iPSC-CM Modeling to Define Sodium-Calcium Dysfunction in Heart Failure
iPSC-CM 建模定义心力衰竭中的钠钙功能障碍
基本信息
- 批准号:10677713
- 负责人:
- 金额:$ 51.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAnimal ModelArrhythmiaBAG3 geneBiological AssayCalciumCellular MorphologyClinicalComputer ModelsDantroleneDataDilated CardiomyopathyDiseaseDisease susceptibilityDrug TargetingEconomic BurdenElectrophysiology (science)ExhibitsFailureFeedbackFiberFunctional disorderGene ExpressionGenesGenetic HeterogeneityGenetic Predisposition to DiseaseGenetic VariationGenotypeGoalsHeart failureHomeostasisHumanImpairmentIndividualIon ChannelLamin Type ALinkMechanicsModelingMolecularMorbidity - disease rateMuscle CellsMutationNational Heart, Lung, and Blood InstitutePDGFRB genePathogenesisPathway interactionsPatientsPersonsPharmaceutical PreparationsPharmacotherapyPhenotypePositioning AttributeProgram Research Project GrantsPropertyProtocols documentationPublic HealthPumpRecording of previous eventsRegulationRiskRisk ReductionRoleRyR2SeveritiesSignal PathwaySignal TransductionSodiumTestingTreatment EfficacyUnited States National Institutes of HealthVariantbeta-adrenergic receptorcalmodulin-dependent protein kinase IIcarvedilolcausal variantclinically significantdrug response predictioneconomic impactgenome editingheart cellhigh throughput screeninghuman stem cellsimprovedinduced pluripotent stem cellinduced pluripotent stem cell derived cardiomyocytesinhibitorinsightmortalitymulti-electrode arraysnew therapeutic targetnovel therapeuticspatch clamppharmacologicprecision medicineprotein functionresponsestem cell modeltargeted treatmenttherapeutic targettranscriptometranscriptomicsvoltage
项目摘要
Project Summary
Heart failure (HF) continues to have a major clinical and economic burden with stagnation in new therapies
over the past two decades. A significant barrier to improved therapies is the incomplete understanding of the
role of Na+/Ca2+ dysregulation in HF and its contribution to electrical and mechanical dysfunction. Project 1 of
this Program Project Grant (PPG) aims to elucidate the role of Na+/Ca2+ dysregulation in electro-mechanical
dysfunction associated with (HF) using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-
CMs) based modeling. The Project will first phenotype DCM iPSC-CMs from individuals with heterogeneous
causative variants and genome edited controls. Then the role of molecular pathways that regulate Na+/Ca2+
homeostasis will be examined in each of the iPSC-CMs to define major pathways implicated in electro-
mechanical dysfunction and delineate genotype-specific mechanisms within DCM. Drug treatment cellular
responses and gene expression profiles will then be used to define genotype-specific drug responses and
novel drug targets. We are well positioned to achieve the project goals within five years. The ability to define
genotype-based mechanisms and drug treatments within HF is well aligned with NIH and NHLBI goals of
precision medicine models.
项目总结
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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Joseph C. Wu其他文献
Clinical Neurochemical Implications of Sleep Deprivation's Effects on the Anterior Cingulate of Depressed Responders
睡眠剥夺对抑郁反应者前扣带回影响的临床神经化学意义
- DOI:
10.1016/s0893-133x(01)00336-0 - 发表时间:
2001 - 期刊:
- 影响因子:7.6
- 作者:
Joseph C. Wu;M. Buchsbaum;W. Bunney - 通讯作者:
W. Bunney
In Vivo Tomographic Cardiac Imaging: Positron Emission Tomography and Magnetic Resonance Imaging
体内断层心脏成像:正电子发射断层扫描和磁共振成像
- DOI:
10.1002/9781118495148.ch34 - 发表时间:
2013 - 期刊:
- 影响因子:14
- 作者:
B. Huber;P. Nguyen;Joseph C. Wu - 通讯作者:
Joseph C. Wu
Evaluating Gene and Cell Therapy
评估基因和细胞疗法
- DOI:
10.1007/978-0-387-38295-1_25 - 发表时间:
2007 - 期刊:
- 影响因子:4.1
- 作者:
Ahmad Y. Sheikh;Joseph C. Wu - 通讯作者:
Joseph C. Wu
A novel platform device for rodent echocardiography.
