Oxysterol Regulation of Mast Cell Biology
肥大细胞生物学的氧甾醇调节
基本信息
- 批准号:10237850
- 负责人:
- 金额:$ 10.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-13 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:25-hydroxycholesterol7alpha hydroxylaseAddressAirway DiseaseAllergensAllergicAsthmaAtopic DermatitisAutomobile DrivingBiological ModelsCell CompartmentationCell CountCell Culture SystemCell DegranulationCell LineageCell SurvivalCellsCellular biologyCharacteristicsChemotaxisCholesterolCollaborationsComplement 3d ReceptorsContact DermatitisDataData SetDiseaseDoctor of PhilosophyEarEffector CellEnzymesEosinophilic EsophagitisEpithelial CellsFutureG-Protein-Coupled ReceptorsGTP-Binding Protein alpha Subunits, GsGene ExpressionGenerationsGenetic TranscriptionHistamineHumanHuman Herpesvirus 4In VitroInflammationInflammation MediatorsInflammatoryInhalationInterleukin-13LaboratoriesLigandsLigationLungLung InflammationManuscriptsMediatingMixed Function OxygenasesModelingMouse StrainsMucous MembraneMusMyelogenousNasal PolypsOrphanOxidesPassive Cutaneous AnaphylaxisPathogenesisPathogenicityPathway interactionsPatientsPeptide HydrolasesPlayPolypsProductionProto-Oncogene Protein c-kitPulmonary InflammationRegulationReportingResearchRoleSamplingSwellingTestingTherapeuticTissuesTranscriptUnited States National Institutes of HealthUp-Regulationairway epitheliumairway hyperresponsivenessasthmaticasthmatic airway smooth musclecareercell motilitychronic rhinosinusitiscytokinehuman tissueimprintin vitro Assayin vivointradermal injectionlipid mediatormast cellmouse modelmucosal sitemultiple datasetsnoveloxysterol 7-alpha-hydroxylaseoxysterol binding proteinreceptorrecruitrespiratorysingle-cell RNA sequencingstem cellstargeted treatmenttoolvirtual
项目摘要
PROJECT SUMMARY/ABSTRACT
This proposal details a two-year plan to allow the candidate, Daniel Dwyer, PhD, to transition to a stable
independent research career. The focus of this study is on characterizing a novel regulatory axis capable of
mediating the recruitment and activation of mast cells (MCs) during type 2 inflammation (T2I). MCs are potent
effector cells that play key pathogenic roles in type 2 inflammatory diseases through the generation and
release of a broad range of inflammatory mediators, including histamine, proteases, lipid mediators, and
cytokines. The specific mechanisms underlying the expansion of MC during type 2 inflammation or the
persistent activation of these cells associated with these diseases are unclear. This proposal identifies novel
expression of a G protein-coupled receptor (GPCR) in both human and mouse MCs. Ligation of this receptor
elicits mediating MC migration in vitro and additionally induces MC activation both in vivo and in vitro. Further,
this proposal further identifies upregulation of a necessary enzyme for synthesis of the ligand across a
spectrum of human T2I disease and finds that murine MC progenitor recruitment during allergic pulmonary
inflammation is virtually absent in mice lacking the enzyme. Aim 1 of this proposal will utilize two murine
models of allergic lung inflammation to assess which cells express and upregulate the enzyme in the context of
T2I, followed by in vitro approaches to determine the mechanism driving this upregulation. Aim 2 of this
proposal details the generation of a novel mouse strain in which the GPCR is specifically deleted in MC. After
an initial confirmation of specific deletion and characterization of the MC compartment across tissues, the
specific role of this GPCR in regulating constitutive MC activation and MC progenitor recruitment will be
assessed in two inflammatory models.
项目摘要/摘要
该建议详细介绍了为期两年的计划,允许候选人Daniel Dwyer,博士过渡到稳定
独立研究职业。这项研究的重点是表征一个能够
在2型炎症(T2I)期间介导肥大细胞(MC)的募集和激活。 MC是有效的
效应细胞通过一代人在2型炎症性疾病中起关键的致病作用,
释放广泛的炎症介质,包括组胺,蛋白酶,脂质介质和
细胞因子。 2型炎症期间MC膨胀的基础的特定机制或
这些与这些疾病相关的细胞的持续激活尚不清楚。该提议确定了小说
G蛋白偶联受体(GPCR)在人和小鼠MC中的表达。该受体的连接
引发体外介导MC迁移的介导,并在体内和体外诱导MC激活。更远,
该提案进一步确定了必要酶合成跨A的必要酶
人类T2I疾病的频谱发现过敏性肺部鼠类MC祖细胞的募集
缺乏酶的小鼠实际上没有炎症。该提案的目标1将利用两个鼠
过敏性肺部炎症的模型,以评估哪种细胞在中间表达和上调酶
T2i,然后采用体外方法来确定推动这种上调的机制。目标2
建议详细介绍了在MC中特异性删除GPCR的新型小鼠菌株的产生。后
对跨组织MC室特异性缺失和表征的初步确认,
该GPCR在调节构型MC激活和MC祖细胞募集中的具体作用将是
在两个炎症模型中进行了评估。
项目成果
期刊论文数量(2)
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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Daniel F Dwyer其他文献
SARS-CoV-2 Receptor ACE2 is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Enriched in Specific Cell Subsets Across Tissues
SARS-CoV-2 受体 ACE2 是人气道上皮细胞中的干扰素刺激基因,富含组织中的特定细胞亚群
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:0
- 作者:
Carly N Ziegler;Samuel J. Allon;Sarah K Nyquist;Ian M. Mbano;Vincent N Miao;Yuming Cao;Ashraf S. Yousif;Julia Bals;B. Hauser;J. Feldman;Christoph Muus;Marc H Wadsworth Ii;S. Kazer;T. Hughes;B. Doran;G. J. Gatter;Marko Vukovic;C. Tzouanas;F. Taliaferro;Zhiru Guo;Jennifer P. Wang;Daniel F Dwyer;K. Buchheit;Joshua A. Boyce;Nora A. Barrett;T. Laidlaw;Shaina L. Carroll;Lucrezia Colonna;V. Tkachev;Alison Yu;Henqi Betty Zheng;H. Gideon;Caylin G. Winchell;P. Lin;Bonnie Berger;A. Leslie;JoAnne L. Flynn;Sarah M Fortune;R. Finberg;Leslie S. Kean;Manuel Garber;Aaron Schmidt;D. Lingwood;A. Shalek;J. Ordovas;Hca Lung Biological Network - 通讯作者:
Hca Lung Biological Network
Optimizing cryopreservation of nasal polyp tissue for cellular functional studies and single‐cell RNA sequencing
优化鼻息肉组织冷冻保存以进行细胞功能研究和单细胞 RNA 测序
- DOI:
10.1002/alr.23275 - 发表时间:
2023 - 期刊:
- 影响因子:6.4
- 作者:
Aaqib Sohail;Carolyn H. Baloh;Jonathan Hacker;Laura Cho;Tessa Ryan;R. Bergmark;Stella E. Lee;Alice Z Maxfield;Rachel E. Roditi;Daniel F Dwyer;K. Buchheit;Tanya M. Laidlaw - 通讯作者:
Tanya M. Laidlaw
Daniel F Dwyer的其他文献
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