The primary focus of the research in our lab is to understand the cellular signaling mechanisms that regulate microvascular endothelial permeability, at steady state and during inflammation-induced vascular injury, with specific emphasis on the lung vasculature. The main aspect of endothelial barrier function that is being studied is the process of caveolae-mediated endocytosis and transcytosis of macromolecules through microvessels (transcellular permeability), and whether this process contributes to protein-rich pulmonary edema formation. The overall goal of our studies is to determine how caveolae-mediated transcellular transport functionally regulates vascular permeability of proteins, lipids, and drugs.

Current projects underway in the laboratory include:

• Visualization and quantification of the dynamics of vesicular trafficking in vascular endothelial cells using confocal microscopy and 4D image analysis


• Characterization of the phenotypes and proliferative potential of endothelial cells isolated from mouse lungs. We plan to test the hypothesis that resident endothelial "stem" cells functionally replace damaged vascular endothelium and regenerate new vessels in the lung, and that caveolin-regulated signaling is a critical component of this process


• Visualization of pulmonary vasculature and airway architecture in whole mount preparations using laser scanning/multiphoton microscopy and 3D image analysis


• Determining the role of the cytoskeleton in caveolae mediated endocytosis, with emphasis on phosphorylation-dependent caveolin-1 interactions with actin binding proteins


• Investigating whether activated PMN rapidly increase vascular albumin permeability in a manner that is dependent upon ICAM-1 ligation and neutrophil-derived superoxide generation which results in caveolin-1 phosphorylation and increased caveolae trafficking


• Exploring the regulation of the Src family tyrosine kinases involved in triggering caveolae-mediated endocytosis


• Acute lung injury studies in knockout mice to examine underlying molecular mechanisms and potential therapeutic interventions in vivo

Lab Members