Airway Microbial Community Structure and Function in Chronic Asthma

描述（由申请人提供）：这是Yvonne Huang博士，M.D.，加州大学旧金山弗朗西斯科的肺/重症监护医学医师。Huang博士正在确立自己作为气道微生物定植（气道微生物群）在哮喘中作用的临床研究者的地位。该K23奖项将为黄博士提供必要的支持，以实现以下职业发展目标：（1）获得领先的哮喘临床转化研究的培训和实践经验;（2）学习和应用先进的统计方法，结合微阵列和下一代测序方法生成的气道微生物组数据分析临床数据;以及（3）获得关于研究气道环境中的整体功能基因表达的方法的进一步知识和经验。为了实现这些目标，黄博士组建了一个多学科的指导团队，在这三个领域都有互补的专业知识。该团队由一位主要导师，加州大学旧金山分校肺医学教授，国际公认的哮喘临床研究者Homer Boushey博士和两位共同导师组成：加州大学旧金山分校生物统计学教授，生物信息学和分子生物统计学中心主任Mark Segal博士，复杂分子和基因组数据分析的高级统计技术专家;苏珊·林奇博士，加州大学旧金山分校医学助理教授，一位微生物专家，指导加州大学旧金山分校医学部胃肠病学分部的微生物组研究核心。哮喘是一种常见的气道疾病，其病因尚不清楚，并承担着重大的社会经济负担。哮喘的临床异质性已被公认，导致研究人员认为可能存在不同的发病机制。一个越来越感兴趣的领域是气道细菌定植在哮喘或特定哮喘表型的发病机制中的潜在作用。Huang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性皮质类固醇或大环内酯类抗生素的影响，这两种药物用于治疗哮喘（目标1和2）。她还将研究哮喘气道微生物组中的全球功能基因表达谱，以研究它们如何与疾病的临床特征相关（目标3）。Huang博士将利用UCSF气道临床研究中心的基础设施招募哮喘和健康志愿者进行前瞻性试点研究，研究哮喘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的气道微生物组进行系统发育和功能分析。这项研究将为未来在更大规模的哮喘患者或特定哮喘表型人群中研究气道微生物组奠定重要基础。

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.