Christopher Lee Holley, MD, PhD

Assistant Professor of Medicine
Assistant Research Professor of Molecular Genetics and Microbiology
Campus mail 203 Research Drive, Msrb1 Rm 321, Durham, NC 27710
Phone (919) 668-2688

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

Publications

Gokhale, Nandan S., Alexa B. R. McIntyre, Michael J. McFadden, Allison E. Roder, Edward M. Kennedy, Jorge A. Gandara, Sharon E. Hopcraft, et al. “N6-Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection..” Cell Host Microbe 20, no. 5 (November 9, 2016): 654–65. https://doi.org/10.1016/j.chom.2016.09.015.

PMID
27773535
Full Text

Lindman, Brian R., Jared G. Breyley, Joel D. Schilling, Anna M. Vatterott, Alan Zajarias, Hersh S. Maniar, Ralph J. Damiano, et al. “Prognostic utility of novel biomarkers of cardiovascular stress in patients with aortic stenosis undergoing valve replacement..” Heart 101, no. 17 (September 2015): 1382–88. https://doi.org/10.1136/heartjnl-2015-307742.

PMID
26037104
Full Text

Holley, Christopher L., Melissa W. Li, Benjamin S. Scruggs, Scot J. Matkovich, Daniel S. Ory, and Jean E. Schaffer. “Cytosolic accumulation of small nucleolar RNAs (snoRNAs) is dynamically regulated by NADPH oxidase..” J Biol Chem 290, no. 18 (May 1, 2015): 11741–48. https://doi.org/10.1074/jbc.M115.637413.

PMID
25792744
Full Text

Holley, C. L. “Evaluation of Acute Chest Pain.” In The Washington Manual Cardiology Subspecialty Consult, edited by P. Cuculich and A. Kates. Philadelphia, PA: Lippencott Williams & Wilkins, 2014.

Scholars@Duke

Holley, C. L., D. H. Cooper, and S. M. Nordlich. “Approach to Syncope.” In The Washington Manual Cardiology Subspecialty Consult, edited by P. S. Cuculich and A. M. Kates. Philadelphia, PA: Lippencott Williams & Wilkins, 2014.

Scholars@Duke

Holley, C. L. “Quantification of Left Ventricular Systolic and Diastolic Function.” In The Washington Manual of Echocardiography, edited by R. Rasalingam, M. Makan, and J. Perez. Lippincott Williams & Wilkins, 2012.

Scholars@Duke

Holley, C. L. “Cardiomyopathies.” In The Washington Manual of Echocardiography, edited by R. Rasalingam, M. Makan, and J. Perez. Lippincott Williams & Wilkins, 2012.

Scholars@Duke

Michel, Carlos I., Christopher L. Holley, Benjamin S. Scruggs, Rohini Sidhu, Rita T. Brookheart, Laura L. Listenberger, Mark A. Behlke, Daniel S. Ory, and Jean E. Schaffer. “Small nucleolar RNAs U32a, U33, and U35a are critical mediators of metabolic stress..” Cell Metab 14, no. 1 (July 6, 2011): 33–44. https://doi.org/10.1016/j.cmet.2011.04.009.

PMID
21723502
Full Text

Pages