Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not fully reversible. It is a disabling condition associated with progressive breathlessness. COPD will account for over 6 million deaths per year in 2020 (3rd major cause of death), and move from the sixth- to the third-leading cause of death worldwide. In America, COPD affects 9% of residents aged 60 years and above and it ranked fourth in the recent morbidity survey of the elderly population. It is estimated that approximately 23.4 million people in the US have COPD and the health burden is $36.1 billions per year. At present, there is no effective treatment exists to halt the decline in lung function in response to smoking. This in turn reflects a lack of understanding of the specific cellular and molecular pathways triggered in the lung by tobacco smoke/oxidants.

Our laboratory is interested in understanding the redox signaling, mechanism of proinflammatory gene expression by studying the chromatin remodeling-epigenetic changes (histone acetylation/deacetylation) on pro-inflammatory genes, involvement of anti-inflammatory and anti-aging proteins sirtuins, and steroid resistance in chronic inflammatory diseases/COPD. Recent research includes in understanding the role of sirtuins in aging and accelerated decline in lung function and regulation of circadian genes. Our long-term goal is to understand the cellular and molecular mechanisms involved in pathogenesis of COPD, and the potential benefit of therapeutic interventions in this debilitating disease.

Yao H, Chung S, Hwang JW, Rajendrasozhan S, Sundar IK, Dean DA, McBurney MW, Guarente L, Gu W, Rönty M, Kinnula VL, Rahman I. SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice. J Clin Invest. 2012; 122: 2032-2045. PMID: 22546858

Chung S, Sundar IK, Hwang JW, Yull FE, Blackwell TS, Kinnula VL, Bulger M, Yao H, Rahman I . NF-κB inducing kinase, NIK mediates cigarette smoke/TNFα-induced histone acetylation and inflammation through differential activation of IKKs. PLoS One. 2011; 6: e23488. PMID: 21887257

Sundar IK, Chung S, Hwang JW, Lapek JD Jr, Bulger M, Friedman AE, Yao H, Davie JR, Rahman I . Mitogen- and stress-activated kinase 1 (MSK1) regulates cigarette smoke-induced histone modifications on NF-κB-dependent genes. PLoS One. 2012; 7: e31378. PMID: 22312446

Yao H, Rahman I . Perspectives on translational and therapeutic aspects of SIRT1 in inflammaging and senescence. Biochem Pharmacol. 2012; 84: 1332-1339. PMID: 22796566

Rahman I. Pharmacological antioxidant strategies as therapeutic interventions for COPD. Biochim Biophys Acta. 2012; 1822: 714-728. Review. PMID: 22101076

Yao H, Rahman I . Role of histone deacetylase 2 in epigenetics and cellular senescence: implications in lung inflammaging and COPD. Am J Physiol Lung Cell Mol Physiol. 2012; 303: L557-566. Review. PMID: 22842217

Sundar IK, Yao H, Rahman I. Oxidative Stress and Chromatin Remodeling in Chronic Obstructive Pulmonary Disease and Smoking-Related Diseases. Antioxid Redox Signal. 2012; In Press. PMID: 22978694

Hwang JW, Rajendrasozhan S, Yao H, Chung S, Sundar IK, Kinnula VL, Rahman I. FoxO3 deficiency leads to increased susceptibility to cigarette smoke-induced inflammation, airspace enlargement, and chronic obstructive pulmonary disease. J Immunol. 2011; 187:987-998. PMID: 21690325

Yao H, Rahman I. Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease, and therapeutic targets. Toxicol Appl Pharmacol 2011; 254: 72-85. PMID: 21296096

Sundar IK, Mullapudi N, Yao H, Spivack SD, Rahman I. Lung cancer and its association with COPD: update on the nexus of COPD and lung cancer. Curr Opin Pul Med 2011; 17:279–285. PMID: 21537190

Chung S, Yao H, Caito S, Hwang JW, Arunachalam G, Rahman I. Regulation of SIRT1 in cellular functions: role of polyphenols. Arch Biochem Biophys 2010; 501: 79-90. PMID: 20450879

Adenuga D, Caito S, Yao H, Sundar IK, Hwang JW, Chung S, Rahman I. Nrf2 Deficiency influences susceptibility to steroid resistance via HDAC2 reduction. Biochem Biophys Res Commun 2010; 403:452-456. PMID: 21094147

Yao H, Arunachalam G, Hwang JW, Chung S, Sundar IK, Kinnula VL, Crapo JD, Rahman I. Extracellular superoxide dismutase protects against pulmonary emphysema by attenuating oxidative fragmentation of ECM. Proc Natl Acad Sci USA 2010; 107: 15571-15576. PMID: 20713693

Hwang JW, Chung S, Sundar IK, Yao H, Arunachalam G, McBurney MW, Rahman I. Cigarette smoke-induced autophagy is regulated by SIRT1-PARP-1-dependent mechanism: implication in pathogenesis of COPD. Arch Biochem Biophys 2010; 500: 203-209. PMID: 20493163

Adenuga D, Rahman I. Protein kinase CK2-mediated phosphorylation of HDAC2 regulates co-repressor formation, deacetylase activity and acetylation of HDAC2 by cigarette smoke and aldehydes. Arch Biochem Biophys 2010; 498: 62-73. PMID: 20388487

Caito S, Rajendrasozhan S, Cook S, Chung S, Yao H, Friedman AE, Brookes PS, Rahman I. SIRT1 is a redox-sensitive deacetylase that is post-translationally modified by oxidants and carbonyl stress. FASEB J 2010; 24: 3145-59. PMID: 20385619

Rajendrasozhan S, Hwang JW, Yao H, Kishore N, Rahman I. Anti-inflammatory effect of a selective IkappaB kinase-beta inhibitor in rat lung in response to LPS and cigarette smoke. Pulm Pharmacol Ther 2010; 23:172-81. PMID: 20080200

Caito S, Hwang JW, Chung S, Yao H, Sundar IK, Rahman I. PARP-1 inhibition does not restore oxidant-mediated reduction in SIRT1 activity. Biochem Biophys Res Commun 2010; 392:264-70. PMID: 20060806

Yao H, Hwang JW, Moscat J, Diaz-Meco MT, Leitges M, Kishore N, Li X, Rahman I. Protein kinase C zeta mediates cigarette smoke/aldehyde- and lipopolysaccharide-induced lung inflammation and histone modifications. J Biol Chem 2010; 285: 5405-16. PMID: 20007975

Rajendrasozhan S, Chung S, Sundar IK, Yao H, Rahman I. Targeted disruption of NF-{kappa}B1 (p50) augments cigarette smoke-induced lung inflammation and emphysema in mice: a critical role of p50 in chromatin remodeling. Am J Physiol Lung Cell Mol Physiol 2010; 298: L197-209. PMID: 19965984