Professor
Beeghley 104
voice 202.885.1750 |ache@american.edu
Quick Links: CV | Cheh Lab (under construction)
My research focuses on the mechanisms by which polycyclic aromatic hydrocarbon diol epoxides (PAH DEs, major carcinogenic components of cigarette smoke) damage DNA and initiate mutagenesis and carcinogenesis. Recently we have focused on the behavior of members of the novel Y-family of bypass DNA polymerases when they encounter PAH DE addition products (adducts) in DNA. We identify the types of mistakes (misincorporations) made by these polymerases as they bypass PAH DE adducts, to help elucidate the mechanisms of early steps in PAH DE carcinogenesis. We study the behavior of the enzymes at different stereoisomeric adducts to shed light on the nature of the enzyme active sites and the enzymatic mechanisms leading to misincorporation. This work is being done in close collaboration with the Laboratory of Bioorganic Chemistry, NIDDK, NIH. Another research area has been the development of rapid methods for determining the spectrum of DNA mutations produced by carcinogens. We correlate these mutational spectra with the degree of carcinogenicity exhibited by different PAH diol epoxides.