Wood Smoke and Genetic Susceptibility to Asthma in An Honduran Population

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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).