Project 1: Translational Science of Alopecia Areata

项目1：斑秃的转化科学

• 批准号: 10091984
• 负责人: Angela M Christiano
• 金额: $ 61.2万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-16 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10091984
• 关键词: Address; Alopecia Areata; Antibiotic Therapy; Antigens; Autoantigens; Autoimmune Diseases; Bioinformatics; Biological; Biological Markers; Biology; C3H/HeJ Mouse; Clinical; Clinical Trials; Collection; Complement; Complex; Correlative Study; DNA Sequence Alteration; Data; Development; Disease; Drug Screening; Drug Targeting; Environment; Environmental Risk Factor; Epigenetic Process; Epitopes; Evaluation; Experimental Designs; Foundations; Functional disorder; Gene Expression; Genetic; Genomics; Goals; Hair follicle structure; High-Throughput Nucleotide Sequencing; Human; Immune Targeting; Immunology; Infiltration; JAK1 gene; Lesion; Mass Spectrum Analysis; Mediating; Mediator of activation protein; Modeling; Molecular; Mus; Oral; Pathogenesis; Pathogenicity; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phenocopy; Phenotype; Predisposition; Proteins; Proteomics; Publishing; Research; Research Project Grants; Role; Scalp structure; Services; Study models; Systems Biology; T-Cell Receptor; T-Lymphocyte; Translational Research; Work; bench to bedside; biomarker development; clinical biomarkers; cohort; computer science; design; drug candidate; drug discovery; endophenotype; experimental study; flexibility; genome wide association study; gut microbiome; gut microbiota; human model; inhibitor/antagonist; innovation; member; microbiome; microbiome research; molecular pathology; mouse model; novel therapeutics; patient population; pre-clinical; recruit; response; single cell sequencing; skin microbiota; transcriptomics; translational medicine; treatment response

ABSTRACT The Research Project serves as the principal research directive of the AACORT. The overall goal of the AACORT is the comprehensive study of the pathology of Alopecia Areata, which the Research Project formalizes into four key goals: 1) the study of the microbiome, 2) proteomic research into AA autoantigens, 3) mouse model studies of AA pathology and drug discovery, 4) and studies of human AA patients for molecular pathology and drug response. These four goals will result in the full characterization of the microbiome, genomic, transcriptomic, and proteomic loads that contribute to AA pathology. This, in turn, will provide the foundation for the development of biomarkers to track AA progression and response to treatment (both genomic and molecular), and the identification of drug targets and drug candidates. To drive the pursuit of these objectives, the Research Project will serve as a key mediator between the TRAC Core, which will be responsible for designing and acquiring human patient biosamples for analysis, and the DATA Core, which will oversee the annotation, storage, and analysis of all data generated by the TRAC. It will be one of the Research Project’s roles to identify targetable biological objectives to these two cores, which will then acquire the data and analyze it for the key molecular drivers that the Research Project can then validate as a complement to their ongoing research. Experiments pursued by the Research Project, in human or mouse models, will be continuously cross-checked with the bioinformatic analyses of human cohorts to develop an unprecedented systemic model of AA pathology. In this manner, all ongoing research in the AACORT will be mediated by the central biological questions posed by the Research Project, thereby providing uniform objectives for which the AACORT can leverage its multiple analytic pipelines.

摘要 该研究项目是AACOT的主要研究指导。的总目标 AACORT是对斑秃病理学的综合研究， 该项目形成了四个关键目标：1）微生物组的研究，2）蛋白质组学研究， AA自身抗原，3）AA病理学和药物发现的小鼠模型研究，4）和人的研究。 AA患者的分子病理学和药物反应。这四个目标将导致全面 微生物组、基因组、转录组和蛋白质组负荷的表征， 戒酒会病理学。这反过来将为生物标志物的发展提供基础， AA进展和对治疗的反应（基因组和分子），以及 药物靶标和候选药物。为了实现这些目标，研究项目 将作为核心预算资源调拨目标核心预算之间的关键调解人，核心预算资源调拨目标将负责设计和 获取人类患者生物样本进行分析，以及数据核心，它将监督 对TRAC产生的所有数据进行注释、储存和分析。这将是一个研究 项目的作用，以确定有针对性的生物目标，这两个核心，然后将 获取数据并分析其关键分子驱动因素，然后研究项目可以 作为他们正在进行的研究的补充。研究项目进行的实验， 人类或小鼠模型，将与人类的生物信息学分析进行持续的交叉检查。 队列开发前所未有的AA病理学系统模型。通过这种方式，所有正在进行的 AACORT的研究将由研究提出的中心生物学问题介导。 项目，从而提供统一的目标，AACORT可以利用其多个 分析管道。