Defining T helper cell associated cytokines and mechanisms in Alopecia Areata

斑秃中 T 辅助细胞相关细胞因子和机制的定义

基本信息

批准号：
9979751
负责人：
Ali Jabbari
金额：
$ 17.09万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9979751
关键词：
Acute Acute Graft Versus Host Disease Address Affect Allergic rhinitis Alopecia Areata Antibodies Area Asthma Atopic Dermatitis Autoimmune Diseases Award Basic Science Bone Marrow Bone Marrow Cells C57BL/6 Mouse Case Series Cell physiology Chimera organism Clinical Research Clinical Trials Contact Dermatitis Core Facility Data Databases Deposition Dermatology Development Disease Disease remission Effector Cell Evidence based treatment Exhibits Five-Year Plans Gene Expression Gene Expression Profile Genetic Models Genetic Transcription Hair Hair follicle structure Head Helper-Inducer T-Lymphocyte Heterogeneity High Prevalence Human Immunotherapy Inbreeding Individual Inflammatory Institution Interferons Interleukin-12 Interleukin-12 Gene International Laboratories Lupus Mediating Mentors Microarray Analysis Modeling Molecular Molecular Profiling Mus Pathogenesis Pathogenicity Pathology Pathway interactions Patients Pharmacology Physicians Play Positioning Attribute Prevention Process Psoriasis Receptor Signaling Recording of previous events Regulator Genes Reporting Resolution Role Sampling Scientist Signal Transduction Skin Skin graft Stimulus Systems Biology T-Cell Receptor T-Lymphocyte Th2 Cells Therapeutic Therapeutic antibodies Training Translational Research Transplantation United States Universities Yang alopecia areata registry atopy autoreactive T cell base career career development cytokine design experience genetic signature human subject humanized mouse improved individualized medicine inhibitor/antagonist interest interleukin-12 receptor lupus cutaneous molecular phenotype mouse model new therapeutic target prevent public health relevance response risk benefit ratio skin disorder small molecule targeted agent tool transcriptomics translational scientist treatment strategy

项目摘要

DESCRIPTION (provided by applicant): This K08 proposal details a comprehensive five-year plan for Dr. Ali Jabbari's career development in basic and translational research in Dermatology. Dr. Jabbari is an early career physician scientist in the Department of Dermatology at Columbia University. Dr. Jabbari's prior clinical and research experience has him uniquely positioned to study alopecia areata (AA), an autoimmune disease in which the hair follicle is the target of attack. Despite its high prevalence, there are no evidence-based treatments for AA. Studies in a C3H/HeJ AA mouse model have shown that the development of AA is critically dependent on the T-helper 1 (Th1)-associated cytokine interferon-γ, and an initial microarray-based assessment of gene expression signatures in the skin of a limited number of human subjects with AA identified the presence of a prominent interferon signature. Dr. Jabbari's proposal addresses the role of IL-12, a prototypical Th1 cytokine, in the pathogenesis of AA. Additionally, he will compare the transcriptional profile of AA, generated from dozens of samples collected through the National Alopecia Areata Registry, to publically available profiles from archetypal Th-associated inflammatory skin diseases. In this proposal, Dr. Jabbari proposes to (i) assess the role of IL-12 in AA development using genetic models of AA, (ii) assess the use of anti-IL- 12 or anti-IL-12R antibodies for therapeutic purposes in AA, and (iii) conduct transcriptomic comparisons of human AA with prototypical Th-associated skin diseases and an IL-12 gene signature. Results from this proposal address the pivotal role IL-12 may be playing in AA and may identify Th-associated signature heterogeneity among human AA samples. This mentored award will provide the training framework for transitioning into an independent position. His mentors will be Dr. Angela Christiano, an internationally-recognized skin and hair biologist and translational scientist, and Dr. Andrea Califano, a renowned expert in systems biology whose interests reside in the assembly and interrogation of gene regulatory models for the elucidation of mechanisms presiding over cell physiology and their dysregulation in disease. Dr. Yong-Guang Yang, Director of the Humanized Mouse Core Facility and head of a laboratory that focuses on transplantation and acute graft versus host disease, will also serve as an advisor for Dr. Jabbari's training plan. The comprehensive training plan described within is critical for Dr. Jabbari's transition to an independent scientist and to position him for applying for a career in academic dermatology.

描述（由适用提供）：该K08提案详细介绍了Ali Jabbari博士在皮肤病学基础和翻译研究方面的职业发展的全面五年计划。 Jabbari博士是哥伦比亚大学皮肤病学系的早期职业生理科学家。 Jabbari博士先前的临床和研究经验使他独特地研究了脱发区（AA），这是一种自身免疫性疾病，其中毛囊是攻击的目标。尽管患病率很高，但没有针对AA的证据治疗。在C3H/HEJ AA小鼠模型中的研究表明，AA的发展至关重要，取决于T-助手1（TH1）相关的细胞因子干扰素-γ，以及对有限数量的人类受试者的皮肤中基于微阵列的最初基于微阵列的基因表达信号评估，而AA识别出突出的识别出突出的干扰素。 Jabbari博士的建议介绍了IL-12（原型Th1细胞因子）在AA发病机理中的作用。此外，他将比较AA的转录概况，该概况是由通过国家脱发Areata注册中心收集的数十个样本与来自原型TH相关炎症性皮肤疾病的公开概况进行比较。 In this proposal, Dr. Jabbari proposals to (i) assessment the role of IL-12 in AA development using Genetic models of AA, (ii) assess the use of anti-IL- 12 or anti-IL-12R antibodies for therapeutic purposes in AA, and (iii) conduct transcriptomic comparisons of human AA with prototypical Th-associated skin diseases and an IL-12 gene signature.该提案的结果解决了IL-12的关键作用IL-12可能在AA中扮演，并且可以鉴定人类AA样品之间与TH相关的签名异质性。该裁判奖将为过渡到独立职位的培训框架。他的导师将是安吉拉·克里斯蒂安诺（Angela Christiano）博士，他是国际认可的皮肤和毛发生物学家和翻译科学家，以及著名的系统生物学专家安德里亚·卡利卡诺（Andrea Califano）博士，其兴趣依赖于基因调节模型的组装和询问，用于阐明基于细胞物理学及其疾病失调的机制机制。人源化小鼠核心设施的主任，专注于移植和急性移植与宿主疾病的实验室负责人杨阳博士还将担任Jabbari博士的培训计划的顾问。其中描述的全面培训计划对于Jabbari博士向独立科学家的过渡至关重要，并将他定位为申请学术皮肤病学职业。