Characterization of degranulation regulators in human mast cells
人类肥大细胞脱颗粒调节剂的表征
基本信息
- 批准号:10284390
- 负责人:
- 金额:$ 23.62万
- 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:2021-06-01 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffinityAllergensAllergic DiseaseAllergic ReactionAmericanAsthmaAtopic DermatitisAutoimmune DiseasesAvidinBindingCD34 geneCRISPR libraryCRISPR/Cas technologyCell Culture TechniquesCell DegranulationCell LineCell SeparationCell physiologyCellsCellular biologyClustered Regularly Interspaced Short Palindromic RepeatsConfocal MicroscopyCoupledDataDevelopmentDiseaseEconomic BurdenEczemaEffector CellFood HypersensitivityGenesGenomic LibraryGoalsGrowth FactorHay feverHealthHeparinHistamineHumanHypersensitivityIL3 GeneIgEIgE ReceptorsImmunityInflammation MediatorsInterleukin-6Leukotriene C4LibrariesMediatingMediator of activation proteinModelingMusMutationParasitesPathologyPathway interactionsPatientsPeptide HydrolasesPhenotypePhosphotransferasesPreventionProcessProductionProstaglandin D2RegulationResearchResolutionRodentRoleSchoolsSignal PathwaySignal TransductionSignal Transduction PathwaySurfaceTechnologyTherapeutic AgentsTimeTransfectionWorkbasecell preparationcellular imagingconfocal imagingcostcrosslinkcytokinedesignexperiencefunctional genomicshealth care deliveryhealth economicshuman subjectimmunoregulationlipid mediatormast cellmastocytosismouse modelnew technologynovelnovel therapeutic interventionpathogenperipheral bloodpreventresponsetherapy designvector
项目摘要
PROJECT SUMMARY/ABSTRACT
This project’s long-term goals are to understand the regulation of human mast cell (MC) function and to
elucidate the roles of MCs in human health and disease. MCs are major effector cells in IgE-associated
responses (e.g., asthma, allergy, parasite immunity). These cells also may contribute to certain autoimmune
disorders and in the initiation of responses to pathogens and other agents. Upon activation, MCs undergo
degranulation, leading to the secretion of many mediators (including stored products, e.g., histamine, heparin
and proteases), as well as the production of lipid mediators, e.g., LTC4 and PGD2, and many cytokines and
growth factors. Depending on the setting, MCs can have effector and/or immunoregulatory roles. Most
research investigating MC development and function has employed various mouse models. However, we
know considerably less about the mechanisms that regulate the activation of human MCs. Similarly, relatively
little is known about how the perturbation of signaling pathways in human MCs can contribute to MC-
associated pathology. This, in turn, has hampered the design of therapeutic agents for the treatment and/or
prevention of allergies and other mast cell-associated diseases in human subjects. We recently developed a
technology platform employing functional genomics, coupled with high-resolution single-cell confocal imaging,
which can rapidly identify regulators of degranulation in human mast cells. We now propose to use this
platform to identify key regulators of IgE/FceRI-dependent signal transduction pathways in cultured, donor-
derived, primary human mast cells. Specifically, we will attempt to validate, in primary human mast cells,
selected major degranulation regulators previously identified in rodent mast cells. We also will use targeted
arrayed human CRISPR-Cas9 libraries to identify novel (i.e., previously unidentified) regulators of IgE/FceRI-
dependent signaling pathways in primary human mast cells. In addition, we will investigate the functional
significance of the KIT D816V mutation detected in mastocytosis patients by using the CRISPR-Cas9-based
gene editing technologies to induce/correct the same mutation in human HMC-1 cell lines and primary human
mast cells. To achieve our goals, we propose two aims. In Aim 1, we will identify novel human mast cell
degranulation regulators and systematically define IgE/FceRI-dependent signaling pathways in primary
human mast cells. In Aim 2, we will use CRISPR-Cas9 “prime editing” to perform mutational studies of HMC-
1 human mast cell lines and primary human mast cells. Together, this work will help create a detailed model
of mast cell degranulation in human mast cells and will begin to analyze how the KIT D816V mutation may
influence human mast cell biology.
