Transcriptional control of stress-induced resistance to retinal degeneration
Transcriptional control of stress-induced resistance to retinal degeneration
批准号:
10296291
负责人:
John D Ash
金额:
$38.37万
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
项目状态:
未结题
起止时间:
2021-09-01 至 2026-08-31
关键词:
AffectAge related macular degenerationBindingBlindnessCell DeathCellsCessation of lifeChIP-seqCytoprotectionDataData SetDiseaseDisease ClusteringsFGF2 geneGene ExpressionGene MutationGenesGenetic TranscriptionGliosisIndividualInflammationInflammatoryInjectionsInjuryKnockout MiceKnowledgeLIF geneLIFR geneLeadLightMediatingMethodsMicrogliaModelingMuller&aposs cellMusMutationNF-kappa BPathologicPhotoreceptorsPhototransductionPlayPublicationsPublishingQuality of lifeRegulationResearchResistanceRetinaRetinal DegenerationRodRoleSignal TransductionSiteStressTechniquesTestingTissuesTranscription CoactivatorTranscriptional ActivationTranscriptional RegulationTransducersUnited StatesWorkbiological adaptation to stresscell typecytokinedesigndifferential expressioninherited retinal degenerationinjurednovel therapeuticspromoterreceptorresponseretinal neuronretinal rodssingle-cell RNA sequencingstress statetranscription factor
中文摘要
摘要:
视网膜变性是一大簇疾病,其特征在于不可逆的视网膜变性。
光感受器这些细胞的死亡会导致永久性的视力丧失,
对个人生活质量的影响。尽管视网膜变性的诱因多种多样,
光感受器死亡的机制通常是相似的,这表明有可能发生
基因/突变独立的方法,以减少失明的多种形式的视网膜变性。我们
其他研究表明,STAT 3在所有视网膜细胞中都被激活,包括光感受器和Müller细胞
遗传性视网膜退化另外的研究表明,STAT 3的激活在细胞凋亡中起着至关重要的作用。
在促进广泛的基因表达变化以增加细胞抵抗细胞死亡的能力中起作用。
然而,尽管有这些令人印象深刻的发现,在确定机制方面进展甚微,
其中STAT 3调节保护。在这个项目中,我们将使用最先进的技术,包括单细胞
RNA-seq并将数据与细胞特异性ChIP-seq整合,以全面鉴定所有基因,
视网膜Müller细胞和视杆细胞中STAT 3调控的转录网络。
英文摘要
Abstract:
Retinal degenerations are a large cluster of diseases characterized by the irreversible loss of
photoreceptors. The death of these cells results in a permanent loss of vision that can have debilitating
impacts on an individual's quality of life. Despite the diversity among triggers for retinal degenerations, the
mechanisms surrounding photoreceptor death are often similar, suggesting the possibility of developing
gene/mutation-independent approaches to reduce blindness from multiple forms of retinal degeneration. We
and others have shown that STAT3 is activated in all retinal cells, including photoreceptors and Müller cells
during inherited retinal degeneration. Additional work has shown that activation of STAT3 plays an essential
role in promoting a wide array of gene expression changes to increase the cell’s capacity to resist cell death.
However, despite these impressive findings, little progress has been made in identifying the mechanisms by
which STAT3 regulates protection. In this project, we will use state of the art techniques including single-cell
RNA-seq and integrating the data with cell-specific ChIP-seq to comprehensively identify all genes and
transcriptional networks regulated by STAT3 in retinal Müller cells and rods.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Retinal Degeneration Conference
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批准号:10785476
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项目类别:
-
资助金额:$5.5万
-
财政年份:2023
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负责人:John D Ash
-
依托单位:
Dual Targeting Mitochondria and GPCR in Retinal Protection
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批准号:10383538
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项目类别:
-
资助金额:$25.57万
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财政年份:2022
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负责人:John D Ash
-
依托单位:
Transcriptional control of stress-induced resistance to retinal degeneration
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批准号:10477262
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项目类别:
-
资助金额:$37.22万
-
财政年份:2021
-
负责人:John D Ash
-
依托单位:
Transcriptional control of stress-induced resistance to retinal degeneration
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批准号:10842755
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项目类别:
-
资助金额:$38.37万
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财政年份:2021
-
负责人:John D Ash
-
依托单位:
Regulators of retinal metabolism in healthy and degenerating retinas
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批准号:10028851
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项目类别:
-
资助金额:$46.71万
-
财政年份:2020
-
负责人:John D Ash
-
依托单位:
Regulators of retinal metabolism in healthy and degenerating retinas
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批准号:10455542
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项目类别:
-
资助金额:$44.03万
-
财政年份:2020
-
负责人:John D Ash
-
依托单位:
Regulators of retinal metabolism in healthy and degenerating retinas
-
批准号:10247603
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项目类别:
-
资助金额:$44.03万
-
财政年份:2020
-
负责人:John D Ash
-
依托单位:
Regulators of retinal metabolism in healthy and degenerating retinas
-
批准号:10834510
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项目类别:
-
资助金额:$45.39万
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财政年份:2020
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负责人:John D Ash
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依托单位:
Administrative Supplement to Regulators of retinal metabolism in healthy and degenerating retinas
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批准号:10361928
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项目类别:
-
资助金额:$13.05万
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财政年份:2020
-
负责人:John D Ash
-
依托单位:
Comparative transcriptomic and epigenomic analyses of Muller glia reprogramming
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批准号:9551199
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项目类别:
-
资助金额:$57.62万
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财政年份:2016
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负责人:John D Ash
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依托单位:
Retinal Degeneration Conference
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批准号:9993713
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项目类别:
-
资助金额:$5.5万
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财政年份:2012
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负责人:John D Ash
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依托单位:
Cytokine Regulation of Photoreceptor Gene Expression
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批准号:8413002
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项目类别:
-
资助金额:$35.16万
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财政年份:2012
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负责人:John D Ash
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依托单位:
Retinal Degeneration Conference
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批准号:10364600
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项目类别:
-
资助金额:$0.0万
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财政年份:2012
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负责人:John D Ash
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依托单位:
Cytokine Regulation of Photoreceptor Gene Expression
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批准号:8332337
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项目类别:
-
资助金额:$35.52万
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财政年份:2012
-
负责人:John D Ash
-
依托单位:
MOLECULAR BIOLOGY
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批准号:8360405
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项目类别:
-
资助金额:$11.01万
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财政年份:2011
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负责人:John D Ash
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依托单位:
MOLECULAR BIOLOGY
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批准号:8168349
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项目类别:
-
资助金额:$14.6万
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财政年份:2010
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负责人:John D Ash
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依托单位:
ROLE OF THE INTERLEUKIN 6 CYTOKINE FAMILY RECEPTOR GP130 IN DIABETES
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批准号:7959971
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项目类别:
-
资助金额:$20.99万
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财政年份:2009
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负责人:John D Ash
-
依托单位:
Cytokine Regulation of Photoreceptor Gene Expression
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批准号:7846053
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项目类别:
-
资助金额:$36.63万
-
财政年份:2009
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负责人:John D Ash
-
依托单位:
MOLECULAR BIOLOGY
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批准号:7959976
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项目类别:
-
资助金额:$12.74万
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财政年份:2009
-
负责人:John D Ash
-
依托单位:
ROLE OF THE INTERLEUKIN 6 CYTOKINE FAMILY RECEPTOR GP130 IN DIABETES
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批准号:7720533
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项目类别:
-
资助金额:$21.41万
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财政年份:2008
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负责人:John D Ash
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依托单位:
海外基金