Development of resident memory T cells in the synovium
滑膜中常驻记忆 T 细胞的发育
基本信息
- 批准号:10427963
- 负责人:
- 金额:$ 17.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-04 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAdoptive TransferAdvisory CommitteesAffectAntibodiesAntigensAreaArthralgiaArthritisAttenuatedAutoimmune DiseasesBioinformaticsBiologyBostonCD8-Positive T-LymphocytesCD8B1 geneCRISPR/Cas technologyCellsCellular Indexing of Transcriptomes and Epitopes by SequencingChildhoodChronicChronic Childhood ArthritisClustered Regularly Interspaced Short Palindromic RepeatsCoculture TechniquesCoupledDataDevelopmentDiseaseDisease remissionDoctor of MedicineDoctor of PhilosophyEffector CellEndothelial CellsEnvironmentEventExhibitsFatty AcidsFibroblastsFlareFoundationsFunctional disorderFundingFutureGene ExpressionGene Expression ProfilingGene TargetingGenesGenetic TranscriptionGoalsHeadHomingHospitalsHumanImmuneImmunologyIndividualInflammationInflammatoryInflammatory ArthritisInstitutionInterruptionJointsKnowledgeLaboratoriesLearningLifeLigandsMaintenanceMediatingMediator of activation proteinMembrane ProteinsMemoryMentorsMentorshipMethodsModelingMusNational Institute of Arthritis and Musculoskeletal and Skin DiseasesOrganoidsPathway interactionsPatientsPatternPediatric HospitalsPeriodicityPeripheralPersonsPharmaceutical PreparationsPhenotypePhysiciansPopulationProcessRUNX3 geneRecurrenceResearch PersonnelResistanceResourcesRheumatoid ArthritisRoleScientistSeriesSignal TransductionSiteSterilityStromal CellsSurfaceSynovial MembraneSystemT memory cellT-Cell ReceptorT-LymphocyteTGFBR2 geneTestingTherapeuticTimeTissue-Specific Gene ExpressionTissuesTrainingTranslational ResearchWomanWorkarthritis therapyarthropathiesbasecareerchemokinechronic autoimmune diseaseconfocal imagingdesigndisorder controlexperiencehuman diseasehuman modelimmune activationinsightjoint inflammationlymph nodesmRNA Expressionmedical schoolsmigrationmouse modelnew therapeutic targetnovel strategiesnovel therapeuticspreventprotein expressionranpirnasereceptorrecruitresidencerheumatologistsingle cell analysissingle cell sequencingsingle-cell RNA sequencingskillstherapeutic targetthree-dimensional modelingtranscriptomicsuptake
项目摘要
Project Summary/Abstract
Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are chronic autoimmune diseases of the joint
punctuated by periodic arthritis flares. Clinicians have long recognized that each affected person develops an
individual pattern of affected joints, and that this pattern remains stable over time through disease remission and
flares. We recently identified the presence of synovial resident memory T cells (TRM) in arthritic joints and showed
that they mediate arthritis flares. Correspondingly, depleting these cells ameliorates disease recurrence,
indicating that TRM can be targeted as a novel approach in arthritis therapy. The long-term objective of the
proposal is to define the mediators of TRM development and maintenance in the synovium and determine if these
pathways can be therapeutically targeted to treat arthritis.
The specific aims of this proposal utilize 2 complementary approaches in mice and human studies to identify the
mediators of synovial TRM development. Aim 1 utilizes a mouse model of inflammatory arthritis developed by the
PI to define the lineage and differentiation process of synovial TRM. Aim 2 utilizes a human synovial organoid
system to interrogate the impact of the synovial microenvironment, namely synovial stromal cells, on TRM
formation and survival. We expect that these studies will identify critical mediators of TRM development, which
may represent novel therapeutic targets for inflammatory arthritis.
The candidate is an M.D./Ph.D. pediatric rheumatologist at Boston Children’s Hospital. This proposal builds upon
her foundational knowledge of immunology to extend her skillset into antibody-coupled single cell sequencing,
bioinformatics, organoid models of human synovium, and CRISPR gene targeting. The proposal includes a
comprehensive mentoring and didactic plan that will allow her to successfully learn new skills and gain expertise
in each of these important areas. The primary mentor, Dr. Peter Nigrovic, is a rheumatologist and expert in the
pathophysiology of inflammatory arthritis. The candidate has assembled a K08 advisory committee consisting of
Dr. Michael Brenner, Dr. Rachael Clark, and Dr. Soumya Raychaudhuri, who each have specific expertise in
various aspects of this proposal such as analysis of single-cell sequencing data, 3D models of human synovium,
and expertise in TRM biology in human disease. The candidate is committed to a career in translational research
with the goal of becoming an independent lab-based investigator focusing on local mechanisms to autoimmune
disorders. The proposed studies, training plan, and exceptional environment at Boston Children’s Hospital,
Brigham and Women’s Hospital and Harvard Medical School will enable her to successfully transition to an
independent PI and leader in this field.
项目总结/文摘
项目成果
期刊论文数量(0)
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Margaret Chang其他文献
Margaret Chang的其他文献
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{{ truncateString('Margaret Chang', 18)}}的其他基金
Development of resident memory T cells in the synovium
滑膜中常驻记忆 T 细胞的发育
- 批准号:
10601115 - 财政年份:2022
- 资助金额:
$ 17.33万 - 项目类别:
Galectin-1's effects on dendritic cell function.
Galectin-1 对树突状细胞功能的影响。
- 批准号:
7676449 - 财政年份:2009
- 资助金额:
$ 17.33万 - 项目类别:
Galectin-1's effects on dendritic cell function.
Galectin-1 对树突状细胞功能的影响。
- 批准号:
8323368 - 财政年份:2009
- 资助金额:
$ 17.33万 - 项目类别:
Galectin-1's effects on dendritic cell function.
Galectin-1 对树突状细胞功能的影响。
- 批准号:
8127678 - 财政年份:2009
- 资助金额:
$ 17.33万 - 项目类别:
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