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: 9316699
• 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/9316699
• 关键词: Accounting; Adult; Affect; Alpha Cell; Amber; Applications Grants; Aspirin; Asthma; Award; B lymphocyte immortalization; 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; Pharmacology; Physicians; Principal Investigator; Process; Public Health; RNA; Recruitment Activity; Research; Research Personnel; Respiratory physiology; Role; Sampling; Signal Pathway; Specificity; Testing; Tissue-Specific Gene Expression; Treatment Efficacy; Treatment Protocols; Variant; Whole Blood; Work; aspirin-exacerbated respiratory disease; asthmatic; asthmatic patient; base; career development; case control; cohort; computer based statistical methods; cysteinyl-leukotriene; 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 分子在哮喘白三烯修饰剂治疗反应中的作用。 首席研究员 Amber Dahlin 博士，博士，理学硕士，致力于成为一名独立的 专注于高度创新、转化、以患者为导向的哮喘研究的研究者。 目标是识别、开发和实施新的知识和方法，以改善治疗结果 该项目的目标是识别 microRNA (miRNA) 并减少全球哮喘的负担。 尽管 miRNA 是已知的，但它们的靶基因有助于哮喘患者的白三烯调节剂反应。 为了影响与哮喘相关的免疫反应途径，迄今为止很少有研究探讨这些因素的作用 miRNA 尚未直接涉及哮喘发生、进展和治疗的分子。 对白三烯调节剂或哮喘亚型（包括阿司匹林相关呼吸道疾病）的临床反应 疾病（AERD），其特征是白三烯产生过多。 Dahlin 提议鉴定与药理学和临床反应相关的 miRNA 及其靶点 使用来自哮喘患者的永生化 B 细胞在白三烯扰动细胞模型中使用孟鲁司特 除了来自病例对照 AERD 患者队列的血清和原代 B 细胞之外，还对患者进行整合 利用生物信息学方法利用这些数据构建孟鲁司特反应的预测网络模型。 了解 miRNA 网络的作用将促进对有效治疗结果的追求 哮喘治疗并提供了与她密切合作减轻公共卫生负担的独特机会。 导师，哈佛医学院的 Scott Weiss 博士，在完成这些研究的同时，她还将建立自己的 通过学习相关课程、参加会议和 会议以及与她的合作临床研究团队的会议。 合作者将支持她在本奖励期的最后几年提交 R01 资助提案。 2014年9月，Dahlin博士晋升为哈佛医学院医学讲师 学校，展示了该机构对她职业发展的承诺。 研究科学家发展奖（K01）将允许达林博士将转化流行病学 使用网络建模方法研究 miRNA 网络与治疗之间的关系 哮喘反应，旨在改善哮喘患者的治疗结果。