About

Deborah G Murdock, PhD, is a Research Associate Professor of Pediatrics in the Department of Pediatrics at the Children's Hospital of Philadelphia, affiliated with the Center for Mitochondrial and Epigenomic Medicine. Her educational background includes a BS in Biology from the University of Georgia (1988) and a PhD in Biological Science from Carnegie Mellon University (1996). Her research focuses on mitochondrial function and epigenomics, particularly in the context of infectious diseases such as COVID-19. She has contributed to studies on mitochondrial metabolic and epigenomic reprogramming during SARS-CoV-2 infection, mitochondrial gene regulation, and mitochondrial dysfunction in pediatric sepsis. Her work involves investigating mitochondrial gene down-regulation, mitochondrial permeability transition, and the impact of mitochondrial variants on disease processes.

Research topics

• Biology
• Medicine
• Genetics
• Internal medicine
• Cell biology

Selected publications

• Author Correction: Partial restoration of mitochondrial dysfunction by AAV-Ant1 protects from dilated cardiomyopathy in Ant1-/- plus mtDNA mutant mice

  Nature Communications · 2026-05-06

  articleOpen access
  PublisherDOI

• Mitochondria and Qi: Merging eastern and western medicine

  Pharmacological Research · 2026-05-12

  articleOpen access

  Since the discovery of mitochondrial DNA (mtDNA) diseases almost 40 years ago, large numbers of diseases have been linked to mutations in both mtDNA and nuclear DNA (nDNA) genes that perturb the mitochondrial energy-generating system, oxidative phosphorylation (OXPHOS). Mitochondrial dysfunction is being implicated not only in rare primary mitochondrial diseases but also a wide range of common diseases, yet the availability of effective mitochondrial therapies remains limited. One potential source of mitochondrial therapeutic approaches is Traditional Chinese Medicine (TCM). TCM emphasizes the health-preservation philosophy and practical experience centered around the concept of "Qi", or vital force, and has generated Qi-oriented therapies over the past several thousand years. We propose that various properties and functions attributed to Qi may be explained by modulation of mitochondrial bioenergetics, the interplay between OXPHOS and fatty acid oxidation versus glycolysis and the pentose phosphate pathway (PPP), and the mitochondrial regulation of the immune system through mitochondrial reactive oxygen species (mROS). Hence, TCM therapeutics may provide approaches for treating the increasing spectrum of mitochondria associated diseases.

  PublisherDOI

• Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts

  UNC Libraries · 2025-03-19

  articleOpen access

  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with coronavirus disease 2019 (COVID-19). In nasopharyngeal samples with declining viral titers, the virus blocked the transcription of a subset of nuclear DNA (nDNA)-encoded mitochondrial OXPHOS genes, induced the expression of microRNA 2392, activated HIF-1α to induce glycolysis, and activated host immune defenses including the integrated stress response. In autopsy tissues from patients with COVID-19, SARS-CoV-2 was no longer present, and mitochondrial gene transcription had recovered in the lungs. However, nDNA mitochondrial gene expression remained suppressed in autopsy tissue from the heart and, to a lesser extent, kidney, and liver, whereas mitochondrial DNA transcription was induced and host-immune defense pathways were activated. During early SARS-CoV-2 infection of hamsters with peak lung viral load, mitochondrial gene expression in the lung was minimally perturbed but was down-regulated in the cerebellum and up-regulated in the striatum even though no SARS-CoV-2 was detected in the brain. During the mid-phase SARS-CoV-2 infection of mice, mitochondrial gene expression was starting to recover in mouse lungs. These data suggest that when the viral titer first peaks, there is a systemic host response followed by viral suppression of mitochondrial gene transcription and induction of glycolysis leading to the deployment of antiviral immune defenses. Even when the virus was cleared and lung mitochondrial function had recovered, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired, potentially leading to severe COVID-19 pathology.

