简介

Research in my laboratory focuses on chemical toxicology understanding how endogenous and exogenous compounds react with DNA bases and change the structure and function of the genes. We determine the solution structures of damaged DNA molecules relating them to DNA mutagenesis and repair. Our main tools are solution state nuclear magnetic resonance (NMR) spectroscopy and restrained molecular dynamics simulations, which in combination can establish the conformation of duplex DNA duplexes and protein at atomic resolution. We are interested in exocyclic DNA adducts, such as ‘etheno’ and ‘acrolein’ lesions, that result from the reaction of endogenous lipid peroxidation products and DNA. In addition, we are looking at abasic sites, 8-oxo-guanine, fapy and 5’-8-cyclopurines, lesions that are steadily present in genomic DNA due to the reaction of oxygen radicals, produced during mitochondrial respiration, and purine bases. Another area of research is the characterization of DNA containing clustered lesions. This type of damage, produced exclusively by ionizing radiation, plays a key role in the cytotoxic properties of gamma radiation. We are also looking at exogenous gene toxicants, such as Aristolochic acids, acetylamino-fluorene, and nitro-benzanthrones, all of which are strong mutagens and mammalian carcinogens. Our hypothesis is that the systematic structural characterization of damaged DNA will permit the mechanistic understanding of chemical genotoxicity, uncover novel protein-DNA interactions and identify useful biomarkers of exposure and disease rick.