About

Suraiya Haroon is a Research Assistant Professor of Pediatrics in the Department of Human Genetics at the Children's Hospital of Philadelphia. She holds a B.A. in Molecular and Cell Biology with an emphasis in Genetics and Development from the University of California-Berkeley, obtained in 2003, and a Ph.D. from the Laboratory of Genetics Graduate Program at the University of Wisconsin-Madison, completed in 2012. Her research focuses on mitochondrial dysfunction, oxidative stress sensitivity, and developmental defects, particularly in relation to mitochondrial diseases such as Cockayne Syndrome and Leigh Syndrome. Haroon has contributed to studies investigating the longevity effects of reduced IGF-1 signaling, mitochondrial stress rescue using FDA-approved compounds, and therapy development for OPA1 disease using various model organisms including C. elegans, zebrafish, and patient fibroblasts. Her work aims to identify therapeutic strategies for mitochondrial-related disorders through high-throughput drug screening and molecular analysis.

Research topics

• Biology
• Genetics
• Cell biology
• Computational biology
• Pathology

Selected publications

• The longevity effects of reduced IGF-1 signaling depend on the stability of the mitochondrial genome

  Science Advances · 2026-04-03

  articleOpen access

  Suppression of insulin-like growth factor-1 (IGF-1) signaling extends mammalian life span and protects against a range of age-related diseases. Unexpectedly, we found that reduced IGF-1 signaling fails to extend the life span of mitochondrial mutator mice. Most of the longevity pathways that are normally initiated by IGF-1 suppression were either blocked or blunted in the mutator mice. These observations suggest that the prolongevity effects of IGF-1 suppression critically depend on the integrity of the mitochondrial genome, revealing an unexpected hierarchy in the pathways that control mammalian aging. Together, these findings deepen our understanding of the interactions between the hallmarks of aging and underscore the need for interventions that preserve the integrity of the mitochondrial genome.

  PublisherDOI

• The longevity effects of reduced IGF-1 signaling depend on the stability of the mitochondrial genome

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-06

  preprintOpen access

  Suppression of insulin-like growth factor-1 (IGF-1) signaling extends mammalian lifespan and protects against a range of age-related diseases. Surprisingly though, we found that reduced IGF-1 signaling fails to extend the lifespan of mitochondrial mutator mice. Accordingly, most of the longevity pathways that are normally initiated by IGF-1 suppression were either blocked or blunted in the mutator mice. These observations suggest that the pro-longevity effects of IGF-1 suppression critically depend on the integrity of the mitochondrial genome and that mitochondrial mutations may impose a hard limit on mammalian lifespan. Together, these findings deepen our understanding of the interactions between the hallmarks of aging and underscore the need for interventions that preserve the integrity of the mitochondrial genome.

  PublisherOA PDFDOI

• Mitophagy modulation rescues single large-scale mitochondrial DNA deletion (SLSMD) disease symptoms in the <i>C. elegans uaDf5</i> animal model

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-27 · 1 citations

  preprintOpen accessSenior authorCorresponding

  ABSTRACT S ingle large s cale m itochondrial DNA (mtDNA) d eletions (SLSMD) underlie a range of sporadic or maternally inherited primary mitochondrial diseases having significant morbidity and mortality, including Pearson syndrome, Kearns-Sayre Syndrome, or Chronic Progressive External Ophthalmoplegia. Therapeutic development has been hindered by limited existing knowledge on mtDNA quality control and a lack of SLSMD animal models. To address this challenge, we utilized the C. elegans heteroplasmic SLSMD strain, uaDf5, to objectively screen for potential therapies. As mitophagy modulation has been implicated in mtDNA homeostasis, we screened a library of mitophagy modulating compounds to determine their comparative effects to rescue mitochondrial unfolded protein (UPR mt ) stress induction in in uaDf5 SLSMD worms. Interestingly, Thiamine was discovered to be an effective positive control, significantly reducing mitochondrial stress in this model. Two lead therapeutic candidates from the mitophagy library screen were Hemin and Celastrol (Tripterin). Celastrol is a mitophagy activating anti-inflammatory and metabolic modifying natural product derived compound, that rescued multiple fitness outcomes (thrashing, development, survival) and reduced the mitochondrial stress in uaDf5 animals in a mitophagy-dependent fashion. This study highlights the utility of the uaDf5 worm model to enable preclinical identification of therapeutic candidate leads for SLSMD-based heteroplasmic mtDNA diseases and identifies possible therapeutic candidates that serve as mitophagy modulators to improve health and specifically reduce heteroplasmy levels in SLSMD diseases.

