Unique Domain Features of GRK2 and Roles in Cardiovascular Disease
GRK2 的独特结构域特征及其在心血管疾病中的作用
基本信息
- 批准号:9899299
- 负责人:
- 金额:$ 24.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-15 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:ADRBK1 geneAcuteAgonistAmericanAtrial FibrillationAwardBindingBinding ProteinsBinding SitesCardiacCardiac developmentCardiovascular DiseasesCardiovascular systemCause of DeathCell Surface ReceptorsCellular biologyChronicComplexCoronary arteryDataDevelopmentDiseaseDisease ProgressionElementsEvaluationFacultyG protein coupled receptor kinaseG-Protein-Coupled ReceptorsGene Transduction AgentGoalsHeartHeart DiseasesHeart HypertrophyHeart InjuriesHeart failureHumanHypertensionHypertrophyImmunohistochemistryIn VitroInfarctionInjuryInterventionInvestigationLeadLeftLeft Ventricular RemodelingLengthLigationLinkMeasuresMediatingModelingMolecularMusMuscle CellsMyocardial InfarctionN-terminalPathway interactionsPatientsPeptidesPharmacologic SubstancePhasePhosphorylationPhysiologicalPhysiologyPlayPositioning AttributeProteinsProteomicsRGS DomainRegulationResearchResourcesRoleSignal PathwaySignal TransductionStructureTechniquesTestingTherapeuticTherapeutic InterventionTimeTrainingTransgenic MiceTransgenic OrganismsUnited States National Institutes of HealthUp-RegulationVentricularVoltage-Gated Potassium ChannelWorkcardiogenesiscareercomorbidityconstrictionexperimental studyfunctional restorationgain of functiongene therapyheart functionheart preservationimmunocytochemistryimprovedin vivoin vivo evaluationinsightischemic injurymouse modelnew therapeutic targetnovelpressurepreventprotein protein interactionprotein transportreceptorreduce symptomsresearch facilityresponsetenure tracktherapeutic developmenttherapeutic targettooltraffickingvector
项目摘要
PROJECT SUMMARY/ABSTRACT
For the past 10 years my scientific career has been devoted to translational cardiovascular research. My
doctoral studies investigated the role of the voltage-gated potassium channel Kv1.5 as a potential therapeutic
target atrial fibrillation. These studies had a strong cell biology focus, determining the mechanisms underlying
channel trafficking and regulation and how these were altered by pharmaceutical intervention. A goal in joining
the Koch lab for my postdoctoral studies was to broaden my understanding of cardiovascular disease
progression within the context of in vivo studies, with a greater focus on therapeutic interventions for human
heart failure (HF). Preliminary data generated for the current proposal shows that both the amino(N)-terminal
RGS (Regulator of G-protein Signaling) domain of GRK2 (aa 45-185, βARKrgs) and a shorter N-terminal
peptide of GRK2 (aa 45-185, βARKnt) can alter cardiac physiology when expressed in myocytes. Of note,
these two peptides both appear to halt HF progression in mice after pressure-overload but have differential
effects on the initial hypertrophic response. The K99 portion of this proposal will focus on whether βARKrgs
and βARKnt can act therapeutically to reverse left-ventricular (LV) remodeling after cardiac injury. These
studies will begin with an evaluation of the in vivo efficacy of βARKrgs or βARKnt gene-therapy to reverse
adaptive hypertrophy acutely or restore function during chronic pressure overload. In addition, I will continue to
practice the murine myocardial infarction (MI) model under the guidance of Dr. Erhe Gao. During the R00
phase of this proposal I will use the cardiac-restricted transgenic βARKrgs and βARKnt mice and my newly-
developed gene therapy vectors to determine whether these peptides prevent adverse remodeling post-MI.
During the K99 phase I will also use proteomic approaches to identify specific binding partners for βARKrgs
and βARKnt in vivo, compared to full-length GRK2, and whether these binding interactions are altered after
cardiac injury or upon agonist stimulation. For these studies I will work closely with Dr. Salim Merali, Director of
the Proteomics Research Facility at Temple, to gain invaluable insight and training in the proper execution and
evaluation of proteomic analysis. In these studies βARKrgs and βARKnt will serve as powerful tools to dissect
the specific domains within the N-terminus of GRK2 responsible for protein interactions and the role they play
in the regulation of cardiovascular cell signaling. Novel protein interactions discovered in this project will
provide new avenues for independent research. A focus of the R00 phase will be to narrow down and pursue
the protein binding partners that represent key elements of cardiac signaling or potential therapeutic targets for
improving cardiac structure and function in disease. Support through the NIH Pathway to Independent
K99/R00 award would provide the necessary time and resources for achieving these important research goals,
and continuing my personal development toward my overall goal of obtaining a tenure-track faculty position.
项目总结/文摘
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
Sarah Marie Bass其他文献
Sarah Marie Bass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('Sarah Marie Bass', 18)}}的其他基金
AS160 as a nodal regulator of the cardiac response to metabolic stress
AS160 作为心脏对代谢应激反应的节点调节剂
- 批准号:
10518319 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别:
AS160 as a nodal regulator of the cardiac response to metabolic stress
AS160 作为心脏对代谢应激反应的节点调节器
- 批准号:
10674917 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别:
Unique Domain Features of GRK2 and Roles in Cardiovascular Disease
GRK2 的独特结构域特征及其在心血管疾病中的作用
- 批准号:
9332419 - 财政年份:2016
- 资助金额:
$ 24.9万 - 项目类别:
相似海外基金
Elucidation of acute poisoning mechanism due to abuse of CB1 receptor agonist.
阐明滥用 CB1 受体激动剂引起的急性中毒机制。
- 批准号:
21K17323 - 财政年份:2021
- 资助金额:
$ 24.9万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of acute poisoning mechanism due to abuse of CB1 receptor agonist.
阐明滥用 CB1 受体激动剂引起的急性中毒机制。
- 批准号:
19K19485 - 财政年份:2019
- 资助金额:
$ 24.9万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Tissue repair effect in acute myocardial infarction through mobilization of endogenous Muse cells by sphingosine-1-phosphate receptor 2 agonist
1-磷酸鞘氨醇受体2激动剂动员内源性Muse细胞对急性心肌梗死的组织修复作用
- 批准号:
18K15843 - 财政年份:2018
- 资助金额:
$ 24.9万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6115624 - 财政年份:1998
- 资助金额:
$ 24.9万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6219539 - 财政年份:1998
- 资助金额:
$ 24.9万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6276858 - 财政年份:1997
- 资助金额:
$ 24.9万 - 项目类别:
ACUTE CHRONIC HORMONAL CHANGES WITH LHRH-AGONIST THERAPY
LHRH 激动剂治疗引起的急性慢性荷尔蒙变化
- 批准号:
6250152 - 财政年份:1997
- 资助金额:
$ 24.9万 - 项目类别:
ACUTE CHRONIC HORMONAL CHANGES WITH LHRH-AGONIST THERAPY
LHRH 激动剂治疗引起的急性慢性荷尔蒙变化
- 批准号:
6279945 - 财政年份:1997
- 资助金额:
$ 24.9万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6246787 - 财政年份:1997
- 资助金额:
$ 24.9万 - 项目类别:
PSYCHOPHARMACOLOGY OF DA AGONIST CNS EFFECTS: ACUTE AND CHRONIC STUDIES
DA 激动剂中枢神经系统影响的精神药理学:急性和慢性研究
- 批准号:
3891471 - 财政年份:
- 资助金额:
$ 24.9万 - 项目类别:














{{item.name}}会员




