We study mechanisms by which the anti-protease alpha 1 antitrypsin (A1AT) protects the lung. We showed that lung endothelial cells take up A1AT, and that A1AT has an anti-apoptotic function in lung vascular cells, which improved our understanding of emphysema pathogenesis and may expand the applications for A1AT therapies. The main established, ongoing projects in the lab are to understand the role and application of sphingolipid signaling in COPD and to investigate the mechanisms by which A1AT has direct cellular protective mechanisms in COPD, with the goal of enhancing its therapeutic application and effectiveness.

Selected related publication

  • Lockett, A. D. et al. Active trafficking of alpha 1 antitrypsin across the lung endothelium. PloS one 9, e93979, doi:10.1371/journal.pone.0093979 (2014).
  • Lockett, A. D. et al. Effect of cigarette smoke exposure and structural modifications on the alpha-1 Antitrypsin interaction with caspases. Molecular medicine (Cambridge, Mass.) 18, 445-454, doi:10.2119/molmed.2011.00207 (2012).
  • Lockett, A. D. et al. alpha(1)-Antitrypsin modulates lung endothelial cell inflammatory responses to TNF-alpha. American journal of respiratory cell and molecular biology 49, 143-150, doi:10.1165/rcmb.2012-0515OC (2013).
  • Sohrab, S. et al. Mechanism of alpha-1 antitrypsin endocytosis by lung endothelium. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23, 3149-3158, doi:10.1096/fj.09-129304 (2009).
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