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.
This study proposes a novel investigation of the relationship between miRNAs and treatment response to leukotriene modifying agents, with the ultimate goal of improving therapeutic outcomes in asthma patients. Understanding which patients are likely to benefit from a particular asthma medication will improve patient care and guide physicians in selecting appropriate treatment regimens for their patients, while developing new insights into molecular pathways involved in leukotriene modifier response is expected to aid in development of more effective therapies for asthma.
