Wood Smoke and Genetic Susceptibility to Asthma in An Honduran Population

描述（由申请人提供）：这是一个修改后的应用程序为病人导向的职业发展奖（K23）博士约书亚Galanter，助理教授在医学和生物工程和治疗科学在加州大学弗朗西斯科分校的部门。Galanter博士是一名年轻的研究人员，在不同人群中研究哮喘的遗传流行病学和药物遗传学。拟议的K23奖将为Galanter博士提供支持，以实现以下目标：（1）培养在不同人群中设计和实施临床研究的技能;（2）学习流行病学和生物统计学方法，以确定影响肺健康的因素;（3）进行哮喘遗传流行病学研究;（4）获得在复杂疾病中进行遗传和基因-环境相互作用研究所需的专业知识;（5）培养评估固体燃料燃烧室内空气污染暴露的技能;最终目标是（6）发展独立的临床研究事业。为了实现这些目标，Galanter博士组建了一个指导团队，由主要导师Esteban Gonz <$lez Burchard博士（UCSF哮喘遗传学实验室主任）和几位共同导师和顾问组成，包括John Balmes博士，Neal Benowitz，Saunak Sen和Mario Castro。 哮喘是一种复杂的疾病，是遗传和环境因素相互作用的结果。加兰特博士的研究将侧重于确定接触燃木炉灶和哮喘之间的联系，以及洪都拉斯奥兰乔人口的严重程度和肺功能等相关特征，在那里使用燃木炉灶很常见（目标1）。他还将进行遗传关联分析，以确定该人群中的遗传风险因素和基因-环境相互作用（目标2）。这些可能有助于识别赋予个体对木材烟雾影响易感性的遗传变异，并阐明暴露于木材烟雾可能导致哮喘的机制。最后，他将进行一项初步研究，以获得哮喘受试者的广泛暴露和表型信息。他将测量常见空气污染物的家庭和个人暴露水平，表征暴露于烟雾的炎症生物标志物和代谢物，并进行详细的哮喘表型分析，包括肺功能和对沙丁胺醇的反应的全面评估，过敏致敏标记物的测量和基因表达分析（目标3）。

DESCRIPTION (provided by applicant): This is a revised application for a Patient Oriented Career Development Award (K23) for Dr. Joshua Galanter, an Assistant Professor in the Departments of Medicine and Bioengineering and Therapeutic Sciences at the University of California, San Francisco. Dr. Galanter is establishing himself as a young investigator in the fields of genetic epidemiology and pharmacogenetics of asthma in diverse populations. The proposed K23 award would provide Dr. Galanter with support to accomplish the following goals: (1) develop skills in the design and implementation of clinical studies in diverse populations; (2 learn the epidemiologic and biostatistical methods required to identify factors that influence lun health; (3) conduct research into the genetic epidemiology of asthma; (4) acquire the expertise required to perform genetic and gene-environment interaction studies in complex diseases; (5) foster skills to assess indoor air pollution exposures from solid fuel combustion; with an ultimat goal of (6) developing an independent clinical research career. In order to achieve these goals, Dr. Galanter has assembled a mentoring team comprised of a primary mentor, Dr. Esteban Gonz¿lez Burchard, Director of the Asthma Genetics Laboratory at UCSF, who conducts clinical research in asthma genetics, and several co-mentors and advisors, including Drs. John Balmes, Neal Benowitz, Saunak Sen, and Mario Castro. Asthma is a complex disease that results from the interplay between genetic and environmental factors. Dr. Galanter¿s research will focus on identifying a link between exposure to wood-burning stoves and asthma and related traits such as severity and lung function in a population in Olancho, Honduras, where the use of woodburning stoves is common (Aim 1). He will also perform a genetic association analysis to identify genetic risk factors and gene-environment interactions in this population (Aim 2). These may help identify genetic variants that confer individual susceptibility to the effects of wood smoke and elucidate the mechanism by which exposure to wood smoke could lead to asthma. Finally, he will perform a pilot study to obtain extensive exposure and phenotype information of asthmatic subjects. He will measure household and personal exposure levels of common air pollutants, characterize inflammatory biomarkers and metabolites of exposure to smoke, and perform a detailed asthma phenotyping, including thorough assessment of pulmonary function and response to albuterol, measurement of markers of allergic sensitization, and gene expression analyses (Aim 3).