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.
Research
- Gene Expression and RNA modification
- ADARs: The RNA binding proteins we love!
- Impacts of A-to-I Editing on Gene Expression
- A-to-I Editing during Development and Disease
- Regulation of A-to-I Editing
- Understanding C. elegans ADAR function
- Human ADARs in normal brain and glioblastoma
