The research interests of our laboratory focus on the field of molecular neurobiology. By integrating the disciplines of peptide biochemistry, cell biology, animal physiology and molecular biology, we hope to gain a better understanding of the cellular and molecular processes underlying neuronal communication in normal and pathophysiological disease states.
Our laboratory is examining the molecular mechanisms involved in the editing of numerous RNA transcripts in the mammalian central nervous system. RNA editing is a post-transcriptional modification in which specific adenosine residues are converted to inosine moieties (A-to-I editing) via the actions of double-stranded RNA-specific adenosine deaminases. As a result of these deamination events, the coding potential of RNAs can be subtly altered to change as little as a single amino acid residue in resultant proteins. In the case of glutamate-gated ion channels, RNA editing can dramatically alter both the ion permeation and electrophysiological properties of these ionotropic receptors. Since glutamate-gated channels are critically involved in processes of excitatory neurotransmission, slight alterations in RNA editing patterns have profound effects upon the normal neurophysiology of the brain. RNA editing events within the 2C-subtype of serotonin receptor can modulate the efficacy by which this seven transmembrane-spanning receptor can couple to its specific intracellular signaling pathways. Since this serotonin receptor has been implicated in a number of neuropsychiatric disease states, including depression and schizophrenia, aberrant RNA editing patterns may play an important role in the etiology of these disorders. Recent studies from our laboratory have also demonstrated that overexpression of ADAR2, a double-stranded RNA-specific adenosine deaminase that catalyzes A-to-I editing results in excessive obesity in transgenic mice, suggesting that misregulation of this post-transcriptional modification can result in severe pathophysiological defects. Current research efforts in the laboratory focus upon the regulation of RNA editing as well as biochemical and bioinformatics strategies for the identification of additional RNAs that are substrates for this type of RNA processing event.