课题基金 / 基金详情

The Role of JunB in Hematopoietic Stem Cell Homeostasis

The Role of JunB in Hematopoietic Stem Cell Homeostasis
JunB 在造血干细胞稳态中的作用
批准号：
8055396
负责人：
Emmanuelle Passegue
金额：
$38.63万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
项目状态：
已结题
起止时间：
2008-04-03 至 2013-03-31
来源：
https://reporter.nih.gov/project-details/8055396
关键词：
AddressBindingBinding SitesBioinformaticsBiologicalBiological ModelsBiological ProcessBlast PhaseBone MarrowCandidate Disease GeneCell CycleCell Cycle RegulationCell MaintenanceCellsChronic Myeloid LeukemiaClinicalDataDevelopmentEngraftmentEnsureEventGene TargetingGenerationsGenesGeneticGenomicsGoalsHematopoiesisHematopoieticHematopoietic stem cellsHomeostasisHumanIn VitroLesionMaintenanceMediator of activation proteinMolecularMolecular TargetMusMyeloid LeukemiaMyeloproliferative diseasePhysiologicalPopulationPropertyRegulationResistanceRoleScanningStem cellsStressTestingTranscription Factor AP-1Transplantationbasechromatin immunoprecipitationgenome wide association studygenome-widein vivoleukemiamouse modeloverexpressionpromoterresearch studyresponsestem cell biologystem cell populationtranscription factor

项目摘要

项目成果

Emmanuelle Passegue的其他基金

相似基金

相关文献

中文摘要
翻译
点击翻译按钮获取中文摘要
英文摘要
DESCRIPTION (provided by applicant): The goal of this project is to elucidate the mechanisms by which the AP-1 transcription factor JunB regulates normal hematopoiesis, and to understand how loss of JunB alters hematopoietic stem cells (HSC) properties and leads to the generation of leukemic stem cells (LSC). These studies will be carried out in mouse models of JunB deficiency that we have generated and characterized. Studies in Specific Aim 1 will investigate how deregulated cell cycle distribution and increased proliferation contribute to the aberrant properties of junB- deficient HSC. We will determine to what extent quiescent vs. cycling junB-deficient HSC are able to provide long-term engraftment, investigate their response to hematopoietic stresses and interrogate the molecular networks controlling their proliferation. These experiments should address the question of how HSC maintenance and proliferation are co-coordinately regulated to ensure homeostasis and how changes innts should increase our understanding of how HSC are maintained in their bone marrow niches and how LSC can escape these microenvironmental regulations. The general goal of Specific Aim 3 is to identify junB target genes in HSC. We will exploit both genome-wide bioinformatics approach to scan for genes with cis-regulatory motifs matching canonical JunB binding sites and chromatin immunoprecipitation (ChIP) approach with genomic array platforms (ChIP-chip). These experiments should uncover important regulatory networks controlling HSC homeostasis and transcriptional abnormalities underlying LSC generation. In Specific Aim 4, we will functionally evaluate the contribution of deregulated proliferation and microenvironmental interactions to the leukemic transformation of junB-deficient HSC. We will test the role of several important candidate genes by either correcting their defective regulation in junB-deficient HSC or by mimicking their alterations in normal HSC. These experiments should identify critical mediators that functionally contribute to LSC generation and function. PROJECT NARRATIVE: Together, these experiments pursue the general goal of identifying molecular targets to destroy the otherwise therapeutically resistant LSC population in human myeloid leukemias.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Emergency Myelopoiesis in the Pathogenesis of Myeloid Malignancies
Mechanisms of Hematopoietic Stem Cell and Blood aging
Emergency Myelopoiesis in the Pathogenesis of Myeloid Malignancies
Emergency Myelopoiesis in the Pathogenesis of Myeloid Malignancies
国内基金
海外基金
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
  • 批准号：
    32170319
  • 项目类别：
    面上项目
  • 资助金额：
    58.00万元
  • 批准年份：
    2021
  • 负责人：
    董春海
  • 依托单位：
    青岛农业大学
帽结合蛋白（cap binding protein）调控乙烯信号转导的分子机制
  • 批准号：
    --
  • 项目类别：
    --
  • 资助金额：
    58万元
  • 批准年份：
    2021
  • 负责人：
    董春海
  • 依托单位：
    青岛农业大学
ID1 (Inhibitor of DNA binding 1) 在口蹄疫病毒感染中作用机制的研究
番茄EIN3-binding F-box蛋白2超表达诱导单性结实和果实成熟异常的机制研究
  • 批准号：
    31372080
  • 项目类别：
    面上项目
  • 资助金额：
    80.0万元
  • 批准年份：
    2013
  • 负责人：
    杨迎伍
  • 依托单位：
    重庆大学