Cytoskeleton and Adhesion

In studying adhesion, our challenge is to alter our static model of adhesion to explain the remarkable cellular events of morphogenesis that shape the embryonic body plan and build tissues and organs. To do so, we must understand the dynamic regulation of cell adhesion and how it is coordinated with the cytoskeleton. We visualize these processes via state-of-the art confocal microscopy and live-imaging, using fluorescently-tagged versions of adhesion and cytoskeletal regulatory proteins, as well as probes that allow us to visualize the actin and
microtubule cytoskeletons. This allows us to examine cell behavior and the cell biological events underlying it during dynamic events of morphogenesis, such as dorsal closure.  In searching for regulators of adhesion and the cytoskeleton, we have focused on the non-receptor tyrosine kinase Abelson (Abl). Mutations in Abl cause two forms of human leukemia. We found that Abl coordinately regulates adhesion and the dynamics of the actin cytoskeleton. We are currently exploring the mechanisms by which Abl regulates complex events of
morphogenesis.  We also are exploring the functions of proteins that directly regulate actin dynamics, including Diaphanous-class formins and Enabled/VASP proteins, some of which are targets of Abl.  In parallel, we are examining proteins that help form the dynamic links between the cadherin-catenin complex and the actomyosin cytoskeleton.   We focus on the small GTPases Rap1 and the junctional protein Canoe/Afadin.  In addition to their role in adhesion, these proteins also regulate cell polarity, and we are actively pursuing their roles in both apical-basal and planar polarity.

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