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

Song, W., Q. Chen, C. Patel, Q. Yang, L. Wang, W. E. Hanshew, A. DeVore, et al. “Pre-Formed Donor-Specific Antibodies Impact Long Term Survival of Heart Transplants.” In The Journal of Heart and Lung Transplantation : The Official Publication of the International Society for Heart Transplantation, 39:S29, 2020. https://doi.org/10.1016/j.healun.2020.01.1173.

Full Text

Gokhale, Nandan S., Alexa B. R. McIntyre, Melissa D. Mattocks, Christopher L. Holley, Helen M. Lazear, Christopher E. Mason, and Stacy M. Horner. “Altered m6A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection.” Mol Cell 77, no. 3 (February 6, 2020): 542-555.e8. https://doi.org/10.1016/j.molcel.2019.11.007.

PMID
31810760
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Song, Wenqian, Qirui Chen, Christopher Holley, Chetan Patel, Qing Yang, Lifang Wang, Wendy E. Hanshew, et al. “P123 Impact of donor specific HLA antibodies on survival of heart transplants.” In Human Immunology, 80:146–146. Elsevier BV, 2019. https://doi.org/10.1016/j.humimm.2019.07.176.

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Courtney, David G., Kevin Tsai, Hal P. Bogerd, Edward M. Kennedy, Brittany A. Law, Ann Emery, Ronald Swanstrom, Christopher L. Holley, and Bryan R. Cullen. “Epitranscriptomic Addition of m5C to HIV-1 Transcripts Regulates Viral Gene Expression.” Cell Host Microbe 26, no. 2 (August 14, 2019): 217-227.e6. https://doi.org/10.1016/j.chom.2019.07.005.

PMID
31415754
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Page, Stephani, Lydia Kwee, William Kraus, Phillip White, Adam Devore, Robert Mentz, Michael Bristow, et al. “Integrated Omics Analysis of Diabetic Heart Failure in Human Myocardium.” In Circulation Research, Vol. 125. LIPPINCOTT WILLIAMS & WILKINS, 2019.

Scholars@Duke

Lerman, Joseph B., Stephanie N. Giamberardino, Steven E. McNulty, William E. Kraus, Christopher L. Holley, Adrian F. Hernandez, Svati H. Shah, and Robert W. McGarrah. “A Unique Acylcarnitine Profile is Independently Associated with Diabetic Heart Failure and Associates with Adverse Clinical Outcomes: Insights from the FIGHT Trial.” In Circulation Research, Vol. 125. LIPPINCOTT WILLIAMS & WILKINS, 2019.

Scholars@Duke

Elliott, Brittany A., Hsiang-Ting Ho, Srivathsan V. Ranganathan, Sweta Vangaveti, Olga Ilkayeva, Hala Abou Assi, Alex K. Choi, Paul F. Agris, and Christopher L. Holley. “Modification of messenger RNA by 2'-O-methylation regulates gene expression in vivo.” Nat Commun 10, no. 1 (July 30, 2019): 3401. https://doi.org/10.1038/s41467-019-11375-7.

PMID
31363086
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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
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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
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