Scholars@Duke
Christopher Lee Holley

Christopher Lee Holley

Associate Professor of Medicine
Medicine, Cardiology
DUMC Box 2647, 2301 Erwin Road, Durham, NC 27710
203 Research Drive, MSRB1 Rm 321, Durham, NC 27710

Selected Publications

Snord67 promotes breast cancer metastasis by guiding U6 modification and modulating the splicing landscape.

Journal Article Nat Commun · May 2, 2025 Previously considered "housekeeping" genes, small nucleolar RNAs (snoRNAs) are increasingly understood to have wide-ranging functions in cancer, yet their role in metastasis has been less well studied. Here, we identify the snoRNA Snord67 as a regulator of ... Full text Link to item Cite

Single-cell m6A profiling in the mouse brain uncovers cell type-specific RNA methylomes and age-dependent differential methylation.

Journal Article Nat Neurosci · December 2024 N6-methyladenosine (m6A) is an abundant mRNA modification in the brain that has important roles in neurodevelopment and brain function. However, because of technical limitations, global profiling of m6A sites within the individual cell types that make up t ... Full text Link to item Cite

SNORD3A: a new possible circulating biomarker of human heart failure

Conference European Heart Journal · October 28, 2024 AbstractBackgroundHeart failure (HF) is a complex clinical syndrome and the leading cause of mortality, morbidity and hospitalization ... Full text Cite

Programmable protein expression using a genetically encoded m6A sensor.

Journal Article Nat Biotechnol · September 2024 The N6-methyladenosine (m6A) modification is found in thousands of cellular mRNAs and is a critical regulator of gene expression and cellular physiology. m6A dysregulation contributes to several human diseases, and the m6A methyltransferase machinery has e ... Full text Link to item Cite

Metabolomic profiling during ex situ normothermic perfusion before heart transplantation defines patterns of substrate utilization and correlates with markers of allograft injury.

Conference J Heart Lung Transplant · May 2024 BACKGROUND: Cardiac metabolism is altered in heart failure and ischemia-reperfusion injury states. We hypothesized that metabolomic profiling during ex situ normothermic perfusion before heart transplantation (HT) would lend insight into myocardial substra ... Full text Link to item Cite

Early Outcomes in Patients With LVAD Undergoing Heart Transplant via Use of the SherpaPak Cardiac Transport System.

Journal Article Circ Heart Fail · May 2024 BACKGROUND: Heart transplant (HT) in recipients with left ventricular assist devices (LVADs) is associated with poor early post-HT outcomes, including primary graft dysfunction (PGD). As complicated heart explants in recipients with LVADs may produce longe ... Full text Link to item Cite

2'-O-methylation (Nm) in RNA: progress, challenges, and future directions.

Journal Article RNA · April 16, 2024 RNA 2'-O-methylation (Nm) is highly abundant in noncoding RNAs including ribosomal RNA (rRNA), transfer RNA (tRNA), and small nuclear RNA (snRNA), and occurs in the 5' cap of virtually all messenger RNAs (mRNAs) in higher eukaryotes. More recently, Nm has ... Full text Link to item Cite

Abstract 18861: Therapeutic Targeting of Rpl13a -Small Nucleolar RNAs Mitigates Atherosclerosis in Apoe-/- Mice

Journal Article Circulation · November 7, 2023 Specific non-coding, small nucleolar (sno) RNAs encoded within introns of the Rpl13a gene elevate cellular levels of reactive oxygen species (ROS), and ROS are known to aggravate ather ... Full text Cite

m6A regulates breast cancer proliferation and migration through stage-dependent changes in Epithelial to Mesenchymal Transition gene expression.

Journal Article Front Oncol · 2023 While many factors have been implicated in breast cancer progression, effective treatments are still lacking. In recent years, it has become clear that posttranscriptional regulation plays a key role in the aberrant gene expression underlying malignancy an ... Full text Open Access Link to item Cite

527 CIRCULATING SMALL NUCLEOLAR RNA SNORD3A AS A NOVEL PREDICTIVE BIOMARKERS OF HEART FAILURE

Conference European Heart Journal Supplements · December 15, 2022 AbstractBackgroundDespite optimal therapy, heart failure (HF) remains a relentless and deadly disease. Given the relative inaccessibil ... Full text Cite

Abstract 15731: Rpl13a Small Nucleolar RNAs Promote Atherosclerosis and Oxidative Stress

Journal Article Circulation · November 8, 2022 Reactive oxygen species (ROS) exacerbate atherosclerosis (athero). ROS levels are elevated by specific non-coding, small nucleolar (sno) RNAs encoded within introns of the Rpl13a gene. ... Full text Cite

One Small Step for a Patient, One Giant Leap for Orthostatic Hypotension.

