I am a fourth year Ph.D. student in Dr. Ray Trievel’s lab. My research involves the characterization of RNA exonucleases involved in the regulation of obesity. This characterization is accomplished using structural and functional approaches including biochemical and cell-based assays. I plan to pursue a career in biotechnology or clinical chemistry.
Obesity affects a significant number of Americans and greatly increases the risk of developing cardiovascular disease, type-II diabetes, fatty liver disease, and certain cancers. Understanding how obesity is regulated opens up new avenues of pharmacological interventions to treat obesity, concurrently reducing the risk of co-morbidities. Nocturnin (NOCT) is broadly expressed enzyme with exoribonuclease activity in in vitro assays and a repressive function against reporter RNAs in vivo. These observations are consistent with a function in RNA decay. Mice lacking NOCT are resistant to diet-induced obesity and other studies have observed a role for NOCT in regulating intestinal trafficking of dietary fats and promoting adipogenesis. These observations suggest that NOCT may have a novel role in the regulation of lipid metabolism by targeting mRNAs for degradation. Though the broader physiological effects of NOC gene deletion have been described, discovering the molecular function of NOC remains an important goal. We are utilizing structural and functional approaches to study determined the first crystal structure of human NOCT to aid in elucidating its RNA substrate specificity and catalytic mechanism. Additionally, we have developed biochemical and cell-based assays that will be used to study NOCT function and analyze the effects of active site mutants. These studies describe the structure and activity of human NOCT and provide the foundation for characterizing NOCT as a potential drug target for obesity and related co-morbidities.