Role of microRNA molecules in therapeutic response to leukotriene modifying agents in asthma

microRNA分子在哮喘白三烯修饰剂治疗反应中的作用

• 批准号: 9175135
• 负责人: Amber Dahlin
• 金额: $ 17.82万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9175135
• 关键词: Accounting; Adult; Affect; Amber; Applications Grants; Aspirin; Asthma; Award; B-Lymphocytes; Bioinformatics; Biological; Blood specimen; Cell model; Cells; Childhood Asthma; Clinical; Clinical Research; Collaborations; Complex; Data; Development; Disease; Doctor of Philosophy; Ensure; Enzyme-Linked Immunosorbent Assay; Epidemiology; Faculty; Gene Expression; Gene Targeting; Genes; Genetic; Genetic Variation; Goals; Immune response; Individual; Institution; Investigation; Knowledge; Leukotriene Production; Leukotriene Receptor; Leukotrienes; Lung diseases; Measures; Medicine; Mentored Research Scientist Development Award; Mentors; Messenger RNA; Methods; MicroRNAs; Microarray Analysis; Molecular; Molecular Profiling; National Heart, Lung, and Blood Institute; Oral; Organ; Pathogenesis; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Physicians; Principal Investigator; Process; Public Health; RNA; Recruitment Activity; Research; Research Personnel; Respiratory physiology; Role; Sampling; Serum; Signal Pathway; Specificity; Testing; Tissue-Specific Gene Expression; Treatment Protocols; Variant; Whole Blood; Work; aspirin-exacerbated respiratory disease; asthmatic; asthmatic patient; base; career development; case control; cohort; computer based statistical methods; differential expression; disease phenotype; effective therapy; experience; gene product; genome wide association study; improved; innovation; insight; instructor; lymphoblastoid cell line; mRNA Expression; medical schools; meetings; montelukast; network models; novel; patient oriented research; personalized medicine; predictive modeling; programs; response; skills; success; symposium; therapy outcome; treatment group; treatment response

Title: Role of microRNA molecules in therapeutic response to leukotriene modifying agents in asthma. The Principal Investigator, Dr. Amber Dahlin, Ph.D., MMSc., is committed to becoming an independent investigator focusing on highly innovative, translational, patient-oriented research in asthma. Her long-term goal is to identify, develop and implement new knowledge and methods to improve therapeutic outcomes for reducing the burden of asthma worldwide. The goal of this project is to identify the microRNAs (miRNAs) and their target genes that contribute to leukotriene modifier response in asthmatics. Although miRNAs are known to affect immune response pathways related to asthma, few studies to date have examined the role of these molecules on asthma development, progression and management. miRNAs are yet to be directly implicated in the clinical response to leukotriene modifiers, or in asthma subtypes including aspirin associated respiratory disease (AERD), which is characterized by excessive production of leukotrienes. In this revised application, Dr. Dahlin proposes to identify miRNAs, and their targets, associated with pharmacological and clinical response to montelukast in a cellular model of leukotriene perturbation using immortalized B cells from asthmatic patients, in addition to sera and primary B cells from a case-controlled AERD patient cohort, and then integrate the these data using bioinformatic approaches to construct predictive network models of montelukast response. Understanding the role of miRNA networks will enhance the pursuit of effective therapeutic outcomes in asthma treatment and provides a unique opportunity to reduce public health burden. Working closely with her mentor, Dr. Scott Weiss at Harvard Medical School, while completing these studies, she will also build her skills as a PI in personalized medicine through taking relevant coursework, attending meetings and conferences, and meeting with her collaborative clinical research team. Her committed mentors and collaborators will support her submission of an R01 grant proposal in the final years of this award period. In September 2014, Dr. Dahlin was promoted to the faculty rank of Instructor in Medicine at Harvard Medical School, demonstrating the institution’s commitment to her career development. This NHLBI Mentored Research Scientist Development Award (K01) will allow Dr. Dahlin to merge a translational epidemiological approach with network modeling to investigate the relationship between miRNA networks and treatment response in asthma, with the goal of improving therapeutic outcomes for asthma patients.

标题：microRNA分子在哮喘中对白三烯修饰剂的热反应中的作用。 首席研究员，MMSc。的Amber Dahlin博士致力于成为独立 研究人员专注于高度创新，翻译，以患者为导向的哮喘研究。她的长期 目标是识别，发展和实施新的知识和方法，以改善治疗结果 减少全球哮喘的燃烧。该项目的目的是识别microRNA（miRNA）和 他们的靶基因在哮喘患者中有助于白三烯修饰剂反应。虽然miRNA是已知的 为了影响与哮喘有关的免疫反应途径，迄今为止很少有研究检查这些作用 关于哮喘发展，进展和管理的分子。 miRNA尚未直接牵连 对白三烯修饰剂或包括阿司匹林相关呼吸的哮喘亚型的临床反应 疾病（AERD），其特征是白细胞生产过多。在此修订的申请中，博士 达林的提议识别与药物和临床反应相关的miRNA及其靶标 使用永生的B细胞的白三烯扰动细胞模型中的蒙特鲁克斯特 患者，除了来自病例控制的AERD患者队列的血清和原代B细胞，然后整合 这些数据使用生物信息学方法来构建Montelukast响应的预测网络模型。 了解miRNA网络的作用将增强对有效治疗结果的追求 哮喘治疗，并为减少公共卫生伯恩提供了独特的机会。与她紧密合作 导师，哈佛医学院的Scott Weiss博士，完成这些研究时，她还将建立她 通过参加相关课程，参加会议和 会议，并与她的协作临床研究团队会面。她坚定的导师和 合作者将支持她在此奖励期的最后几年中提交R01赠款提案。在 2014年9月，达林博士被提升为哈佛医学的医学教师 学校，展示了该机构对她职业发展的承诺。这个NHLBI指导了 研究科学家发展奖（K01）将允许达林博士合并翻译流行病学 与网络建模的方法来研究miRNA网络与治疗之间的关系 哮喘的反应，目的是改善哮喘患者的治疗结果。