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
基本信息
- 批准号:10269336
- 负责人:
- 金额:$ 62.03万
- 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:2021-08-01 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAcuteAffectAir PollutantsAir PollutionAnti-Inflammatory AgentsAntiinflammatory EffectAreaArrhythmiaAsthmaBiological AssayBlood CirculationCalciumCaliberCardiacCardiac MyocytesCardiopulmonaryCardiotoxicityCardiovascular ModelsCardiovascular systemCell SurvivalCellsChronicCytokine SignalingDevelopmentDisease modelDrug CompoundingEndothelial CellsEnvironmental HealthEthnic OriginExposure toFDA approvedFibroblastsGenderGene ExpressionGenetic VariationHealthHeartHeart DiseasesHumanImmune signalingImmune systemIndividualInflammasomeInflammationInflammatoryInterleukin-1Interleukin-1 betaKnowledgeLungMedicalMitochondriaModelingMolecularMorbidity - disease rateMorphologyMyocardial IschemiaOrganOxidative StressParticulate MatterPathologicPathway interactionsPatientsPeripheral Blood Mononuclear CellPharmaceutical PreparationsPhysiologicalPollutionPreventionRaceRegulationRiskSamplingSerumSignal PathwayStrokeStructureStudy modelsSudden DeathTestingTissue EngineeringTissue ModelTissuesToxic effectWildfireWorld Health Organizationbasebiobankcardiac tissue engineeringcardiovascular risk factorcell typecerebrovascularcohortcytokinedrug discoverydrug testinggenotoxicityhigh throughput screeningimprovedinduced pluripotent stem cellinnovationlung injurymortalitynovelpersonalized medicinepollutantpreventracial diversityrecruitrespiratoryresponsetranscriptome
项目摘要
ABSTRACT: PROJECT 3
Air pollution, particularly particulate matter <2.5µm (PM2.5), penetrates into lung passageways and enters the
bloodstream, causing respiratory, cardiovascular, and cerebrovascular damage. Recent studies suggest that
oxidative stress, genotoxicity, and inflammation to be the central mechanisms by which PM2.5 induced damage.
However, there are still many knowledge gaps of the intricate signal pathways and mechanisms that are involved
in the cellular responses to PM2.5. A better understanding of the molecular and cellular basis of the PM2.5-induced
structural and functional remodeling in human cardiac cells will allow us to develop novel medical approaches
that could prevent or reduce air pollution-related cardiovascular risks. Moreover, by utilizing human samples of
different race, ethnicity, and gender, this study will reveal how genetic variations affect the toxicity response to
PM2.5, further facilitating personalized medicine. In this project, we will use human induced pluripotent stem cells
(iPSCs) and 3-D engineered heart tissues (EHTs) that provide innovative opportunities for disease modeling and
drug discovery. Therefore, our specific aims are to: Aim 1. establish EHT models for the study of air pollution-
related cardiovascular risks from a racially diverse group of individuals; Aim 2. elucidate the pathological
remodelling mechanisms of EHT in response to PM2.5 treatment with functional and omics analysis; and Aim 3.
perform drug testing on EHTs and validate the effects of FDA approved drugs in prevention of air pollution-related
cardiovascular risks.
摘要:项目3
空气污染,特别是<2.5µm的颗粒物(PM2.5),会渗透到肺通道并进入呼吸道。
血液,造成呼吸道,心血管和脑血管损伤。最近的研究表明,
氧化应激、遗传毒性和炎症是PM2.5引起损伤的主要机制。
然而,仍然有许多知识空白的复杂的信号通路和机制,涉及
对PM2.5的细胞反应。更好地了解PM2.5诱导的细胞和分子基础
人类心脏细胞的结构和功能重塑将使我们能够开发新的医疗方法,
可以预防或减少与空气污染相关的心血管风险。此外,通过使用人类样本,
不同的种族,种族和性别,这项研究将揭示遗传变异如何影响毒性反应,
PM2.5,进一步促进个性化医疗。在这个项目中,我们将使用人类诱导多能干细胞
(iPSCs)和3-D工程心脏组织(EHT),为疾病建模和
药物发现因此,我们的具体目标是:目标1。建立用于研究空气污染的EHT模型-
相关的心血管风险从一个种族多样化的群体的个人;目的2。阐明病理
EHT对PM2.5处理的反应性重塑机制,功能和组学分析;和目的3.
对EHT进行药物测试,并验证FDA批准的药物在预防与空气污染有关的
心血管风险。
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:
$ 62.03万 - 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:
$ 62.03万 - 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:
$ 62.03万 - 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:
$ 62.03万 - 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:
$ 62.03万 - 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:
$ 62.03万 - 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:
10677713 - 财政年份:2019
- 资助金额:
$ 62.03万 - 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:
$ 62.03万 - 项目类别:
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