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 role of these snoRNAs in cardiovascular diseases such as hypertension, aortic stenosis, and heart failure is an active area of research.
Most recently, Dr. Holley’s work has shown that snoRNAs are themselves regulated by ROS and oxidative stress, with dynamic accumulation of snoRNAs in the cytoplasm in response to oxidative stress. This raises the possibility that snoRNAs, which were thought to be exclusively nuclear, may also have cytoplasmic targets that mediate their novel biologic roles.
Education and Training
- Cardiovascular Research Fellowship, Washington University School of Medicine, 2009 - 2012
- Chief Fellow, Cardiovascular Division, Washington University School of Medicine, 2009 - 2010
- Chief Resident, Internal Medicine, Washington University School of Medicine, 2007 - 2008
- Cardiovascular Clinical Fellowship, Washington University School of Medicine, 2006 - 2009
- Internal Medicine Residency, Washington University School of Medicine, 2004 - 2006
- M.D., Duke University School of Medicine, 2004
- Ph.D., Duke University School of Medicine, 2003
- Epitranscriptomic modification of HIV-1 transcripts: Effects of drugs of abuse
- Medical Scientist Training Program
- Role of RBC Reactive Oxygen Species and Their Vicious Cycle in Sickle Vasculopathy
- Mass Spectrometric Screening of the Effect of Chemical Toxicants on the Human Epitranscriptome during Stem Cell Differentiation
- Role of snoRNAs in regulation of cardiac hypertrophy