One major goal of the lab is to study how Ena/VASP and associated signaling and cytoskeletal protein contribute to chemotactic responses in carcinoma cells. We hypothesize that Ena/VASP proteins integrate signals from second messenger pathways to execute required motile responses, and are thus not only well positioned to control chemotactic motility, but are in fact generally involved in systems that require guided motility.
We are investigating the mechanisms underlying the changes in cell motility that arise during Epithelial-mesenchymal transition (EMT). EMT, a mechanism important for embryonic development, plays a critical role during malignant transformation. Normally, polarized epithelial cells connect to each other by forming adherens junctions, structures that are linked to the actin cytoskeleton by their intracellular components. Loss of apico-basolateral polarity and dissociation of junctions is accompanied by major remodeling of the actin cytoskeleton, leading to an elongated, migratory phenotype characteristic of mesenchymal cells. We have uncovered networks of coordinated changes in signaling and cytoskeletal regulation that are required for EMT and are examining how these changes may contributed to cancer cell invasion and metastasis.
Mena (green) and actin (red) in a fibroblast.