Functional characterization of the Alzheimer's disease Epigenome
阿尔茨海默病表观基因组的功能表征
基本信息
- 批准号:10429504
- 负责人:
- 金额:$ 8.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-07-15 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAlzheimer&aposs DiseaseBiological AssayBrainBrain regionCRISPR interferenceChemicalsChromatinClinicalCodeComplementDNADiseaseEnvironmentEpigenetic ProcessGeneticHeritabilityImpaired cognitionIndividualInstitutesLeadModificationMolecularMutationNerve DegenerationNeurodegenerative DisordersPathogenesisPatientsPlayPreventionPublic HealthRegulatory ElementResearchResearch PersonnelRiskRoleTherapeutic InterventionTimeUnited StatesUntranslated RNAWorkage relatedcell typecognitive functionepigenomeepigenomicsgenome wide association studyhealthy aginglifetime riskmortalitynervous system disordernovelpreventprogramsprogressive neurodegeneration
项目摘要
Project Summary/Abstract
Alzheimer’s disease (AD) manifests as a devastating age-related progressive neurodegeneration. This
neurodegeneration and the concomitant loss of cognitive function plagues more than 44 million individuals
worldwide. Our understanding of the molecular pathogenesis of AD remains incomplete and no therapies exist
to prevent, stop, or cure the associated neurodegeneration. This marks one of the greatest unmet clinical needs
of our time.
Through decades of research, genome-wide association studies have identified heritable coding and non-coding
mutations that lead to an increased risk of developing AD. Many of these mutations, however, remain largely
under-characterized and their contribution to AD pathogenesis remains unclear. Moreover, it has become
increasingly clear that an individual’s lifetime risk of developing AD is not merely governed by genetics. In
addition, the epigenome, the complement of all of the chemical and physical modifications imposed on DNA that
do not change the underlying sequence, is also thought to play a crucial role. This project aims to define the
epigenetic (Aim 1) and genetic (Aim 2) components of AD through profiling of the open chromatin landscapes
and three-dimensional chromatin interactions in brain regions and primary cell types of patients with and without
AD. These characterizations will identify key AD-related regulatory elements that will be functionally validated
with CRISPR interference tiling assays (Aim 3). Taken together, this project will provide an unprecedented
picture of the AD epigenome, identifying novel aspects of AD pathogenesis and nominating putative avenues for
therapeutic intervention.
This work will be performed within the Gladstone Institute of Neurological Disease which is an ideal environment
to perform such disease-relevant research, providing all of the facilities needed for the proposed research and a
collaborative and enriching culture for an early stage investigator. Cumulatively, this work will launch my
independent research program at the intersection of epigenomics and neurological disease.
项目概要/摘要
阿尔茨海默病 (AD) 表现为一种破坏性的与年龄相关的进行性神经变性。这
神经退行性疾病和随之而来的认知功能丧失困扰着超过 4400 万人
全世界。我们对 AD 分子发病机制的理解仍然不完整,并且不存在治疗方法
预防、阻止或治愈相关的神经变性。这标志着最大的未满足的临床需求之一
我们这个时代的。
经过数十年的研究,全基因组关联研究已经确定了可遗传的编码和非编码
导致患 AD 风险增加的突变。然而,其中许多突变在很大程度上仍然存在
其特征不明,其对 AD 发病机制的贡献仍不清楚。而且,它已经成为
人们越来越清楚地认识到,一个人一生中患阿尔茨海默氏症的风险不仅仅取决于遗传因素。在
此外,表观基因组是对 DNA 施加的所有化学和物理修饰的补充,
不改变底层序列,也被认为发挥着至关重要的作用。该项目旨在定义
通过开放染色质景观分析,了解 AD 的表观遗传(目标 1)和遗传(目标 2)成分
以及患有和不患有这种疾病的患者大脑区域和原代细胞类型的三维染色质相互作用
广告。这些特征将确定与 AD 相关的关键监管要素,并对其进行功能验证
使用 CRISPR 干扰平铺分析(目标 3)。总而言之,该项目将提供前所未有的
AD 表观基因组图,识别 AD 发病机制的新方面并提名假定的途径
治疗干预。
这项工作将在格拉德斯通神经疾病研究所内进行,这是一个理想的环境
进行此类与疾病相关的研究,提供拟议研究所需的所有设施和
为早期研究者提供协作和丰富的文化。累积起来,这项工作将启动我的
表观基因组学和神经系统疾病交叉的独立研究项目。
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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Michael Ryan Corces其他文献
Michael Ryan Corces的其他文献
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{{ truncateString('Michael Ryan Corces', 18)}}的其他基金
Project 4: Cross-species Dissection of Cellular Response to APOE Genotype and AD Pathology Using Single-cell Multi-omics
项目 4:利用单细胞多组学对 APOE 基因型和 AD 病理学的细胞反应进行跨物种解析
- 批准号:
10461846 - 财政年份:2021
- 资助金额:
$ 8.94万 - 项目类别:
Project 4: Cross-species Dissection of Cellular Response to APOE Genotype and AD Pathology Using Single-cell Multi-omics
项目 4:利用单细胞多组学对 APOE 基因型和 AD 病理学的细胞反应进行跨物种解析
- 批准号:
10271129 - 财政年份:2021
- 资助金额:
$ 8.94万 - 项目类别:
Project 4: Cross-species Dissection of Cellular Response to APOE Genotype and AD Pathology Using Single-cell Multi-omics
项目 4:利用单细胞多组学对 APOE 基因型和 AD 病理学的细胞反应进行跨物种解析
- 批准号:
10670350 - 财政年份:2021
- 资助金额:
$ 8.94万 - 项目类别:
Functional characterization of the Alzheimer's disease Epigenome
阿尔茨海默病表观基因组的功能表征
- 批准号:
10251365 - 财政年份:2018
- 资助金额:
$ 8.94万 - 项目类别:
Functional characterization of the Alzheimer's disease Epigenome
阿尔茨海默病表观基因组的功能表征
- 批准号:
10414137 - 财政年份:2018
- 资助金额:
$ 8.94万 - 项目类别:
Functional characterization of the Alzheimer's disease Epigenome
阿尔茨海默病表观基因组的功能表征
- 批准号:
10691634 - 财政年份:2018
- 资助金额:
$ 8.94万 - 项目类别:
Functional characterization of the Alzheimer's disease Epigenome
阿尔茨海默病表观基因组的功能表征
- 批准号:
10212522 - 财政年份:2018
- 资助金额:
$ 8.94万 - 项目类别:
Functional significance of Pre-Leukemic HSC in Human Acute Myeloid Leukemia
白血病前期 HSC 在人类急性髓系白血病中的功能意义
- 批准号:
8595776 - 财政年份:2014
- 资助金额:
$ 8.94万 - 项目类别: