Education and Training:
Clinical Fellowship in Pulmonary and Critical Care Medicine – Johns Hopkins University School of Medicine, Baltimore, MD
Research and Clinical Fellowship in Pulmonary and Critical Care Medicine – Johns Hopkins University School of Medicine, Baltimore, MD
Internship and Residency, Internal Medicine – Saint Luke's Medical Center, Case Western Reserve University, Cleveland, Ohio
Doctor of Medicine, M.D. – University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
Critical Care Medicine
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. 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. In addition, we have several ongoing collaborative projects in the lab: 1) with Matthias Clauss, PhD, we study the mechanistic link between apoptosis and inflammation in the lung via the cytokine EMAPII; 2) with Keith March, MD PhD, we investigate the application of adult adipose progenitor cells as regenerative anti-apoptotic therapy in experimental emphysema; 3) with Hal Broxmeyer we investigate the effect of cigarette smoking on hematopoiesis and crosstalk of bone marrow with the lung in COPD; 4) using our expertise in vascular lung biology, with Tim Lahm, MD, we investigate of hypoxic PH both in vivo, in rats and mice, and in vitro, in primary lung endothelial cells; 5) since mechanistic investigation of emphysema and PH requires sophisticated lung function assessment and modern imaging, we implemented a novel intravital two photon excitation microscopy model of the lung in intact rodents, via close collaboration with the IU Biologic Microscopy Core and Robert G. Presson, MD.