DNA methylation in the development of multiple sclerosis
DNA甲基化在多发性硬化症发展中的作用
基本信息
- 批准号:10660209
- 负责人:
- 金额:$ 65.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-15 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:3-Dimensional6p21AffectAfrican AmericanAgeAntibody TherapyAtlasesAutomobile DrivingB-LymphocytesBiological MarkersBloodCD19 geneCaliforniaCell CommunicationCell physiologyCell surfaceCellsCellular AssayCerebrospinal FluidChromatinChromosomesClinicalCoupledDNADNA MethylationDataData SetDevelopmentDiagnosisDiseaseDisease modelDisease susceptibilityEpigenetic ProcessEventGene ExpressionGeneticGenotypeGoalsHeterogeneityImmuneImmunologicsIndividualLigandsLinkMagnetic Resonance ImagingMajor Histocompatibility ComplexMapsMeasurementMeasuresModalityModelingModificationMultiple SclerosisParticipantPathogenesisPathologicPatient RecruitmentsPeripheralPeripheral Blood Mononuclear CellPhenotypePopulationProcessPrognosisQuantitative Trait LociRepressionResearchResolutionRiskRoleSamplingShapesSusceptibility GeneSymptomsSystemTherapeuticTimeUpdateValidationVisualizationbiobankcase controlcohortdisabilitydisorder riskdiverse dataepigenomicsfollow-upgenome wide association studyhistone modificationinsightmultiple omicsmultiple sclerosis patientnovelphenotypic datapolygenic risk scoreprognosticprogramsreceptorsexsingle-cell RNA sequencingstatisticstositumomabtranscriptome
项目摘要
Summary
This application is concerned with the study of epigenetics events affecting multiple sclerosis (MS) risk
and progression. We present preliminary results consistent with widespread differential
hypomethylation in peripheral CD19+ B cells at the time of diagnosis, posing a mechanistic link to the
clinical efficiency of anti-CD20 antibody treatment for this disease. We build on these results and
access to informative and diverse data- and sample-sets to propose in Specific Aim 1 the simultaneous
assessment of single-cell gene expression (scRNA-seq), chromatin accessibility (scATAC-seq), and
cell surface markers in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells from
treatment naïve MS patients at the time of clinical onset and well matched controls, and link in Aim 2 to
the individuals’ DNA variance to develop global and cell-specific genetic burdens associated with
disease expression. In Aim 3 we connect the emerging epigenetic and transcriptome signatures with
cell function using the Beacon® system optofluidic platform to visualize and assess cellular phenotypes
at the single-cell level. In Aim 4 we implement a targeted trimodal single-cell assay to describe the
epigenetic landscape of the principal MS susceptibility locus, the Major Histocompatibility Complex in
chromosome 6p21. By systematically integrating single cell chromatin states, DNA variance, and gene
expression data, we expect to gain important novel information about pathogenesis. Moreover, we will
identify cell-specific epigenetic signatures associated with MS clinical onset, potentially serving as
biomarkers of affectation status. The meticulous clinical follow up of study participants offers an
opportunity to assess their prognostic potential.
总结
项目成果
期刊论文数量(0)
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Jorge R. Oksenberg其他文献
Variable Transskripte von T-Zellen als Marker für Krankheiten
T-Zellen 的可变 Transskripte 为 Krankheiten 标记
- DOI:
- 发表时间:
1991 - 期刊:
- 影响因子:0
- 作者:
Lawrence Steinman;Jorge R. Oksenberg;C. Bernard - 通讯作者:
C. Bernard
New allelic polymorphisms in TAP genes
- DOI:
10.1007/bf00189240 - 发表时间:
1994-03-01 - 期刊:
- 影响因子:2.900
- 作者:
Fanny Szafer;Jorge R. Oksenberg;Lawrence Steinman - 通讯作者:
Lawrence Steinman
T-cell receptor V alpha and C alpha alleles associated with multiple and myasthenia gravis.
T 细胞受体 V α 和 C α 等位基因与多发性肌无力和重症肌无力相关。
- DOI:
- 发表时间:
1989 - 期刊:
- 影响因子:11.1
- 作者:
Jorge R. Oksenberg;Martina Sherritt;A. Begovich;Henry A. Erlich;Claude C. A. Bernard;L. L. Cavalli;Lawrence Steinman - 通讯作者:
Lawrence Steinman
The genetics of multiple sclerosis: SNPs to pathways to pathogenesis
多发性硬化症的遗传学:单核苷酸多态性到通路到发病机制
- DOI:
10.1038/nrg2395 - 发表时间:
2008-06-10 - 期刊:
- 影响因子:52.000
- 作者:
Jorge R. Oksenberg;Sergio E. Baranzini;Stephen Sawcer;Stephen L. Hauser - 通讯作者:
Stephen L. Hauser
Maternal-paternal histocompatibility: lack of association with habitual abortions.
母本组织相容性:与习惯性流产缺乏关联。
- DOI:
- 发表时间:
1984 - 期刊:
- 影响因子:6.7
- 作者:
Jorge R. Oksenberg;E. Persitz;Avraham Amar;C. Brautbar - 通讯作者:
C. Brautbar
Jorge R. Oksenberg的其他文献
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{{ truncateString('Jorge R. Oksenberg', 18)}}的其他基金
The contribution of common and rare variants to autoimmunity in African Americans
常见和罕见变异对非裔美国人自身免疫的贡献
- 批准号:
8462311 - 财政年份:2011
- 资助金额:
$ 65.85万 - 项目类别:
The contribution of common and rare variants to autoimmunity in African Americans
常见和罕见变异对非裔美国人自身免疫的贡献
- 批准号:
8320110 - 财政年份:2011
- 资助金额:
$ 65.85万 - 项目类别:
The contribution of common and rare variants to autoimmunity in African Americans
常见和罕见变异对非裔美国人自身免疫的贡献
- 批准号:
8658489 - 财政年份:2011
- 资助金额:
$ 65.85万 - 项目类别:
The contribution of common and rare variants to autoimmunity in African Americans
常见和罕见变异对非裔美国人自身免疫的贡献
- 批准号:
8214252 - 财政年份:2011
- 资助金额:
$ 65.85万 - 项目类别:
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