My research program takes an integrated approach using both a model organism, Caenorhabditis elegans, and human cell lines to determine the biological impact of RNA editing. RNA editing is a post-transcriptional modification that alters the nucleotide sequence of RNA from that encoded by the genome. The ADAR family of RNA editing enzymes catalyze millions of adenosine (A) to inosine (I) modifications in eukaryotic transcriptomes. Loss of these modifications results in lethality in mice and aberrant editing is characteristic of human cancer transcriptomes, which can result in activation of oncogenes and decreased miRNA-mediated repression of cell migration and invasion genes. Depending upon the cancer type and transcript examined, both hypo- and hyper-editing are observed, indicating that the editing enzymes do not fit into the simple dichotomy between tumor suppressors and oncogenes and modulating the expression of the editing enzymes is not a viable therapeutic approach. Instead, identification of cellular factors and molecular mechanisms that regulate RNA editing is critical for the ability to pharmacologically control editing levels at specific sites.
Using a combination of biochemistry, genomics, and molecular biology, my lab has made significant contributions to this outstanding question by identifying roles for naturally-occurring editing-deficient ADAR proteins in regulating editing. We were the first to demonstrate that RNA binding by a cellular factor could promote RNA editing at specific adenosines in vivo. Our work has also shown that the same factor, an editing-deficient C. elegans ADAR protein, can inhibit editing depending upon the transcript. In addition, we recently determined that the human ortholog, ADAR3, is overexpressed in glioblastoma tumors and results in reduced RNA editing of an essential neuronal gene. Ongoing work in the lab focuses on connecting the molecular mechanisms of RNA recognition by ADARs to functional consequences on RNA editing and gene expression and elucidating how these processes go awry in cancer.
Post-doctoral Fellowship - University of Utah, Salt Lake City, UT 2009
Ph.D. - University of Wisconsin, Madison, WI 2005