一种用于啮齿动物超声心动图的新型平台装置。
- DOI:
10.1093/ilar.49.2.e1 - 发表时间:
2007 - 期刊:
- 影响因子:2.5
- 作者:
I. Kutschka;Ahmad Y. Sheikh;R. Sista;S. Hendry;H. Chun;G. Hoyt;Werner Kutschka;M. Pelletier;T. Quertermous;Joseph C. Wu;R. Robbins - 通讯作者:
R. Robbins
Nanocrown electrodes for reliable and robust intracellular recording of cardiomyocytes and cardiotoxicity screening
纳米冠电极用于可靠、稳健的心肌细胞内记录和心脏毒性筛查
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
Z. Jahed;Yang Yang;Ching;Ethan P. Foster;Allister F. McGuire;Huaxiao Yang;Aofei Liu;Csaba Forró;Zenguang Yan;Xinghong Jiang;Ming;Wei Zhang;Xiao Li;Thomas L. Li;Annalisa Pawlosky;Joseph C. Wu;B. Cui - 通讯作者:
B. Cui
Joseph C. Wu的其他文献
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{{ truncateString('Joseph C. Wu', 18)}}的其他基金
Modeling Cardiovascular Risks of Air Pollutants with Human Induced Pluripotent Stem Cell-Derived Cardiovascular-Associated Cells (Project 3) for the Air pollution disrupts Inflammasome Regulation in
使用人类诱导多能干细胞衍生的心血管相关细胞(项目 3)模拟空气污染物的心血管风险,以了解空气污染扰乱炎症体调节的情况
- 批准号:
10460332 - 财政年份:2021
- 资助金额:
$ 51.4万 - 项目类别:
Modeling Cardiovascular Risks of Air Pollutants with Human Induced Pluripotent Stem Cell-Derived Cardiovascular-Associated Cells (Project 3) for the Air pollution disrupts Inflammasome Regulation in
使用人类诱导多能干细胞衍生的心血管相关细胞(项目 3)模拟空气污染物的心血管风险,以了解空气污染扰乱炎症体调节的情况
- 批准号:
10269336 - 财政年份:2021
- 资助金额:
$ 51.4万 - 项目类别:
Human iPSC Model for Elucidating Crosstalk Signaling and Secretomes: Down Syndrome Administrative Supplement
用于阐明串扰信号和分泌组的人类 iPSC 模型:唐氏综合症行政补充
- 批准号:
9897087 - 财政年份:2019
- 资助金额:
$ 51.4万 - 项目类别:
Elucidating Electro-Mechanical Dysfunction in Heart Failure with Human Stem Cell Models
用人类干细胞模型阐明心力衰竭中的机电功能障碍
- 批准号:
10471335 - 财政年份:2019
- 资助金额:
$ 51.4万 - 项目类别:
iPSC-CM Modeling to Define Sodium-Calcium Dysfunction in Heart Failure
iPSC-CM 建模定义心力衰竭中的钠钙功能障碍
- 批准号:
10471338 - 财政年份:2019
- 资助金额:
$ 51.4万 - 项目类别:
Elucidating Electro-Mechanical Dysfunction in Heart Failure with Human Stem Cell Models
用人类干细胞模型阐明心力衰竭中的机电功能障碍
- 批准号:
10006331 - 财政年份:2019
- 资助金额:
$ 51.4万 - 项目类别:
iPSC-CM Modeling to Define Sodium-Calcium Dysfunction in Heart Failure
iPSC-CM 建模定义心力衰竭中的钠钙功能障碍
- 批准号:
10249147 - 财政年份:2019
- 资助金额:
$ 51.4万 - 项目类别:
iPSC-CM Modeling to Define Sodium-Calcium Dysfunction in Heart Failure
iPSC-CM 建模定义心力衰竭中的钠钙功能障碍
- 批准号:
10006340 - 财政年份:2019
- 资助金额:
$ 51.4万 - 项目类别:
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