  PublisherDOI

• Mitochondrial DNA lineages determine tumor progression through T cell reactive oxygen signaling

  Proceedings of the National Academy of Sciences · 2025-01-03 · 8 citations

  articleOpen access

  Mitochondrial DNA (mtDNA) is highly polymorphic, and host mtDNA variation has been associated with altered cancer severity. To determine the basis of this mtDNA–cancer association, we analyzed conplastic mice with the C57BL/6J (B6) nucleus but two naturally occurring mtDNA lineages, mtDNA B6 and mtDNA NZB , where mtDNA NZB mitochondria generate more oxidative phosphorylation (OXPHOS)-derived reactive oxygen species (mROS). In a cardiac transplant model, mtDNA B6 Foxp3+ T regulatory (Treg) cells supported long-term allograft survival, whereas mtDNA NZB Treg cells failed to suppress host T effector (Teff) cells, leading to acute rejection. When challenged with melanoma or colon cancer cells, the mtDNA NZB mice exhibited strikingly impaired tumor growth while mtDNA B6 mice showed Treg-dependent inhibition of Teff cells and allowed rapid tumor growth. Transcriptional analysis showed that activation of mtDNA NZB Teff cells increased mitochondrial gene expression while activation of mtDNA NZB Treg cells impaired mitochondrial gene expression and resulted in mtDNA NZB Treg cell exhaustion. Induction of the mitochondrially targeted catalytic antioxidant, mCAT, in hematopoietic cells normalized mtDNA NZB Treg function in both transplant and tumor models, indicating a key role for mROS in promoting Treg dysfunction. Anti-PD-L1 therapy did not modulate these effects, indicating that modulation of host mitochondrial function provides an independent approach for enhancing tumor cell destruction.

  PublisherDOI

• Partial restoration of mitochondrial dysfunction by AAV-Ant1 protects from dilated cardiomyopathy in Ant1-/- plus mtDNA mutant mice

  Nature Communications · 2025-12-15

  articleOpen access

  Primary mitochondrial disease (PMD) patients manifesting cardiomyopathy are twice as likely to die as other PMD patients. One PMD with cardiomyopathy is caused by null mutations in the heart-muscle isoform of the adenine nucleotide translocator (SLC25A4, ANT1) gene, with the severity of cardiomyopathy mediated by mitochondrial DNA. To optimize strategies for addressing mitochondrial cardiomyopathy, we generated an Ant1 null mouse and combined it with the ND6P25L mitochondrial DNA mutation to mimic the hypertrophic versus dilated cardiomyopathies observed in patients. Here, we transduce the neonatal Ant1-/- and Ant1-/-+ND6P25L mouse hearts with an AAV2/9-pDes-Gfp-mAnt1 cDNA vector. We show that restoration of just 10% of Ant1 gene expression was sufficient to ameliorate the cardiomyopathies in these mice. Proteomics and single-nucleus RNA sequencing reveal the reversal of dysregulated mitochondrial metabolic genes, including PGC1α, as well as cardiac contractile and extracellular matrix proteins. Hence, a modest increase in cardiac mitochondrial energetics can have profound benefits on cardiac function and is effective in treating mitochondrial cardiomyopathy. Patients with primary mitochondrial disease manifesting cardiomyopathy are twice as likely to die compared to those without cardiomyopathy. Here, the authors show that a modest increase in cardiac mitochondrial energetics via gene therapy can significantly improve cardiac function and is effective in treating mitochondrial cardiomyopathy.

  PublisherOA PDFDOI

• A mouse model of MEPAN demonstrates a role for mitochondrial fatty acid synthesis in iron–sulfur cluster and supercomplex formation

  Proceedings of the National Academy of Sciences · 2025-09-29

  articleOpen access1st author

  MEPAN ( M itochondrial E noyl CoA Reductase P rotein- A ssociated N eurodegeneration) is an early-onset movement disorder characterized by ataxia, dysarthria, and optic atrophy. Here, we report the creation of a mouse model of MEPAN with patient-similar compound heterozygous mutations in the Mecr gene. The MEPAN mouse recapitulates the major hallmarks of MEPAN, including a movement disorder, optic neuropathy, defects in protein lipoylation, and reduced mitochondrial oxidative phosphorylation in the brain. MECR catalyzes the last step in mitochondrial fatty acid synthesis (mtFASII), and the mechanism by which loss of mtFASII leads to neurological disease is unknown. LC–MS/MS-based proteomic analysis of Mecr mutant cerebella identified loss of subunits of complex I of oxidative phosphorylation (OXPHOS) and subunits of the iron–sulfur cluster assembly (ISC) complex. Native gels revealed altered OXPHOS complex and supercomplex formation and changes in binding of the acyl carrier protein (ACP) to mitochondrial complexes. These results demonstrate that MECR plays a key role in the acylation of ACP which is necessary for ACP-LYRM-mediated supercomplex modulation and ISC biogenesis and suggest unique pathways for therapeutics.

