The Epigenome in Substance Abuse Disorders: Engineering New Tools to Dissect Function from Form

药物滥用疾病中的表观基因组：设计新工具从形式中剖析功能

• 批准号: 10250507
• 负责人: Albert Keung
• 金额: $ 45.6万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10250507
• 关键词: Automobile Driving; Disease; Engineering; Epigenetic Process; Etiology; Gene Expression; Genes; Genetic; Genome engineering; Goals; Human Genetics; Knock-out; Maps; Modification; Pharmacology; Phenotype; Physiology; Property; Role; Substance abuse problem; System; Techniques; Work; addiction; epigenome; epigenomics; overexpression; pleiotropism; response; spatiotemporal; tool

Many studies have connected epigenomic changes to substance abuse disorders. However, there is a key barrier to our understanding of the epigenome’s mechanistic roles. While epigenomic modifications have been widely mapped and correlated with changes in gene expression and cellular phenotypes, correlation does not demonstrate function or causation. This barrier arises because widely used techniques to perturb the epigenome, including pharmacological inhibition and genetic knock-outs or overexpressions, suffer from pleiotropic effects. Thus, it is unclear if epigenomic modifications drive, are a result of, or are simply associated with changes in gene states. Two important corollaries arise from this: 1) It is unclear whether and which epigenome modifications drive changes in gene expression, and 2) the temporal stability of epigenome modifications that would result in truly persistent “epigenetic” properties is unknown. The hypothesis of the proposed work is that the epigenome represents a powerful regulatory system layered on top of the genome, and by engineering new tools to interface with and control this system, we can harness its unique properties to understand and tackle substance abuse disorders. A guiding goal is to dissect the function of epigenome modifications from their form and demonstrate their specific relevance to substance abuse disorders. To achieve this, we will develop tools to sense and induce changes in the epigenome, and do so spatiotemporally in systems reflective of human genetics, epigenetics, and physiology.

许多研究将表观基因组变化与药物滥用障碍联系起来。然而，有一个

项目成果

Matrigel Tunes H9 Stem Cell-Derived Human Cerebral Organoid Development.

• DOI: 10.3390/organoids2040013
• 发表时间: 2023-12
• 期刊: Organoids
• 作者: Estridge RC;O'Neill JE;Keung AJ
• 通讯作者: Keung AJ

Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization.

• DOI: 10.3390/cells11091411
• 发表时间: 2022-04-21
• 期刊: CELLS
• 影响因子: 6
• 作者: Tam, Ryan W.;Keung, Albert J.
• 通讯作者: Keung, Albert J.

Effects of early geometric confinement on the transcriptomic profile of human cerebral organoids.

• DOI: 10.1186/s12896-021-00718-2
• 发表时间: 2021-10-12
• 期刊: BMC biotechnology
• 影响因子: 3.5
• 作者: Sen D;Voulgaropoulos A;Keung AJ
• 通讯作者: Keung AJ

Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.

• DOI: 10.1007/978-1-4939-7774-1_3
• 发表时间: 2018
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Sen D;Keung AJ
• 通讯作者: Keung AJ

Chromatin Immunoprecipitation in Human and Yeast Cells.

人类和酵母细胞中的染色质免疫沉淀。

• DOI: 10.1007/978-1-4939-7774-1_14
• 发表时间: 2018
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Lee,JessicaB;Keung,AlbertJ
• 通讯作者: Keung,AlbertJ