Research overview
Our laboratory studies how fundamental mechanisms of membrane traffic control higher order functions such as endothelial cell differentiation and organization, and the effects of different endothelial phenotypes on systemic cardiovascular functions such as microvascular permeability, angiogenesis and inflammation.
We are particularly interested in elucidating the molecular mechanisms involved in the transendothelial exchanges between the blood plasma and the interstitial fluid (in short, vascular permeability) in health and disease states such as cancer and inflammation. Within this, our current focus is the regulation, function and components of endothelial microdomains such as caveolae, other vesicular acrriers, transendothelial channels, fenestrae and vesiculo-vacuolar organelles.
Recent studies done in the laboratory have led to the discovery of PV-1 (PV1, PLVAP, gp68) the first known component for the endothelial stomatal and fenestral diaphragms, structures present on most of the endothelial microdomains involved in permeability. Work in our lab and through varied collaborations, has also shown that PV1 is a reliable marker of activated endothelium in inflammation and of the endothelium in tumors. Moreover, downregulation of this gene product results in impaired tumor growth due to inhibition of angiogenesis.
Our efforts are currently focused on several distinct but interactive project areas, relying on a wide array of experimental approaches from electron microscopy to cell imaging to biochemistry and cell biology to genetics and to whole animal physiology.