Epigenomics of T cells and innate immune cells in human asthma
人类哮喘中 T 细胞和先天免疫细胞的表观基因组学
基本信息
- 批准号:8689150
- 负责人:
- 金额:$ 109.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-23 至 2016-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptedAffectAgingAllergicAllergic DiseaseAmericanAsthmaBasophilsBiopsyBloodBlood CellsBoxingCD4 Positive T LymphocytesCell CountCell LineageCell physiologyCellsChromatinChronicClinicalClinical DataCountryCytosineDNADNA MethylationDataData SetDatabasesDevelopmentDiagnosisDiseaseEnzymesEpigenetic ProcessExtrinsic asthmaGenesGeneticGenetic VariationGenomeGoalsHealthHelper-Inducer T-LymphocyteHistonesHumanHydroxylationIL13 geneIL4 geneIL5 geneImmuneImmunologyIndividualLaboratoriesLinkLung Lavage FluidLysineMalignant NeoplasmsMapsMediatingMethodsMethylationModificationMolecularMusOutputPathogenesisPatientsPatternPharmaceutical PreparationsPolymorphism AnalysisPopulationProteinsRNARNA SequencesReadingResearchRoleSeminalSeveritiesSeverity of illnessSingle Nucleotide PolymorphismSorting - Cell MovementStem cellsSymptomsT-LymphocyteTestingTetanus Helper PeptideTimeWorkWritingairway inflammationasthmatic patientbasecell typecohortcytokinedatabase designdisease phenotypeepigenetic markerepigenomeepigenomicsgenome wide association studygenome-widehistone modificationhuman diseaseinnovationmacrophagenew therapeutic targetnovelresearch clinical testingresponsetranscription factor
项目摘要
PROJECT SUMMARY or ABSTRACT
In this multi-PI proposal we will investigate the role of epigenetic mechanisms in the pathogenesis of allergic
asthma. Asthma affects 1 in 15 Americans -- over 23 million people -- thus making it one of the country's
most common and also costly diseases. Current therapies do not cure asthma or control daily symptoms for
patients with severe disease, prompting us to adopt "out-of-box" approaches to find novel therapies for
asthma. Our goal is to directly address the unmet need for asthma sufferers by harnessing the seminal
discoveries made in the field of epigenetics to benefit asthma research. Multiple lines of evidence suggest
an important role for epigenetic mechanisms in asthma. Specifically, we have identified disease-specific
epigenetic signatures in the T helper 2 (Th2) cytokine locus (encompassing the IL4, IL5 and IL13 genes) in
patients with moderate asthma compared to patients with mild asthma or controls. In addition, we recently
discovered TET proteins that convert 5-methylcytosine (5mC) to 5-hydroxymethyl-cytosine (hmC) in DNA,
thus creating a completely new epigenetic mark; and have shown that Tet proteins and 5hmC are
expressed in T cells. These are exciting findings because hydroxylation of 5mC alters DNA methylation
status in a hitherto unprecedented way, and because DNA methylation is relevant to several fields including
mammalian development, cancer, aging, cell lineage specification, genome defense, stem cell function and
immunology.
We propose to extend these studies genome-wide to identify epigenomic signatures that correlate with
asthma development and severity, by comparing histone modifications and DNA methylation/ hydroxy-
methylation patterns in enriched populations of pathogenic T cells and innate immune cells freshly isolated
from blood and airways of asthmatic patients versus control individuals. Our study will be the first to define
disease-related epigenetic changes in patients with well-characterized asthma, and to correlate these with
disease severity to obtain specific markers for distinguishable disease states.
We will test the hypothesis that asthma - a chronic allergic disease -- is characterized by perturbations in
these epigenetic processes in immune cells, that can be recognized and read out as long-range epigenetic
changes at relevant disease-associated loci. In Aim 1, we will map genome-wide transcriptional and histone
modification patterns in immune cells that initiate and maintain airway inflammation in asthma. In Aim 2, we
will profile patterns of DNA methylation and hydroxymethylation in immune cells in asthma. In Aim 3, we will
identify epigenetic markers of disease by establishing and analyzing an integrated database of epigenomic,
genetic, functional and clinical data. These proposed studies are novel and innovative. They will have a
broad impact on our understanding of asthma, and set an important precedent for investigating the role of
epigenetic mechanisms in other immune-mediated disorders.
)
项目摘要或摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Bjoern Peters其他文献
Bjoern Peters的其他文献
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{{ truncateString('Bjoern Peters', 18)}}的其他基金
THE CANCER EPITOPE DATABASE AND ANALYSIS RESOURCE
癌症表位数据库和分析资源
- 批准号:
10842172 - 财政年份:2023
- 资助金额:
$ 109.23万 - 项目类别:
THE CANCER EPITOPE DATABASE AND ANALYSIS RESOURCE
癌症表位数据库和分析资源
- 批准号:
10187436 - 财政年份:2021
- 资助金额:
$ 109.23万 - 项目类别:
THE CANCER EPITOPE DATABASE AND ANALYSIS RESOURCE
癌症表位数据库和分析资源
- 批准号:
10401896 - 财政年份:2021
- 资助金额:
$ 109.23万 - 项目类别:
THE CANCER EPITOPE DATABASE AND ANALYSIS RESOURCE
癌症表位数据库和分析资源
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10647651 - 财政年份:2021
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Developing computational models to predict the immune response to B. pertussis booster vaccination
开发计算模型来预测百日咳博德特氏菌加强疫苗接种的免疫反应
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10570832 - 财政年份:2020
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Developing computational models to predict the immune response to B. pertussis booster vaccination
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Developing computational models to predict the immune response to B. pertussis booster vaccination
开发计算模型来预测百日咳博德特氏菌加强疫苗接种的免疫反应
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Large Scale T Cell Epitope Discovery: Proteome-wide characterization of T cell epitopes from Mycobacterium tuberculosis in vaccination and active infection
大规模 T 细胞表位发现:疫苗接种和主动感染中结核分枝杆菌 T 细胞表位的全蛋白质组表征
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10610271 - 财政年份:2019
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Large Scale T Cell Epitope Discovery: Proteome-wide characterization of T cell epitopes from Mycobacterium tuberculosis in vaccination and active infection
大规模 T 细胞表位发现:疫苗接种和主动感染中结核分枝杆菌 T 细胞表位的全蛋白质组表征
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