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

标题：微小RNA分子在哮喘白三烯修饰剂治疗反应中的作用。 首席调查员Amber Dahlin博士，博士，MMSc，致力于成为一名独立的 致力于高度创新、翻译性、以患者为中心的哮喘研究。她的长期工作 目标是识别、开发和实施新的知识和方法，以改善治疗结果 在全球范围内减轻哮喘负担。该项目的目标是确定microRNAs(MiRNAs)和 他们的目标基因有助于哮喘患者的白三烯修饰物反应。尽管已知miRNAs 为了影响与哮喘相关的免疫反应途径，到目前为止，很少有研究研究这些途径的作用。 哮喘发生、发展和管理的分子。MiRNAs尚未被直接牵连到 白三烯调节剂或包括阿司匹林相关呼吸系统在内的哮喘亚型的临床反应 疾病(AERD)，其特征是白三烯的过度产生。在这份修订后的申请中，Dr。 Dahlin建议识别与药理学和临床反应相关的miRNAs及其靶点 用哮喘永生化B细胞建立白三烯扰动细胞模型中的孟鲁司特 患者除血清和原发B细胞外，来自病例对照的AERD患者队列，然后整合 这些数据使用生物信息学方法来构建孟鲁司特反应的预测网络模型。 了解miRNA网络的作用将有助于追求有效的治疗结果 治疗哮喘，并提供了一个独特的机会，以减轻公共卫生负担。与她密切合作 导师，哈佛医学院的Scott Weiss博士，在完成这些研究的同时，她还将建立她的 通过参加相关课程、参加会议和在个性化医疗中担任私人助理的技能 会议，并与她的合作临床研究团队会面。她忠心耿耿的导师和 合作者将支持她在颁奖期的最后几年提交的R01赠款提案。在……里面 2014年9月，达林博士被提升为哈佛医学院的医学讲师 这表明了学校对她职业发展的承诺。这位NHLBI指导 研究科学家发展奖(K01)将允许Dahlin博士合并翻译流行病学 用网络建模方法研究miRNA网络与治疗的关系 哮喘的反应，目标是改善哮喘患者的治疗结果。

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.