Licensing LncRNAs in Atherosclerosis
Licensing LncRNAs in Atherosclerosis
批准号:
10318206
负责人:
Tamer Sallam
金额:
$62.7万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-12-15 至 2024-11-30
关键词:
ATP binding cassette transporter 1AddressAffectAffinityAnimalsAtherosclerosisBindingBinding SitesBiologicalBiological AssayBiologyBone MarrowCardiometabolic DiseaseCardiovascular DiseasesCardiovascular systemCellsCessation of lifeCholesterolChromatinComb animal structureCoronary ArteriosclerosisCuesDataDevelopmentDiagnosticDietEnsureEvolutionFoam CellsGene ExpressionGene Expression RegulationGenesGeneticGoalsHeart DiseasesHepaticHomeostasisHumanImmune signalingInflammationJunk DNAKnock-outKnowledgeLesionLicensingLinkLipidsLiverManuscriptsMetabolicMetabolic DiseasesMetabolismMethodologyModelingMolecularMorbidity - disease rateMusPathologic ProcessesPathway interactionsPhenotypePhysiologicalPlasmaPlayRecurrenceRegulationReportingRoleSeriesSpecificitySterolsTestingTherapeuticTimeTreatment EfficacyUntranslated RNAWorkbaseburden of illnesscardiogenesiscardiometabolismcardiovascular risk factordefined contributiondietarydisease phenotypeefficacy testingepigenomicsfatty liver diseasegain of functiongene therapygenome wide association studygenome-wideheart disease riskhuman diseaseimprovedin vivoin vivo evaluationinnovationinsightlipid metabolismloss of functionmacrophagemortalitymouse modelnonalcoholic steatohepatitisnovelpleiotropismpreferencereverse cholesterol transportscreeningtherapeutic RNAtherapeutic targettooltraittreatment strategy
中文摘要
项目摘要
全世界1800万心血管死亡中的大多数被认为是由于动脉粥样硬化,
也许是影响人类的最具破坏性的病理过程。最近新陈代谢的激增
干扰将确保动脉粥样硬化不会消失。本申请解决了大量
知识差距,并利用我们小组的最新发现和新的初步证据
提示长链非编码RNA(lncRNA)影响动脉粥样硬化的发展,
心脏代谢异常本提案的目的是:1)定义lncRNA在
心血管代谢疾病,2)提高我们对lncRNA之间复发关系的理解
3)测试基于lncRNA的治疗策略在心血管疾病中的功效。
疾病与本申请的目标一致,我们的多中心协作小组在以下方面拥有集体专业知识:
lncRNA生物学、动脉粥样硬化和代谢疾病、表观基因组分析方法学和解剖
人类疾病中的基因-表型关系。这一提议的首要假设是,
是在脂质代谢中起作用的lncRNA,其特征尚待描述,并且当与背景靶向时,
特异性,它们可以减轻相关模型中的疾病表型。使用综合筛选平台
结合小鼠和人类的研究,我们发现了新的lncRNA参与肝脏脂质代谢,开发了一种新的lncRNA,
强大的管道,优先考虑lncRNA的功能发现,并引入新的工具,lncRNA在体内
扰动目的1、探讨巨噬细胞lncRNAs在动脉粥样硬化中的作用,
用于靶向病变的基于lncRNA的治疗。目的2:研究lncRNA在肝细胞中的作用。
脂质代谢和测试跨物种功能保守的证据,尽管序列进化。
这些研究有望揭示非编码基因调控在人类免疫系统中的重要性。
心脏代谢控制,并为心血管疾病中基于lncRNA的治疗提供框架。在
总之,这个以发现为导向的建议将填补动脉粥样硬化领域的大量知识空白
和lncRNA生物学
英文摘要
PROJECT SUMMARY
The majority of the 18 million worldwide cardiovascular deaths are thought to be due to atherosclerosis,
perhaps the single most devastating pathologic process affecting mankind. The recent surge in metabolic
disturbances will ensure that atherosclerosis will not just fade away. This application addresses substantial
knowledge gaps and capitalizes on recent discoveries from our group and new preliminary evidence
suggesting that long noncoding RNAs (lncRNAs) influence the development of atherosclerosis and
cardiometabolic abnormalities. The objective of this proposal is to 1) define the contributions of lncRNAs in
cardiometabolic diseases, 2) improve our understanding of recurrent relationships between lncRNA
conservation and function and 3) test the efficacy of lncRNA-based therapeutic strategies in cardiovascular
disease. Aligned with goals of this application our multicenter collaborative group has collective expertise in
lncRNA biology, atherosclerosis and metabolic disease, epigenomic profiling methodologies, and dissecting
gene-phenotype relationships in human disease. The overarching hypothesis of this proposal is that there may
be lncRNAs with roles in lipid metabolism that are yet to be characterized and when targeted with context
specificity they can mitigate disease phenotypes in relevant models. Using an integrative screening platform
combing mouse and human studies, we identify novel lncRNA involved in hepatic lipid metabolism, develop a
robust pipeline that prioritizes lncRNA functional discovery, and introduce new tools for lncRNA in vivo
perturbations. Aim 1, will determine role of macrophage lncRNAs in atherosclerosis and explore opportunities
