Our lab is interested in the mechanisms modulating cell adhesions and cell migration. The status of cells to associate with the surrounding microenvironment including the neighboring cells and underlying matrix is essential for their morphology and behavior. In turn, it affects numerous life events such as embryogenesis, differentiation, angiogenesis, tissue repair, immune response, and cancer metastasis. We have been focusing on how type Iγ phosphatidylinositol bisphosphate kinase (PIPKIγ), generating lipid second messenger phosphatidylinositol-4,5-bisphosphate (PI4,5P2), could participate in cell adhesion and migration.
PI4,5P2 is a key regulator of focal adhesions and actin cytoskeleton. Besides functioning as a substrate of PLC and PI3K to influence signaling events in adhesion and migration, PI4,5P2 directly binds to and regulates the function of both structural and signaling proteins involved in these events, such as talin, vinculin, and Rho family small G proteins. PI4,5P2 is also an important regulator in vesicular trafficking, which has been indicated playing a role in assembly of cell adhesions. We and others have observed that PIPKIγ, the dominate generator of PI4,5P2 in brain, directly interacts with multiple structural and signaling molecules to support many life events. These include cell adhesion, epithelial morphogenesis, cell migration, metastasis, vesicular trafficking, as well as development of organs like brain and heart. The intent of our lab is to understand the role of PIPKIγ in these processes, and make substantial contributions to the definition of these important life events.