K99 to R00 Transition-Neural Crest Migration and Survival in Zebrafish
K99 to R00 Transition-Neural Crest Migration and Survival in Zebrafish
批准号:
8099548
负责人:
Rodney A. Stewart
金额:
$24.9万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-07-15 至 2013-06-30
关键词:
AddressAnimalsApoptosisAppointmentBehaviorBiochemistryBlood CirculationBlood capillariesCell Adhesion MoleculesCell DeathCell SurvivalCell-Cell AdhesionCellsDataDefectDevelopmentDistantDorsalE-CadherinEmbryoEndotheliumEnvironmentEpithelialEventFacultyFamilyFamily memberGene ExpressionGenesGeneticGenetic EpistasisGliomaGoalsHuman GenomeHuntsman Cancer Institute at the University of UtahInstitutesKnowledgeLaboratoriesLinkMalignant NeoplasmsMediatingMediator of activation proteinMesenchymalModelingMolecularMusMutationNeoplasm MetastasisNeural CrestNeural Crest CellNeural tubeNeurobiologyNeuroblastomaOncogenicOrganOrthologous GenePathway interactionsPatternPeripheral Nerve Sheath NeoplasmPhasePhenocopyPhenotypeProcessProliferatingPropertyProteinsPumaRNAResearchResearch PersonnelResearch ProposalsRoleScienceSignal TransductionSiteSnailsStagingStem cellsSyntenySystemTestingTissuesTrainingTranscription factor genesTumor-DerivedZebrafishbasecadherin-6cancer cellcapillarycareercell motilitydesignin vivomelanomamembermigrationmutantneoplastic cellnovelnull mutationoncologyoverexpressionprogenitorslugtooltranscription factortumor
中文摘要
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英文摘要
The goal oflhis application is to use the zebrafish as a |nodel to dissect the molecular connponents of Foxd3-mediated neural crest (NC) cell survival and migration end to determine if these pathways promote metastasis in NG-derived tumors in vivo. The zebrafish with its close synteny to the human genome and its conserved molecular pathways regulating the development of tissues and organs, Offers a powerful tool with which to conduct such research. We previoulsy identified and characterized a zebrafish foxd3 mutant line that has specific NC ceil survival and migration defects. We also identified the Snai1b transcription factor-as a critical mediator of Foxd3 function. The underlying hypothesis of this applicatipn is that knowledge of the Foxd3 pathway wiII provide an understanding environments, requirement for the metaststasis of NC-derived tumors. In Aim 1, genetic epistasis and biochemistry will determine if Foxd3 directly activates snai1b expression. This aim will also will also determine whether Snai 1b inhibits NC apoptosis by repressing the expression of one or more BH3-only genes, and promotes NC migration by repressing cadherin-6 expression . In Aim 2, a list of genes identified in a microarray screen during the bK99 phase will abe analyzed for thier NC expression pattern and knockdown phenotypes, as well as their ability to
rescue NC defects in foxd3 mutant and snai 1b MO-injected embryos. In Aim 3, foxd3 and snai1b will be expressed in developing NC cells to examine their potential roles in promoting metastasis in established zebrafish NC tumors, including a new model identified during the K99 phase.
Rodney Stewart will continue to receive advanced training in genetics, neurobiology and oncology
throughout his career. This research proposal is designed to support the candidate as an independent investigator during the first 3 years of a faculty appointment in the Department of Oncology Sciences at the Huntsman Cancer Institute at the University of Utah.
Huntsrnan Cancer Institute at the yniyersity of-Utahnd
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会议论文
Developmental Mechanisms Driving Cell Invasion in Pediatric Brain Cancers
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批准号:10215629
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项目类别:
-
资助金额:$33.36万
-
财政年份:2018
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负责人:Rodney A. Stewart
-
依托单位:
Developmental Mechanisms Driving Cell Invasion in Pediatric Brain Cancers
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批准号:10436201
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项目类别:
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资助金额:$33.36万
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财政年份:2018
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负责人:Rodney A. Stewart
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依托单位:
K99 to R00 Transition-Neural Crest Migration and Survival in Zebrafish
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批准号:7874867
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项目类别:
-
资助金额:$24.9万
-
财政年份:2009
-
负责人:Rodney A. Stewart
-
依托单位:
K99 to R00 Transition-Neural Crest Migration and Survival in Zebrafish
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批准号:7894554
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项目类别:
-
资助金额:$24.9万
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财政年份:2009
-
负责人:Rodney A. Stewart
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依托单位:
Neural Crest Cell Survival and Migration in Zebrafish
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批准号:7393681
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项目类别:
-
资助金额:$9.0万
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财政年份:2007
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负责人:Rodney A. Stewart
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依托单位:
Neural Crest Cell Survival and Migration in Zebrafish
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批准号:7247609
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项目类别:
-
资助金额:$9.0万
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财政年份:2007
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负责人:Rodney A. Stewart
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依托单位:
海外基金