Diversity Supplement Denzel Deo Omengan
多样性补充剂 Denzel Deo Omengan
基本信息
- 批准号:10381108
- 负责人:
- 金额:$ 3.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdultAnimalsAreaArrhythmiaAutomobile DrivingBasal metabolic rateBiogenesisBiological AssayBiologyBirthCardiacCardiac MyocytesCell CycleCell Cycle ArrestCell Cycle RegulationCessation of lifeChemicalsCicatrixCytokinesisDNA biosynthesisDataDevelopmentDiploidyDown-RegulationEndocrine systemEvolutionFamily DasypodidaeGene Expression RegulationGenesGeneticGrowthHeartHeart BlockHigh PrevalenceLifeMammalsMetabolic PathwayMitochondriaMole RatsMolecularMononuclearMusMuscle CellsMutant Strains MiceMyocardial InfarctionMyrmecophagidaeNatural regenerationNeonatalNewborn InfantNewtsNuclear Hormone ReceptorsOrganOrganismOxidative StressPathway interactionsPatientsPerinatalPharmacologyPhylogenetic AnalysisPhylogenyPhysiologicalPloidiesProcessRattusReactive Oxygen SpeciesReceptor ActivationRegenerative capacityReportingResearchRoleSignal TransductionSourceSpiny AnteaterStimulusTestingThyroid Function TestsThyroid HormonesThyroxineTissuesUp-RegulationVertebratesWorkZebrafishbasecardiac regenerationcardiogenesiscomparativeexperimental studyfallsfunctional improvementhemodynamicshormonal signalshormone deficiencyin vivoischemic injuryloss of functionmouse modelmyocardial injuryneonatal micenovelparent grantpostnatalpreservationregeneration potentialregenerativetooltranscriptometranscriptome sequencing
项目摘要
Project Summary/Abstract
Most adult mammalian tissues and organs have very limited regenerative potential. In patients with a heart
attack, the death and loss of heart muscle cells is irreversible and often results in permanent scarring and
potentially life-threatening arrhythmias. In contrast, neonatal mice and adult zebrafish are able to rapidly
regenerate their hearts. Genetic lineage-tracing experiments have revealed proliferation of pre-existing
cardiomyocytes as the dominant mechanism to generate new muscle cells. However shortly after birth, the
majority of cardiomyocytes in most mammalian species undergoes a last round of DNA replication without
cytokinesis, become binucleated, and withdraw from the cell cycle. What physiological signals trigger
mammalian cardiomyocyte perinatal binucleation and cell cycle arrest, and how these stimuli are differentially
regulated in animals with distinct cardiac regenerative potentials are among the most long-standing questions in
cardiomyocyte biology. Our preliminary observations from comparative analyses of cardiomyocytes across
phylogeny, in vivo chemical screens of candidate pathways, together with functional studies in both mice and
zebrafish suggest a critical role of the perinatal changes of endocrine systems in driving cardiomyocyte
proliferative and regenerative potential loss in the mammalian heart. In this proposal, we plan to combine a
novel cardiomyocyte quantification assay with state-of-art genetic tools to investigate the functions of nuclear
hormone receptor activation in regulating cardiomyocyte proliferation during postnatal growth (Aim 1) and heart
regeneration following myocardial injury (Aim 2). In addition, we will examine the underpinning cellular and
molecular basis, and determine the function of novel downstream target genes in cardiomyocyte cell cycle
control through gain- and loss-of-function approaches (Aim 3). Successful completion of the proposed work will
thus reveal mechanisms underlying the loss of cardiomyocyte regenerative potential in ontogeny and
phylogeny.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Guo Huang的其他文献
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{{ truncateString('Guo Huang', 18)}}的其他基金
Genetic circuitry governing heart growth and repair
控制心脏生长和修复的遗传电路
- 批准号:
10565925 - 财政年份:2022
- 资助金额:
$ 3.86万 - 项目类别:
Genetic circuitry governing heart growth and repair
控制心脏生长和修复的遗传电路
- 批准号:
10770716 - 财政年份:2022
- 资助金额:
$ 3.86万 - 项目类别:
Genetic circuitry governing heart growth and repair
控制心脏生长和修复的遗传电路
- 批准号:
10340058 - 财政年份:2022
- 资助金额:
$ 3.86万 - 项目类别:
Molecular control of cardiac regenerative potential
心脏再生潜力的分子控制
- 批准号:
10512418 - 财政年份:2017
- 资助金额:
$ 3.86万 - 项目类别:
Molecular control of cardiac regenerative potential
心脏再生潜力的分子控制
- 批准号:
10518101 - 财政年份:2017
- 资助金额:
$ 3.86万 - 项目类别:
Molecular control of cardiac regenerative potential
心脏再生潜力的分子控制
- 批准号:
10308456 - 财政年份:2017
- 资助金额:
$ 3.86万 - 项目类别:
Retinoic Acid Signaling in Heart Development and Regeneration
心脏发育和再生中的视黄酸信号传导
- 批准号:
8523967 - 财政年份:2012
- 资助金额:
$ 3.86万 - 项目类别:
Retinoic Acid Signaling in Heart Development and Regeneration
心脏发育和再生中的视黄酸信号传导
- 批准号:
8353358 - 财政年份:2012
- 资助金额:
$ 3.86万 - 项目类别:
Retinoic Acid Signaling in Heart Development and Regeneration
心脏发育和再生中的视黄酸信号传导
- 批准号:
9031130 - 财政年份:2012
- 资助金额:
$ 3.86万 - 项目类别:
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