ArticleScience translational medicine2021
Targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas.
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Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35citing papers in PubMed
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Who cites it
35 citing papers in PubMed.
- Epigenetic Alterations in Meningiomas-A Review.Biomedicines · 2026Review
- The future of targeted therapies for pediatric central nervous system tumors.Neuro-oncology advances · 2026Review
- Article
- Patient-derived complex organoids are a critical tool to understand and explore pediatric malignant brain tumors.Cancer metastasis reviews · 2026Review
- Developing an advanced risk stratification model for pediatric intracranial ependymoma based on the prospective trial E-HIT2000 and subsequent registries.Neuro-oncology · 2026Article
- EZHIP in Pediatric Brain Tumors: From Epigenetic Mimicry to Therapeutic Vulnerabilities.International journal of molecular sciences · 2026Review
- A gasdermin-based life-death evolution system for reprogramming protease specificity.Nature chemical biology · 2026Article
- Integrative network toxicology and molecular docking reveal epigenetic and endocrine-disrupting mechanisms of PFAS in ovarian cancer.Frontiers in pharmacology · 2026Article
- EZHIP boosts neuronal-like synaptic gene programs and depresses polyamine metabolism.Acta neuropathologica communications · 2025Article
- Glutamine antagonism suppresses tumor growth in adrenocortical carcinoma through inhibition of de novo nucleotide biosynthesis.bioRxiv : the preprint server for biology · 2025Article
- The Bermuda Triangle of paediatric brain cancers: epigenetics, developmental timing window and cell of origin.Cancer metastasis reviews · 2025Review
- Article
- Inhibition of mitochondrial bioenergetics and hypoxia to radiosensitize diffuse intrinsic pontine glioma.Neuro-oncology · 2025Article
- Advances in molecular prognostication and treatments in ependymoma.Journal of neuro-oncology · 2025Review
- Bridging epigenomics and tumor immunometabolism: molecular mechanisms and therapeutic implications.Molecular cancer · 2025Review
- Metabolism-driven chromatin dynamics: Molecular principles and technological advances.Molecular cell · 2025Review
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Combating multidrug-resistant (MDR) Staphylococcus aureus infection using terpene and its derivative.World journal of microbiology & biotechnology · 2024Review
- Metabolic reprogramming by histone deacetylase inhibition preferentially targets NRF2-activated tumors.Cell reports · 2024Article
Corrections and comments
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Authors and funding
45 authors.
Pooja PanwalkarLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0001-7223-0452
Benita TamraziDepartment of Radiology, Children's Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA 90027, USA.ORCID 0000-0003-4795-8454
Derek DangLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0003-2071-4898
Chan ChungDepartment of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea.ORCID 0000-0003-0510-8996
Stefan SwehaLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-1807-6770
Siva Kumar NatarajanLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-9663-079X
Matthew PunLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-4766-4301
Jill BaylissLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-7995-5584
Martin P OgrodzinskiDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
Drew PrattLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0003-3583-8308
Brendan MullanDepartment of Pediatrics, Michigan Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Debra HawesDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA 90027, USA.
Fusheng YangDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA 90027, USA.ORCID 0000-0002-8040-6312
Chao LuDepartment of Genetics and Development and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.ORCID 0000-0003-0982-8122
Benjamin R SabariLaboratory of Chromatin Biology and Epigenetics, Rockefeller University, New York, NY 10065, USA.
Abhinav AchrejaBiomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Jin HeonBiomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-8427-8514
Olamide AnimasahunBiomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-4032-3619
Marcin CieslikLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Christopher DunhamDivision of Anatomic Pathology, British Columbia Children's Hospital, Vancouver, British Columbia V6H 3N1, Canada.
Stephen YipDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.ORCID 0000-0002-8514-9861
Juliette HukinDivision of Hematology and Oncology, Children's and Women's Health Centre of B.C., University of British Columbia, Vancouver, British Columbia V6H 3N1, Canada.ORCID 0000-0002-8727-8456
Joanna J PhillipsDepartment of Pathology, University of California San Francisco, San Francisco, CA 94132, USA.ORCID 0000-0002-3789-8120
Miriam BornhorstResearch Center for Genetic Medicine, Children's National Health System, Washington, DC 20012, USA.ORCID 0000-0002-7595-7726
Andrea M GriesingerDepartment of Pediatrics, University of Colorado, Denver, Aurora, CO 80045, USA.
