Christopher Lee Holley, MD, PhD

Associate 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

Truby, L. K., L. C. Kwee, R. Agarwal, E. Grass, A. D. Devore, C. B. Patel, G. Rogers, et al. “Proteomic Profiling of Heart Transplant Recipients Identifies CLE4C Expression as a Novel Biomarker of Primary Graft Dysfunction.” In Journal of Heart and Lung Transplantation, 40:S49–S49, 2021.

Scholars@Duke

Chao, Yvonne, Yinzhou Zhu, Hannah J. Wiedner, Yi-Hsuan Tsai, Lily Wilkinson, Alessandro Porrello, Amanda E. D. Van Swearingen, et al. “Snord67 promotes lymph node metastasis through U6-mediated alternative splicing in breast cancer.” In Cancer Research, Vol. 81, 2021.

Scholars@Duke

Abou Assi, Hala, Atul K. Rangadurai, Honglue Shi, Bei Liu, Mary C. Clay, Kevin Erharter, Christoph Kreutz, Christopher L. Holley, and Hashim M. Al-Hashimi. “2'-O-Methylation can increase the abundance and lifetime of alternative RNA conformational states.” Nucleic Acids Res 48, no. 21 (December 2, 2020): 12365–79. https://doi.org/10.1093/nar/gkaa928.

PMID
33104789
Full Text

Abdulrahim, Jawan W., Lydia Coulter Kwee, Fawaz Alenezi, Albert Y. Sun, Aris Baras, Teminioluwa A. Ajayi, Ricardo Henao, et al. “Identification of Undetected Monogenic Cardiovascular Disorders.” J Am Coll Cardiol 76, no. 7 (August 18, 2020): 797–808. https://doi.org/10.1016/j.jacc.2020.06.037.

PMID
32792077
Full Text

Das, Saumya, Ravi Shah, Stefanie Dimmeler, Jane E. Freedman, Christopher Holley, Jin-Moo Lee, Kathryn Moore, et al. “Noncoding RNAs in Cardiovascular Disease: Current Knowledge, Tools and Technologies for Investigation, and Future Directions: A Scientific Statement From the American Heart Association.” Circ Genom Precis Med 13, no. 4 (August 2020): e000062. https://doi.org/10.1161/HCG.0000000000000062.

PMID
32812806
Full Text

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
Full Text

Abdulrahim, Jawan W., Lydia C. Kwee, Fawaz Alenezi, Aris Baras, Teminioluwa Ajayi, Christopher L. Holley, Robert W. McGarrah, et al. “Whole Exome Sequencing in a Cardiovascular Cohort Identifies Previously Undiagnosed Monogenic Cardiovascular Diseases.” In Circulation, Vol. 140, 2019.

Scholars@Duke

Pages