COPD, Emphysema, Alpha-1 Antitrypsin Deficiency, Sarcoidosis, Acute Lung Injury, Cystic Fibrosis, Pulmonary Hypertension Our laboratory investigates the pathogenesis of and repair strategies for the lung injury that occurs in emphysema (COPD). Primarily caused by cigarette smoking, COPD is now the 3rd cause of mortality in the US. For the past decades the predominant paradigm in the emphysema research was that of a protease /antiprotease imbalance. Our work contributed to solidify the notion that cell death of structural components of the lung alveolus, epithelial and endothelial cells is sufficient to cause emphysema. We demonstrated that modifications in the abundance of the signaling sphingolipid ceramide trigger a cascade of events that culminates in emphysema-like disease in animals. To rebalance the sphingolipid homeostasis, we recently demonstrated that augmentation of endothelial pro-survival signaling with sphingosine-1 phosphate agonists is effective in preventing lung structural cell apoptosis and airspace enlargement. In addition, our laboratory studies mechanisms by which the anti-protease alpha 1 antitrypsin (A1AT) protects the lung.
