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.
Selected related publications
Justice, M. J. et al. Effects of lipid interactions on model vesicle engulfment by alveolar macrophages. Biophysical journal 106, 598-609, doi:10.1016/j.bpj.2013.12.036 (2014).
Petrache, I. et al. Ceramide synthases expression and role of ceramide synthase-2 in the lung: insight from human lung cells and mouse models. PloS one 8, e62968, doi:10.1371/journal.pone.0062968 (2013).
Kamocki, K. et al. RTP801 is required for ceramide-induced cell-specific death in the murine lung. American journal of respiratory cell and molecular biology 48, 87-93, doi:10.1165/rcmb.2012-0254OC (2013).
Petrache, I. et al. Ceramide causes pulmonary cell apoptosis and emphysema: a role for sphingolipid homeostasis in the maintenance of alveolar cells. Proceedings of the American Thoracic Society 3, 510, doi:10.1513/pats.200603-071MS (2006).
Petrache, I. et al. Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice. Nature medicine 11, 491-498, doi:10.1038/nm1238 (2005).