The Genomic Analysis of Erythrocyte microRNA in Sickle Cell Diseases
镰状细胞病中红细胞 microRNA 的基因组分析
基本信息
- 批准号:8011820
- 负责人:
- 金额:$ 10万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-03-12 至 2011-04-30
- 项目状态:已结题
- 来源:
- 关键词:AchievementAffectAnemiaBeliefBioinformaticsBiologicalBiological AssayBiologyCellsClinicalCommunicable DiseasesDevelopmentDiagnosticDiseaseDisease OutcomeEconomicsErythrocytesErythroidErythropoiesisExplosionFigs - dietaryFunctional RNAGene ExpressionGene Expression RegulationGeneticGenetic DeterminismGenetic TranscriptionGenomicsGoalsGrowthHemoglobinopathiesHeterogeneityHumanIn VitroInfectionKnowledgeLeadLearningMalariaMicroRNAsMicroarray AnalysisMolecularMutationNucleotidesParasitesPatientsPatternPhenotypePlasmodium falciparumPlayPredispositionProceduresRaceRecording of previous eventsRoleSickle CellSickle Cell AnemiaSickle Cell TraitStagingTherapeuticTimeVariantasexualbaseclinical phenotypedisease phenotypedisorder subtypeexperiencehemoglobin AAhuman diseaseimprovedinsightnovelpublic health relevanceresearch studysocialtool
项目摘要
DESCRIPTION (provided by applicant): Human red blood cell (erythrocyte) diseases, including anemia and malaria, pose a huge burden for the human race. Our understanding of these diseases is rather limited. For example, while the genetic cause of sickle cell diseases (SCD) and the positive selection of them imposed by malaria infection have been long established, much remains to be learned about how SCD erythrocyte phenotypes contribute to diverse clinical manifestations and to altered interaction with malaria parasites. Human mature erythrocytes are thought to lack most RNA expression. With a procedure capturing small-sized RNAs, we have found that human mature erythrocytes still possess abundant and diverse microRNAs (miRNAs), a class of 21-23 nucleotide non-coding RNA with important regulatory functions. Given the potential regulatory roles of miRNAs during erythropoiesis, the erythrocyte miRNA pool is likely to contain important biological information, indicate developmental history, and show biological phenotypes of erythrocytes. The analysis of miRNA expression with miRNA microarrays indeed reveals a dramatic difference between normal and SCD erythrocytes. Erythrocyte miRNAs may also play a functional role in the mature erythrocyte. Several miRNAs have been found to be translocated into malaria parasites during intraerythrocytic infection. These transferred miRNAs disrupt the growth and replication of malaria parasites. We hypothesize that the altered miRNA expression in SCD erythrocytes compared to normal erythrocytes may contribute to their decreased susceptibility to malaria infection. In this proposal, we plan to apply genomic tools and advanced bioinformatics to examine the role of miRNAs as genetic determinants of SCD phenotypes and malaria susceptibility. In the first specific aim, we will identify erythrocyte miRNAs whose expression can distinguish between normal erythrocytes, different SCD subtypes, and other anemia disorders. The identification of these miRNAs will hold diagnostic value for anemia disorders and lead to fresh insights into relevant underlying pathophysiological mechanisms. In the second aim, we will determine whether the differences in miRNA composition among different types of erythrocytes contribute to their differing susceptibility to malaria infection. The completion of these experiments will result in a better understanding of the role of miRNAs in determining erythrocyte phenotypes in hemoglobinopathies and infectious diseases as well as provide better therapeutic strategies for SCD and malaria infection. PUBLIC HEALTH RELEVANCE: In this proposal titled "The Genomic Analysis of Erythrocyte microRNA in Sickle Cell Diseases", I plan to use novel genomic tools and advanced bioinformatics to analyze the erythrocyte microRNA contents in sickle cell diseases. We expect that our study will determine the role of erythrocyte microRNAs in informing the erythrocyte phenotypes and clinical manifestations of sickle cell diseases. We will also define the role of erythrocyte microRNA in determining the in vitro susceptibility to Plasmodium falciparum among the normal and sickle erythrocytes.
