Using siglecs and their ligands to treat allergic diseases SALTAD
使用siglecs及其配体治疗过敏性疾病SALTAD
基本信息
- 批准号:10097976
- 负责人:
- 金额:$ 151.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-02-06 至 2023-01-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAllergensAllergicAllergic DiseaseAllergic ReactionAllergic inflammationAnimal ModelAsthmaBindingBinding ProteinsBiochemistryBiologicalBiopsy SpecimenCellsChronicDevelopmentDiseaseEffector CellElementsFamilyFoodFunctional disorderGastrointestinal DiseasesGastrointestinal tract structureGlycobiologyGoalsHealthHumanHypersensitivityIgEImmune System DiseasesImmunoglobulinsIn VitroInflammationInflammatoryInflammatory ResponseKnock-inKnock-in MouseKnowledgeLectinLigandsLiposomesMediatingModelingMolecularMolecular and Cellular BiologyMonoclonal AntibodiesMouse StrainsMusOutcomePathway interactionsPharmaceutical PreparationsPharmacologyPolysaccharidesProductivityPropertyReagentResearchRoleSamplingSialic AcidsSignal TransductionSkinStructureTestingTissuesTranslatingallergic responseanalogchronic rhinosinusitisdesensitizationeosinophileosinophilic inflammationexperiencehuman tissuehumanized mouseimprovedin vivoinsightinterestmast cellmembermouse modelnanoparticlenovelnovel strategiespreventprogramsresponsesialic acid binding Ig-like lectinskin disordersynergism
项目摘要
OVERALL ABSTRACT
Mast cells and eosinophils are essential effector cells in both acute and chronic allergic inflammatory
responses. The overall goal of this Program is to exploit eosinophil and mast cell Siglecs (sialic acid binding,
immunoglobulin-like lectins) to prevent or treat immediate allergic reactions and chronic allergic inflammation.
The overarching hypothesis is that specific mAbs, endogenous tissue glycans, or synthetic ligand analogs, can
specifically and selectively engage complementary glycan binding Siglecs (CD33, Siglec-6, and Siglec-8) on
eosinophils and/or mast cells to prevent or limit IgE-dependent and IgE-independent eosinophil and mast cell-
related allergic responses.
This application focuses on the role of three mast cell and eosinophil Siglecs that we hypothesize provide
ideal targets for dampening allergic effector cell responses in a variety of acute and chronic allergy-related
disorders. Dr. Bruce Bochner will serve as the PI of Project 1 (Defining Siglec-6 and Siglec-8 function on
effector cells of allergic diseases as well as Core A (Administration) and Core B (Human mast cell and tissue
acquisition core). Dr. James Paulson will serve as the PI of Project 2 (Siglec-targeted nanoparticles for
treating mast cell mediated allergic disease) while Dr. Ronald Schnaar will serve as the PI of Project 3 (Human
siglec ligands control mast cell and eosinophil mediated inflammation). This is a Program team with a proven
track record of productivity and synergy.
This application includes projects that examine Siglec/eosinophil/mast cell pathways from various
perspectives including pharmacology, biochemistry, cell signaling, glycobiology, and cellular and molecular
biology, using in vitro experimentation and in vivo humanized models. The majority of the proposed research
utilizes human material including primary human cells and biologic samples, along with animal models
involving humanized mast cell mice and novel knock-in strains of mice expressing human Siglecs of interest to
provide more in-depth hypothesis testing on mechanisms and outcomes that cannot yet be assessed with
human research. Each Project provides numerous elements of novelty ranging from human Siglec knock-in
mice to development of unique reagents for targeting specific Siglecs to discovery of endogenous human
tissue ligands for specific Siglecs.
总体摘要
肥大细胞和嗜酸性粒细胞是急性和慢性变态反应性炎症中必不可少的效应细胞
回应。该计划的总体目标是利用嗜酸性粒细胞和肥大细胞Siglecs(唾液酸结合,
免疫球蛋白样凝集素),用于预防或治疗即时过敏反应和慢性过敏性炎症。
最重要的假设是,特定的单抗、内源性组织多糖或合成配体类似物可以
特异性和选择性地结合互补的糖链结合Siglecs(CD33、Siglec-6和Siglec-8)
嗜酸性粒细胞和/或肥大细胞,以防止或限制IgE依赖和非IgE依赖的嗜酸性粒细胞和肥大细胞
相关过敏反应。
这个应用着重于我们假设提供的三个肥大细胞和嗜酸性粒细胞标志的作用
抑制各种急慢性变态反应相关变态反应效应细胞反应的理想靶点
精神错乱。Bruce Bochner博士将担任项目1的PI(定义Siglec-6和Siglec-8功能
过敏性疾病的效应细胞以及核心A(给药)和核心B(人肥大细胞和组织
收购核心)。詹姆斯·保尔森博士将担任项目2的PI(Siglec-靶向纳米颗粒
治疗肥大细胞介导的过敏性疾病),而罗纳德·施纳尔博士将担任项目3的PI(人类
Siglec配体控制肥大细胞和嗜酸性粒细胞介导的炎症)。这是一个经过验证的计划团队
工作效率和协同效应的跟踪记录。
这个应用程序包括检查Siglec/嗜酸性粒细胞/肥大细胞途径的项目
观点包括药理学、生物化学、细胞信号、糖生物学以及细胞和分子
生物学,采用体外实验和体内人性化模型。大多数拟议的研究
利用人类材料,包括原代人类细胞和生物样本,以及动物模型
涉及人源化肥大细胞小鼠和表达感兴趣的人Siglecs的新敲入小鼠品系
对尚不能评估的机制和结果提供更深入的假设测试
人类研究。每个项目都提供了许多新奇的元素,从人类签名敲门到
小鼠发展独特的靶向特异性Siglecs的试剂来发现内源性人类
特定Siglecs的组织配体。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)
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Bruce S Bochner其他文献
Bruce S Bochner的其他文献
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{{ truncateString('Bruce S Bochner', 18)}}的其他基金
Exploiting Siglec-6 for targeted anti-allergy drug delivery into human mast cells
利用 Siglec-6 将靶向抗过敏药物输送到人体肥大细胞中
- 批准号:
10194041 - 财政年份:2021
- 资助金额:
$ 151.6万 - 项目类别:
Exploiting Siglec-6 for targeted anti-allergy drug delivery into human mast cells
利用 Siglec-6 将靶向抗过敏药物输送到人体肥大细胞中
- 批准号:
10368109 - 财政年份:2021
- 资助金额:
$ 151.6万 - 项目类别:
Using siglecs and their ligands to treat allergic diseases SALTAD
使用siglecs及其配体治疗过敏性疾病SALTAD
- 批准号:
10331722 - 财政年份:2018
- 资助金额:
$ 151.6万 - 项目类别:
Defining Siglec-6 and Siglec-8 function on effector cells of allergic diseases
定义 Siglec-6 和 Siglec-8 对过敏性疾病效应细胞的功能
- 批准号:
10097994 - 财政年份:2018
- 资助金额:
$ 151.6万 - 项目类别:
Defining Siglec-6 and Siglec-8 function on effector cells of allergic diseases
定义 Siglec-6 和 Siglec-8 对过敏性疾病效应细胞的功能
- 批准号:
10331725 - 财政年份:2018
- 资助金额:
$ 151.6万 - 项目类别:
Northwestern University Allergy and Immunology Research (NUAIR) Program
西北大学过敏与免疫学研究 (NUAIR) 项目
- 批准号:
10207416 - 财政年份:2010
- 资助金额:
$ 151.6万 - 项目类别:
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