Clinical Interests:COPD, Emphysema, Alpha-1 Antitrypsin Deficiency, Sarcoidosis, Acute Lung Injury, Cystic Fibrosis, Pulmonary Hypertension
Research Interests: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 currently work on the following projects:
1. Role of sphingolipid metabolites in the lung: 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 endothelial pro-survival sphingosine-1 phosphate agonists may be effective in preventing lung structural cell apoptosis and airspace enlargement. The role of sphingolipid metabolites is now investigated in the complex context of cigarette smoke-induced emphysema, using a translational approach.
2. 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. We investigate the mechanisms by which A1AT has direct cellular protective mechanisms in COPD, with the goal of enhancing its therapeutic application and effectiveness.
3. Collaborations related to vascular lung biology: with Tim Lahm, MD, we investigate mechanisms of hypoxic PH both in vivo and in primary lung endothelial cells; and with Robert G. Presson, MD and Beth M. Brown, PhD, we utilize the novel tool of intravital two photon excitation microscopy of the lung at the IU Biologic Microscopy Core.
4.Collaborations with investigators of the ICVBM and the VA Center for Regenerative Medicine, including Matthias Clauss, PhD, on the mechanistic link between apoptosis and inflammation in the lung via the cytokine EMAPII and with Keith March, MD PhD, on application of adult adipose progenitor cells as regenerative anti-apoptotic therapy in experimental emphysema.
5. Collaboration within the IU Cancer Center, in particular with Hal Broxmeyer , MD PhD, on the effect of cigarette smoking on hematopoiesis and the crosstalk between the bone marrow and the lung in COPD.
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
Board Certifications:Internal Medicine
Critical Care Medicine
Recent Publications:PubMed listings