Center for Cellular Metabolism Research in Oklahoma
俄克拉荷马州细胞代谢研究中心
基本信息
- 批准号:10853688
- 负责人:
- 金额:$ 57.17万
- 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:2021-02-05 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AcetylationAction PotentialsAreaArrhythmiaAwardBiological AssayBlood VesselsCalciumCalcium SignalingCardiacCardiac MyocytesCellsCenters of Research ExcellenceCollaborationsComplexConsciousCouplingDataDefectDelawareDiabetes MellitusDisease ProgressionEFRACElectrocardiogramEventFibroblastsFoundationsFunctional disorderGenesGeometryGlucoseGoalsGrantHeartHeart AtriumHeart DiseasesHeart failureImpairmentIncidenceIsoproterenolKineticsLaboratoriesLaboratory StudyLeftLinkLipidsMalignant - descriptorMapsMeasuresMedicalMetabolicMetabolismMitochondriaMolecularMorphologyMusNeuronsObesityOklahomaOsmosisOxidation-ReductionParentsPatientsPatternPerfusionPhenotypePilot ProjectsPredispositionProteinsPumpResearchResearch Project GrantsResearch SupportResourcesRiskRisk FactorsRoleSedation procedureSeriesSignal TransductionSodium-Calcium ExchangerStressStress TestsStrokeSudden DeathSurfaceSystemTelemetryTestingTissuesTrainingTranscriptUniversitiesVentricularVentricular Arrhythmiaaqueouscalmodulin-dependent protein kinase IIcell typecellular targetingdesigndiabetic cardiomyopathyexperienceexperimental studyheart metabolismhypertensivein vivoinduced pluripotent stem celllive cell imagingmetabolic phenotypemetabolomicsmitochondrial dysfunctionmitochondrial metabolismmouse modelnew therapeutic targetnovelprogramssudden cardiac deathtranscriptomicsuptake
项目摘要
The goal of the parent COBRE award (P20GM139763) is to support research project leaders (RPL) to
scientific independence in area of cellular metabolism by creating and unifying resources under the COBRE-
supported Center of Cellular Metabolism Research in Oklahoma (CMRO). Dr. Chi Fung Lee has been
supported by the CMRO-COBRE as a RPL. The Lee lab has created a research program that investigates
how metabolism regulates heart disease progression. With the current COBRE support, the Lee lab is
examining mechanisms by which mitochondrial dysfunction and NAD+ redox imbalance promotes diabetic
cardiomyopathy. Patients with heart disease are associated with arrhythmias, which increase risks of patients
to heart failure, stroke and sudden death. In this supplement award, the Lee lab seeks support to continue a
collaboration with the Lam Lab at the University of Delaware on cardiac electrical/calcium signaling, and to
together examine the mechanistic roles of mitochondrial dysfunction and metabolism in arrhythmogenesis.
We aim to examine how mitochondrial metabolism regulates electrical/calcium signals to promote
arrhythmias, a hypothesis that has not been rigorously and directly tested. Dr. Chi Keung Lam was well-trained
in laboratories studying electrical/calcium signaling in mouse models and using induced pluripotent stem cell
platforms to identify mechanisms of arrhythmias. Our pilot data using cardiac-specific mitochondrial
dysfunction mice (Ndufs4-cKO) showed that mitochondrial dysfunction increases susceptibility of hearts to
arrhythmias and promotes sudden death. We found that calcium signaling is altered in cardiomyocytes isolated
from the arrhythmic Ndufs4-cKO hearts. In this supplement award, we plan to thoroughly characterize changes
in mitochondrial function and metabolism, and electrical/calcium signaling in these arrhythmias hearts.
