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: 9926305
• 负责人: Amber Dahlin
• 金额: $ 10.53万
• 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/9926305
• 关键词: Accounting; Adult; Affect; Amber; Applications Grants; Aspirin; Asthma; Award; B lymphocyte immortalization; B-Lymphocytes; Bayesian Network; 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; Expression Profiling; Faculty; Gene Expression; Genes; Genetic; Genetic Variation; Goals; Immune response; 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; National Heart, Lung, and Blood Institute; Oral; Organ; Pathogenesis; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Pharmacology; Physicians; Principal Investigator; Process; Public Health; RNA; Research; Research Personnel; Respiratory physiology; Role; Sampling; Signal Pathway; Specificity; Testing; Tissue-Specific Gene Expression; Translational Research; Treatment Efficacy; Treatment Protocols; Variant; Whole Blood; Work; aspirin-exacerbated respiratory disease; asthmatic; asthmatic patient; base; career development; cohort; cysteinyl-leukotriene; differential expression; disease phenotype; effective therapy; experience; gene product; genome wide association study; improved; innovation; insight; instructor; inter-individual variation; lymphoblastoid cell line; mRNA Expression; medical schools; meetings; montelukast; network models; novel; patient oriented research; patient response; personalized medicine; predictive modeling; programs; recruit; 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：微小RNA分子在哮喘中对白三烯修饰剂的治疗反应中的作用。 主要研究者Amber Dahlin博士，MMSC.，致力于成为一个独立的 研究人员专注于高度创新，转化，以患者为导向的哮喘研究。她的长期 目标是识别，开发和实施新的知识和方法，以改善治疗结果， 减轻全球哮喘的负担。该项目的目标是识别microRNA（miRNAs）， 他们的靶基因有助于哮喘患者的白三烯调节剂反应。尽管已知miRNAs 影响与哮喘相关的免疫反应途径，迄今为止很少有研究检查这些蛋白的作用。 分子对哮喘的发展、进展和管理的影响。miRNAs还没有直接参与 对白三烯调节剂的临床反应，或哮喘亚型，包括阿司匹林相关的呼吸道疾病， 疾病（AERD），其特征在于过量产生白三烯。在这一修改后的申请，博士。 Dahlin建议识别与药理学和临床反应相关的miRNAs及其靶点 在使用来自哮喘患者的永生化B细胞的白三烯扰动细胞模型中， 除了来自病例对照AERD患者队列的血清和原代B细胞外， 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网络的作用将促进对有效治疗结果的追求， 哮喘治疗，并提供了一个独特的机会，以减少公共卫生负担。同她密切配合 导师，哈佛医学院的斯科特韦斯博士，在完成这些研究的同时，她还将建立自己的 通过参加相关课程，参加会议， 会议，并与她的合作临床研究团队会面。她忠诚的导师和 合作者将支持她在本奖项期的最后几年提交R01赠款提案。在 2014年9月，Dahlin博士晋升为哈佛医学院医学讲师 学校，表明该机构的承诺，她的职业发展。NHLBI指导 研究科学家发展奖（K01）将允许Dahlin博士合并一个转化流行病学 用网络建模的方法研究miRNA网络与治疗之间的关系 哮喘反应，目的是改善哮喘患者的治疗效果。