Website: http://1234jc4321.github.io/

Twitter: @1234jc4321

LinkedIn: www.linkedin.com/in/1234jc4321

ResearchGate: www.researchgate.net/profile/Jean-Christophe_Berube

ORCID: www.orcid.org/0000-0002-7634-5270

Genetics of gene expression in the lung to elucidate asthma susceptibility

Asthma is a disease affecting more than 2 million Canadians, which includes 8% of adults and 16% of children younger than 12 years of age. The disease affects the airways in several manners, reducing the breathing capacity and causing mild to severe symptoms to patients. In addition to environmental factors, a considerable proportion of the disease is due to genetic factors transmitted from the parents to their child.

Such genetic factors are recognized by the scientific community, but many remain to be discovered. Some variations in our genetic code may influence asthma susceptibility by modifying the expression of one or several genes in the lung. Genes are responsible for specific chemical reactions. Increasing or decreasing the level of gene expression may alter functions necessary to the health of the lung.

In short, the goal of this project is to take advantage of modern genomic approaches coupled with unique resources available at our institution to study genetic variations modulating the levels of genes in the lung.

Why is the research project/program important?

This research project combines modern tools and genomic approaches to a group of clinical and basic researchers in the field of asthma. We have recently analyzed gene levels of human lung tissues in a large number of subjects. Furthermore, we have collected a case-control asthma cohort composed of well-characterized subjects with precise measurements useful for specific and clinically important analyses. Thus, the research project is taking advantage of two unique genomic datasets to address timely scientific questions in the field of asthma.

The project is also important because it has the potential to provide some insights about asthma heterogeneity. Asthma patients do not share the same disease mechanisms. With our studies, specific factors of asthma subtypes may be revealed, thus leading to more personalised treatments for patients and an increased cost effectiveness.

What was the result of the project and what impact will it have?

This is an ongoing project. For now, new genes expressed in the lungs have been associated with asthma. Their precise role in the development of asthma remains to be validated with further experiments.

This project will have an impact on many levels. First, understanding the molecular basis of asthma is much needed to develop new medical strategies. Many drugs are available on the market but they are not necessarily suitable for all asthmatic patients. This research is an important step to eventually identify the right drug for the right patient. In addition, finding biomarkers to refine disease classification and guide targeted therapies would have a great impact for respirologists and asthma

Another impact of the project is the possibility to identify individuals at greater risk to develop asthma. Knowing which individuals possess a greater genetic predisposition will shift the medical approach toward prevention instead of pharmacological treatments.

Ultimately, the proposed research will improve our understanding of the mechanisms underlying asthma, which will likely lead to improve prevention, management and treatment.

Publications

Lavoie-Charland É, Bérubé JC, Boulet LP, Bossé Y Asthma susceptibility genetic variants are more strongly associated with phenotypically similar subgroups of patients. J Asthma. 2016 Apr 8:1-6.

Bérubé JC, Lavoie-Charland E, Gaudreault N, Sbarra L, Henry C, Boulet LP, Bossé Y. Identification of Susceptibility Genes of Adult Asthma in French Canadian Women. CanRespirJ. 2016; 2016: 3564341.

Veilleux A, Mayeur S, Bérubé JC, Beaulieu JF, Tremblay E, Hould FS, Bossé Y, Richard D, Levy E, Altered intestinal functions and increased local inflammation in insulin-resistant obese subjects: a gene-expression profile analysis. BMC Gastroenterology. 2015 Sep 16;15:119.

Haj-Salem I, Fakhfakh R, Bérubé JC, Jacques E, Plante S, Simard M, Bossé Y, Chakir J. MicroRNA-19a enhances proliferation of bronchial epithelial cells by targeting TGFBR2 gene in severe asthma. Journal of Allergy and Clinical Immunology. Allergy. 2015 Feb;70(2):212-9.

Saferali, A, Bossé Y, Bérubé JC, Laviolette M, Obeidat M, Hao K, Nickle DC, Timens W, Sin DD, Postma DS, Durie PR, Strug LJ, Paré PD, Bingle CD, Sandford AJ. Polymorphisms associated with cystic fibrosis severity modulate expression of BPIFA1/BPIFB1. American Journal of Respiratory Cell Molecular Biology. . 2015 Nov;53(5):607-14.

Bérubé JC, Bossé Y. Future clinical implications emerging from recent genome-wide expression studies in asthma. Expert Review of Clinical Immunology 2014; 10(8): 985-1004.

Akhabir L, Bérubé JC, Bossé Y, Laviolette M, Hao K, Nickle DC, Timens W, Sin DD, Paré PD, Postma DS, Sandford AJ. Lung expression quantitative trait loci data set identifies important functional polymorphisms in the asthma-associated IL1RL1 region. Journal of Allergy and Clinical Immunology 2014; 134(3): 729-31.

Morissette MC, Lamontagne M, Bérubé JC, Gaschler G, Couture C, Laviolette M, Hogg JC, Timens W, Halappanavar S, Stampfli MR, Bossé Y. Impact of cigarette smoke on the human and mouse lungs: a gene-expression comparison study. PLoS One 2014, 9(3): e92498.

Lavoie-Charland É, Bérubé JC, Laviolette M, Boulet LP, Bossé Y. Multivariate Asthma Phenotypes in Adults: The Quebec City Case-Control Asthma Cohort. Open Journal of Respiratory Diseases 2013; 3(4):133-142.

Bérubé JC, Lamontagne M, Couture C, Nickle D, Timens W, Postma D, Sin D, Paré P, Laviolette M, Bossé Y. Genome-wide genetic ancestry measurements to predict lung function in European population. The European Respiratory Journal 2013; 42(4): 1144-7.