  PublisherOA PDFDOI

• <i>N</i>-acetylcysteine and cysteamine bitartrate prevent azide-induced neuromuscular decompensation by restoring glutathione balance in two novel <i>surf1</i> <i>−/−</i> zebrafish deletion models of Leigh syndrome

  Human Molecular Genetics · 2023-02-16 · 14 citations

  articleOpen access1st authorCorresponding

  SURF1 deficiency (OMIM # 220110) causes Leigh syndrome (LS, OMIM # 256000), a mitochondrial disorder typified by stress-induced metabolic strokes, neurodevelopmental regression and progressive multisystem dysfunction. Here, we describe two novel surf1-/- zebrafish knockout models generated by CRISPR/Cas9 technology. While gross larval morphology, fertility, and survival into adulthood appeared unaffected, surf1-/- mutants manifested adult-onset ocular anomalies and decreased swimming activity, as well as classical biochemical hallmarks of human SURF1 disease, including reduced complex IV expression and enzymatic activity and increased tissue lactate. surf1-/- larvae also demonstrated oxidative stress and stressor hypersensitivity to the complex IV inhibitor, azide, which exacerbated their complex IV deficiency, reduced supercomplex formation, and induced acute neurodegeneration typical of LS including brain death, impaired neuromuscular responses, reduced swimming activity, and absent heartrate. Remarkably, prophylactic treatment of surf1-/- larvae with either cysteamine bitartrate or N-acetylcysteine, but not other antioxidants, significantly improved animal resiliency to stressor-induced brain death, swimming and neuromuscular dysfunction, and loss of heartbeat. Mechanistic analyses demonstrated cysteamine bitartrate pretreatment did not improve complex IV deficiency, ATP deficiency, or increased tissue lactate but did reduce oxidative stress and restore glutathione balance in surf1-/- animals. Overall, two novel surf1-/- zebrafish models recapitulate the gross neurodegenerative and biochemical hallmarks of LS, including azide stressor hypersensitivity that was associated with glutathione deficiency and ameliorated by cysteamine bitartrate or N-acetylcysteine therapy.

  PublisherOA PDFDOI

• Novel Development of Magnetic Resonance Imaging to Quantify the Structural Anatomic Growth of Diverse Organs in Adult and Mutant Zebrafish

  Zebrafish · 2023-08-21 · 3 citations

  articleOpen access

  Zebrafish ( Danio rerio ) is a widely used vertebrate animal for modeling genetic diseases by targeted editing strategies followed by gross phenotypic and biomarker characterization. While larval transparency permits microscopic detection of anatomical defects, histological adult screening for organ-level defects remains invasive, tedious, inefficient, and subject to technical artifact. Here, we describe a noninvasive magnetic resonance imaging (MRI) approach to systematically screen adult zebrafish for anatomical growth defects. An anatomical atlas of wild-type (WT) zebrafish at 5–31 months post-fertilization was created by ex vivo MRI with a 9.4 T magnet. Volumetric growth over time was measured of animals and major organs, including the brain, spinal cord, heart, eyes, optic nerve, ear, liver, kidneys, and swim bladder. Subsequently, surf1 −/− , fbxl4 −/− , and opa1 +/− mitochondrial disease mutant adult zebrafish were quantitatively studied to compare organ volumes with age-matched WT zebrafish. Results demonstrated that MRI enabled noninvasive, high-resolution, rapid screening of mutant adult zebrafish for overall and organ-specific growth abnormalities. Detailed volumetric analyses of three mitochondrial disease mutants delineated specific organ differences, including significantly increased brain growth in surf1 −/− and opa1 +/− , and marginally significant decreased heart and spinal cord volumes in surf1 −/− mutants. This is interesting as we know neurological involvement can be seen in SURF1 − /− patients with ataxia, dystonia, and lesions in basal ganglia, as well as in OPA1 +/− patients with spasticity, ataxia, and hyperreflexia indicative of neuropathology. Similarly, cardiomyopathy is a known sequelae of cardiac pathology in patients with SURF1 − /− -related disease. Future studies will define MRI signaling patterns of organ dysfunction to further delineate specific pathology.

  PublisherOA PDFDOI

• Evolutionary conservation of the fidelity of transcription

  Nature Communications · 2023-03-20 · 29 citations

  articleOpen access

  Abstract Accurate transcription is required for the faithful expression of genetic information. However, relatively little is known about the molecular mechanisms that control the fidelity of transcription, or the conservation of these mechanisms across the tree of life. To address these issues, we measured the error rate of transcription in five organisms of increasing complexity and found that the error rate of RNA polymerase II ranges from 2.9 × 10 −6 ± 1.9 × 10 −7 /bp in yeast to 4.0 × 10 −6 ± 5.2 × 10 −7 /bp in worms, 5.69 × 10 −6 ± 8.2 × 10 −7 /bp in flies, 4.9 × 10 −6 ± 3.6 × 10 −7 /bp in mouse cells and 4.7 × 10 −6 ± 9.9 × 10 −8 /bp in human cells. These error rates were modified by various factors including aging, mutagen treatment and gene modifications. For example, the deletion or modification of several related genes increased the error rate substantially in both yeast and human cells. This research highlights the evolutionary conservation of factors that control the fidelity of transcription. Additionally, these experiments provide a reasonable estimate of the error rate of transcription in human cells and identify disease alleles in a subunit of RNA polymerase II that display error-prone transcription. Finally, we provide evidence suggesting that the error rate and spectrum of transcription co-evolved with our genetic code.