  PublisherDOI

• Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes

  Proceedings of the National Academy of Sciences · 2024-11-27 · 17 citations

  articleOpen access

  Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are upregulated in the heart, lung, kidney, and liver, but not mediastinal lymph nodes. Twenty-two of these are "noncanonical" immune genes, which we link to components of the renin-angiotensin-activation-system that manifest as increased fibrin deposition, leaky vessels, thrombotic tendency, PANoptosis, and mitochondrial dysfunction. Immunohistochemistry of mediastinal lymph nodes reveals altered architecture, excess collagen deposition, and pathogenic fibroblast infiltration. Many of the above findings are paralleled in animal models of SARS-CoV-2 infection and human peripheral blood mononuclear and whole blood samples from individuals with early and later SARS-CoV-2 variants. We then redefine cytokine storm in lethal COVID-19 as driven by upstream immune gene and mitochondrial signaling producing downstream RAAS (renin-angiotensin-aldosterone system) overactivation and organ damage, including compromised mediastinal lymph node function.

  PublisherOA PDFDOI

• Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes.

  UNC Libraries · 2024-12-05

  articleOpen access

  Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are upregulated in the heart, lung, kidney, and liver, but not mediastinal lymph nodes. Twenty-two of these are "noncanonical" immune genes, which we link to components of the renin-angiotensin-activation-system that manifest as increased fibrin deposition, leaky vessels, thrombotic tendency, PANoptosis, and mitochondrial dysfunction. Immunohistochemistry of mediastinal lymph nodes reveals altered architecture, excess collagen deposition, and pathogenic fibroblast infiltration. Many of the above findings are paralleled in animal models of SARS-CoV-2 infection and human peripheral blood mononuclear and whole blood samples from individuals with early and later SARS-CoV-2 variants. We then redefine cytokine storm in lethal COVID-19 as driven by upstream immune gene and mitochondrial signaling producing downstream RAAS (renin-angiotensin-aldosterone system) overactivation and organ damage, including compromised mediastinal lymph node function.

  PublisherDOI

• SARS-CoV-2 mitochondrial metabolic and epigenomic reprogramming in COVID-19

  Pharmacological Research · 2024-04-12 · 41 citations

  articleOpen access

  To determine the effects of SARS-CoV-2 infection on cellular metabolism, we conducted an exhaustive survey of the cellular metabolic pathways modulated by SARS-CoV-2 infection and confirmed their importance for SARS-CoV-2 propagation by cataloging the effects of specific pathway inhibitors. This revealed that SARS-CoV-2 strongly inhibits mitochondrial oxidative phosphorylation (OXPHOS) resulting in increased mitochondrial reactive oxygen species (mROS) production. The elevated mROS stabilizes HIF-1α which redirects carbon molecules from mitochondrial oxidation through glycolysis and the pentose phosphate pathway (PPP) to provide substrates for viral biogenesis. mROS also induces the release of mitochondrial DNA (mtDNA) which activates innate immunity. The restructuring of cellular energy metabolism is mediated in part by SARS-CoV-2 Orf8 and Orf10 whose expression restructures nuclear DNA (nDNA) and mtDNA OXPHOS gene expression. These viral proteins likely alter the epigenome, either by directly altering histone modifications or by modulating mitochondrial metabolite substrates of epigenome modification enzymes, potentially silencing OXPHOS gene expression and contributing to long-COVID.

  PublisherDOI

• Right Ventricular Failure Following Progression of Pulmonary Metastatic Burden in Primary Breast Cancer

  2024-04-30 · 1 citations

  article
  PublisherDOI

Recent grants

• NIH Grant R01GM090308

  NIH · $1.8M · 2014

• NIH Grant R21AG026646

  NIH · $355k · 2010

Frequent coauthors

• Douglas C. Wallace

  Children's Hospital of Philadelphia

  43 shared

• Sabrina L. Mitchell

  Vanderbilt University Medical Center

  23 shared

• Siddharth Pratap

  Meharry Medical College

  16 shared

• Konstantin Mischaikow

  16 shared

• Tomáš Gedeon

  Montana State University

  16 shared

• K. Sam Wells

  16 shared

• Terrance Cooper

  16 shared

• Erik M. Boczko

  Ohio University

  16 shared

Labs

• Deborah G Murdock LaboratoryPI

Education

• PhD, Department of Biological Sciences

  Carnegie Mellon University

  1996

• BS, Biological Sciences

  University of Georgia

  1988