Genetic dissection of Cardiac Conduction System homeostasis and regeneration
心脏传导系统稳态和再生的基因剖析
基本信息
- 批准号:10084306
- 负责人:
- 金额:$ 35.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-15 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAdultAgingAntibodiesArrhythmiaBioinformaticsBiological AssayCalciumCalcium ionCardiac Function StudyCardiac MyocytesCardiac ablationCardiac conduction systemCardiac developmentCardiovascular DiseasesCause of DeathCell DeathCell physiologyCellsCessation of lifeChIP-seqDataDefectDevelopmentDissectionDrug toxicityElectrophysiology (science)Expression ProfilingFibrosisFunctional disorderGene ExpressionGenesGeneticGenetic TranscriptionGoalsHeartHeart ContractilitiesHeart DiseasesHistologyHomeostasisHumanHypertrophyImmunofluorescence ImmunologicImpairmentIn VitroInfarctionInheritedInjuryKnock-inLuciferasesMethodsMicroRNAsMolecularMorbidity - disease rateMusMutationMyocardial InfarctionMyocardial IschemiaMyocardial dysfunctionNatural regenerationOrgan SizePathologicPathway interactionsPatientsPeriodicityPhosphotransferasesRNA SequencesRegulationReporterRepressionRoleRyR2Ryanodine Receptor Calcium Release ChannelSamplingSignal TransductionSyndromeTechniquesTestingTissuesToxic effectdiphtheria toxin fragment Again of functiongenome-wideheart functionheart rhythmin vivoinsightmortalitynoveloverexpressiontargeted treatment
项目摘要
Abstract
Genetic dissection of Cardiac Conduction System homeostasis and regeneration
The cardiac conduction system (CCS) is required for initiating and maintaining regular rhythmic heartbeats.
CCS defects commonly give rise to arrhythmia, a leading cause of morbidity and death worldwide. CCS
dysfunction can be inherited or acquired due to conditions such as drug toxicity or myocardial infarction. It is
imperative to elucidate the molecular mechanisms underlying CCS homeostasis to facilitate development of
cardiac therapies. Importantly, these mechanisms are poorly understood owing to numerous technical
challenges. Hippo signaling, a pivotal organ size control pathway, inhibits cardiomyocyte proliferation and
regeneration. However, the role of Hippo signaling in the CCS is unclear. Here we will determine whether Hippo
signaling regulates CCS homeostasis. Additionally, we will identify regulators and targets of Hippo signaling in
the CCS. Our preliminary observations revealed that disruption of Hippo signaling in the CCS caused cardiac
arrhythmias in mice, suggesting an important role of Hippo signaling in CCS homeostasis. Notably, deletion of
Hippo signaling rescued cardiac rhythm and function after CCS cell ablation, suggesting that repression of Hippo
signaling protects the CCS from damage. In addition, we identified candidate microRNA regulators and
downstream targets of Hippo signaling. Here we propose to investigate the function and molecular regulatory
mechanism of Hippo signaling in the CCS through in the following specific aims: 1) To define Hippo signaling
function in CCS homeostasis and elucidate the mechanism by which repression of Hippo signaling protects the
CCS from damage, 2) Identify upstream microRNA regulators of Hippo signaling in the CCS, and 3) Identify
downstream targets of the Hippo pathway that modulate CCS function.
摘要
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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Jun Wang其他文献
Spiking Neural Systems with Weights
带权重的尖峰神经系统
- DOI:
- 发表时间:
- 期刊:
- 影响因子:2.9
- 作者:
Jun Wang;Hendrik Jan Hoogeboom;Gheorghe Paun;Linqiang Pan - 通讯作者:
Linqiang Pan
Jun Wang的其他文献
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