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Tissue Morphogenesis

We are interested in the mechanism by which the local growth differentials that drive tissue pattern formation, such as the branching capillary networks of the vascular system, are established and maintained. Our work has revealed the importance of cell-ECM binding and associated changes in cell shape and cytoskeletal tension for spatial control of cell growth and function. Specifically, we have shown that ECM and tension-dependent changes in cell shape regulate cell growth, differentiation, movement, contractility and apoptosis in response to soluble hormones, growth factors and vasoagonists. Similar results have been demonstrated in various cell types, including capillary endothelial cells, vascular smooth muscle cells, and primary liver epithelial cells. These findings have changed the paradigm in cell growth regulation and developmental control by placing molecular signaling cascades in context of the structural and mechanical complexity of living tissues. Current studies focus on analysis of the mechanical basis of developmental control in situ within embryonic lung rudiments and three-dimensional cultures of growing capillary blood vessels. This work should have widespread implications for control of tissue physiology and may facilitate the development of new therapeutic modalities for various diseases, including cancer, rheumatoid arthritis, and hypertension as well as novel approaches for tissue engineering.



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