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).
This study will improve the understanding of genetic and environmental risk factors for asthma. Given the global levels of exposure to solid fuels, and the public health consequences of the growing asthma epidemic, establishing an association between the two is of critical public health importance. This study may discover variants that confer genetic susceptibility to the effects of solid fuel combustion (gene-environment interactions), which may identify vulnerable populations, and help elucidate wood smoke exposure leads to asthma.
| Park, Danny S; Eskin, Itamar; Kang, Eun Yong et al. (2018) An ancestry-based approach for detecting interactions. Genet Epidemiol 42:49-63 |
| Oh, Sam S; Du, Randal; Zeiger, Andrew M et al. (2017) Breastfeeding associated with higher lung function in African American youths with asthma. J Asthma 54:856-865 |
| Rahmani, Elior; Zaitlen, Noah; Baran, Yael et al. (2017) Correcting for cell-type heterogeneity in DNA methylation: a comprehensive evaluation. Nat Methods 14:218-219 |
| Galanter, Joshua M; Gignoux, Christopher R; Oh, Sam S et al. (2017) Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures. Elife 6: |
| Rahmani, Elior; Shenhav, Liat; Schweiger, Regev et al. (2017) Genome-wide methylation data mirror ancestry information. Epigenetics Chromatin 10:1 |
| Rahmani, Elior; Zaitlen, Noah; Baran, Yael et al. (2016) Sparse PCA corrects for cell type heterogeneity in epigenome-wide association studies. Nat Methods 13:443-5 |
| Pino-Yanes, Maria; Gignoux, Christopher R; Galanter, Joshua M et al. (2015) Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos. J Allergy Clin Immunol 135:1502-10 |
| Pino-Yanes, Maria; Thakur, Neeta; Gignoux, Christopher R et al. (2015) Genetic ancestry influences asthma susceptibility and lung function among Latinos. J Allergy Clin Immunol 135:228-35 |
| Oh, Sam S; Galanter, Joshua; Thakur, Neeta et al. (2015) Diversity in Clinical and Biomedical Research: A Promise Yet to Be Fulfilled. PLoS Med 12:e1001918 |
| Moreno-Estrada, Andrés; Gignoux, Christopher R; Fernández-López, Juan Carlos et al. (2014) Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science 344:1280-5 |
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