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Christopher Lee Holley

Associate Professor of Medicine
Medicine, Cardiology
DUMC Box 102149, 2301 Erwin Road, Durham, NC 27710
213 Research Drive, CARL Bldg Rm 128, Durham, NC 27710

Featured Works


Transcriptome-Wide Identification of 2'-O-Methylation Sites with RibOxi-Seq.

Journal article Methods Mol Biol · 2022 Featured Publication The ability to detect 2'-O-methylation sites (Nm) in high-throughput fashion is important, as increasing evidence points to a more diverse landscape for this RNA modification as well as the possibility of yet unidentified functions. Here we describe an opt ... Full text Link to item Cite

Proteomic profiling identifies CLEC4C expression as a novel biomarker of primary graft dysfunction after heart transplantation.

Journal article J Heart Lung Transplant · December 2021 Featured Publication PURPOSE: Clinical models to identify patients at high risk of primary graft dysfunction (PGD) after heart transplantation (HT) are limited, and the underlying pathophysiology of this common post-transplant complication remains poorly understood. We sought ... Full text Link to item Cite

2'-O-Methylation can increase the abundance and lifetime of alternative RNA conformational states.

Journal article Nucleic Acids Res · December 2, 2020 Featured Publication 2'-O-Methyl (Nm) is a highly abundant post-transcriptional RNA modification that plays important biological roles through mechanisms that are not entirely understood. There is evidence that Nm can alter the biological activities of RNAs by biasing the ribo ... Full text Link to item Cite

Noncoding RNAs in Cardiovascular Disease: Current Knowledge, Tools and Technologies for Investigation, and Future Directions: A Scientific Statement From the American Heart Association.

Journal article Circ Genom Precis Med · August 2020 Featured Publication BACKGROUND: The discovery that much of the non-protein-coding genome is transcribed and plays a diverse functional role in fundamental cellular processes has led to an explosion in the development of tools and technologies to investigate the role of these ... Full text Link to item Cite

Epitranscriptomic Addition of m5C to HIV-1 Transcripts Regulates Viral Gene Expression.

Journal article Cell Host Microbe · August 14, 2019 Featured Publication How the covalent modification of mRNA ribonucleotides, termed epitranscriptomic modifications, alters mRNA function remains unclear. One issue has been the difficulty of quantifying these modifications. Using purified HIV-1 genomic RNA, we show that this R ... Full text Link to item Cite

Modification of messenger RNA by 2'-O-methylation regulates gene expression in vivo.

Journal article Nat Commun · July 30, 2019 Featured Publication Epitranscriptomic modifications of mRNA are important regulators of gene expression. While internal 2'-O-methylation (Nm) has been discovered on mRNA, questions remain about its origin and function in cells and organisms. Here, we show that internal Nm mod ... Full text Open Access Link to item Cite

Long-range function of secreted small nucleolar RNAs that direct 2'-O-methylation.

Journal article J Biol Chem · August 24, 2018 Featured Publication Small nucleolar RNAs (snoRNAs) are noncoding RNAs that guide chemical modifications of structural RNAs. Whereas snoRNAs primarily localize in the nucleolus, where their canonical function is to target nascent ribosomal RNAs for 2'-O-methylation, recent stu ... Full text Link to item Cite

N6-methyladenosine is required for the hypoxic stabilization of specific mRNAs.

Journal article RNA · September 2017 Featured Publication Post-transcriptional regulation of mRNA during oxygen deprivation, or hypoxia, can affect the survivability of cells. Hypoxia has been shown to increase stability of a subset of ischemia-related mRNAs, including VEGF. RNA binding proteins and miRNAs have b ... Full text Link to item Cite

Rpl13a small nucleolar RNAs regulate systemic glucose metabolism.

Journal article J Clin Invest · December 1, 2016 Featured Publication Small nucleolar RNAs (snoRNAs) are non-coding RNAs that form ribonucleoproteins to guide covalent modifications of ribosomal and small nuclear RNAs in the nucleus. Recent studies have also uncovered additional non-canonical roles for snoRNAs. However, the ... Full text Link to item Cite

N6-Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection.

Journal article Cell Host Microbe · November 9, 2016 Featured Publication The RNA modification N6-methyladenosine (m6A) post-transcriptionally regulates RNA function. The cellular machinery that controls m6A includes methyltransferases and demethylases that add or remove this modification, as well as m6A-binding YTHDF proteins t ... Full text Link to item Cite

Cytosolic accumulation of small nucleolar RNAs (snoRNAs) is dynamically regulated by NADPH oxidase.

Journal article J Biol Chem · May 1, 2015 Featured Publication Small nucleolar RNAs (snoRNAs) guide nucleotide modifications of cellular RNAs in the nucleus. We previously showed that box C/D snoRNAs from the Rpl13a locus are unexpected mediators of physiologic oxidative stress, independent of their predicted ribosoma ... Full text Link to item Cite

Small nucleolar RNAs U32a, U33, and U35a are critical mediators of metabolic stress.

Journal article Cell Metab · July 6, 2011 Featured Publication Lipotoxicity is a metabolic stress response implicated in the pathogenesis of diabetes complications and has been shown to involve lipid-induced oxidative stress. To elucidate the molecular mechanisms of lipotoxicity, we used retroviral promoter trap mutag ... Full text Link to item Cite

Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition.

Journal article Nat Cell Biol · June 2002 Featured Publication Inhibitors of apoptosis (IAPs) inhibit caspases, thereby preventing proteolysis of apoptotic substrates. IAPs occlude the active sites of caspases to which they are bound and can function as ubiquitin ligases. IAPs are also reported to ubiquitinate themsel ... Full text Link to item Cite