Research Interests:
Our laboratory is focused on how endothelial NOS (eNOS) is regulated in the context of normal physiology and in disease. Endothelial cells that line all blood vessels continually produce nitric oxide (NO) to maintain normal blood flow and pressure and the production of NO is necessary for vascular remodeling, angiogenesis and blood pressure control. Presently, we are focused on three areas of NO biology: 1. The cell biology of eNOS; 2. Elucidation of the signal transduction mechanisms required for NO production and 3. Characterization the role of NO in angiogenesis and vascular remodeling. In the first area, we have showm that wild- type eNOS localizes on the Golgi complex and in caveolae. Acylation-deficient, mutant forms of eNOS do not compartmentalize as the wild-type protein, and this lack of compartmentalization attenuates stimulated NO release. The relationships between localization and other post-translational control mechanisms are being explored. In the second area, we have demonstrated that agonists that promote NO release increase the association of eNOS with Hsp90 and stimulate Akt dependent phosphorylation of eNOS. The molecular mechanisms of how this protein-protein interaction and phosphorylation regulates the enzyme is being explored. In the third area, we have shown that growth factor-induced angiogenesis, tumour angiogenesis and changes in vascular structure are mediated via NO. Using these models systems we are examining the NO responsive genes and processes that important for angiogenesis and remodeling.

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