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COBRE奖(P20GM139763)的目标是支持研究项目负责人(RPL)
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)