This Mentored Patient-Oriented Career Development Award will provide the Principal Investigator (PI) with knowledge, skills, and expertise in the genomic study of patients with asthma with an emphasis on the pharmacogenetics of asthma therapy. The PI is trained in pediatric and adult pulmonology and has completed his fellowship in respiratory epidemiology at the Channing Laboratory, concurrently receiving his MPH from the Harvard School of Public Health. He also currently runs a pediatric asthma clinic. Further training and research will be carried out under the supervision of a highly qualified advisory committee, with expertise in asthma epidemiology and clinical studies, molecular biology, genetic epidemiology, and statistics, and will include course work, hands-on genetic laboratory experience, and patient recruitment. This award will facilitate the development of a successful independent research career in the application of pharmacogenomics to patient care. The overall scientific goal of this proposal is to investigate the relationship of cellular corticosteroid induced expression changes to clinical outcomes in childhood asthmatics. We hypothesize that corticosteroid gene expression response within families will serve as biomarkers of, and identify novel genomic regions associated with, the response to inhaled corticosteroids in asthma. We seek to investigate this hypothesis by evaluating the clinical response to inhaled corticosteroids in asthma as an outcome in response to a) corticosteroid induced cellular expression changes themselves, b) positional candidate genes in regions linked to the expression changes, and c) expression candidate genes that significantly vary with corticosteroid administration. Each of these will be accomplished using cell lines, DNA, and phenotypic characteristics from a cohort of childhood asthmatics with whom the PI will directly interact and actively follow. Through the practical attention to the details of this project, the PI will garner a thorough understanding of current molecular, genetic, and statistical methods, as well as develop a solid foundation for patient-oriented research. Successful completion of this award will provide the necessary background to commence an independent career in translational pharmacogenomics. ? ? ?
| Qiu, Weiliang; Guo, Feng; Glass, Kimberly et al. (2018) Differential connectivity of gene regulatory networks distinguishes corticosteroid response in asthma. J Allergy Clin Immunol 141:1250-1258 |
| Vijverberg, S J H; Koster, E S; Tavendale, R et al. (2015) ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic children and young adults. Clin Exp Allergy 45:1051-9 |
| Qiu, Weiliang; Rogers, Angela J; Damask, Amy et al. (2014) Pharmacogenomics: novel loci identification via integrating gene differential analysis and eQTL analysis. Hum Mol Genet 23:5017-24 |
| Duan, Q L; Lasky-Su, J; Himes, B E et al. (2014) A genome-wide association study of bronchodilator response in asthmatics. Pharmacogenomics J 14:41-7 |
| Tantisira, Kelan G; Lasky-Su, Jessica; Harada, Michishige et al. (2011) Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N Engl J Med 365:1173-83 |
| Xu, Mousheng; Tantisira, Kelan G; Wu, Ann et al. (2011) Genome Wide Association Study to predict severe asthma exacerbations in children using random forests classifiers. BMC Med Genet 12:90 |
| Kho, Alvin T; Bhattacharya, Soumyaroop; Tantisira, Kelan G et al. (2010) Transcriptomic analysis of human lung development. Am J Respir Crit Care Med 181:54-63 |
| Tantisira, Kelan G; Drazen, Jeffrey M (2009) Genetics and pharmacogenetics of the leukotriene pathway. J Allergy Clin Immunol 124:422-7 |
| Rogers, Angela J; Tantisira, Kelan G; Fuhlbrigge, Anne L et al. (2009) Predictors of poor response during asthma therapy differ with definition of outcome. Pharmacogenomics 10:1231-42 |
| Tantisira, Kelan G (2009) In asthma, the apple falls faster than the pear. J Allergy Clin Immunol 123:1075-6 |
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