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Mechanisms of angiogenesis
This project is focussed on the molecular mechanisms of angiogenesis, with particular emphasis on signalling by the Rho family of small GTPases. Endothelial cells respond to extracellular signals, which promote sprouting angiogenesis and remodelling of capillary networks. The intracellular signalling pathways co-ordinating the endothelial cell response to such cues are poorly understood. The Rho family of small molecular weight GTPases are important regulators of the actin cytoskeleton, each influencing the formation of distinct cytoskeletal structures. Using a variety of molecular techniques such as microinjection of recombinant proteins and eukaryotic expression vectors in primary endothelial cells, the mechanisms of capillary assembly signal transduction in endothelial cells, are being studied. Development of a novel in vitro model of capillary assembly has allowed the role of each of the GTPases in this process to be defined and has led to the identification of a novel role for the microtubule cytoskeleton in capillary morphogenesis. This work is being extended to study the mechanisms of renal capillary morphogenesis.
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