|Department of Physiology|
McIntyre Medical Sciences Building,
3655 Promenade Sir William Osler
Montréal, Québec H3G 1Y6
(514) 398-8320 (office),
john [dot] hanrahan [at] mcgill [dot] ca
Laboratory web site:
Research Area: Cell and Molecular Biology
Our main goal is to understand epithelial chloride transport at the molecular level. Most of our effort focuses on CFTR (cystic fibrosis transmembrane conductance regulator), a low-conductance channel which mediates cAMP-stimulated chloride and bicarbonate secretion and is defective in the disease cystic fibrosis. We use site-directed mutagenesis, electrophysiological and imaging methods to study the structure and function of CFTR in heterologous expression systems, cell lines, and primary epithelial cell cultures. A recent emphasis has been the development of F508del-CFTR correctors for the treatment of CF. Other projects investigate the role of CFTR in mucus production and in chronic obstructive pulmonary disease.
Education: BSc(Hon), Dalhousie; PhD, UBC; Postdoc, Yale
Selected Recent Publications:
Billet A, Luo Y, Balghi H, Hanrahan JW 2013. Role of tyrosine phosphorylation in the muscarinic activation of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR). J Biol Chem. 288:21815-23.
LeSimple P, Goepp J, Palmer ML, Fahrenkrug SC, O’Grady SM, Ferraro P, Robert R, Hanrahan JW 2013. CFTR is expressed in mucin granules from Calu-3 and primary human airway epithelial cells. Am. J. Resp Cell Mol. Biol. 49(4):511-6.
Hanrahan JW, Sampson HM, Thomas DY 2013. Novel pharmacological strategies to treat cystic fibrosis. Trends Pharmacol Sci. 34:119-25.
Carlile GW, Keyzers RA, Teske KA, Robert R, Williams DE, Linington RG, Gray CA, Anjos SM, Sampson HM, Zhang D, Liao J, Hanrahan JW, Andersen RJ, Thomas DY 2012. Correction of the ΔF508 CFTR trafficking by inhibition of PARP with the sponge alkaloid Latonduine. Chemistry & Biology 19:1288-1299.
Zhang D, Ciciriello F, Anjos SM, Carissimo A, Liao J, Carlile GW, Balghi H, Robert R, Luini A, Hanrahan JW, Thomas DY 2012. Ouabain mimics low temperature rescue of F508del-CFTR in cystic fibrosis epithelial cells. Frontiers in Pharmacology 3:176.
Huang J, Shan J, Kim D, Liao J, Evagelidis A, Alper SL, Hanrahan JW 2012. Basolateral chloride loading by AE2: Role in fluid secretion by the human airway epithelial cell line Calu-3. J Physiol. 590:5299-5316.
Shan J, Liao J, Huang J, Robert R, Palmer ML, Fahrenkrug SC, O'Grady SM, Hanrahan JW 2012. Bicarbonate-dependent chloride transport drives fluid secretion by the human airway epithelial cell line Calu-3. J Physiol. 590:5273-5297.