Airway Microbial Community Structure and Function in Chronic Asthma

慢性哮喘气道微生物群落结构和功能

• 批准号: 8969807
• 负责人: Yvonne Jean Huang
• 金额: $ 15.1万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-26 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8969807
• 关键词: Airway; Microbial; Community; Structure; Function

DESCRIPTION (provided by applicant): This is an application for a K23 mentored patient-oriented research career development award for Dr. Yvonne Huang, M.D., a pulmonary/critical care medicine physician at the University of California, San Francisco. Dr. Huang is establishing herself as a clinical investigator of the role of airway microbial colonization (airway microbiota) in asthma. This K23 award will provide Dr. Huang with the support necessary to accomplish the following career development goals: (1) to obtain training and practical experience in leading clinical- translational research studies of asthma; (2) to learn and apply advanced statistical methods to analyze clinical data in conjunction with airway microbiome data generated from microarray and next-generation sequencing approaches; and (3) to acquire further knowledge and experience on methods for studying global functional gene expression in the airway environment. To achieve these goals, Dr. Huang has assembled a multidisciplinary mentoring team with complementary expertise in each of these three areas. This team is comprised of a primary mentor, Dr. Homer Boushey, Professor of Pulmonary Medicine at UCSF and an internationally recognized clinical investigator of asthma, and two co-mentors: Dr. Mark Segal, Professor of Biostatistics at UCSF and Director of the Center for Bioinformatics and Molecular Biostatistics, an expert in advanced statistical techniques for the analysis of complex molecular and genomic data; and Dr. Susan Lynch, Assistant Professor of Medicine at UCSF, an expert microbiologist who directs the microbiome research core in the Division of Gastroenterology, Department of Medicine at UCSF. Asthma is a common airway disease of still unknown etiology that bears significant socioeconomic burden. Clinical heterogeneity in asthma is now well-recognized, leading researchers to consider that different pathogenetic mechanisms may exist. One area of increasing interest is the potential role of airway bacterial colonization in the pathogenesis of asthma or of specific asthma phenotypes. Dr. Huang's research will examine if the composition of bacterial microbiota found in respiratory specimens from asthma patients are influenced by the use of inhaled corticosteroids or macrolide antibiotics, two medications used in the management of asthma (Aims 1 and 2). She additionally will study global functional gene expression profiles in the asthma airway microbiome to examine how they may relate to clinical features of disease (Aim 3). Dr. Huang will use the infrastructure of the UCSF Airway Clinical Research Center to enroll asthmatic and healthy volunteers for a prospective pilot study of differences in the airway microbiome between asthmatic and healthy individuals, and the impact of commonly prescribed therapies on the microbiome. She also will apply innovative, high-throughput approaches to perform phylogenetic and functional profiling of the airway microbiome in asthmatic patients. This research will lay important groundwork for future studies of the airway microbiome in larger populations of asthma patients or of specific asthma phenotypes.

描述（由申请人提供）：这是为 Yvonne Huang 博士（医学博士）申请 K23 指导的以患者为导向的研究职业发展奖，Yvonne Huang 博士是旧金山加利福尼亚大学的肺/重症监护医学医师。黄博士正在将自己定位为气道微生物定植（气道微生物群）在哮喘中的作用的临床研究者。该K23奖项将为黄博士提供实现以下职业发展目标所需的支持：（1）获得领导哮喘临床转化研究的培训和实践经验； (2) 学习并应用先进的统计方法，结合微阵列和新一代测序方法生成的气道微生物组数据来分析临床数据； (3) 获得有关研究气道环境中整体功能基因表达的方法的更多知识和经验。为了实现这些目标，黄博士组建了一支多学科指导团队，在这三个领域中具有互补的专业知识。该团队由一位主要导师、加州大学旧金山分校肺科教授、国际公认的哮喘临床研究者 Homer Boushey 博士和两位共同导师：加州大学旧金山分校生物统计学教授兼该中心主任 Mark Segal 博士组成。生物信息学和分子生物统计学专家，用于分析复杂分子和基因组数据的先进统计技术专家；加州大学旧金山分校医学助理教授 Susan Lynch 博士是一位微生物学家专家，负责指导加州大学旧金山分校医学系胃肠病学部的微生物组研究核心。哮喘是一种病因尚不清楚的常见气道疾病，带来重大的社会经济负担。哮喘的临床异质性现已得到广泛认可，这使得研究人员认为可能存在不同的发病机制。人们越来越感兴趣的一个领域是气道细菌定植在哮喘或特定哮喘表型发病机制中的潜在作用。黄博士的研究将检查哮喘患者呼吸道标本中发现的细菌微生物群的组成是否受到吸入皮质类固醇或大环内酯类抗生素（这两种用于治疗哮喘的药物）的影响（目标 1 和 2）。此外，她还将研究哮喘气道微生物组中的整体功能基因表达谱，以研究它们与疾病临床特征的关系（目标 3）。黄博士将利用加州大学旧金山分校气道临床研究中心的基础设施，招募哮喘患者和健康志愿者进行一项前瞻性试点研究，研究哮喘患者和健康个体之间气道微生物组的差异，以及常用处方疗法对微生物组的影响。她还将应用创新的高通量方法对哮喘患者气道微生物组进行系统发育和功能分析。这项研究将为未来研究更多哮喘患者或特定哮喘表型的气道微生物组奠定重要基础。