Andrew M DonsonDepartment of Pediatrics, University of Colorado, Denver, Aurora, CO 80045, USA.ORCID 0000-0003-1153-6911
Nicholas K ForemanMorgan Adams Foundation Pediatric Brain Tumor Research Program, Children's Hospital Colorado, Aurora, CO 80045, USA.
Hugh J L GartonDepartment of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-2573-2246
Jason HethDepartment of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0001-5463-4066
Karin MuraszkoDepartment of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.
Javad NazarianResearch Center for Genetic Medicine, Children's National Health System, Washington, DC 20012, USA.
Carl KoschmannDepartment of Pediatrics, Michigan Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Li JiangDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02115, USA.
Mariella G FilbinDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02115, USA.ORCID 0000-0002-2613-8126
Deepak NagrathBiomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-8999-2282
Marcel KoolHopp Children's Cancer Center (KiTZ), Heidelberg 69120, Germany.
Andrey KorshunovDepartment of Neuropathology, German Cancer Research Center (DKFZ), University Hospital Heidelberg and CCU Neuropathology, Heidelberg 69120, Germany.
Stefan M PfisterHopp Children's Cancer Center (KiTZ), Heidelberg 69120, Germany.ORCID 0000-0002-5447-5322
Richard J GilbertsonCancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
C David AllisLaboratory of Chromatin Biology and Epigenetics, Rockefeller University, New York, NY 10065, USA.ORCID 0000-0001-7589-713X
Arul M ChinnaiyanLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0001-9282-3415
Sophia Y LuntDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.ORCID 0000-0003-4522-6065
Stefan BlümlDepartment of Radiology, Children's Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA 90027, USA.ORCID 0000-0003-2124-797X
Alexander R JudkinsDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA 90027, USA.ORCID 0000-0002-9242-3769
Sriram VennetiLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0001-9764-0423
Funding
Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4MMICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3MCELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8MUnravelling metabolic dependencies in H3K27M mutant DIPGR01NS110572 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sriram Venneti · 2019 to 2026
$2.7MTargeting Stromal Influences on Glutamine Addiction in Ovarian CancerR01CA227622 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOK, SAMUEL C, NAGRATH, DEEPAK · 2018 to 2022
$2.3MIdentification of USP13 as a therapeutic target for ovarian cancerR01CA222251 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI LU, XIONGBIN, NAGRATH, DEEPAK · 2018 to 2022
$1.8MUncovering Role of Exosomes in Regulating Pancreatic Cancer Cell MetabolismR01CA204969 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NAGRATH, DEEPAK · 2017 to 2021
$1.7MTargeting ATRX-Deficient Pediatric GBMK08NS099427 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOSCHMANN, CARL J · 2017 to 2021
$811kEvaluating the role of EZH2-interacting protein (EZHIP) in pediatric posterior fossa ependymoma metabolismF31CA260935 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DANG, DEREK · 2021 to 2022
$77kCancer Research UK 22492Cancer Research UK 26398Cancer Research UK 28598NCI NIH HHS F31 CA260935NCI NIH HHS P50 CA097257NCI NIH HHS R01 CA204969NCI NIH HHS R01 CA222251NCI NIH HHS R01 CA227622NIGMS NIH HHS T32 GM007315NIGMS NIH HHS T32 GM007863NINDS NIH HHS K08 NS099427NINDS NIH HHS R01 NS110572
Abstract
Childhood posterior fossa group A ependymomas (PFAs) have limited treatment options and bear dismal prognoses compared to group B ependymomas (PFBs). PFAs overexpress the oncohistone-like protein EZHIP (enhancer of Zeste homologs inhibitory protein), causing global reduction of repressive histone H3 lysine 27 trimethylation (H3K27me3), similar to the oncohistone H3K27M. Integrated metabolic analyses in patient-derived cells and tumors, single-cell RNA sequencing of tumors, and noninvasive metabolic imaging in patients demonstrated enhanced glycolysis and tricarboxylic acid (TCA) cycle metabolism in PFAs. Furthermore, high glycolytic gene expression in PFAs was associated with a poor outcome. PFAs demonstrated high EZHIP expression associated with poor prognosis and elevated activating mark histone H3 lysine 27 acetylation (H3K27ac). Genomic H3K27ac was enriched in PFAs at key glycolytic and TCA cycle–related genes including
Indexed as
EpendymomaHistonesAnimalsChildEpigenesis, GeneticEpigenomicsHumansMetabolic Networks and PathwaysMiceHistones
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