Basic Science and Discovery Platform

Platform Leader: Dr. Andrew Halayko

Team Members:

Dr. Michel Aliani
Dr. Carolyn Baglole
Dr. Yohan Bosse
Dr. Christopher Carlsten
Dr. James Davie
Dr. Gail Gauvreau
Dr. Robert Hancock
Dr. Jeremy Hirota
Dr. Richard Leigh
Dr. David Marsolais
Dr. James Martin
Dr. Neeloffer Mokherjee
Dr. Mathieu Morissette
Dr. Robert Newton
Dr. Paul O’Byrne
Dr. David Proud
Dr. Amir Ravandi
Dr. Martin Stampfli
Dr. Adrian West
Dr. John Wilkins
Aruni Jha

Goals

• To identify markers and mechanisms of disease origin and progression that can be targets for novel drug and biomarker discovery for future pre-clinical studies and network clinical trials
• interrogate biological specimens from human subjects in current cohorts for comprehensive molecular characterization.

Publications

Ano S, Panariti A, Allard B, O'Sullivan M, McGovern TK, Hamamoto Y, Ishii Y, Yamamoto M, Powell WS, Martin JG. Inflammation and airway hyperresponsiveness after chlorine exposure are prolonged by Nrf2 deficiency in mice. Free Radic Biol Med. 102:1-15 2017.

Shariff S, Shelfoon C, Holden NS, Traves SL, Wiehler S, Kooi C, Proud D, Leigh R. Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration. Am J Respir Cell Mol Biol. 56(6):796-803 2017.

Boulay MÈ, Henry C, Bossé Y, Boulet LP, Morissette MC. Acute effects of nicotine-free and flavour-free electronic cigarette use on lung functions in healthy and asthmatic individuals. Respir Res. 18(1):33 2017.

A Faiz, C Donovan, MAE Nieuwenhuis, M van den Berge, D Postma, S Yao, CY Park, R Hirsch, JJ Fredberg, G Tjin, AJ Halayko, KL Rempel, JPT Ward, T Lee, Y Bossé, DC Nickle, M Obeidat, JM Vonk, JL Black, BG Oliver, R Krishnan, B McFarland, JE Bourke & JK Burgess. Latrophilin receptors: novel bronchodilator targets in asthma. Thorax 72:74-82  2017

A Jha, MH Ryu, OO Ojo, H Bews, J Carlson, J Schwartz, S Basu, C Wong & AJ Halayko. Prophylactic benefits of systemically delivered simvastatin treatment in a house dust mite challenged murine model of allergic asthma. Submitted to Brit J Pharmacol (MS# 2017-BJP-1037-RP) August 11 2017.

Shen P, Whelan FJ, Schenck LP, McGrath JJC, Vanderstocken G, Bowdish DME, Surette MG, Stämpfli MR. Streptococcus pneumoniae colonization is required to alter the nasal microbiota in cigarette smoke-exposed mice. Infect Immun. [Epub ahead of print] July 31 2017.

JK Burgess, A Ketheson, A Faiz, KA Limbert Rempel, BG Oliver, JPT Ward & AJ Halayko. Human telomerase reverse transcriptase immortalised human airway smooth muscle cells retain unique features of trimary asthmatic and non-asthmatic cell cultures. Submitted to Sci Reports (MS# SREP-17-33625) July 21 2017.

Hamamoto Y, Ano S, Allard B, O'Sullivan M, McGovern TK, Martin JG. MK reduces inhaled chlorine triggered AHR and airway inflammation in the mouse. Br J Pharmacol. [Epub ahead of print] July 18 2017.

O'Sullivan MJ, Gabriel E, Panariti A, Park CY, Ijpma G, Fredberg JJ, Lauzon AM, Martin JG. Epithelial Cells Induce a Cyclooxygenase-1-dependent Endogenous Reduction in Airway Smooth Muscle Contractile Phenotype. Am J Respir Cell Mol Biol. [Epub ahead of print] July 14 2017.

