The Role of Follistatin Like Protein 1 in the cardiac inflammation of Kawasaki Disease
卵泡抑素样蛋白1在川崎病心脏炎症中的作用
基本信息
- 批准号:10091126
- 负责人:
- 金额:$ 16.55万
- 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:2021-01-01 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAcute DiseaseAdvisory CommitteesAffectAftercareAneurysmAnticoagulationAttenuatedBasic ScienceBiological ProcessBlood VesselsCardiacCardiac MyocytesCell LineCell WallCellsChildChildhoodCoculture TechniquesColorComplementCoronaryCysteineDataDevelopmentDiagnosisDiseaseDisease modelDissectionEpithelialEquipmentEventFamilyFamily memberFeverFibroblastsFlow CytometryFollistatin-Related Protein 1Functional disorderFundingGlycoproteinsGoalsHeartHeart DiseasesHumanHuman ResourcesImmune responseImmunohistochemistryImmunologyIn VitroInflammationInflammation MediatorsInflammatoryInflammatory ResponseInjectionsIntentionInterventionInvestigationKnock-outLaboratoriesLactobacillus caseiLesionLifeLocationMediator of activation proteinMentorsMentorshipMesenchymalMethodsModelingMolecularMolecular BiologyMonitorMorbidity - disease rateMucocutaneous Lymph Node SyndromeMusMuscle CellsMutationMyocardial InfarctionMyocardial ruptureMyocarditisParentsPathogenesisPatientsPhasePhenotypePlant RootsPlayPost-Translational Protein ProcessingProcessProductionProgram DevelopmentProtein IsoformsProteinsRecombinantsResearchResearch PersonnelRiskRoleSamplingScientistSerumSeveritiesSignal PathwaySignal TransductionSiteSpleenStenosisStimulusSyndromeT-LymphocyteTestingTimeTissuesToddlerTrainingTranslatingTranslational ResearchTransplantationTunica AdventitiaUniversitiesVasculitiscardioprotectioncareercareer developmentclinical applicationcoronary lesioncytokineexperienceexperimental studyglycosylationheart functionimmune functionin vivoinduced pluripotent stem cellintima mediamacrophagemedical schoolsmortalitymouse modelnovelpostnatalprofessorresponseskillssystemic inflammatory response
项目摘要
Project Summary/Abstract: Kawasaki disease (KD), a predominantly coronary vasculitis of childhood, is
the most common cause of acquired heart disease of childhood in the developed world. Despite current best
treatments, approximately one quarter of patients will have persistent morbidity. This proposal presents a five
year research career development program with a focus on the study of inflammation in KD, with the goals of
expanding understanding of KD and cardiac inflammation, and developing of skills and experience of the
applicant. The study builds on the candidate's initial human finding and subsequent murine data relating to the
role of an important cardiac-related protein known as Follistatin-Like Protein 1 (FSTL-1) in KD. FSTL-1 has
been shown to have defined and critical roles in protecting cardiac myocytes and fibroblasts after myocardial
infarct, but its role in inflammation has not been well characterized. Preliminary data shows that FSTL-1 is
associated with inflammation in Kawasaki disease in humans, and that in a mouse model, knockout of the
protein aggravates disease while treatment with exogenous protein attenuates inflammation. Glycosylated
FSTL-1 can downregulate macrophage inflammatory responses, and macrophages are critical for the
development of KD. The candidate will study the role of FSTL-1 in cardiac inflammation, hypothesizing that
the glycosylated form of FSTL-1 is a counter-regulator of cardiac inflammation, promoting a Th2 T-cell
phenotype and down-regulating the macrophage inflammatory response.
The aims of the proposal are 1): Determine whether exogenous glycosylated FSTL-1 promotes a Th2 T-
cell phenotype and downregulates the inflammatory macrophage response in the mouse model of KD. 2)
Establish whether glycosylated and non-glycosylated FSTL-1 differentially affect the human macrophage
inflammatory response in vitro. 3) Define whether inflammatory stimulus in KD induces differential FSTL-1
isoforms in cardiac tissue lines, using human induced pluripotent stem cells (iPSC).
The accomplishment of these aims would clarify the role of FSTL-1 (a critical mediator of cardiac function)
in the setting of cardiac inflammation and allow investigation into novel methods of modulating cardiac and
systemic inflammation. The candidate is an assistant professor at the Columbia University School of Medicine
and is firmly committed to a career in basic and translational research in inflammation and immunology. The
candidate has 75% protected time for research, laboratory and office space, and funding for supplies,
equipment and personnel. The current proposal includes a comprehensive mentorship and didactic plan to
advance the candidate's skills and in molecular biology required for developing expertise in immunology and
cardiac inflammation. Under the guidance of his mentor and advisory team, he will advance his basic and
translational research skills. Completion of this training plan will provide the candidate with the skills and
experience to become a successful independent investigator.
项目摘要/摘要:川崎病(Kawasaki disease, KD)是一种以儿童冠脉血管炎为主的疾病
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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Mark Gorelik其他文献
Mark Gorelik的其他文献
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{{ truncateString('Mark Gorelik', 18)}}的其他基金
The Role of Follistatin Like Protein 1 in the cardiac inflammation of Kawasaki Disease
卵泡抑素样蛋白1在川崎病心脏炎症中的作用
- 批准号:
10322089 - 财政年份:2021
- 资助金额:
$ 16.55万 - 项目类别:
The Role of Follistatin Like Protein 1 in the cardiac inflammation of Kawasaki Disease
卵泡抑素样蛋白1在川崎病心脏炎症中的作用
- 批准号:
10543843 - 财政年份:2021
- 资助金额:
$ 16.55万 - 项目类别:
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