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 }}
Stephen Joseph Galli其他文献
Stephen Joseph Galli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('Stephen Joseph Galli', 18)}}的其他基金
Characterization of innate and IgE-mediated mast cell functions in honeybee venom allergy using Collaborative Cross mice
使用 Collaborative Cross 小鼠表征蜜蜂毒液过敏中的先天和 IgE 介导的肥大细胞功能
- 批准号:
10681390 - 财政年份:2021
- 资助金额:
$ 23.62万 - 项目类别:
Characterization of innate and IgE-mediated mast cell functions in honeybee venom allergy using Collaborative Cross mice
使用 Collaborative Cross 小鼠表征蜜蜂毒液过敏中的先天和 IgE 介导的肥大细胞功能
- 批准号:
10331200 - 财政年份:2021
- 资助金额:
$ 23.62万 - 项目类别:
Characterization of degranulation regulators in human mast cells
人类肥大细胞脱颗粒调节剂的表征
- 批准号:
10415223 - 财政年份:2021
- 资助金额:
$ 23.62万 - 项目类别:
Role of nociceptive sensory neuron/mast cell interactions in cutaneous allergic inflammation
伤害性感觉神经元/肥大细胞相互作用在皮肤过敏性炎症中的作用
- 批准号:
9363714 - 财政年份:2017
- 资助金额:
$ 23.62万 - 项目类别:
Role of nociceptive sensory neuron/mast cell interactions in cutaneous allergic inflammation
伤害性感觉神经元/肥大细胞相互作用在皮肤过敏性炎症中的作用
- 批准号:
9922209 - 财政年份:2017
- 资助金额:
$ 23.62万 - 项目类别:
RabGEF1 in MyD88 signaling, skin immunity, and atopic dermatitis
RabGEF1 在 MyD88 信号传导、皮肤免疫和特应性皮炎中的作用
- 批准号:
9293893 - 财政年份:2015
- 资助金额:
$ 23.62万 - 项目类别:
RabGEF1 in MyD88 signaling, skin immunity, and atopic dermatitis
RabGEF1 在 MyD88 信号传导、皮肤免疫和特应性皮炎中的作用
- 批准号:
9068815 - 财政年份:2015
- 资助金额:
$ 23.62万 - 项目类别:
RabGEF1 in MyD88 signaling, skin immunity, and atopic dermatitis
RabGEF1 在 MyD88 信号传导、皮肤免疫和特应性皮炎中的作用
- 批准号:
8960798 - 财政年份:2015
- 资助金额:
$ 23.62万 - 项目类别:
Integrated Genomic and Functional Studies of Tolerance Therapy for Peanut Allerg
花生过敏耐受疗法的综合基因组和功能研究
- 批准号:
8699865 - 财政年份:2013
- 资助金额:
$ 23.62万 - 项目类别:
Integrated Genomic and Functional Studies of Tolerance Therapy for Peanut Allerg
花生过敏耐受疗法的综合基因组和功能研究
- 批准号:
8462368 - 财政年份:2013
- 资助金额:
$ 23.62万 - 项目类别:
相似海外基金
The early-life mycobiome as a determinant of oral tolerance to food allergens
生命早期的真菌组是食物过敏原口腔耐受性的决定因素
- 批准号:
498187 - 财政年份:2023
- 资助金额:
$ 23.62万 - 项目类别:
Operating Grants
Quantitative risk assessment of unintended allergens in school-provided lunch and food service at nursery.
对学校提供的午餐和托儿所食品服务中的意外过敏原进行定量风险评估。
- 批准号:
23K07902 - 财政年份:2023
- 资助金额:
$ 23.62万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Reassessment of the diversity and commonality of food allergens using transdermal sensitization capacity and digestive resistance as indicators.
以透皮致敏能力和消化阻力为指标重新评估食物过敏原的多样性和共性。
- 批准号:
23K05103 - 财政年份:2023
- 资助金额:
$ 23.62万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of analysis techniques for precise epitopes of food allergens
食品过敏原精确表位分析技术的开发
- 批准号:
23K17976 - 财政年份:2023
- 资助金额:
$ 23.62万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Discovering epitope mimics (mimitopes) of chemical allergens that cause occupational asthma
发现导致职业性哮喘的化学过敏原的模拟表位(模拟表位)
- 批准号:
10741979 - 财政年份:2023
- 资助金额:
$ 23.62万 - 项目类别:
Age-Related Alterations in Neuro-Immune Recognition of Allergens
过敏原神经免疫识别中与年龄相关的变化
- 批准号:
10373431 - 财政年份:2022
- 资助金额:
$ 23.62万 - 项目类别:
Do allergens contribute to neurodegeneration?
过敏原会导致神经退行性变吗?
- 批准号:
10542643 - 财政年份:2022
- 资助金额:
$ 23.62万 - 项目类别:
Age-Related Alterations in Neuro-Immune Recognition of Allergens
过敏原神经免疫识别中与年龄相关的变化
- 批准号:
10559576 - 财政年份:2022
- 资助金额:
$ 23.62万 - 项目类别:
Do allergens contribute to neurodegeneration?
过敏原会导致神经退行性变吗?
- 批准号:
10190052 - 财政年份:2021
- 资助金额:
$ 23.62万 - 项目类别:
Lateral flow array for undeclared food allergens
用于未申报食物过敏原的侧流阵列
- 批准号:
10320285 - 财政年份:2021
- 资助金额:
$ 23.62万 - 项目类别: