Reprogramming the Human Glioma Genome
Reprogramming the Human Glioma Genome
批准号:
9064865
负责人:
Chun-Li Zhang
金额:
$24.28万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-05-15 至 2018-04-30
关键词:
ASCL1 geneAdultBETA2 proteinBehaviorBehavior ControlBindingBinding SitesBoxingBrainBrain DiseasesBrain NeoplasmsCellsChIP-seqChromatin StructureDNA BindingDNA MethylationDataData SetDeoxyribonuclease IDevelopmentEctopic ExpressionEnhancersEnvironmentEpigenetic ProcessFibroblastsGene ExpressionGene Expression ProfilingGenesGenomeGlioblastomaGliomaGoalsGrantHealthHumanLeadMaintenanceMalignant - descriptorMalignant GliomaMediatingModificationMolecularMusNatureNeuronsNodalNucleic Acid Regulatory SequencesPhenotypeProcessResearchRoleSOX11 geneSignal PathwaySiteTherapeuticTimeTransplantationTumor Cell InvasionVirusWorkbasecell behaviorcell typecellular transductionchromatin remodelingcombinatorialeffective therapygenome-widein vivoneoplastic cellnervous system disorderneurotrophic factornew therapeutic targetnovel therapeuticspromoterrapid growthsexsynergismtranscription factortranscriptometranscriptome sequencingtumor
中文摘要
英文摘要
DESCRIPTION (provided by applicant): SUMMARY Malignant gliomas, the most deadly neurological disease in the brain, are essentially incurable due to their rapid growth and very invasive nature. One paradigm-shifting therapeutic approach to eliminating brain tumors is to change the fate of glioma cells so that they are non-proliferative and non-invasive. We previously showed that virus-mediated expression of two transcription factors directly converts human fibroblasts to neurons with extremely high efficiency. Unexpectedly, our preliminary results also revealed that malignant human glioma cells can be very efficiently converted to neuron-like cells, which are no longer proliferative or invasive. Even the cells that are transduced but not yet fate-converted stopped proliferation, indicating a dominant role for these factors in governing the behavior of human glioma cells. Our preliminary results further show that majority of the in vivo converted cells cannot survive in the adult brain environment. Based on these very exciting findings, we propose to tease out the molecular mechanism underlying forced terminal differentiation of human glioma cells that is mediated by a synergistic action of two transcription factors. We will specifically focus on transcriptome, cistrome, global chromatin structure and epigenetic modifications during the reprogramming process. Results from this study may lead to the identification of nodal points controlling the behavior of human glioma cells, which can be targeted for developing novel therapeutics against the most deadly brain disease-glioblastoma.
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会议论文
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In Vivo Reprogramming of Glial Fate for Spinal Cord Repair
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Transcriptional Control of Adult Neural Stem Cells
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Transcriptional Control of Adult Neural Stem Cells
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Transcriptional Control of Adult Neural Stem Cells
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资助金额:$34.78万
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财政年份:2011
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Transcriptional Control of Adult Neural Stem Cells
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Transcriptional Control of Adult Neural Stem Cells
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