  PublisherOA PDFDOI

• Evolutionary conservation of the fidelity of transcription

  Research Square · 2022-02-09 · 1 citations

  preprintOpen access

  Abstract Accurate transcription is required for the faithful expression of genetic information. Surprisingly though, little is known about the molecular mechanisms that control the fidelity of transcription, or the conservation of these mechanisms across the tree of life. To address this issue, we measured the error rate of transcription in five organisms of increasing complexity and identified various genes, alleles and processes that control transcriptional fidelity in multicellular organisms. In doing so, they highlight the evolutionary conservation of fidelity factors and open up new opportunities to probe the impact of transcription errors on intact organisms and human physiology. Finally, our experiments provide the first reasonable estimate of the error rate of transcription in human cells, identify the first disease associated with error-prone RNA polymerases and suggest that transcription errors may have contributed to the evolution of our genetic code.

  PublisherOA PDFDOI

• Dichloroacetate improves mitochondrial function, physiology, and morphology in FBXL4 disease models

  JCI Insight · 2022-07-26 · 14 citations

  articleOpen access

  Pathogenic variants in the human F-box and leucine-rich repeat protein 4 (FBXL4) gene result in an autosomal recessive, multisystemic, mitochondrial disorder involving variable mitochondrial depletion and respiratory chain complex deficiencies with lactic acidemia. As no FDA-approved effective therapies for this disease exist, we sought to characterize translational C. elegans and zebrafish animal models, as well as human fibroblasts, to study FBXL4-/- disease mechanisms and identify preclinical therapeutic leads. Developmental delay, impaired fecundity and neurologic and/or muscular activity, mitochondrial dysfunction, and altered lactate metabolism were identified in fbxl-1(ok3741) C. elegans. Detailed studies of a PDHc activator, dichloroacetate (DCA), in fbxl-1(ok3741) C. elegans demonstrated its beneficial effects on fecundity, neuromotor activity, and mitochondrial function. Validation studies were performed in fbxl4sa12470 zebrafish larvae and in FBXL4-/- human fibroblasts; they showed DCA efficacy in preventing brain death, impairment of neurologic and/or muscular function, mitochondrial biochemical dysfunction, and stress-induced morphologic and ultrastructural mitochondrial defects. These data demonstrate that fbxl-1(ok3741) C. elegans and fbxl4sa12470 zebrafish provide robust translational models to study mechanisms and identify preclinical therapeutic candidates for FBXL4-/- disease. Furthermore, DCA is a lead therapeutic candidate with therapeutic benefit on diverse aspects of survival, neurologic and/or muscular function, and mitochondrial physiology that warrants rigorous clinical trial study in humans with FBXL4-/- disease.

  PublisherOA PDFDOI

• Transcription errors induce proteotoxic stress and shorten cellular lifespan

  Digital Commons@Becker (Washington University School of Medicine) · 2020-11-06

  articleOpen access

  Transcription errors occur in all living cells; however, it is unknown how these errors affect cellular health. To answer this question, we monitored yeast cells that were genetically engineered to display error-prone transcription. We discovered that these cells suffer from a profound loss in proteostasis, which sensitizes them to the expression of genes that are associated with protein-folding diseases in humans; thus, transcription errors represent a new molecular mechanism by which cells can acquire disease. We further found that the error rate of transcription increases as cells age, suggesting that transcription errors affect proteostasis particularly in aging cells. Accordingly, transcription errors accelerate the aggregation of a peptide that is implicated in Alzheimer’s disease, and shorten the lifespan of cells. These experiments reveal a novel, basic biological process that directly affects cellular health and aging.

  PublisherOA PDFDOI

• Genome-wide surveillance of transcription errors in response to genotoxic stress

  Proceedings of the National Academy of Sciences · 2020-12-23 · 37 citations

  articleOpen access

  Mutagenic compounds are a potent source of human disease. By inducing genetic instability, they can accelerate the evolution of human cancers or lead to the development of genetically inherited diseases. Here, we show that in addition to genetic mutations, mutagens are also a powerful source of transcription errors. These errors arise in dividing and nondividing cells alike, affect every class of transcripts inside cells, and, in certain cases, greatly exceed the number of mutations that arise in the genome. In addition, we reveal the kinetics of transcription errors in response to mutagen exposure and find that DNA repair is required to mitigate transcriptional mutagenesis after exposure. Together, these observations have far-reaching consequences for our understanding of mutagenesis in human aging and disease, and suggest that the impact of DNA damage on human physiology has been greatly underestimated.

  PublisherOA PDFDOI

Frequent coauthors

• Marc Vermulst

  University of Southern California

  21 shared

• Marni J. Falk

  13 shared

• Zarko Manojlovic

  12 shared

• Manuela Lavorato

  Children's Hospital of Philadelphia

  8 shared

• Eiko Nakamaru‐Ogiso

  Children's Hospital of Philadelphia

  8 shared

• Christoph Seiler

  Children's Hospital of Philadelphia

  6 shared

• Tomas A. Prolla

  University of Wisconsin–Madison

  5 shared

• Jean-François Goût

  Mississippi State University

  5 shared

Education

• PhD, Genetics

  University of Wisconsin–Madison

  2012

• Bachelor, Molecular and Cell Biology

  University of California, Berkeley

  2003