion and metastasis. Modification of adhesive strength is required for the initiation and maintenance of cell migration. As the primary link between the contractile actin cytoskeleton and the extracellular matrix, focal adhesions are essential loci for the regulation of cell adhesion and motility. The long-term goal of my research program is to understand the signaling mechanisms regulating cellular adhesive strength and migration. Phosphoinositides, in particular PtdIns (4,5)-P2 and PtdIns (3,4,5)-P3, have been demonstrated to play an important role in the regulation cell motility. Although several binding proteins have been identified, the mechanisms involved in the regulation of motility by phosphoinositides are not clear. We have demonstrated that the activation of phosphoinositide 3-kinase and production of PtdIns (3,4,5)-P3 induce the restructuring of focal adhesions in fibroblasts stimulated to migrate with platelet-derived growth factor. Using this model system, we identified a-actinin as a key target for PtdIns (3,4,5)-P3 involved in the restructuring of focal adhesions. As an abundant protein in focal adhesions, a-actinin modulates cell adhesion and motility by bundling and linking actin microfilaments to integrin receptors. The current focus of my research is to test the hypothesis that differential regulation of a-actinin function by phosphoinositide binding modulates cellular adhesive strength and motility. Understanding these mechanisms could lead to the development of therapeutic agents targeted at mimicking the interaction of specific phosphoinositides with a-actinin to control desirable or undesirable cell migration in human disease.