The research in the lab is directed toward understanding the molecular mechanisms of lung and vascular diseases (acute lung injury/acute respiratory distress syndrome and pulmonary hypertension) and providing novel therapeutic approaches for these complex human diseases. We are employing the state-of-art technologies such as genetically modified mouse models of human diseases and endothelial progenitor cells/stem cells as well as translational research approach to delineate signaling pathways regulating vascular injury and repair. The lab is mainly focused on the following two research directions:
1) Molecular mechanisms of intrinsic endothelial regeneration and endothelial barrier repair program following inflammatory vascular injury as well as mechanism of action of endothelial progenitor cells/stem cells-mediated endothelial regeneration and resolution of inflammation. We will build upon our previous findings that have defined the key role of the reparative transcription factor FoxM1 in activating lung endothelial regeneration and endothelial barrier re-annealing for restoration of endothelial barrier integrity and vascular homeostasis following inflammatory vascular injury (J. Clin. Invest. 2006, 116: 2333; J. Exp. Med. 2010, 207:1675), and identify novel druggable targets to activate the intrinsic endothelial repair mechanisms to restore endothelial barrier integrity and reverse edema formation for the prevention and treatment of acute lung injury and acute respiratory distress syndrome in patients.
2) Novel signaling mechanisms underlying the pathogenesis of pulmonary hypertension (PH). Following our discovery of the critical role of Caveolin-1 deficiency in the pathogenesis of PH, we have recently identified a novel molecular mechanism of PH using genetic knockout mouse models and pharmacological as well as translational approaches (J. Clin. Invest. 2009, 119: 2009). eNOS activation secondary to Caveolin-1 deficiency induces PH through tyrosine nitration-mediated impairment of PKG activity. The main features of the molecular basis of PH identified in mouse models are recapitulated in lung tissues from patients with idiopathic pulmonary arterial hypertension (IPAH). It is our goal to elucidate the signaling pathways regulating oxidative and nitrative stress underlying the pathogenesis of PH in animal models and humans and thereby provide novel therapeutic approaches for the therapy of this devastating disease.