H Piyadasa, M Hemshekhar, A Altieri, S Basu, AM van der Does, AJ Halayko, PS Hiemstra & N Mookherjee. An innate defence regulator peptide alleviates airway inflammation and hyperresponsiveness by regulating the cytokine IL-33. Submitted to Thorax (MS #: thoraxjnl-2017-210739) July 10 2017.

OO Ojo, S Basu, A Jha, MH Ryu, TH Mahood, S Ghavami, J Schwartz, J Chakir, M Laviolette, D Doeing, J McConville, T Vogl, J Roth & AJ Halayko. Alarmin S100A8/A9 promotes pathophysiological hallmarks of allergic asthma.  Submitted to J Allergy Clin Invest  (MS#: JACI-D-17-00458), May 20 2017.

Obeidat M, Nie Y, Fishbane N, Li X, Bossé Y, Joubert P, Nickle DC, Hao K, Postma DS, Timens W, Sze MA, Shannon CP, Hollander Z, Ng RT, McManus B, Miller BE, Rennard S, Spira A, Hackett TL, Lam W, Lam S, Faner R, Agusti A, Hogg JC, Sin DD, Paré PD. Integrative Genomics of Emphysema Associated Genes Reveals Potential Disease Biomarkers. Am J Respir Cell Mol Biol. [Epub ahead of print] May 1 2017.

C Michaeloudes, C-H Kuo, G Haji, D Finch, R Mayer, AJ Halayko, P Kirkham, KF Chung & I Adcock. Metabolic repatterning in chronic obstructive pulmonary disease airway smooth muscle cells. Submitted to Eur Respir J (MS# ERJ-00132-2017) January 20 2017.

Dvorkin-Gheva A, Vanderstocken G, Yildirim AÖ, Brandsma CA, Obeidat M, Bossé Y, Hassell JA, Stampfli MR. Total particulate matter concentration skews cigarette smoke's gene expression profile. ERJ Open Res. 2(4). pii: 00029-2016.

Thayaparan D, Shen P, Stämpfli MR, Morissette MC. Induction of pulmonary antibodies against oxidized lipids in mice exposed to cigarette smoke. Respir Res. 17(1):97 2016.

Morissette MC, Gao Y, Shen P, Thayaparan D, Bérubé JC, Paré PD, Brandsma CA, Hao K, Bossé Y, Ettinger R, Herbst R, Humbles AA, Kolbeck R, Zhong N, Chen R, Stämpfli MR. Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice. Physiol Rep. 4(24). pii: e13057 2016.

Shelfoon C, Shariff S, Traves SL, Kooi C, Leigh R, Proud D. Chemokine release from human rhinovirus-infected airway epithelial cells promotes fibroblast migration. J Allergy Clin Immunol. 138(1):114-122 2016.

K Dessalle, V Narayanan, S Kyoh, A Mogas, AJ Halayko, P Nair, C Baglole, D Eidelman, M Ludwig & Q Hamid.  Human bronchial and parenchymal fibroblasts display differences in basal inflammatory phenotype and response to IL-17A. Clin Exp Allergy 46:945-956 2016.

H Zhang, AT Kho, Q Wu, AJ Halayko, K Limbert-Rempel, NB Sweezey, RP Chase, S TWeiss & F Kaplan. CRISPLD2 (LGL1) inhibits pro-inflammatory mediators in human fetal, adult, and COPD lung fibroblasts and epithelial cells. Physiol Rpts Sep;4(17) pii: e12942 2016.

Biosignature for airway inflammation in a house dust mite-challenged murine model of allergic asthma.
Piyadasa H, Altieri A, Basu S, Schwartz J, Halayko AJ, Mookherjee N. Biosignature for airway inflammation in a house dust mite-challenged murine model of allergic asthma. Biol Open. 2016 Jan 6;5(2):112-21. doi: 10.1242/bio.014464.

Disruption of pulmonary lipid homeostasis drives cigarette smoke-induced lung inflammation in mice
Morissette MC, Shen P, Thayaparan D, Stämpfli MR. Disruption of pulmonary lipid homeostasis drives cigarette smoke-induced lung inflammation in mice. Eur Respir J. 46(5):1451-1460 2015.