STAT3 variants as a rheostat of immune tolerance
STAT3 变体作为免疫耐受的变阻器
基本信息
- 批准号:10328097
- 负责人:
- 金额:$ 176.58万
- 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:2022-02-17 至 2027-01-31
- 项目状态:未结题
- 来源:
- 关键词:Animal ModelAutoantibodiesAutoimmune DiabetesAutoimmunityCRISPR/Cas technologyCell modelCellsChildhoodClustered Regularly Interspaced Short Palindromic RepeatsCollaborationsComplexCritical PathwaysDefectDiagnosisDiseaseEpistatic GeneFunctional disorderGenetic EngineeringGenetic ModelsGrantHealthHumanHuman GeneticsImmuneImmune System DiseasesImmune ToleranceImmune systemInflammationInsulin-Dependent Diabetes MellitusLeadMapsMediatingMethodsModelingMusMutationOutcomePathogenesisPatientsPersonal SatisfactionPhage ImmunoPrecipitation SequencingPopulationProcessProgram Research Project GrantsResourcesSTAT3 geneSamplingSignal TransductionSkinSyndromeT-LymphocyteVariantWorkbasecentral tolerancegain of functiongene interactiongenetic variantgenome editingimprovedmouse modelnovelperipheral toleranceprogramsrepairedresponsesynergismtherapy developmenttreatment strategy
项目摘要
Project Summary/Abstract (Overall)
Dysregulation of the immune system can have severe consequences on health and wellbeing. Although this is
often a complex process, recent progress in human genetics has allowed for the identification of single gene
variants that are strongly associated with immune dysregulation. Here, in this program project grant three
complementary teams will be working together to further unravel how heterozygous mutations that lead to gain
of function activity (GOF) of the STAT3 gene can strongly predispose to disease. Moreover, through our efforts
we hope to discover potential new methods to reverse this defect. This program project will have three highly
collaborative and interactive projects headed by Drs. Megan Cooper, Mark Anderson, and Alex Marson
along with two scientific cores. The major themes of the grant are:
1. More refined analysis of the immune cell dysfunction in STAT3 GOF patients
2. Using state of the art animal modeling approaches to interrogate STAT3 GOF mutations in triggering
skin inflammation and type 1 diabetes
3. Utilizing state of the art CRISPR/Cas9 methods to interrogate STAT3 GOF dysfunction
4. Modeling methods to genetically repair defective STAT3 in human cells
The long-term objectives of this work are to improve our understanding of how STAT3 can serve as a tunable
rheostat to control immune tolerance and immune dysregulation. Results of these studies will help further
refine our understanding of autoimmunity inflammation and help improve methods for its treatment and
diagnosis.
项目概要/摘要(总体)
免疫系统的失调可能对健康和福祉产生严重后果。虽然这是
通常是一个复杂的过程,人类遗传学的最新进展允许识别单个基因
与免疫失调密切相关的变异。在这个项目中,
互补团队将共同努力,进一步阐明杂合突变如何导致增益
STAT 3基因的功能活性(GOF)的降低可强烈地易感疾病。此外,通过我们的努力,
我们希望发现潜在的新方法来扭转这一缺陷。该项目将有三个高度
由Megan库珀、Mark安德森和Alex Marson博士领导的协作和互动项目
沿着的还有两个科学核心。赠款的主要主题是:
1. STAT 3 GOF患者免疫细胞功能障碍的更精确分析
2.使用最先进的动物建模方法来询问触发中的STAT 3 GOF突变
皮肤炎症与1型糖尿病
3.利用最先进的CRISPR/Cas9方法来询问STAT 3 GOF功能障碍
4.基因修复人类细胞中有缺陷的STAT 3的建模方法
这项工作的长期目标是提高我们对STAT 3如何作为可调
变阻器来控制免疫耐受和免疫失调。这些研究结果将有助于进一步
完善我们对自身免疫性炎症的理解,并帮助改善其治疗方法,
诊断.
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 S Anderson其他文献
The sickness unto Deaf
致聋之病
- DOI:
10.1038/ni0909-934 - 发表时间:
2009-09-01 - 期刊:
- 影响因子:27.600
- 作者:
James M Gardner;Mark S Anderson - 通讯作者:
Mark S Anderson
Mark S Anderson的其他文献
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{{ truncateString('Mark S Anderson', 18)}}的其他基金
Project 2: STAT3 as a trigger for T1D
项目 2:STAT3 作为 T1D 的触发因素
- 批准号:
10576386 - 财政年份:2022
- 资助金额:
$ 176.58万 - 项目类别:
Tuning peptide specifities for T cell tolerance in Type 1 diabetes
调整 1 型糖尿病 T 细胞耐受性的肽特异性
- 批准号:
10630946 - 财政年份:2022
- 资助金额:
$ 176.58万 - 项目类别:
Alterations of leukocyte integrin signaling leading to diabetes and autoimmunity
白细胞整合素信号的改变导致糖尿病和自身免疫
- 批准号:
10502136 - 财政年份:2022
- 资助金额:
$ 176.58万 - 项目类别:
Project 2: STAT3 as a trigger for T1D
项目 2:STAT3 作为 T1D 的触发因素
- 批准号:
10328102 - 财政年份:2022
- 资助金额:
$ 176.58万 - 项目类别:
Tuning peptide specifities for T cell tolerance in Type 1 diabetes
调整 1 型糖尿病 T 细胞耐受性的肽特异性
- 批准号:
10503923 - 财政年份:2022
- 资助金额:
$ 176.58万 - 项目类别:
Alterations of leukocyte integrin signaling leading to diabetes and autoimmunity
白细胞整合素信号的改变导致糖尿病和自身免疫
- 批准号:
10683384 - 财政年份:2022
- 资助金额:
$ 176.58万 - 项目类别:
STAT3 variants as a rheostat of immune tolerance
STAT3 变体作为免疫耐受的变阻器
- 批准号:
10576375 - 财政年份:2022
- 资助金额:
$ 176.58万 - 项目类别:
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