Journal Article Cureus · November 2022 A 52-year-old man with ischemic cardiomyopathy presented with progressive, severe orthostatic hypotension refractory to medical therapy. Standard abdominal and leg compression devices were used without success. A novel, inflatable abdominal compression dev ... Full text Open Access Link to item Cite

Donation After Circulatory Death in Heart Transplantation: History, Outcomes, Clinical Challenges, and Opportunities to Expand the Donor Pool.

Journal Article J Card Fail · September 2022 Heart transplantation remains the gold-standard therapy for end-stage heart failure; the expected median survival range is 12-13 years. More than 30,000 heart transplants have been performed globally in the past decade alone. With advances in medical and s ... Full text Link to item Cite

RBM45 is an m6A-binding protein that affects neuronal differentiation and the splicing of a subset of mRNAs.

Journal Article Cell Rep · August 30, 2022 N6-methyladenosine (m6A) is deposited co-transcriptionally on thousands of cellular mRNAs and plays important roles in mRNA processing and cellular function. m6A is particularly abundant within the brain and is critical for neurodevelopment. However, the m ... Full text Link to item Cite

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

Improved Methods for Deamination-Based m6A Detection.

Journal Article Front Cell Dev Biol · 2022 N 6-methyladenosine (m6A) is a critical regulator of gene expression and cellular function. Much of our knowledge of m6A has been enabled by the identification of m6A sites transcriptome-wide. However, global m6A profiling methods require high amounts of i ... Full text Link to item Cite

183 Small nucleolar RNA SNORD3A: a potential new biomarker and molecular player in heart failure

Conference European Heart Journal Supplements · December 8, 2021 AbstractAimsDespite optimal therapy, heart failure (HF) remains a relentless and deadly disease. Given the relative inaccessibility of ... Full text 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

Mapping of pseudouridine residues on cellular and viral transcripts using a novel antibody-based technique.

Journal Article RNA · November 2021 Pseudouridine (Ψ) is the most common noncanonical ribonucleoside present on mammalian noncoding RNAs (ncRNAs), including rRNAs, tRNAs, and snRNAs, where it contributes ∼7% of the total uridine level. However, Ψ constitutes only ∼0.1% of the uridines presen ... Full text Link to item Cite

Mapping of pseudouridine residues on cellular and viral transcripts using a novel antibody-based technique

Journal Article · 2021 Pseudouridine (Ψ) is the most common non-canonical ribonucleoside present on mammalian non-coding RNAs (ncRNAs), including rRNAs, tRNAs and snRNAs, where it contributes ∼7% of the total uridine level. However, Ψ constitutes only ∼0.1% of the uridines prese ... Full text Open Access Cite

Assessing 2'-O-Methylation of mRNA Using Quantitative PCR.

Journal Article Methods Mol Biol · 2021 2'-O-methylation (Nm) is an RNA modification commonly found on rRNA and snRNA, and at the mRNA 5'-cap, but has more recently been found internally on mRNA. The study of internal Nm modifications on mRNA is in the early stages, but we have reported that thi ... 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

Identification of Undetected Monogenic Cardiovascular Disorders.

Journal Article J Am Coll Cardiol · August 18, 2020 BACKGROUND: Monogenic diseases are individually rare but collectively common, and are likely underdiagnosed. OBJECTIVES: The purpose of this study was to estimate the prevalence of monogenic cardiovascular diseases (MCVDs) and potentially missed diagnoses ... 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

Abstract 378: Physiologic Role of Rpl13a SnoRNAs in Cell Size Regulation

Conference Circulation Research · July 31, 2020 Objectives: Box C/D small nucleolar RNAs (snoRNA) are a multifunctional family of ncRNAs that play a critical role in guiding 2'- O -methylation (Nm) ... Full text Cite

Pre-Formed Donor-Specific Antibodies Impact Long Term Survival of Heart Transplants

Conference The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · April 1, 2020 PURPOSE: We previously reported that heart transplant (HTx) recipients with pre-formed, anti-HLA antibodies at low titer had one-year survival that was comparable to patients without any anti-HLA antibodies. As a result, we defined unacceptable HLA antigen ... Full text Cite

Altered m6A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection.

Journal Article Mol Cell · February 6, 2020 The RNA modification N6-methyladenosine (m6A) modulates mRNA fate and thus affects many biological processes. We analyzed m6A across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C vir ... 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

Cardiac Allograft Vasculopathy: A Formidable Foe.

Journal Article J Am Coll Cardiol · July 9, 2019 Full text Link to item Cite

Extensive Epitranscriptomic Methylation of A and C Residues on Murine Leukemia Virus Transcripts Enhances Viral Gene Expression.

Journal Article mBio · June 11, 2019 While it has been known for several years that viral RNAs are subject to the addition of several distinct covalent modifications to individual nucleotides, collectively referred to as epitranscriptomic modifications, the effect of these editing events on v ... Full text 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 contributes to cellular phenotype in a genetically-defined model of breast cancer progression.

