My laboratory has been investigating for over 25 years the role of reactive oxygen species (ROS) and bioactive lipids in vascular endothelial signaling, injury and barrier integrity. ROS have been implicated in the pathophysiology of several respiratory diseases including ARDS, COPD, pulmonary hypertension and bronchopulmonary dysplasia and our current primary focus is on the role and regulation of NADPH Oxidase and NOX proteins in hyperoxia- and sepsis-induced lung injury. We were the first to demonstrate that sphingosine-1-phosphate (S1P) is an agonist in endothelial cell signal transduction and S1P is the most potent angiogenic naturally occurring bioactive lipid that is present in plasma and tissues. My laboratory has been studying mechanisms of generation of intracellular S1P mediated by sphingosine kinases and degradation catalyzed by lipid phosphate phosphatases and S1P lyase in the endothelium and S1P lyase as a novel target of sepsis-mediated lung injury. Our investigations suggest a role of intracellular S1P in lung inflammation, injury, cell motility and NADPH Oxidase dependent ROS production. More recently, we have been investigating the role of HATS and HDACs in Mesothelioma and potential regulation of HATs/HDACs by sphingosine kinases and S1P lyase. These ongoing projects involve basic and translational research to develop novel therapeutic strategies and targets to limit the adverse effects of inflammatory lung injury.

$12 million funds interdisciplinary investigation of acute lung injury