MicroRNA 23 Cluster Regulation of Helper T cell Differentiation and Function

MicroRNA 23 簇对辅助 T 细胞分化和功能的调节

基本信息

批准号：
9002894
负责人：
Heather H Pua
金额：
$ 16.85万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-01 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9002894
关键词：
Affect Allergic Allergic Disease Asthma Binding Biological Assay Biology CD4 Positive T Lymphocytes California Cell Culture Techniques Cell Differentiation process Cell physiology Cells Cessation of life Chronic Chronic lung disease Clinical Clinical Immunology Collaborations Data Analyses Development Disease Doctor of Philosophy Effector Cell Elements Expenditure Extrinsic asthma Family member Fostering Foundations Gene Targeting Generations Genes Goals Growth Health Healthcare Helper-Inducer T-Lymphocyte Human Hypersensitivity IL4 gene Immune Immune System Diseases Immune response Immunity Immunology Immunology procedure Individual Infection Inflammatory Response Interleukin-13 Interleukin-4 Interleukin-5 K-Series Research Career Programs Knockout Mice Knowledge Lead Lung Lung Inflammation Mediating Medical Mentors Mentorship Messenger RNA MicroRNAs Mission Modeling Molecular Morbidity - disease rate Mus National Institute of Allergy and Infectious Disease Pathogenesis Pathology Pathway interactions Patients Physicians Population Production Quality of life Recurrence Regulation Regulatory Pathway Research Role San Francisco Scientist Site T cell differentiation T-Lymphocyte Testing Th2 Cells Training Transcript Universities Visit Work airway hyperresponsiveness asthmatic base cell mediated immune response cytokine disorder subtype human disease in vivo inflammatory lung disease inhibitor/antagonist interest meetings molecular pathology mouse model multidisciplinary novel novel therapeutics overexpression pathogen prediction algorithm response transcription factor transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): Asthma is a clinically heterogeneous chronic airway disease which affects 7% of the US population and results in substantial morbidity and healthcare expenditure. Advances in the molecular characterization of asthma have led to the identification of disease subtypes, leading to novel treatment approaches. Many patients with asthma have disease that is driven by type 2 helper T (Th2) cells, immune cells critical for orchestrating inflammatory responses in the lung. Recently, molecules called microRNAs have been identified as critical regulators of T cells. The long-term goal of Dr. Pua is to identify miRNA-mediated regulatory networks in immune responses and to determine their impact on inflammatory lung diseases. The objectives of this proposal are to define the mechanism by which a specific group of microRNAs, called the miR-23 cluster, regulate type 2 immune responses and leverage this knowledge to better understand allergic lung inflammation. Since microRNAs act by inhibiting networks of target genes within a cell, Dr. Pua hypothesizes that individual microRNAs of the miR-23 cluster act together to limit the development and activity of Th2 cells, including those cells which contribute to the pathogenesis of asthma. Dr. Pua will test this hypothesis using three specific aims. In Aim 1, Dr. Pua will determine the network of target genes regulated by the miR-23 cluster, with the hope of identifying novel cellular pathways important for type 2 immune responses. In Aim 2, she will explore how microRNA interactions with their target genes are critical in specifically regulating Th2 cell function. In Aim 3, Dr. Pu will investigate the role of the miR-23 cluster in regulating human T cells as well as immune responses of asthma/allergic airway hypersensitivity as well as infection. This project is relevant to asthma as well as the mission of the NIAID because it explores a novel microRNA-mediated regulatory pathway in Th2 cells and has the potential to uncover new therapeutic avenues involving microRNAs and their target genes. Dr. Pua is an MD PhD who completed her graduate work in immunology and clinical training in molecular pathology. She is currently a pathology fellow at the University of California, San Francisco, and is applying for a K08 Mentored Clinical Scientist Research Career Development Award. The critical elements of her training plan which will help to support her goal of becoming an academic physician scientist include mentorship by Dr. Mark Ansel, a leading expert in the field of microRNAs in T cells; guidance by a multidisciplinary committee which includes numerous physician scientists as well as leaders in the field of immunology and microRNA biology; coursework in data analysis; attendance at meeting to foster scientific growth and collaboration; and professional development activities. This will provide her the essential foundation to combine her interest with her growing expertise in the molecular regulation of immune responses to the exploration and practice of pathology.

描述（由应用提供）：哮喘是一种临床上异质性气道疾病，影响美国人口的7％，并导致大量发病率和医疗保健支出。哮喘的分子表征的进步导致疾病亚型的鉴定，导致了新的治疗方法。许多哮喘患者患有由2型辅助助手T（Th2）细胞驱动的疾病，免疫细胞对于策划肺部炎症反应至关重要。最近，称为microRNA的分子已被鉴定为T细胞的关键调节剂。 PUA博士的长期目标是确定免疫调查中的miRNA介导的调节网络，并确定其对炎症性肺部疾病的影响。该提案的目的是定义一种特定的microRNA（称为miR-23群集）调节2型免疫调查的机制，并利用这些知识以更好地理解过敏性肺注射。由于microRNA通过抑制细胞内的靶基因网络来起作用，PUA博士假设miR-23簇的单个microRNA共同起作用以限制Th2细胞的发育和活性，包括那些有助于哮喘发病机理的细胞。 PUA博士将使用三个特定目标检验这一假设。在AIM 1中，PUA博士将确定由miR-23簇调节的靶基因网络，希望识别新的细胞途径对于2型免疫调查员重要。在AIM 2中，她将探讨MicroRNA与目标基因的相互作用在专门调节Th2细胞功能方面至关重要。在AIM 3中，PU博士将研究miR-23簇在确定人类T细胞以及哮喘/过敏性气道超敏反应和感染的免疫回应中的作用。这个项目很重要哮喘以及NIAID的使命是因为它探索了TH2细胞中新型的MicroRNA介导的调节途径，并且有可能发现涉及microRNAS及其靶基因的新的治疗途径。 PUA博士是医学博士学位，完成了她在分子病理学领域的免疫学和临床培训方面的研究生工作。她目前是加州大学旧金山分校的病理研究员，并正在申请K08指导的临床科学家研究职业发展奖。她的培训计划中的关键要素将有助于她成为学术科学家的目标，包括Mark Ansel博士的心态，Mark Ansel博士是T细胞中MicroRNA领域的主要专家。多学科委员会的指导，其中包括众多物理科学家以及免疫学和microRNA生物学领域的领导者；数据分析课程；参加会议以促进科学成长与协作；和专业发展活动。这将为她提供基础，将她的兴趣与她对病理探索和实践的免疫反应的分子调节相结合的专业知识融为一体。