Augustine M. K. Choi, Professor
M.D. 1984 University of Louisville
Division of Pulmonary, Allergy, and Critical Care Medicine
Business Phone: (412) 692-2117
Business Fax: (412) 692-2260
E-Mail Address: choiam@upmc.edu
Dr. Choi's research efforts focus on the regulation and function of the stress response genes and antioxidant enzymes in response to oxidative stress, in particular the role of heme oxygenase-1 (HO-1) in a variety of models of lung injury. His laboratory has shown that the molecular regulation of HO-1 gene expression after oxidative stress is primarily at the level of gene transcription. His laboratory also showed that HO-1 confers cytoprotection against oxidative stress using transgenic mice for HO-1, and that carbon monoxide may mediate this cytoprotection. His laboratory has demonstrated that low concentration of CO imparts potent anti-inflammatory effects in subclinical models of hyperoxia-induced lung injury, endotoxin-induced septicemia, allergen-induced airway inflammation and orthotopic lung transplantation. Furthermore, these anti-inflammatory effects of carbon monoxide are mediated via the mitogen activated protein kinase pathway. The laboratory uses both in vitro culture systems (endothelial cells, epithelial cells, fibroblasts, and macrophages) and in vivo models (murine and rat) to delineate the functional role of carbon monoxide and its' signaling pathway by which carbon monoxide exerts cytoprotective effects.
Recent Publication
Otterbein LE, Kolls JK, Mantell LL, Cook JL, Alam J and Choi AMK. Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury. J Clin Inv. 103:1047-1054, 1999.
Alam J, Stewart D, Touchard C, Boinapally S, Choi, AMK and Cook JL. Nrf2, a Cap' n' collar transcription factor, regulates induction of the heme oxygenase-1 gene. J Biol Chem. 274:26071-26078, 1999.
Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, Davis RJ, Flavell RA and Choi AMK. Carbon monoxide has anti-inflammatory effects involving the mitogen activated protein kinase pathway. Nature Medicine. 6:422-428, 2000.
Brouard S, Otterbein LE, Anrather J, Tobiasch E, Bach FH, Choi AMK and Soares MP. Carbon monoxide generated by heme oxygenase-1 suppresses endothelial cell apoptosis. J Exp Med. 192:1015-1026, 2000. (Choi and Soares: equal contributors as senior authors).
He CH. Gong P. Hu B. Stewart D. Choi ME. Choi AMK and Alam J. Identification of activating transcription factor 4 (ATF4) as an Nrf2-interactingprotein. Implication for heme oxygenase-1 gene regulation. J Biol Chem. 276(24): 20858-65, 2001. (Choi and Alam: equal contributors as senior authors).
Song R, Liu F, Mahidhara RS, Ning W, Otterbein LE and Choi AMK. Carbon monoxide inhibits human airway smooth muscle cell proliferation via mitogen activated protein kinase pathway. Am J Resp Cell & Mol Biol. 27:603-610, 2002.
Otterbein LE, Haga M, Zuckerbaun BS, Liu F, Song R, Usheva A, Stachulak C, Bodyak N, Smith RN, Csizmadia E, Tyagi S, Akamatsu Y, Flavell RJ, Billiar TR, Tzeng E, Bach FB, Choi AMK and Soares MP. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nature Medicine. 9:183-190, 2003. (Choi and Bach; Co-Corresponding author).
Song R, Kubo M, Morse D, Zhou Z, Zhang X, Dauber J, Fabisiak J, Alber SM, Watkins SC, Zuckerbraun B, Otterbein LE, Ning W, Oury TD, Lee PJ, McCurry KR and Choi AMK. Carbon monoxide induces cytoprotection in rat orthotopic lung transplantation via anti-inflammatory and anti-apoptotic effects. Am J Pathology. 163:1-231-242, 2003.
Wang X, Ryter SW, Dai C, Tang ZL, Watkins SC, Yin XM, Song R and Choi AMK. Necrotic cell death in response to oxidant stress involves the activation of the apoptogenic caspase-8/bid pathway. J Biol Chem. 278(31): 29184-91, 2003.
Morse D, Pischke SE, Zhou Z, Davis RJ, Flavell RA, Loop T, Otterbein SL, Otterbein LE and Choi AMK. Suppression of inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1. J Biol Chem. 278(39): 36993-8, 2003.
Zhang X, Shan P, Otterbein LE, Alam J, Flavell RA, Davis RJ, Choi AMK and Lee PJ. Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury in dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3. J Biol Chem. 278(2): 1248-58, 2003.
Wang X, Zhou Y, Kim HP, Song R, Zarnegar R, Ryter SW and Choi AMK. Hepatocyte growth factor protects against hypoxia/reoxygenation-induced apoptosis in endothelial cells. J Biol Chem. (10): 1074, 2003.
Ryter SW, Morse D and Choi AMK. Carbon monoxide: to boldly go where NO has gone before. Science STKE. (230):RE6, 2004.
Sarady JK, Zuckerbraun BS, Bilban M, Wagner O, Usheva A, Liu F, Ifedigbo E, Zamora R, Choi AMK and Otterbein LE. Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver. FASEB J. (7): 854-6, 2004.
Song R, Mahidhara RS, Zhou Z, Hoffman RA, Seol DW, Flavell RA, Billiar TR, Otterbein LE and Choi AMK. Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent pathway. J Immunol. 172 (2): 1220-6, 2004.
Zuckerbraun BS, Billiar TR, Otterbein SL, Kim PK, Liu F, Choi AMK, Bach FH and Otterbein LE. Carbon monoxide protects against liver failure through nitric oxide-induced heme oxygenase 1. J. Exp Med. 198 (11):1707-16, 2003.
Otterbein LE, Otterbein SL, Ifedigbo E, Liu F, Morse DE, Fearns C, Ulevitch RJ, Knickelbein R, Flavell RA and Choi AMK. MKK3 mitogen-activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury. Am J. Pathol. 163 (6): 2555-63, 2003.
