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

Holley, C. L., and M. W. Rich. “Chronic Heart Failure.” In Handbook of Clinical Nutrition and Aging, edited by C. W. Bales and C. S. Ritchie. Humana Press, 2009.

Scholars@Duke

Holley, C. L., and S. Subherwal. “Evaluation of Chest Pain.” In The Washington Manual Cardiology Subspecialty Consult, edited by P. Cuculich. Lippincott Williams & Wilkins, 2008.

Scholars@Duke

Holley, C. L. “Syncope.” In The Washington Manual Cardiology Subspecialty Consult, edited by P. Cuculich. Lippincott Williams & Wilkins, 2008.

Scholars@Duke

Holley, C. L., and G. A. Ewald. “Acute decompensated heart failure.” In The Washington Manual of Critical Care, edited by M. H. Kollef, T. J. Bedient, T. J. Isakow W, and C. A. Witt. Lippincott Williams & Wilkins, 2008.

Scholars@Duke

Olson, Michael R., Christopher L. Holley, Eugene C. Gan, Daniel A. Colón-Ramos, Bruce Kaplan, and Sally Kornbluth. “A GH3-like domain in reaper is required for mitochondrial localization and induction of IAP degradation..” J Biol Chem 278, no. 45 (November 7, 2003): 44758–68. https://doi.org/10.1074/jbc.M308055200.

PMID
12917412
Full Text

Olson, Michael R., Christopher L. Holley, Soon Ji Yoo, Jun R. Huh, Bruce A. Hay, and Sally Kornbluth. “Reaper is regulated by IAP-mediated ubiquitination..” J Biol Chem 278, no. 6 (February 7, 2003): 4028–34. https://doi.org/10.1074/jbc.M209734200.

PMID
12446669
Full Text

Holley, Christopher L., Michael R. Olson, Daniel A. Colón-Ramos, and Sally Kornbluth. “Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition..” Nat Cell Biol 4, no. 6 (June 2002): 439–44. https://doi.org/10.1038/ncb798.

PMID
12021770
Full Text

Noel, L. S., B. R. Champion, C. L. Holley, C. J. Simmons, D. C. Morris, J. A. Payne, J. M. Lean, et al. “RoBo-1, a novel member of the urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family selectively expressed in rat bone and growth plate cartilage..” J Biol Chem 273, no. 7 (February 13, 1998): 3878–83. https://doi.org/10.1074/jbc.273.7.3878.

PMID
9461570
Full Text

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