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.
COBRE奖(P20 GM 139763)的目标是支持研究项目领导者(RPL),
通过在COBRE下创建和统一资源,在细胞代谢领域实现科学独立性-
支持的俄克拉荷马州细胞代谢研究中心(CMRO)。李志凤医生
由CMRO-COBRE作为RPL支持。李实验室创建了一个研究项目,
代谢如何调节心脏病的进展在目前的COBRE支持下,Lee实验室
研究线粒体功能障碍和NAD+氧化还原失衡促进糖尿病的机制
心肌病心脏病患者与心律失常有关,这增加了患者的风险
心力衰竭中风和猝死在这个补充奖,李实验室寻求支持,继续
与特拉华州大学的Lam实验室合作研究心脏电/钙信号,
一起研究线粒体功能障碍和代谢在肿瘤发生中的机制作用。
我们的目标是研究线粒体代谢如何调节电/钙信号,以促进
心律失常,这一假设尚未得到严格和直接的检验。林志强医生训练有素,
在实验室中研究小鼠模型中的电/钙信号,并使用诱导多能干细胞
识别心律失常机制的平台。我们的试验数据使用心脏特异性线粒体
功能障碍小鼠(Ndufs 4-cKO)显示,线粒体功能障碍增加了心脏对
心律失常,并促进猝死。我们发现,在分离的心肌细胞中,
从心脏移植的Ndufs 4-cKO。在这个补充奖,我们计划彻底表征变化
线粒体功能和代谢,以及这些心律失常心脏中的电/钙信号。
为了了解线粒体功能障碍是如何促进心房和心室心肌事件的,我们将
使用最先进的电标测(eMapping)分析空间特异性变化(心房和心室),
Lam实验室可以获得的Ndufs 4-cKO心脏。空间转录组学和代谢组学分析
靶向细胞和线粒体代谢将被使用,可用于李实验室。通过将专业知识
电/钙信号(Lam实验室)和代谢(Lee实验室),这一系列实验将提供
将线粒体功能障碍与心律失常联系起来的重要机制靶点有待进一步探索。我们
长期目标是申请一个多PI R 01资助,剖析详细的分子机制,如何
线粒体代谢调节心律失常中的电/钙信号传导。我们的试点数据已经支持
线粒体改变NAD+依赖的代谢信号的可能机制之一是,
钙处理蛋白(如CaMKII乙酰化)失调的功能障碍。互补的专业知识
在李和林实验室将有协同效应,在发展我们的年轻的研究计划,
了解心律失常的新机制。
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:
相似海外基金
Kilohertz volumetric imaging of neuronal action potentials in awake behaving mice
清醒行为小鼠神经元动作电位的千赫兹体积成像
- 批准号:
10515267 - 财政年份:2022
- 资助金额:
$ 57.17万 - 项目类别:
Signal processing in horizontal cells of the mammalian retina – coding of visual information by calcium and sodium action potentials
哺乳动物视网膜水平细胞的信号处理 â 通过钙和钠动作电位编码视觉信息
- 批准号:
422915148 - 财政年份:2019
- 资助金额:
$ 57.17万 - 项目类别:
Research Grants
CAREER: Resolving action potentials and high-density neural signals from the surface of the brain
职业:解析来自大脑表面的动作电位和高密度神经信号
- 批准号:
1752274 - 财政年份:2018
- 资助金额:
$ 57.17万 - 项目类别:
Continuing Grant
Development of Nanosheet-Based Wireless Probes for Multi-Simultaneous Monitoring of Action Potentials and Neurotransmitters
开发基于纳米片的无线探针,用于同时监测动作电位和神经递质
- 批准号:
18H03539 - 财政年份:2018
- 资助金额:
$ 57.17万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Population Imaging of Action Potentials by Novel Two-Photon Microscopes and Genetically Encoded Voltage Indicators
通过新型双光子显微镜和基因编码电压指示器对动作电位进行群体成像
- 批准号:
9588470 - 财政年份:2018
- 资助金额:
$ 57.17万 - 项目类别:
Enhanced quantitative imaging of compound action potentials in multi-fascicular peripheral nerve with fast neural Electrical Impedance Tomography enabled by 3D multi-plane softening bioelectronics
通过 3D 多平面软化生物电子学实现快速神经电阻抗断层扫描,增强多束周围神经复合动作电位的定量成像
- 批准号:
10009724 - 财政年份:2018
- 资助金额:
$ 57.17万 - 项目类别:
Enhanced quantitative imaging of compound action potentials in multi-fascicular peripheral nerve with fast neural Electrical Impedance Tomography enabled by 3D multi-plane softening bioelectronics
通过 3D 多平面软化生物电子学实现快速神经电阻抗断层扫描,增强多束周围神经复合动作电位的定量成像
- 批准号:
10467225 - 财政年份:2018
- 资助金额:
$ 57.17万 - 项目类别:
Fast high-resolution deep photoacoustic tomography of action potentials in brains
大脑动作电位的快速高分辨率深度光声断层扫描
- 批准号:
9423398 - 财政年份:2017
- 资助金额:
$ 57.17万 - 项目类别:
NeuroGrid: a scalable system for large-scale recording of action potentials from the brain surface
NeuroGrid:用于大规模记录大脑表面动作电位的可扩展系统
- 批准号:
9357409 - 财政年份:2016
- 资助金额:
$ 57.17万 - 项目类别:
Noval regulatory mechanisms of axonal action potentials
轴突动作电位的新调节机制
- 批准号:
16K07006 - 财政年份:2016
- 资助金额:
$ 57.17万 - 项目类别:
Grant-in-Aid for Scientific Research (C)