We are interested in understanding the role of the cytoskeleton during development and in diseases such as cancer. Specifically, the work in my laboratory is focused on three cytoskeletal proteins. Paxillin and cortactin are targets of the oncogenic tyrosine kinases, v-src and BCR-Abl while Hic-5 may be a potential tumor suppressor gene. In addition, amplification of the human cortactin gene is associated with a certain percentage of breast, head and neck tumors. Paxillin and hic-5 are components of focal adhesions, structures involved in adherence of cells to the extracellular matrix. Cortactin, which is localized to the membrane cytoskeleton, may play a role in regulation of cell shape and in some cases function in regulating cell adhesion. A major approach of my laboratory involves the generation of mice carrying targeted disruptions in these genes. Generation of these mice provides a unique tool to analyze the function of these genes not only in vivo, but also in vitro, through the derivation of cell lines from these animals. By combining genetic, biochemical, and cell biological approaches we hope to 1) understand the role of these genes during development, 2) elucidate the signaling pathways these proteins are involved in, and 3) understand their role in transformation and the metastatic process.