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.