0000000000714552

AUTHOR

Roderick T. Bronson

showing 3 related works from this author

Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer.

2016

Abstract As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non–small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways, leading to epigenetic transformation independent of canonical growth factor pathway activation. As such, tumors feature a transcrip…

0301 basic medicineModels MolecularLung Neoplasmsmedicine.medical_treatmentMolecular ConformationGene ExpressionAntineoplastic Agentsmacromolecular substancesBiologymedicine.disease_causeArticleMalignant transformationTargeted therapy03 medical and health sciencesMiceStructure-Activity RelationshipCell Line TumormedicineAnimalsHumansEnhancer of Zeste Homolog 2 ProteinMolecular Targeted TherapyLung cancerPromoter Regions GeneticGene Expression ProfilingEZH2Cancermedicine.diseaseMagnetic Resonance ImagingXenograft Model Antitumor AssaysChromatinrespiratory tract diseasesGene Expression Regulation NeoplasticDisease Models Animal030104 developmental biologyCell Transformation NeoplasticEnhancer Elements GeneticOncologyDrug DesignCancer researchAdenocarcinomaKRASEpigenetic therapyCancer discovery
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Reversible neural stem cell niche dysfunction in a model of multiple sclerosis

2011

Objective The subventricular zone (SVZ) of the brain constitutes a niche for neural stem and progenitor cells that can initiate repair after central nervous system (CNS) injury. In a relapsing-remitting model of experimental autoimmune encephalomyelitis (EAE), the neural stem cells (NSCs) become activated and initiate regeneration during acute disease, but lose this ability during the chronic phases of disease. We hypothesized that chronic microglia activation contributes to the failure of the NSC repair potential in the SVZ. Methods Using bromodeoxyuridine injections at different time points during EAE, we quantified the number of proliferating and differentiating progenitors, and evaluate…

Encephalomyelitis Autoimmune ExperimentalMultiple SclerosisTime FactorsSubventricular zoneCell CountMinocyclineBiologyArticleMiceSOX2Microscopy Electron TransmissionNeural Stem CellsCell MovementmedicineSecondary PreventionAnimalsProgenitor cellStem Cell NicheMyelin Proteolipid ProteinCell ProliferationMicrogliaExperimental autoimmune encephalomyelitismedicine.diseaseNeural stem cellOligodendrocytePeptide FragmentsAnti-Bacterial Agentsnervous system diseasesDisease Models AnimalOligodendrogliamedicine.anatomical_structureNeurologyBromodeoxyuridinenervous systemNeurology (clinical)MicrogliaStem cellNeuroscience
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D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice.

2014

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in several cancer types and cause the neurometabolic syndrome D2-hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in production of D2-hydroxyglutaric acid (D-2HG). To study the pathophysiological consequences of the accumulation of D-2HG, we generated transgenic mice with conditionally activated IDH2R140Q and IDH2R172K alleles. Global induction of mutant IDH2 expression in adults resulted in dilated cardiomyopathy, white matter abnormalities throughout the central nervous system (CNS), and muscular dystrophy. Embryonic activation of mutant IDH2 resulted in more pronounced ph…

Genetically modified mouseTransgeneMutantCardiomyopathyMice NudeBiologyIDH2Cell LineGlutarateschemistry.chemical_compoundMiceGeneticsmedicineAnimalsHumansMuscular dystrophyMice Inbred BALB CGlycogenGene Expression ProfilingGene Expression Regulation DevelopmentalHeartNeurodegenerative Diseasesmedicine.diseaseMolecular biologyIsocitrate DehydrogenaseIsocitrate dehydrogenasechemistryMutationCardiomyopathiesDevelopmental BiologyResearch PaperGenesdevelopment
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