Journal Article Oncotarget · July 27, 2018 The mRNA modification N6-methyladenosine (m6A) is involved in many post-transcriptional regulatory processes including mRNA stability and translational efficiency. However, it is also imperative to correlate these processes with phenotypic outputs during c ... 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

Targeting the mitochondrial pyruvate carrier attenuates fibrosis in a mouse model of nonalcoholic steatohepatitis.

Journal Article Hepatology · May 2017 UNLABELLED: Diseases of the liver related to metabolic syndrome have emerged as the most common and undertreated hepatic ailments. The cause of nonalcoholic fatty liver disease is the aberrant accumulation of lipid in hepatocytes, though the mechanisms whe ... 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

Pre-Extra Corporeal Membrane Oxygenation (ECMO) MELD Score May Predict Meaningful Survival

Conference The Journal of Heart and Lung Transplantation · April 2016 Full text Cite

Prognostic utility of novel biomarkers of cardiovascular stress in patients with aortic stenosis undergoing valve replacement.

Journal Article Heart · September 2015 OBJECTIVE: In heart failure populations without aortic stenosis (AS), the prognostic utility of multiple biomarkers in addition to clinical factors has been demonstrated. We aimed to determine whether multiple biomarkers of cardiovascular stress are associ ... 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

Handbook of clinical nutrition and aging, third edition

Chapter · January 1, 2015 This is the new and fully revised third edition of the well-received text that is the benchmark book in the field of nutrition and aging. The editors (specialists in geriatric nutrition, medical sociology, and clinical nutrition, respectively) and contribu ... Full text Cite

Chronic heart failure

Chapter · January 1, 2015 Age-related changes in the cardiovascular system coupled with the increasing prevalence of cardiovascular disorders with advancing age, especially hypertension, coronary artery disease, and valvular heart disease, lead to a progressive rise in the prevalen ... Full text Cite

Evaluation of Acute Chest Pain

Chapter · May 19, 2014 Prepared by residents, fellows, and attending physicians at the Washington University School of Medicine, this handbook is a practical quick-reference guide to the diagnosis and treatment of cardiovascular diseases. ... Cite

Approach to Syncope

Chapter · May 19, 2014 Prepared by residents, fellows, and attending physicians at the Washington University School of Medicine, this handbook is a practical quick-reference guide to the diagnosis and treatment of cardiovascular diseases. ... Cite

Quantification of Left Ventricular Systolic and Diastolic Function

Chapter · August 6, 2012 Supervised and edited by faculty from the Washington University School of Medicine, The Washington Manual of Echocardiography provides quick insight into the successful performance and interpretation of echocardiographic images. ... Cite

Cardiomyopathies

Chapter · August 6, 2012 Supervised and edited by faculty from the Washington University School of Medicine, The Washington Manual of Echocardiography provides quick insight into the successful performance and interpretation of echocardiographic images. ... 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

An introduction to small non-coding RNAs: miRNA and snoRNA.

Journal Article Cardiovasc Drugs Ther · April 2011 Research into small non-coding RNAs (ncRNA) has fundamentally transformed our understanding of gene regulatory networks, especially at the post-transcriptional level. Although much is now known about the basic biology of small ncRNAs, our ability to recogn ... Full text Link to item Cite

Chronic Heart Failure

Chapter · April 28, 2009 The authors outline the physiological basis for each disorder, provide the latest information about the interaction of nutrition with these conditions, and review the potential routes and mechanisms for clinical intervention. ... Cite

Evaluation of Chest Pain

Chapter · July 1, 2008 Cite

Syncope

Chapter · July 1, 2008 Cite

Acute decompensated heart failure

Chapter · February 10, 2008 The Washington Manual of Critical Care is a concise pocket manual for physicians and nurses. ... Cite

A GH3-like domain in reaper is required for mitochondrial localization and induction of IAP degradation.

Journal Article J Biol Chem · November 7, 2003 Reaper is a potent pro-apoptotic protein originally identified in a screen for Drosophila mutants defective in apoptotic induction. Multiple functions have been ascribed to this protein, including inhibition of IAPs (inhibitors of apoptosis); induction of ... Full text Link to item Cite

Reaper is regulated by IAP-mediated ubiquitination.

Journal Article J Biol Chem · February 7, 2003 In most cases, apoptotic cell death culminates in the activation of the caspase family of cysteine proteases, leading to the orderly dismantling and elimination of the cell. The IAPs (inhibitors of apoptosis) comprise a family of proteins that oppose caspa ... 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

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.

Journal Article J Biol Chem · February 13, 1998 Using differential display polymerase chain reaction, we cloned a novel cDNA named RoBo-1 from rat tibia. RoBo-1 is abundantly expressed in bone, including the hypertrophic chondrocytes of the growth plate where cartilage is remodeled into bone. RoBo-1 mRN ... Full text Link to item Cite

ROBO-1 - A NOVEL RAT BONE GENE IDENTIFIED BY DIFFERENTIAL DISPLAY PCR

Conference JOURNAL OF BONE AND MINERAL RESEARCH · 1995 Cite