Airway Microbial Community Structure and Function in Chronic Asthma

描述(申请人提供)：这是为加州大学旧金山分校的肺部/重症监护内科医生Yvonne Huang医学博士申请K23指导的以患者为导向的研究职业发展奖。黄医生将自己确立为呼吸道微生物定植(呼吸道微生物区系)在哮喘中的作用的临床调查员。这一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)获得领导哮喘临床-翻译研究研究的培训和实践经验；(2)学习和应用先进的统计学方法，结合从微阵列和下一代测序方法产生的呼吸道微生物组数据来分析临床数据；以及(3)获得关于研究呼吸道环境中全球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，在这三个领域的每个领域都有互补的专业知识。该团队由一名主要导师、加州大学旧金山分校肺科教授、国际公认的哮喘临床研究员Hmer Boushey博士和两名共同导师组成：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中心主任Mark Segl博士，用于分析复杂分子和基因组数据的高级统计技术专家；以及加州大学旧金山分校医学助理教授Susan Lynch博士，他是微生物学家，领导加州大学旧金山分校医学系消化内科的微生物群研究核心。哮喘是一种常见的呼吸道疾病，其病因尚不清楚，具有重大的社会经济负担。哮喘的临床异质性现已得到公认，这导致研究人员认为可能存在不同的致病机制。人们越来越感兴趣的一个领域是呼吸道细菌定植在哮喘发病机制或特定哮喘表型中的潜在作用。黄博士的研究将检查哮喘患者呼吸道样本中发现的细菌微生物区系是否受到吸入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和目标2)。此外，她还将研究哮喘呼吸道微生物组中的全球功能基因表达谱，以检查它们可能如何与疾病的临床特征相关(目标3)。黄博士将利用加州大学旧金山分校航空临床研究中心的基础设施，招募哮喘患者和健康志愿者，进行一项前瞻性的先导性研究，研究哮喘患者和健康人之间的呼吸道微生物组差异，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来对哮喘患者的呼吸道微生物组进行系统发育和功能分析。这项研究将为未来对更多哮喘患者的呼吸道微生物组或特定哮喘表型的研究奠定重要基础。

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.