Our laboratory investigates the pathogenesis of and repair strategies for the lung injury that occurs in emphysema (COPD). 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…
more 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 showed 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 and the endothelium. We were the first to show that lung endothelial cells take up A1AT, and that A1AT has an anti-apoptotic function in lung vascular cells, which led to a paradigm shift in our understanding of emphysema pathogenesis and in expanding the applications for A1AT therapies. Collaboratively, our lab also investigates mechanistic links between apoptosis and inflammation in the lung and explores the application of adult adipose progenitor cells as regenerative anti-apoptotic therapy in experimental emphysema.
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