Molecular and Cellular Mechanisms of Neonatal Cardiac Development and Repair
新生儿心脏发育和修复的分子和细胞机制
基本信息
- 批准号:9024262
- 负责人:
- 金额:$ 10.25万
- 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:2016-01-15 至 2017-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAnimalsBiological AssayBiologyBiomedical EngineeringBirthCardiacCardiac MyocytesCardiac developmentCardiovascular PhysiologyCellsCellular biologyCessation of lifeCollagenCongenital Heart DefectsDataDevelopmentDevicesDiseaseEmbryoEmbryonic DevelopmentEngineeringEtiologyFamily suidaeGoalsGrowthHealedHeartHeart AbnormalitiesHeart DiseasesHeart InjuriesImageIn VitroInfantInfarctionInjuryLifeMEKsMediatingMediator of activation proteinMentorsMolecularMolecular and Cellular BiologyMusMuscle CellsMyocardialMyocardial InfarctionMyocardial IschemiaMyocardiumNatural regenerationNeonatalOperative Surgical ProceduresOutcomePhysiologicalPopulationPopulation SizesProcessProliferatingPropertyRecruitment ActivityRegenerative responseRegulationReporterResearchResearch PersonnelRoleScientistSignal PathwaySignal TransductionSiteStagingStem cellsStructureTestingTherapeuticTherapeutic InterventionTissuesTrainingTransforming Growth Factor betaTransgenic MiceWorkbasecardiac regenerationcardiac repaircardiogenesiscareercareer developmentfetalgenome-widehealingimprovedin vivoinjuredmacromoleculemedical schoolsmouse modelmultidisciplinaryneonatenovelnovel therapeuticsprenatalprogenitorprogramsrepairedresponsesmall moleculetargeted delivery
项目摘要
DESCRIPTION (provided by applicant): This proposal describes a five-year career development program to prepare the candidate, Dr. Vahid Serpooshan, for a career as an independent investigator. This program will build upon Dr. Serpooshan's multidisciplinary background as a bioengineer scientist, trained in cardiac cellular biology, by providing expertise in cellular and molecular biology underlying heart development. The main goal of the proposed research is to identify the key mechanisms underlying neonatal heart development that could be exploited - via an engineered patch - to regulate mammalian heart development and repair, following ischemic heart injury. The PI will be mentored at Stanford Medical School by Drs. Sean Wu and Daniel Bernstein. Dr. Wu has extensive expertise in investigating the mechanisms regulating cardiac lineage commitment during embryonic development and the biology of cardiac progenitor cells in development and disease. Dr. Bernstein is the director of the small animal surgery and imaging facilities at the Stanford, and his research focuses on regulation of cardiovascular function in both normal physiologic states as well as in disease states. Recent findings by our group and others have demonstrated that neonatal mammalian hearts possess several evolutionarily conserved mechanisms for myocardial regeneration, including activation of committed progenitors and/or cardiomyocytes proliferation. However, the cellular/molecular mechanisms underlying these processes and whether they can be employed to repair neonatal heart remains elusive. Our preliminary data demonstrates the existence of a population of TGFβ and MEK signaling-regulated Nkx2.5+ cardiomyoblasts in neonatal mice with the potential to proliferate and differentiate into cardiomyocytes. In the proposed study, I will test the hypothesi that a cell-based regenerative response is present in the neonatal heart that can be recruited, via a bioengineered cardiac patch delivery of small molecules, for the treatment of myocardium injury. Results from this research are expected to have positive translational impact as they will introduce a novel cell-free delivery approach for therapeutic interventions in the adult mammalian heart. My specific aims are: Aim 1: Identify an Nkx2.5+ cardiomyoblast population and their function in the neonatal mouse heart. An Nkx2.5 enh-Cre/eGFP reporter mouse model will be used to identify the activated Nkx2.5 cardiomyogenic progenitors in neonatal heart. Aim 2: Determine the signal and pathways involved in Nkx2.5+ cardiomyoblasts proliferation and differentiation. Small molecule regulation of TGFβ and MEK signaling pathways will be used to induce the expansion and cardiomyogenic differentiation of the neonatal Nkx2.5+ cardiomyoblasts. Aim 3: Examine the role of Nkx2.5 cardiomyoblasts and developmental signals to mediate cardiac repair following ischemic heart injury. I will assess the changes to the cardiomyoblast population size and their response to signaling pathway stimulation following ischemic injury.
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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Vahid Serpooshan其他文献
Vahid Serpooshan的其他文献
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{{ truncateString('Vahid Serpooshan', 18)}}的其他基金
Leveraging 3D bioprinted organoid constructs to pattern and model human brain development
利用 3D 生物打印类器官结构来模拟人类大脑发育
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10184225 - 财政年份:2021
- 资助金额:
$ 10.25万 - 项目类别:
Leveraging 3D bioprinted organoid constructs to pattern and model human brain development
利用 3D 生物打印类器官结构来模拟人类大脑发育
- 批准号:
10550132 - 财政年份:2021
- 资助金额:
$ 10.25万 - 项目类别:
Leveraging 3D bioprinted organoid constructs to pattern and model human brain development
利用 3D 生物打印类器官结构来模拟人类大脑发育
- 批准号:
10380006 - 财政年份:2021
- 资助金额:
$ 10.25万 - 项目类别:
Myocardial remuscularization by cardiac patch delivery of epicardial FSTL1 and CCND2 overexpressing cardiomyocytes
通过心脏补片递送心外膜 FSTL1 和 CCND2 过表达心肌细胞进行心肌再肌化
- 批准号:
10375894 - 财政年份:2016
- 资助金额:
$ 10.25万 - 项目类别:
Supplement of HL131017: Myocardial remuscularization by cardiac patch delivery of epicardial FSTL1 and CCND2 overexpressing cardiomyocytes
HL131017 补充:通过心外膜 FSTL1 和 CCND2 过表达心肌细胞的心脏补片递送进行心肌再肌化
- 批准号:
10797360 - 财政年份:2016
- 资助金额:
$ 10.25万 - 项目类别:
Myocardial remuscularization by cardiac patch delivery of epicardial FSTL1 and CCND2 overexpressing cardiomyocytes
通过心脏补片递送心外膜 FSTL1 和 CCND2 过表达心肌细胞进行心肌再肌化
- 批准号:
10538614 - 财政年份:2016
- 资助金额:
$ 10.25万 - 项目类别:
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