Sottile Lab

Remodelling of extracellular matrices occurs during development, wound healing, and in a variety of pathological processes including atherosclerosis, ischemic injury, and angiogenesis. Perturbing matrix remodelling events by preventing the turnover of extracellular matrix molecules, or by increasing the levels of matrix degrading proteases or inhibitors has been shown to result in fibrosis, arthritis, reduced angiogenesis, and developmental abnormalities. Thus, processes which control the rate and extent of matrix deposition and degradation play key roles during tissue remodelling events. The studies in my laboratory are aimed at understanding the molecular mechanisms by which the extracellular matrix controls cell behavior. Most of our studies focus on the extracellular matrix protein, fibronectin, and on the functional consequence of its polymerization into the extracellular matrix. Using fibronectin-null cells that our laboratory isolated, we found that fibronectin polymerization regulates adhesion-dependent cell growth, endothelial and smooth muscle cell migration, and endothelial cell tube formation. We have also found that the process of fibronectin deposition into the extracellular matrix is a key regulator involved in maintenance of extracellular matrix architecture. The ability of fibronectin polymerization to act as a switch that controls the organization and composition of the extracellular matrix provides cells with a means of precisely controlling cell-extracellular matrix signalling events that regulate cell proliferation, migration, and differentiation. Our current research is focused on understanding how fibronectin and fibronectin polymerization regulate vascular cell proliferation and extracellular matrix remodelling events that play critical roles during angiogenesis and during the cell response to injury.