Associate Professor of Medicinal Chemistry

One of our long-standing research interests involves the biosynthesis and physiological roles of modified nucleosides in nucleic acids. The process of base modification in RNA has many implications in human disease including autoimmune disease, cancer, and viral disease. Almost all tRNAs are post-transcriptionally modified such that anywhere from 5% to 20% (depending upon the species) of the bases contain some covalent modification. These modifications vary from the very simple, such as methylation, to the very elaborate. The exact roles of most of these post-transcriptional modifications are not yet known, however, it has been shown some modifications alter the amino acid identity of the tRNA and others are linked to differentiation and proliferation.

Our research on base modification involves the study of tRNA-guanine transglycosylases (TGT) from archaebacteria, eubacteria, and eukaryotes. In eubacteria and eukaryotes, TGT is the key enzyme responsible for the incorporation of queuine into the anticodon of certain tRNAs (and archaeosine for Archaea). We have recently initiated studies to probe the physiological role(s) of queuine in eubacteria and eukaryotes. We are also interested in probing the prevalence of base modifications across other RNA species.