The research in my laboratory primarily involves the study of interactions of chemical and physical agents with DNA, and the processing of the resulting damage by cells. To that end, we have been examining the removal of chemical adducts from discrete regions of the genome. This is being done in an effort to characterize a phenomenon known as DNA repair heterogeneity that is typified by the preferential removal of DNA damage from active genetic loci. The implications of biases in DNA repair are vast: Certain segments of the chromosome might be more susceptible to mutagenesis than other domains, making them hot spots for the induction of a variety of detrimental biological outcomes including tumorigenesis and cell death.
A second area of ongoing research involves investigating the effect of site-specific DNA damage on transcription by a variety of RNA polymerases. We use oligonucleotides containing polycyclic aromatic hydrocarbons, an important class of chemical carcinogens, for these studies. We have shown that some of these adducts impede transcription elongation; furthermore, the degree of inhibition is dependent upon the stereochemical configuration of the DNA lesion.