EPH-RECEPTOR SIGNALING IN LENS DEVELOPMENT AND AGING
EPH-RECEPTOR SIGNALING IN LENS DEVELOPMENT AND AGING
批准号:
8557740
负责人:
Alan Shiels
金额:
$35.23万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-08-01 至 2018-07-31
关键词:
AgingAllelesArchitectureBiological ProcessBlindnessCataractCellsChildhoodCodeCollaborationsComplexCrystalline LensDevelopmentEmbryonic DevelopmentEnvironmentEnvironmental Risk FactorEph Family ReceptorsFaceFamilyFrequenciesFunctional RNAFunctional disorderGene TargetingGenesGenetic VariationGerm LinesGiant CellsGoalsHumanImageImaging TechniquesImmunologic SurveillanceInheritedInterdisciplinary StudyKnock-in MouseKnockout MiceLens FiberLinkMass Spectrum AnalysisMembraneModelingMolecularMolecular GeneticsMusMutant Strains MiceMutationOpticsPathologic ProcessesPhenotypePhosphorylationPrevalenceProcessPropertyProteolytic ProcessingProteomeProteomicsReceptor Protein-Tyrosine KinasesReceptor SignalingReporterResearchRiskRoleSignal TransductionSiteSunlightSurgical suturesTechniquesTestingTransgenic OrganismsUltraviolet B RadiationUniversitiesVariantVirus DiseasesVisual impairmentWorkage relatedbasecase controlcohortcomparativecomputerized data processingcongenital cataractfiber cellgain of functionhuman EPHA2 proteininsightinterdisciplinary approachlenslens transparencyloss of functionmembermutantnext generation sequencingprotein functionprotein protein interactionpublic health relevancereceptortissue regenerationtumor progression
中文摘要
项目摘要
Eph受体酪氨酸激酶激活复杂的信号网络,参与不同的生物和
病理过程包括胚胎发育、组织再生、免疫监测、肿瘤
进展和病毒感染。最近,编码其中一种受体EphA2的基因发生了变异
与遗传性和年龄相关的人类白内障有关,而EphA2已被发现是一种
晶状体膜蛋白质组有丰富的成分,但知之甚少。这个项目的总体目标是
研究是为了促进对EPH受体信号在晶状体发育和老化中的理解。在这
建议我们将采用跨学科的方法来阐明连接基因的分子机制
EphA2随晶状体表型的变化。首先,我们将执行定向测序以确定
EphA2编码变异与晶状体老化的关系第二,我们将使用基因靶向的小鼠和
用于表征EphA2在晶状体发育过程中的功能和功能障碍的成像技术。最后我们会
采用蛋白质组学技术来表征EphA2信号和在晶状体中的处理。结果来自
这些研究将为EPH受体信号在晶状体发育和发育中的作用提供新的见解
衰老,在白内障形成的背景下--视力受损的一个重要原因。
英文摘要
Project Summary
EPH-receptor tyrosine kinases activate complex signaling networks involved in diverse biological and
pathological processes including embryonic development, tissue regeneration, immune surveillance, tumor
progression and viral infection. Recently, variations in the gene encoding one of these receptors, EPHA2, have
been associated with inherited and age-related forms of human cataract, and EPHA2 has been identified as an
abundant, but poorly understood, component of the lens membrane proteome. The overall goal of this
research is to advance understanding of EPH-receptor signaling in lens development and aging. In this
proposal we will conduct an interdisciplinary approach to elucidate molecular mechanisms that connect genetic
variation in EPHA2 with lens phenotype. First, we will perform targeted-sequencing to determine the
relationship between EPHA2 coding variation and lens aging. Second, we will use gene-targeted mice and
imaging techniques to characterize EPHA2 function and dysfunction during lens development. Finally we will
undertake proteomics techniques to characterize EPHA2 signaling and processing in the lens. Results from
these studies will provide new insights regarding the role of EPH-receptor signaling in lens development and
aging, within the context of cataract formation - an important cause of visual impairment.
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会议论文
TRP-CHANNELS IN LENS DEVELOPMENT AND CATARACT
-
批准号:10557158
-
项目类别:
-
资助金额:$38.09万
-
财政年份:2019
-
负责人:Alan Shiels
-
依托单位:
TRP-CHANNELS IN LENS DEVELOPMENT AND CATARACT
-
批准号:10327301
-
项目类别:
-
资助金额:$36.94万
-
财政年份:2019
-
负责人:Alan Shiels
-
依托单位:
EPH-RECEPTOR SIGNALING IN LENS DEVELOPMENT AND AGING
-
批准号:8705525
-
项目类别:
-
资助金额:$33.88万
-
财政年份:2013
-
负责人:Alan Shiels
-
依托单位:
EPH-RECEPTOR SIGNALING IN LENS DEVELOPMENT AND AGING
-
批准号:9310254
-
项目类别:
-
资助金额:$34.2万
-
财政年份:2013
-
负责人:Alan Shiels
-
依托单位:
HUMAN LENS CONNEXIN GENES IN HEREDITARY CATARACT
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批准号:2888631
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项目类别:
-
资助金额:$22.5万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
Genetic Determinants of Cataract
-
批准号:8113414
-
项目类别:
-
资助金额:$32.5万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
Genetic Determinants of Cataract
-
批准号:7927837
-
项目类别:
-
资助金额:$5.62万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
GENETIC DETERMINANTS OF CATARACT
-
批准号:8629744
-
项目类别:
-
资助金额:$43.28万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
HUMAN LENS CONNEXIN GENES IN HEREDITARY CATARACT
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批准号:2687610
-
项目类别:
-
资助金额:$28.09万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
HUMAN LENS CONNEXIN GENES IN HEREDITARY CATARACT
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批准号:6179043
-
项目类别:
-
资助金额:$23.82万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
Genetic Determinants of Cataract
-
批准号:7452324
-
项目类别:
-
资助金额:$33.52万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
Genetic determinants of cataract
-
批准号:6896174
-
项目类别:
-
资助金额:$34.43万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
Genetic Determinants of Cataract
-
批准号:7260923
-
项目类别:
-
资助金额:$34.2万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
Genetic determinants of cataract
-
批准号:7068481
-
项目类别:
-
资助金额:$53.16万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
Genetic Determinants of Cataract
-
批准号:7633213
-
项目类别:
-
资助金额:$34.2万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
Genetic determinants of cataract
-
批准号:6614471
-
项目类别:
-
资助金额:$34.43万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
Genetic determinants of cataract
-
批准号:7121696
-
项目类别:
-
资助金额:$15.62万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
GENETIC DETERMINANTS OF CATARACT
-
批准号:8292357
-
项目类别:
-
资助金额:$42.99万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
Genetic determinants of cataract
-
批准号:6763198
-
项目类别:
-
资助金额:$34.43万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
GENETIC DETERMINANTS OF CATARACT
-
批准号:8449087
-
项目类别:
-
资助金额:$46.62万
-
财政年份:1998
-
负责人:Alan Shiels
-
依托单位:
海外基金