Innate immune signaling and stress response
Innate immune signaling and stress response
批准号:
9901240
负责人:
Thirumala-Devi Kanneganti
金额:
$53.85万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
未结题
起止时间:
2016-03-15 至 2026-02-28
关键词:
AffectAffinity ChromatographyAntiviral AgentsApoptosisAreaBiological ProcessCASP1 geneCell DeathCell SurvivalCellsCellular StressCellular Stress ResponseCommunicable DiseasesCuesCytosolDataGrantHealthHomeostasisHumanImmuneImmune responseImmune signalingImmunityImmunologyInfectionInflammasomeInflammationInflammatoryInflammatory ResponseInfluenza A virusInnate Immune ResponseInterleukin-1 betaInterleukin-18LinkMalignant NeoplasmsMass Spectrum AnalysisMediatingMolecularMusMutationMyeloid CellsNatural ImmunityNatureNeurodegenerative DisordersPathogenicityPathway interactionsPatternPhysiologicalPlayPositioning AttributeProductionProgress ReportsPublicationsPublishingRNARegulationRoleScienceSignal PathwaySignal TransductionStressStructureSyndromeTestingViralVirusVirus DiseasesZ-DNA Binding Proteinbiological adaptation to stresscytokineexperimental studyhelicasehuman diseasein vivoinfluenza infectioninfluenzavirusinnate immune pathwaysinterestmicrobialnew therapeutic targetpathogenpathogenic microbeprotein complexreceptorresponsesensorstress granuletargeted treatment
中文摘要
摘要
无膜区室在维持细胞和生物体内平衡中起着至关重要的作用,
调节细胞存活和细胞死亡。 应激颗粒和炎性小体诱导的斑点,
无膜区室,为细胞提供不同的细胞命运选择-存活或焦亡
(程序性细胞死亡)。 NLRP 3,全球传感器
病原体相关分子模式(PAMP)和病原体相关分子模式(DAMP),
感知胞质溶胶中的细胞扰动以触发大的半胱天冬酶-1-1激活蛋白的装配
称为NLRP 3炎性体的复合物。 NLRP 3导致的caspase-11的自身蛋白水解成熟
炎性小体激活导致细胞凋亡,促炎性细胞因子白细胞介素(IL)-β成熟
1β和IL-18。尽管NLRP 3能够响应细胞或病毒诱导的应激的不同线索,
控制炎性小体和应激颗粒之间的相互作用的机制仍然难以捉摸。 在我们
为了研究这种交叉作用,我们确定了DDX 3X,一种应激颗粒成分,作为上游的
NLRP 3炎性体的调节剂对典型和病毒触发剂的作用。在此次R 01更新中,我们建议确定
DDX 3X-β介导的NLPR 3炎性小体激活的分子和细胞机制及其对NLPR 3炎性小体的影响
在炎症和病毒感染期间通过应激信号进行调节。理解这些人之间的
细胞应激反应分子和先天免疫信号传导将产生新的治疗靶点,
炎症和感染性疾病。
英文摘要
ABSTRACT
Membraneless compartments play a vital role in maintaining cellular and organismal homeostasis by
modulating cell survival and cell death. Stress granules, and inflammasome-induced specks are
membraneless compartments that provide contrasting cell fate choices to the cells – survival or pyroptosis
(programmed cell death) during physiological or virus induced cellular stress. NLRP3, a global sensor of
pathogen–associated molecular patterns (PAMPs) and danger–associated molecular patterns (DAMPs),
senses cellular perturbations in the cytosol to trigger the assembly of a large caspase-1-activating protein
complex termed the NLRP3 inflammasome. Autoproteolytic maturation of caspase-1 due to NLRP3
inflammasome activation leads to pyroptosis, and maturation of pro-inflammatory cytokines interleukin (IL)-
1β and IL-18. Despite the ability of NLRP3 to respond to diverse cues of cellular or virus induced stress,
mechanisms controlling the cross-talk between inflammasomes and stress granules remain elusive. In our
quest to study this cross-talk, we have identified DDX3X, a stress granule component, as an upstream
regulator of NLRP3 inflammasome to canonical and viral triggers. In this R01 renewal, we propose to identify
the molecular and cellular mechanisms of DDX3X-mediated NLPR3 inflammasome activation and its
modulation by stress signals during inflammation and viral infections. Understanding the cross-talk between
cellular stress response molecules and innate immune signaling will lead to novel therapeutic targets for
inflammatory and infectious diseases.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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批准号:10631757
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资助金额:$39.34万
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财政年份:2021
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依托单位:
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批准号:10622511
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Targeting innate immune pathways, and inflammatory cell death in cytokine-mediated diseases
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批准号:10428652
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资助金额:$76.38万
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财政年份:2021
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Targeting innate immune pathways, and inflammatory cell death in cytokine-mediated diseases
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批准号:10311802
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资助金额:$76.38万
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财政年份:2021
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依托单位:
Innate immune sensors, inflammasomes, and inflammasome-mediated processes in cancer
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批准号:10633206
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资助金额:$105.55万
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财政年份:2020
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Innate immune sensors, inflammasomes, and inflammasome-mediated processes in cancer
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批准号:10220912
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项目类别:
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资助金额:$107.7万
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财政年份:2020
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Innate immune sensors, inflammasomes, and inflammasome-mediated processes in cancer
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批准号:10442693
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项目类别:
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资助金额:$100.88万
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财政年份:2020
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负责人:Thirumala-Devi Kanneganti
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依托单位:
The Non-Inflammasome NLRs in Immunity and Host defense
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批准号:9243972
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项目类别:
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资助金额:$44.88万
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财政年份:2016
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Innate immune signaling and stress response
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批准号:10327667
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项目类别:
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资助金额:$53.85万
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财政年份:2016
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Innate immune signaling and stress response
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批准号:10574531
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项目类别:
-
资助金额:$53.85万
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财政年份:2016
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负责人:Thirumala-Devi Kanneganti
-
依托单位:
Inflammatory Caspases in Innate Immunity and Inflammation
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批准号:9127673
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项目类别:
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资助金额:$44.88万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
NLR signaling in colitis and colorectal tumorigenesis
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批准号:8831610
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项目类别:
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资助金额:$36.31万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Inflammatory Caspases in Innate Immunity and Inflammation
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批准号:9912091
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项目类别:
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资助金额:$44.88万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Inflammatory Caspases in Innate Immunity and Inflammation
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批准号:8827667
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项目类别:
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资助金额:$43.75万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Innate signaling pathways in colitis and colorectal tumorigenesis
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批准号:9120535
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项目类别:
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资助金额:$42.63万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Inflammatory Caspases in Innate Immunity and Inflammation
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批准号:10295212
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项目类别:
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资助金额:$45.5万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Inflammatory Caspases in Innate Immunity and Inflammation
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批准号:8365332
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项目类别:
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资助金额:$43.75万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
NLR signaling in colitis and colorectal tumorigenesis
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批准号:8373063
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项目类别:
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资助金额:$36.31万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
NLR signaling in colitis and colorectal tumorigenesis
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批准号:8507633
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项目类别:
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资助金额:$34.13万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
NLR signaling in colitis and colorectal tumorigenesis
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批准号:8658700
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项目类别:
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资助金额:$35.22万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
-
依托单位:
海外基金