The Role of Airway Microbiota in Nontuberculous Mycobacterial Infection in Cystic Fibrosis

气道微生物群在囊性纤维化非结核分枝杆菌感染中的作用

• 批准号: 10393861
• 负责人: Lindsay J Caverly
• 金额: $ 5.1万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2022-01-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10393861
• 关键词: Affect; Bioinformatics; Biology; Biometry; Child Health; Childhood; Clinical Data; Clinical Research; Complement; Complex; Computational Biology; Computational Technique; Cystic Fibrosis; Cystic Fibrosis sputum; DNA sequencing; Development; Disease; Disease Progression; Doctor of Philosophy; Ecology; Foundations; Functional disorder; Goals; Junior Physician; Knowledge; Lung; Lung diseases; Lung infections; Master' s Degree; Medical Care Costs; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic; Michigan; Morbidity - disease rate; Mycobacterium Infections; Observational Study; Outcome; Pathogenesis; Patients; Research; Research Methodology; Research Training; Risk Factors; Role; Sampling; Scientist; Senior Scientist; Structure; Testing; Training; United States; Universities; career; clinical database; clinical decision-making; cost; cystic fibrosis airway; cystic fibrosis patients; improved; metabolomics; microbial; microbial community; mortality; non-tuberculosis mycobacteria; novel; patient oriented; predictive modeling; preventive intervention; prospective; repository; respiratory microbiota; risk prediction; screening; skills; success; targeted treatment

PROJECT SUMMARY/ABSTRACT Lindsay Caverly, MD is a pediatric pulmonologist and scientist at the University of Michigan. This K23 proposal will complete Dr. Caverly's training towards her long-term career goal of improving the health of children with lung diseases through a better understanding of the lung microbial ecology. This proposal will build on Dr. Caverly's previously acquired expertise in pulmonary pathophysiology and nontuberculous mycobacterial (NTM) infection to provide her with new expertise in clinical research methodology and computational biology. In the proposed project, she will integrate her established and newly-acquired skills to elucidate the role of airway microbiota in the pathogenesis of NTM infection in individuals with cystic fibrosis (CF). This research and training will be guided by her primary mentor, John J. LiPuma MD, co-mentor Patrick D. Schloss PhD, and an advisory board of accomplished senior scientists with expertise in clinical research methods, computational biology, microbial ecology, and biostatistics, and success in mentoring junior physician-scientists. Dr. Caverly's three year plan includes formal coursework to obtain a Master's Degree in Bioinformatics, professional development activities, and progressively independent research. Although NTM pulmonary infections cause significant morbidity and mortality for individuals with CF, the determinants of NTM pulmonary disease, including risk factors for NTM acquisition and variables impacting disease progression, are largely unknown. The increasing appreciation that the CF airways harbor complex microbial communities provides an opportunity to investigate the role of airway microbiota in the pathogenesis of NTM disease. Aim 1 will test the hypothesis that features of CF airway microbiota will predict NTM acquisition, while Aim 2 will test the hypothesis that features of CF airway microbiota will predict NTM disease course. To complete these aims, Dr. Caverly will capitalize on an existing repository of CF sputum samples and a comprehensive database of clinical information. She will also execute a prospective, observational study of individuals with CF and NTM infection to complement the existing samples and to gain expertise in clinical research methods. Dr. Caverly will use state-of-the art DNA sequencing and metabolomics platforms to characterize the structure and metabolic activities of CF airway microbiota, and will integrate the microbial and clinical data using novel analytic techniques of computational biology to build predictive models of patient-relevant outcomes. Dr. Caverly anticipates that these results will have an important positive impact in informing risk prediction for NTM infection, guiding clinical decision making, and illuminating novel biology. This K23 award will establish a foundation for a programmatic line of research to understand the role of airway microbiota in CF and NTM infection, and will equip Dr. Caverly with the skills to be a leader in the field of patient-oriented pediatric pulmonary research.

项目总结/摘要 医学博士林赛卡弗利是密歇根大学的儿科肺病学家和科学家。K23提案 将完成博士的培训，实现她的长期职业目标，改善儿童的健康， 通过更好地了解肺部微生物生态学来治疗肺部疾病。这将建立在博士。 Caverly以前在肺部病理生理学和非结核分枝杆菌方面获得的专业知识 (NTM)感染，为她提供新的专业知识，在临床研究方法和计算生物学。 在拟议的项目中，她将结合她的既定和新获得的技能，阐明的作用， 在囊性纤维化（CF）患者中NTM感染发病机制中的气道微生物群。本研究 和培训将由她的主要导师，约翰J。利普马医学博士，共同导师帕特里克D。施洛斯博士， 一个由在临床研究方法、计算方法和生物医学方面具有专长的资深科学家组成的咨询委员会。 生物学、微生物生态学和生物统计学，以及指导初级医生科学家的成功。凯弗利医生的 三年计划包括正式课程，以获得生物信息学硕士学位，专业 开发活动，并逐步独立的研究。虽然NTM肺部感染导致 CF患者的显著发病率和死亡率是NTM肺病的决定因素， 包括NTM获得的风险因素和影响疾病进展的变量，在很大程度上是未知的。 越来越多的人认识到CF气道含有复杂的微生物群落， 研究呼吸道微生物群在NTM疾病发病机制中的作用。目标1将测试 假设CF气道微生物群的特征将预测NTM的获得，而Aim 2将测试 假设CF气道微生物群的特征将预测NTM病程。为了实现这些目标，博士。 Caverly将利用现有的CF痰液样本库和全面的数据库， 临床信息。她还将对CF和NTM患者进行前瞻性观察研究 感染，以补充现有的样本，并获得临床研究方法的专业知识。凯弗利医生 将使用最先进的DNA测序和代谢组学平台来表征结构， CF气道微生物群的代谢活动，并将使用新的微生物和临床数据整合 计算生物学的分析技术，以建立患者相关结果的预测模型。博士 Caverly预计，这些结果将对NTM的风险预测产生重要的积极影响 感染，指导临床决策，并阐明新的生物学。K23奖项将建立一个 为了解气道微生物群在CF和NTM中的作用的研究项目奠定了基础 感染，并将装备博士Caverly的技能，成为一个领导者，在该领域的病人为导向的儿科 肺研究