The LaFlamme laboratory is interested in the molecular mechanisms governing integrin-mediated adhesion and adhesion-dependent processes. Integrins are receptors used by cells to adhere to insoluble matrix proteins (ECM). Integrins form transmembrane links between the ECM and the cell's actin cytoskeleton and activate intracellular signaling pathways to regulate cell proliferation, survival, differentiation and migration. The LaFlamme laboratory recently identified a novel role for integrins in regulating cytokinesis by promoting the formation of a bipolar spindle at mitosis. Perturbing integrin function leads to extra centrosomes, multipolar spindles, a decrease in microtubule assembly and failed cytokinesis. A major focus of laboratory is to identify the molecular mechanisms by which integrins regulate these processes and to understand the contribution of integrin-regulated bipolar spindle assembly in preventing tumorigenesis. Another central interest of the laboratory is to identify the function of the alpha6/beta4 integrin in microvascular endothelial cells. Developmental and cutaneous wound healing studies demonstrated that the endothelial expression of alpha6/beta4 is down-regulated during early stages of angiogenesis and up-regulated during vessel maturation. The LaFlamme laboratory is interested in identifying the mechanisms that regulate the endothelial expression of alpha6/beta4 and whether this regulation is required for angiogenesis, vessel maturation and/or function. The information gained from these studies will likely have important implications for wound healing and tumor angiogenesis. Lastly, continued expression of integrins at the cell surface is required for cell adhesion and the regulation of adhesion-dependent processes. The LaFlamme laboratory has identified a role for the small GTP-binding protein Cdc42 in regulating the surface expression of beta1 integrins. The laboratory is interested in identifying the signaling mechanisms involved and the contribution of Cdc42-regulated integrin trafficking in cell migration, which is important for many physiological processes including embryonic development, wound healing and tumor metastasis.