To understand how mitochondrial dysfunction promotes atrial and ventricular arrhythmic events, we will
dissect spatial-specific changes (atrial and ventricular) using state-of-the-art electrical mapping (eMapping) of
the arrhythmic Ndufs4-cKO hearts available to the Lam lab. Spatial transcriptomic and metabolomic analyses
targeting cellular and mitochondrial metabolism will be used, available to the Lee lab. By coupling the expertise
of electrical/calcium signaling (Lam lab) and metabolism (Lee lab), this series of experiments will provide
important mechanistic targets to be further explored linking mitochondrial dysfunction to arrhythmias. Our
long-term goal is to apply for a multi-PIs R01 grant that dissects detailed molecular mechanisms how
mitochondrial metabolism regulates electrical/calcium signaling in arrhythmias. Our pilot data already support
one of the possible mechanisms in related to NAD+-dependent metabolic signaling altered by mitochondrial
dysfunction to deregulate calcium handling proteins (e.g. CaMKII acetylation). The complementary expertise
in the Lee and Lam labs will have synergistic effects in developing our young research programs and
understanding novel mechanisms of arrhythmias.
父母柯布尔奖(P20GM139763)的目标是支持研究项目负责人(RPL)
通过在卵石下创造和统一资源,在细胞代谢领域的科学独立性
俄克拉荷马州(CMRO)的细胞代谢研究支持中心。 Chi Fung Lee博士一直是
由Cmro-Cobre支持作为RPL。 Lee Lab创建了一个研究计划,调查
新陈代谢如何调节心脏病的进展。有了当前的毛线支撑,Lee Lab是
检查线粒体功能障碍和NAD+氧化还原不平衡的机制可促进糖尿病
心肌病。心脏病患者与心律不齐有关,这会增加患者的风险
心力衰竭,中风和猝死。在此补充奖中,Lee Lab寻求支持以继续
在特拉华大学与心脏电气/钙信号的LAM实验室合作,并
共同研究线粒体功能障碍和代谢在心律失常发生中的机械作用。
我们旨在研究线粒体代谢如何调节电/钙信号以促进
心律不齐,这是一个尚未经过严格和直接检验的假设。 Chi Keung Lam博士训练有素
在研究小鼠模型中的电气/钙信号转导并使用诱导多能干细胞中的实验室中
识别心律不齐的机制的平台。我们使用心脏特异性线粒体的飞行员数据
功能障碍小鼠(NDUFS4-CKO)表明,线粒体功能障碍会增加心脏对心脏的敏感性
心律不齐并促进猝死。我们发现钙信号在分离的心肌细胞中发生了改变
来自心律不齐的NDUFS4-CKO心。在此补充奖中,我们计划彻底表征变化
在线粒体功能和代谢中,以及这些心律不齐心脏中的电气/钙信号传导。
要了解线粒体功能障碍如何促进心房心律不齐事件,我们将
使用最先进的电气映射(Emapping)的解剖空间特异性变化(心房和心室)
LAM实验室可用的心律失常NDUFS4-CKO心脏。空间转录组和代谢组分析
将使用靶向细胞和线粒体代谢,可用于Lee Lab。通过耦合专业知识
电气/钙信号传导(LAM LAB)和代谢(Lee Lab),这一系列实验将提供
要进一步探索的重要机械目标,将线粒体功能障碍与心律不齐联系起来。我们的
长期目标是申请多PIS R01赠款,该赠款剖析了详细的分子机制
线粒体代谢调节心律不齐的电/钙信号传导。我们的飞行员数据已经支持
与线粒体改变了与NAD+依赖性的代谢信号有关的可能机制之一
失调钙处理蛋白的功能障碍(例如,CAMKII乙酰化)。补充专业知识
在Lee和Lam Labs中,将对我们的年轻研究计划和
了解心律不齐的新机制。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
SARM1 NAD Hydrolase Deficiency Normalizes Fibrosis and Ameliorates Cardiac Dysfunction in Diabetic Hearts.
SARM1 NAD 水解酶缺乏可使糖尿病心脏的纤维化正常化并改善心脏功能障碍。
- DOI:
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:Lee,ChiFung;Nizami,Hina;Gu,Haiwei;Light,Christine
- 通讯作者:Light,Christine
Sexually dimorphic effects of SARM1 deletion on cardiac NAD+ metabolism and function.
