cystic fibrosis • bacterial infections • signal transduction • protein phosphorylation • inflammation
My research focuses on investigating the intracellular signaling mechanisms evolved by the host to respond and fight infections in the airways. Infections are a major cause of morbidity in humans, and over time the complex interaction between pathogens and their hosts has led to adaptations on both sides. A major focus of our recent work has been to understand the role of chronic infections in lung tissue destruction in cystic fibrosis. We discovered a heightened response to infection in airway epithelial cells lacking CFTR, which may contribute to the destructive inflammation responsible for lung tissue destruction over time. Therefore, preventing this heightened response may control inflammation, allowing more time for lung transplantation and increasing life expectancy for cystic fibrosis sufferers. We are currently researching specific signalling pathways that can decrease Pseudomonas aeruginosa-induced inflammation while preserving the host's defence mechanism. We hope to use this strategy to decrease inflammation while leaving other cellular functions intact, so as to slow or halt the decline in lung function of CF patients.
Roussel L1, Houle F, Chan C, Yao Y, Bérubé J, Olivenstein R, Martin JG, Huot J, Hamid Q, Ferri L, Rousseau S. IL-17 promotes p38 MAPK-dependent endothelial activation enhancing neutrophil recruitment to sites of inflammation. J Immunol. 2010 Apr 15;184(8):4531-7. doi: 10.4049/jimmunol.0903162. Epub 2010 Mar 12. PMID: 20228195.
Bérubé J, Roussel L, Nattagh L, Rousseau S. Loss of cystic fibrosis transmembrane conductance regulator function enhances activation of p38 and ERK MAPKs, increasing interleukin-6 synthesis in airway epithelial cells exposed to Pseudomonas aeruginosa. J Biol Chem. 2010 Jul 16;285(29):22299-307. doi: 10.1074/jbc.M109.098566. Epub 2010 May 11. PMID: 20460375.
Beaudoin T, LaFayette S, Roussel L, Bérubé J, Desrosiers M, Nguyen D, Rousseau S. The level of p38α mitogen-activated protein kinase activation in airway epithelial cells determines the onset of innate immune responses to planktonic and biofilm Pseudomonas aeruginosa. J Infect Dis. 2013 May 15;207(10):1544-55. doi: 10.1093/infdis/jit059. Epub 2013 Feb 12. PMID: 23402824.
Chow SC, Gowing SD, Cools-Lartigue JJ, Chen CB, Berube J, Yoon HW, Chan CH, Rousseau MC, Bourdeau F, Giannias B, Roussel L, Qureshi ST, Rousseau S, Ferri LE. Gram negative bacteria increase non-small cell lung cancer metastasis via Toll-like receptor 4 activation and mitogen-activated protein kinase phosphorylation. Int J Cancer. 2015 Mar 15;136(6):1341-50. doi: 10.1002/ijc.29111. Epub 2014 Aug 11. PMID: 23219168.
Martel G, Roussel L, Rousseau S. The protein kinases TPL2 and EGFR contribute to ERK1/ERK2 hyperactivation in CFTRΔF508-expressing airway epithelial cells exposed to Pseudomonas aeruginosa. Biochem Biophys Res Commun. 2013 Nov 22;441(3):689-92. PMID: 24404585.