描述(申请人提供):人类红细胞(红细胞)疾病,包括贫血和疟疾,给人类带来了巨大的负担。我们对这些疾病的了解相当有限。例如,虽然疟疾感染引起的镰状细胞病(SCD)的遗传原因和积极选择早已确定,但关于SCD红细胞表型如何有助于不同的临床表现和改变与疟疾寄生虫的相互作用,仍有许多有待了解。人类成熟的红细胞被认为缺乏大部分RNA的表达。通过捕获小型RNA的过程,我们发现人类成熟的红细胞仍然拥有丰富多样的microRNAs(MiRNAs),这是一类具有重要调控功能的21-23个核苷酸的非编码RNA。鉴于miRNAs在红细胞生成过程中的潜在调节作用,红细胞miRNA池可能包含重要的生物信息,指示发育历史,并显示红细胞的生物学表型。用miRNA微阵列分析miRNA的表达确实揭示了正常和SCD红细胞之间的显著差异。红细胞miRNAs也可能在成熟红细胞中发挥作用。在红细胞内感染期间,已发现几个miRNAs转位到疟疾寄生虫中。这些转移的miRNAs干扰了疟疾寄生虫的生长和复制。我们推测,与正常红细胞相比,SCD红细胞中miRNA表达的改变可能有助于降低其对疟疾感染的易感性。在这项提案中,我们计划应用基因组学工具和先进的生物信息学来研究miRNAs作为SCD表型和疟疾易感性的遗传决定因素的作用。在第一个特定目标中,我们将鉴定其表达可以区分正常红细胞、不同SCD亚型和其他贫血疾病的红细胞miRNAs。这些miRNAs的鉴定将对贫血疾病具有诊断价值,并导致对相关潜在病理生理机制的新见解。在第二个目标中,我们将确定不同类型红细胞之间miRNA组成的差异是否有助于它们对疟疾感染的不同易感性。这些实验的完成将使人们更好地了解miRNAs在确定血红蛋白疾病和传染病的红细胞表型中的作用,并为SCD和疟疾感染提供更好的治疗策略。公共卫生相关性:在这项题为《镰状细胞疾病中的红细胞microRNA的基因组分析》的提案中,我计划使用新的基因组工具和先进的生物信息学来分析镰状细胞疾病的红细胞microRNA含量。我们期望我们的研究将确定红细胞microRNAs在告知镰状细胞疾病的红细胞表型和临床表现方面的作用。我们还将确定红细胞microRNA在确定正常红细胞和镰刀状红细胞对恶性疟原虫体外敏感性方面的作用。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin.
- DOI:10.1371/journal.pgen.1003408
- 发表时间:2013-04
- 期刊:
- 影响因子:4.5
- 作者:Sangokoya C;Doss JF;Chi JT
- 通讯作者:Chi JT
Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum.
研究恶性疟原虫小 RNA 和核糖体占据的调节作用的方法。
- DOI:10.3791/53214
- 发表时间:2015
- 期刊:
- 影响因子:0
- 作者:LaMonte,Gregory;Walzer,KatelynA;Lacsina,Joshua;Nicchitta,Christopher;Chi,Jen-Tsan
- 通讯作者:Chi,Jen-Tsan
Isolation and characterization of microRNAs of human mature erythrocytes.
- DOI:10.1007/978-1-60761-811-9_13
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
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Jen-Tsan Ashley Chi其他文献
Lysyl oxidase is essential for hypoxia-induced metastasis
赖氨酰氧化酶对于缺氧诱导的转移是必不可少的
- DOI:
10.1038/nature04695 - 发表时间:
2006-04-27 - 期刊:
- 影响因子:48.500
- 作者:
Janine T. Erler;Kevin L. Bennewith;Monica Nicolau;Nadja Dornhöfer;Christina Kong;Quynh-Thu Le;Jen-Tsan Ashley Chi;Stefanie S. Jeffrey;Amato J. Giaccia - 通讯作者:
Amato J. Giaccia
Jen-Tsan Ashley Chi的其他文献
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{{ truncateString('Jen-Tsan Ashley Chi', 18)}}的其他基金
Development of MESH1 inhibitors to treat ferroptosis-associated neurodegeneration
开发 MESH1 抑制剂来治疗铁死亡相关的神经变性
- 批准号:
10432233 - 财政年份:2022
- 资助金额:
$ 10万 - 项目类别:
Biochemical and functional investigation of the novel enzymatic activities of MESH1
MESH1 新型酶活性的生化和功能研究
- 批准号:
10237887 - 财政年份:2018
- 资助金额:
$ 10万 - 项目类别:
Biochemical and functional investigation of the novel enzymatic activities of MESH1
MESH1 新型酶活性的生化和功能研究
- 批准号:
10372271 - 财政年份:2018
- 资助金额:
$ 10万 - 项目类别:
Gene expression programs of lactic acidosis in human cancers
人类癌症中乳酸性酸中毒的基因表达程序
- 批准号:
7810437 - 财政年份:2009
- 资助金额:
$ 10万 - 项目类别:
The Genomic Analysis of Erythrocyte microRNA in Sickle Cell Diseases
镰状细胞病中红细胞 microRNA 的基因组分析
- 批准号:
7530022 - 财政年份:2008
- 资助金额:
$ 10万 - 项目类别:
The Genomic Analysis of Erythrocyte microRNA in Sickle Cell Diseases
镰状细胞病中红细胞 microRNA 的基因组分析
- 批准号:
7681606 - 财政年份:2008
- 资助金额:
$ 10万 - 项目类别:
Gene expression programs of lactic acidosis in human cancers
人类癌症中乳酸性酸中毒的基因表达程序
- 批准号:
8296379 - 财政年份:2007
- 资助金额:
$ 10万 - 项目类别:
Gene expression programs of lactic acidosis in human cancers
人类癌症中乳酸性酸中毒的基因表达程序
- 批准号:
8064456 - 财政年份:2007
- 资助金额:
$ 10万 - 项目类别:
Gene expression programs of lactic acidosis in human cancers
人类癌症中乳酸性酸中毒的基因表达程序
- 批准号:
8244657 - 财政年份:2007
- 资助金额:
$ 10万 - 项目类别:
Gene expression programs of lactic acidosis in human cancers
人类癌症中乳酸性酸中毒的基因表达程序
- 批准号:
8657837 - 财政年份:2007
- 资助金额:
$ 10万 - 项目类别:
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