Academic & Research Interests
In the past two decades, Dr. Cheng has identified and characterized five novel members of NADPH oxidases (Nox enzymes), two regulatory proteins of Nox enzymes, and two members of heme-containing peroxidase family (e.g. Nox3, Nox4, Nox5, NOXO1, NOXA1, VPO1 and VPO2). Based on the intrinsic association of the two enzyme families (where RH is an organic substrate, while X- is a halide ion or thiocyanate ion) and his previous findings in these fields, Dr. Cheng now focuses on understanding the synergistic functions of these two enzyme families in maintaining the balance of reactive oxygen species (ROS) in cells, and in pathology, the outcome of ROS imbalance (i.e. the regulatory mechanism of expression and activation of Nox enzymes and heme-peroxidases) in cardiovascular and respiratory systems.
Growing evidence indicates that H2O2 functions as a signaling molecule cells. Recently, Dr. Cheng's group has identified that vascular peroxidase1 (VPO1) is an endogenous negative regulator of H2O2-mediated cellular signaling. The group's current working hypothesis is that VPO1 mediates diverse physiological and pathological processes via H2O2 effects on cell proliferation, differentiation, and inflammatory responses.
Heme-containing peroxidases catalyze peroxidase reactions and halide ion oxidation, and may produce toxic oxidants. VPO1 is highly expressed in the cardiovascular system and lung, leading to the hypothesis that VPO1 plays an important role in the genesis and development of atherosclerosis and other inflammatory diseases such as asthma and fibrosis. In addition, VPOs may be also involved in the metabolism of nitric oxide, the formation of di-tyrosine cross-link and the chlorination of proteins.
Dr. Cheng's research interests also include the innate host defense of VPO1 and MPO, including drug-resistant microbes, and developing hPx enzymes as antimicrobial agents.
Yang, Y., Cao, Z., Tian, L., Garvey, WT., Cheng, G. VPO1 Mediates ApoE Oxidation and Impairs the Clearance of Plasma Lipids. PLOS ONE. 2013. 8(2):e57571.
Li, H., Cao, Z., Zhang, G., Thannickal, V.J., Cheng, G. Vascular peroxidase 1 catalyzes the formation of hypohalous acids: characterization of its substrate specificity and enzymatic properties. Free Radical Biology & Medicine. 2012. 53:1954-1959.
Li, H., Cao, Z., Moor, D.R., Jackson, P.L., Barnes, S., Lambeth, J.D., Thannickal, V.J. and Cheng, G. Microbicidal Activity of VPO1 in Human Plasma via generation of HOCl. Infection and Immunity. 2012. 80 (7): 2528-2537. PMID: 22526679
Cheng, G., Li, H., Cao, Z., Qiu, X., McCormick, S., Thannickal, V.J., and Nauseef, W. 2011. VPO1 is Rapidly Secreted, Circulates in Plasma, and Supports Dityrosine Cross-linking Reactions and HOCl Generation. Free Radical Biology & Medicine. 2012. 51(7):1445-53.
Cheng. G., Salerno, J.C., Cao, Z., Pagano, P.J., and Lambeth, J.D. Identification and characterization of VPO1, a new animal heme-containing peroxidase. Free Radical Biology & Medicine. 2008. 45(12):1682-1694.
Cheng, G., Diebold, B.A., Hughes, Y. and Lambeth, J.D. NOX1-Dependent Reactive Oxygen Generation is Regulated by Rac1. J Biol Chem. 2006. 281: 17718-17726.
Cheng, G., Ritsick, D. and Lambeth, J.D. Nox3 regulation by NOXO1, p47phox and p67phox. J Biol Chem. 2004. 279(33): 34250-34255.
Cheng, G. and Lambeth, J.D. NOXO1: Regulation of Lipid Binding, Localization and Activation of Nox1 by the PX Domain. J Biol Chem. 2004. 279: 4737-4742.
Cheng, G. Cao, Z., Xu, X., Meir, E.G., Lambeth J.D. Holologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene. 2001. 269(1-2): 131-140.
Please click here for Dr. Cheng's complete publications listing.