for lncRNA-based therapeutics targeting lesions. In Aim 2, we investigate the function of lncRNAs in hepatic
lipid metabolism and test for evidence of cross-species functional conservation despite sequence evolution.
These studies are expected to shed fundamental insight into the significance of noncoding gene regulation in
cardiometabolic control and provide a framework for lncRNA-based therapeutics in cardiovascular disease. In
summary, this discovery-oriented proposal will fill substantial knowledge gaps in the fields of atherosclerosis
and lncRNA biology.
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会议论文
RNA modification in cardiometabolic disease
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批准号:10295370
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项目类别:
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资助金额:$55.97万
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财政年份:2021
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负责人:Tamer Sallam
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依托单位:
RNA modification in cardiometabolic disease
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批准号:10618327
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项目类别:
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资助金额:$55.97万
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财政年份:2021
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负责人:Tamer Sallam
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依托单位:
RNA modification in cardiometabolic disease
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批准号:10445063
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项目类别:
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资助金额:$55.97万
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财政年份:2021
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负责人:Tamer Sallam
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依托单位:
Licensing LncRNAs in Atherosclerosis
-
批准号:10533322
-
项目类别:
-
资助金额:$62.7万
-
财政年份:2020
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负责人:Tamer Sallam
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依托单位:
Long Non-coding RNAs in the Regulation of Adipogenesis and Obesity
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批准号:10394951
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项目类别:
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资助金额:$38.08万
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财政年份:2018
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负责人:Tamer Sallam
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依托单位:
Long Non-coding RNAs in the Regulation of Adipogenesis and Obesity
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批准号:10163175
-
项目类别:
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资助金额:$38.08万
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财政年份:2018
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负责人:Tamer Sallam
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依托单位:
RNA-binding proteins in atherosclerosis
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批准号:10375500
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项目类别:
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资助金额:$38.03万
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财政年份:2018
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负责人:Tamer Sallam
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依托单位:
Long Non-coding RNAs in the Regulation of Adipogenesis and Obesity
-
批准号:9920138
-
项目类别:
-
资助金额:$38.08万
-
财政年份:2018
-
负责人:Tamer Sallam
-
依托单位:
RNA-binding proteins in atherosclerosis
-
批准号:9888406
-
项目类别:
-
资助金额:$38.07万
-
财政年份:2018
-
负责人:Tamer Sallam
-
依托单位:
Long Non-coding RNAs in Cardiometabolic Disease
-
批准号:8949599
-
项目类别:
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资助金额:$14.45万
-
财政年份:2015
-
负责人:Tamer Sallam
-
依托单位:
Long Non-coding RNAs in Cardiometabolic Disease
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批准号:9108166
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项目类别:
-
资助金额:$18.49万
-
财政年份:2015
-
负责人:Tamer Sallam
-
依托单位:
海外基金