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

Courtney, David G., Andrea Chalem, Hal P. Bogerd, Brittany A. Law, Edward M. Kennedy, Christopher L. Holley, and Bryan R. Cullen. “Extensive Epitranscriptomic Methylation of A and C Residues on Murine Leukemia Virus Transcripts Enhances Viral Gene Expression..” Mbio 10, no. 3 (June 11, 2019). https://doi.org/10.1128/mBio.01209-19.

PMID
31186331
Full Text

Rimer, Jamie M., Jiyeon Lee, Christopher L. Holley, Robert J. Crowder, Delphine L. Chen, Phyllis I. Hanson, Daniel S. Ory, and Jean E. Schaffer. “Long-range function of secreted small nucleolar RNAs that direct 2'-O-methylation..” J Biol Chem 293, no. 34 (August 24, 2018): 13284–96. https://doi.org/10.1074/jbc.RA118.003410.

PMID
29980600
Full Text

Fry, Nate J., Brittany A. Law, Olga R. Ilkayeva, Kristen R. Carraway, Christopher L. Holley, and Kyle D. Mansfield. “N6-methyladenosine contributes to cellular phenotype in a genetically-defined model of breast cancer progression..” Oncotarget 9, no. 58 (July 27, 2018): 31231–43. https://doi.org/10.18632/oncotarget.25782.

PMID
30131850
Full Text

Fry, Nate J., Brittany A. Law, Olga R. Ilkayeva, Christopher L. Holley, and Kyle D. Mansfield. “N6-methyladenosine is required for the hypoxic stabilization of specific mRNAs..” Rna 23, no. 9 (September 2017): 1444–55. https://doi.org/10.1261/rna.061044.117.

PMID
28611253
Full Text

McCommis, Kyle S., Wesley T. Hodges, Elizabeth M. Brunt, Ilke Nalbantoglu, William G. McDonald, Christopher Holley, Hideji Fujiwara, Jean E. Schaffer, Jerry R. Colca, and Brian N. Finck. “Targeting the mitochondrial pyruvate carrier attenuates fibrosis in a mouse model of nonalcoholic steatohepatitis..” Hepatology 65, no. 5 (May 2017): 1543–56. https://doi.org/10.1002/hep.29025.

PMID
28027586
Full Text

Lee, Jiyeon, Alexis N. Harris, Christopher L. Holley, Jana Mahadevan, Kelly D. Pyles, Zeno Lavagnino, David E. Scherrer, et al. “Rpl13a small nucleolar RNAs regulate systemic glucose metabolism..” J Clin Invest 126, no. 12 (December 1, 2016): 4616–25. https://doi.org/10.1172/JCI88069.

PMID
27820699
Full Text

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

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