Christopher Lee Holley

The Holley Laboratory is focused on the role of non-coding RNA (ncRNA) in cardiovascular health and disease, with a special emphasis on snoRNA (small nucleolar RNA).  snoRNAs are canonically known to guide the chemical modification of other RNAs, with ribosomal RNA being the primary target.  Dr. Holley’s research has helped to uncover a novel biologic role for the Rpl13a snoRNAs in the regulation of reactive oxygen species (ROS) and oxidative stress.  These four snoRNAs (U32a, U33, U34, and U35a) have a critical role in the oxidative stress response to a variety of stimuli, including saturated fatty acids, lipopolysaccharide, doxorubicin, and hydrogen peroxide.

The Holley Lab has shown that at least one mechanism linking the Rpl13a snoRNAs to ROS and oxidative stress is snoRNA-guided methylation of mRNA. This methylation in an mRNA coding sequence inhibits subsequent protein translation. We have also shown that snoRNA-guided methylation alters RNA conformational ensembles, which can stabilize short-lived structures.

Currently, the lab is studying the role of Rpl13a snoRNAs in atherosclerosis, where loss or inhibition of these snoRNAs reduces athero by ~50%. We are actively pursuing translational research opportunities to design "RNA therapeutics" targeting these snoRNAs for potential clinical use.