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

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。
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:
Immunogenetic Studies in Multiple Sclerosis
多发性硬化症的免疫遗传学研究
  • 批准号:
    6669494
  • 财政年份:
    2003
  • 资助金额:
    $ 65.85万
  • 项目类别:
Immunogenetic Studies in Multiple Sclerosis
多发性硬化症的免疫遗传学研究
  • 批准号:
    8004925
  • 财政年份:
    2003
  • 资助金额:
    $ 65.85万
  • 项目类别:
Immunogenetic Studies in Multiple Sclerosis
多发性硬化症的免疫遗传学研究
  • 批准号:
    7758767
  • 财政年份:
    2003
  • 资助金额:
    $ 65.85万
  • 项目类别:
Immunogenetic Studies in Multiple Sclerosis
多发性硬化症的免疫遗传学研究
  • 批准号:
    7052789
  • 财政年份:
    2003
  • 资助金额:
    $ 65.85万
  • 项目类别:
Immunogenetic Studies in Multiple Sclerosis
多发性硬化症的免疫遗传学研究
  • 批准号:
    8409799
  • 财政年份:
    2003
  • 资助金额:
    $ 65.85万
  • 项目类别:
Immunogenetic Studies in Multiple Sclerosis
多发性硬化症的免疫遗传学研究
  • 批准号:
    6884631
  • 财政年份:
    2003
  • 资助金额:
    $ 65.85万
  • 项目类别:

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High-resolution characterization of human leukocyte antigen genes in diverse populations to study the genetics of food allergy
对不同人群中的人类白细胞抗原基因进行高分辨率表征,以研究食物过敏的遗传学
  • 批准号:
    10665162
  • 财政年份:
    2022
  • 资助金额:
    $ 65.85万
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The landscape of HLA mediated variation in health and immunity
HLA 介导的健康和免疫力变化
  • 批准号:
    10182837
  • 财政年份:
    2021
  • 资助金额:
    $ 65.85万
  • 项目类别:
MHC Variation in Host Response to SARS-CoV2 and COVID-19 Outcomes
宿主对 SARS-CoV2 和 COVID-19 结果反应的 MHC 变化
  • 批准号:
    10655366
  • 财政年份:
    2021
  • 资助金额:
    $ 65.85万
  • 项目类别:
MHC Variation in Host Response to SARS-CoV2 and COVID-19 Outcomes
宿主对 SARS-CoV2 和 COVID-19 结果反应的 MHC 变化
  • 批准号:
    10450114
  • 财政年份:
    2021
  • 资助金额:
    $ 65.85万
  • 项目类别:
The landscape of HLA mediated variation in health and immunity
HLA 介导的健康和免疫力变化
  • 批准号:
    10402884
  • 财政年份:
    2021
  • 资助金额:
    $ 65.85万
  • 项目类别:
MHC Variation in Host Response to SARS-CoV2 and COVID-19 Outcomes
宿主对 SARS-CoV2 和 COVID-19 结果反应的 MHC 变化
  • 批准号:
    10297642
  • 财政年份:
    2021
  • 资助金额:
    $ 65.85万
  • 项目类别:
The landscape of HLA mediated variation in health and immunity
HLA 介导的健康和免疫力变化
  • 批准号:
    10609519
  • 财政年份:
    2021
  • 资助金额:
    $ 65.85万
  • 项目类别:
The role of germline and somatic DNA mutations in oral and oropharyngeal cancers
种系和体细胞 DNA 突变在口腔癌和口咽癌中的作用
  • 批准号:
    10221124
  • 财政年份:
    2020
  • 资助金额:
    $ 65.85万
  • 项目类别:
Atopic Dermatitis and High Resolution HLA
特应性皮炎和高分辨率 HLA
  • 批准号:
    9550908
  • 财政年份:
    2017
  • 资助金额:
    $ 65.85万
  • 项目类别:
Integrated Exchange and Storage of Current- and Future-Generation Immunogenomic Data
当前和未来一代免疫基因组数据的集成交换和存储
  • 批准号:
    10442226
  • 财政年份:
    2017
  • 资助金额:
    $ 65.85万
  • 项目类别:
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