SARM1 缺失对心脏 NAD 代谢和功能的性别二态性影响。
- DOI:10.1152/ajpheart.00370.2022
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:Nizami,HinaLateef;Minor,KeatonE;Chiao,YingAnn;Light,ChristineM;Lee,ChiFung
- 通讯作者:Lee,ChiFung
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Lijun Xia其他文献
Lijun Xia的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Lijun Xia', 18)}}的其他基金
Center for Cellular Metabolism Research in Oklahoma
俄克拉荷马州细胞代谢研究中心
- 批准号:
10797920 - 财政年份:2021
- 资助金额:
$ 57.17万 - 项目类别:
Center for Cellular Metabolism Research in Oklahoma
俄克拉荷马州细胞代谢研究中心
- 批准号:
10399960 - 财政年份:2021
- 资助金额:
$ 57.17万 - 项目类别:
Center for Cellular Metabolism Research in Oklahoma
俄克拉荷马州细胞代谢研究中心
- 批准号:
10571889 - 财政年份:2021
- 资助金额:
$ 57.17万 - 项目类别:
Center for Cellular Metabolism Research in Oklahoma
俄克拉荷马州细胞代谢研究中心
- 批准号:
10339346 - 财政年份:2021
- 资助金额:
$ 57.17万 - 项目类别:
Center for Cellular Metabolism Research in Oklahoma
俄克拉荷马州细胞代谢研究中心
- 批准号:
10090975 - 财政年份:2021
- 资助金额:
$ 57.17万 - 项目类别:
Site-1 protease-mediated lipid metabolism in lymphatic vascular development
位点 1 蛋白酶介导的淋巴血管发育中的脂质代谢
- 批准号:
10400114 - 财政年份:2020
- 资助金额:
$ 57.17万 - 项目类别:
Site-1 protease-mediated lipid metabolism in lymphatic vascular development
位点 1 蛋白酶介导的淋巴管发育中的脂质代谢
- 批准号:
10629188 - 财政年份:2020
- 资助金额:
$ 57.17万 - 项目类别:
相似国自然基金
神经系统中动作电位双稳传导研究
- 批准号:12375033
- 批准年份:2023
- 资助金额:52 万元
- 项目类别:面上项目
与痛觉相关的动作电位传导失败的动力学与调控机制
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
与痛觉相关的动作电位传导失败的动力学与调控机制
- 批准号:12202147
- 批准年份:2022
- 资助金额:30.00 万元
- 项目类别:青年科学基金项目
神经元离子通道-动作电位-量子化分泌关系研究
- 批准号:31930061
- 批准年份:2019
- 资助金额:303 万元
- 项目类别:重点项目
仿生味觉自适应柔性纳米电极阵列构建研究
- 批准号:61901469
- 批准年份:2019
- 资助金额:24.5 万元
- 项目类别:青年科学基金项目
相似海外基金
Characterizing the functional heterogeneity of the mouse paralaminar nucleus
表征小鼠板旁核的功能异质性
- 批准号:
10678525 - 财政年份:2023
- 资助金额:
$ 57.17万 - 项目类别:
Spatial and Single Cell Transcriptomics Approach to Understand Neuron-Oligodendrocyte Communication in Human Synaptic Development
了解人类突触发育中神经元-少突胶质细胞通讯的空间和单细胞转录组学方法
- 批准号:
10646970 - 财政年份:2023
- 资助金额:
$ 57.17万 - 项目类别:
Cellular Basis for Autonomic Regulation of Cardiac Arrhythmias
心律失常自主调节的细胞基础
- 批准号:
10627578 - 财政年份:2023
- 资助金额:
$ 57.17万 - 项目类别:
An Autonomous Rapidly Adaptive Multiphoton Microscope for Neural Recording and Stimulation
用于神经记录和刺激的自主快速自适应多光子显微镜
- 批准号:
10739050 - 财政年份:2023
- 资助金额:
$ 57.17万 - 项目类别: