My research focuses around the oxidative stress response. My interest is in studying the effects of carbon monoxide and its ability to provide a cytoprotective response both in vitro and in vivo. Carbon monoxide at low concentrations has been shown by my myself and others to exert potent anti-inflammatory, anti-proliferative and anti-apoptotic effects. In models of endotoxic shock, acute hepatitis, organ transplantation, ischemia/reperfusion injury, and arteriosclerosis among others, CO has been shown to reestablish homeostasis and provide potent protection. My research also examines the role of the inducible enzyme heme oxygenase-1 (HO-1), an enzyme present in all cells that produces CO endogenously. HO-1 has been characterized as a protective gene in that if induced prior to an insult exerts potent protective effects. We hypothesized that CO, one of three products of heme catalysis by HO-1, was a potential mechanism. My current area of focus include investigations examining the mechanism by which CO functions to exert such potent anti-inflammatory effects. To date, there are a number of gene targets including the nitric oxide synthases, mitochondrial oxidases as well as signaling molecules that are being explored including the MAP kinases, PPARg, and HIF1-a. We have shown that CO differentially regulates these gene products depending on the model, the cell type and organ system involved. Increasing our understanding of how CO functions to exert its effects will lead potentially to a novel therapeutic modality and translate into a treatment for a variety of disorders including vascular injury ischemia/reperfusion injury and organ transplantation.
Chin, B.Y., Jiang, G., Wegiel, B., Wang, H., MacDonald, T., Zhang, X., Cszimadia, E., Bach, F.H., Lee, P.J., Otterbein, L.E. HIF1a Stabilization by Carbon Monoxide Results in Cytoprotective Preconditioning. Proc. Natl. Acad. Sci.USA. 2007. 104:5109-14.
Otterbein LE, Zuckerbraun BS, Bach FH, Billiar TR, Choi AM, Soares MP. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and balloon injury. Nature Medicine 2003;2:183-190.
Otterbein LE, Bach FH, Alam J, Soares MP, Lu HT, Wysk M, Davis RJ, Flavell RA, Choi AMK. Carbon monoxide mediates anti-inflammatory effects via the mitogen-activated protein kinase pathway. Nature Medicine 2000;6:422-428.
Bilban M, Bach FH, Otterbein SL, Ifedigbo E, de Costa d'Avila J, Esterbauer H, Chin BY, Usheva A, Robson SC, Wagner O, Otterbein LE. Carbon monoxide orchestrates a protective response through PPARgamma. Immunity 2006; 24:601-10
Zuckerbraun, BS, Chin, BY, Wegiel, B, Billiar, TR, Csizmadia, E, Rao, J, Shimoda, L, Kano, S, Otterbein, LE. Carbon monoxide reverses established pulmonary hypertension. J. Exp. Med. 2006; 203: 2109-19.
External Recognition:
2004-present - Member, NIH Study Section; Physician/Scientist KO8 Grants Review
2006 (summer) - visiting professor, Carderelli Hospital, Center for Biotechnology
2002-2004 Grant Reviewer, Vienna National Funding Agency
2003-2004 Member Mid-Atlantic Affiliate American Heart Association Grant Review Panel
2004 Member, NIH Special Emphasis RFA Review Panel for Progression of
Cardiovascular Disease in Type I Diabetes
2004-2008 American Heart Association - Northeast Affiliate Grant Review Panel
2005 Member Scientific Advisory Board for iNO Therapeutics
2005-2009 Member New England Affiliate American Heart Association Grant Review Panel
2005-2009 Member NIH Study Section; Physican/Scientist KO8 Grants Review
1996 President’s Award for outstanding contribution to the company. Scios, Inc.
2000 Travel Award for best student abstract. American Thoracic Society
2003 Senior Vice Chancellor’s Research Seminar Award for extraordinary contribution to the Medical School. University of Pittsburgh
School of Medicine; Pittsburgh, PA
Major Collaborative Activities:
MIT department of Chemical Engineering (Clark Colton) - effects of carbon monoxide on oxygen consumption
Brigham and Womens Hospital (Mark Perrella) - joint interest in heme oxygenase (cardiopulmonary)
Childrens Hospital (Stella Kourembanas) - joint interest in heme oxygenase (cardiopulmonary)
BIDMC - (Frank Selke) - effects of CO in vascular biology
