Cardiology

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

Grants

Publications

Rimer, JM, Lee, J, Holley, CL, Crowder, RJ, Chen, DL, Hanson, PI, Ory, DS, and Schaffer, JE. "Long-Range Function of Secreted Small Nucleolar RNAs that Direct 2'-O-Methylation." The Journal of Biological Chemistry (July 6, 2018).

PMID
29980600
Full Text

Fry, NJ, Law, BA, Ilkayeva, OR, Holley, CL, and Mansfield, KD. "N6-methyladenosine is required for the hypoxic stabilization of specific mRNAs." Rna (New York, N.Y.) 23, no. 9 (September 2017): 1444-1455.

PMID
28611253
Full Text

McCommis, KS, Hodges, WT, Brunt, EM, Nalbantoglu, I, McDonald, WG, Holley, C, Fujiwara, H, Schaffer, JE, Colca, JR, and Finck, BN. "Targeting the mitochondrial pyruvate carrier attenuates fibrosis in a mouse model of nonalcoholic steatohepatitis." Hepatology (Baltimore, Md.) 65, no. 5 (May 2017): 1543-1556.

PMID
28027586
Full Text

Holley, CL. "The Challenges of Bedside-to-Bench Research in Pediatric Cardiology." Journal of cardiac failure 23, no. 1 (January 2017): 81-82.

PMID
27697503
Full Text

Lee, J, Harris, AN, Holley, CL, Mahadevan, J, Pyles, KD, Lavagnino, Z, Scherrer, DE, Fujiwara, H, Sidhu, R, Zhang, J, Huang, SC-C, Piston, DW, Remedi, MS, Urano, F, Ory, DS, and Schaffer, JE. "Rpl13a small nucleolar RNAs regulate systemic glucose metabolism." The Journal of Clinical Investigation 126, no. 12 (December 2016): 4616-4625.

PMID
27820699
Full Text

Gokhale, NS, McIntyre, ABR, McFadden, MJ, Roder, AE, Kennedy, EM, Gandara, JA, Hopcraft, SE, Quicke, KM, Vazquez, C, Willer, J, Ilkayeva, OR, Law, BA, Holley, CL, Garcia-Blanco, MA, Evans, MJ, Suthar, MS, Bradrick, SS, Mason, CE, and Horner, SM. "N6-Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection." Cell Host & Microbe 20, no. 5 (November 2016): 654-665.

PMID
27773535
Full Text

Lindman, BR, Breyley, JG, Schilling, JD, Vatterott, AM, Zajarias, A, Maniar, HS, Damiano, RJ, Moon, MR, Lawton, JS, Gage, BF, Sintek, MA, Aquino, A, Holley, CL, Patel, NM, Lawler, C, Lasala, JM, and Novak, E. "Prognostic utility of novel biomarkers of cardiovascular stress in patients with aortic stenosis undergoing valve replacement." Heart (British Cardiac Society) 101, no. 17 (September 2015): 1382-1388.

PMID
26037104
Full Text

Holley, CL, Li, MW, Scruggs, BS, Matkovich, SJ, Ory, DS, and Schaffer, JE. "Cytosolic accumulation of small nucleolar RNAs (snoRNAs) is dynamically regulated by NADPH oxidase." The Journal of biological chemistry 290, no. 18 (May 2015): 11741-11748.

PMID
25792744
Full Text

Vader, JM, Holley, CL, and Rich, MW. "Chronic heart failure." In Handbook of Clinical Nutrition and Aging, Third Edition, 215-236. January 1, 2015.

Full Text

Holley, CL. "Evaluation of Acute Chest Pain." In The Washington Manual Cardiology Subspecialty Consult,edited by P Cuculich and A Kates. Philadelphia, PA: Lippencott Williams & Wilkins, May 19, 2014. (Chapter)

Scholars@Duke

Pages