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Department of Physiology McGill University McIntyre Medical Sciences Building, Room 1016A 3655 Promenade Sir William Osler Montréal, Québec H3G 1Y6 (514) 398-8320 (office), john.hanrahan [at] mcgill.ca Laboratory web site: |
Research Area: Cell and Molecular Biology
Research Description:
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:
*Abu-Arish A, Panďzíc E, Luo Y, Sato Y, Turner MJ, Wisem PW, Hanrahan JW. (2022). Lipid-driven CFTR clustering is impaired in CF and restored by corrector drugs. Journal of Cell Science.
*Lopes-Pacheco M, Bacalhau M, Ramalho SS, Silva IAL, Ferreira FC, Carlile GW, Thomas DY, Farinha CM, Hanrahan JW, Amaral MD. (2022). Rescue of Mutant CFTR Trafficking Defect by the Investigational Compound MCG1516A. Cells. 11(1): 136-158.
*Turner MJ, Sato Y, Thomas DY, Abbott-Banner K, Hanrahan JW. (2021). Phosphodiesterase 8A Regulates CFTR Activity in Airway Epithelial Cells. Cellular Physiology and Biochemistry. 55: 784-804.
*Sato Y, Mustafina KR, Luo Y, Martini C, Thomas DY, Wiseman PW, Hanrahan JW. (2021). Nonspecific binding of common anti-CFTR antibodies in ciliated cells of human airway epithelium. Scientific Reports. 11(1): 23256-23271.
*Turner MJ, Abbott-Banner K, Thomas DY, Hanrahan JW. (2021). Cyclic nucleotide phosphodiesterase inhibitors as therapeutic interventions for cystic fibrosis. Pharmacology and Therapeutics. 224: 1-14.
*Kim D, Liao J, Scales N, Martini C, Luan X, AbuArish A, Robert R, Luo Y, McKay GA, Nguyen D, Tewfik MA, Poirier CD, Matouk E, Ianowski JP, Frenkiel S, Hanrahan JW. (2021). Large pH oscillations promote host defense against human airways infection. J Exp Med. 218(4): 1-15.
*Kouthouridis S, Goepp J, Martini C, Matthes E, Hanrahan JW, Moraes C. (2021). Oxygenation as a driving factor in epithelial differentiation at the air-liquid interface. Integrative Biology. 13(3): 61-72.
*Veltman M, De Sanctis JB, Stolarczyk M, Klymiuk N, Bähr A, Brouwer RWW, Oole E, Shah J, Ozdian T, Liao J, Martini, Radzioch D, Hanrahan JW, Scholte BJ. (2021). CFTR correctors and antioxidants partially normalize lipid imbalance butnot abnormal basal inflammatory cytokine profile in CF bronchial epithelial cells. Frontiers in Physiology. 12: 1-18.
*Turner MJ, Dauletbaev N, Lands LC, Hanrahan JW. (2020). The phosphodiesterase inhibitor ensifentrine reduces production of proinflammatory mediators in well differentiated bronchial epithelial cells by inhibiting PDE4. J Pharmacol Exp Ther. 375(3): 414-429.
*Lopes-Pacheco M, Silva IAL, Turner MJ, Carlile GW, Sondo E, Thomas DY, Pedemonte N, Hanrahan JW, Amaral MD. (2020). Characterization of the mechanism of action of RDR01752, a novel corrector of F508del-CFTR. Biochem Pharmacol. 180: 1-11.
*Turner MJ, Luo Y, Thomas DT, Hanrahan JW. (2020). The dual phosphodiesterase 3/4 inhibitor RPL554 stimulates rare class III and IV CFTR mutants. Am. J. Physiol. - Lung Cell and Mol. Physiol.318(5): L908- L920.
*Garíc D, De Sanctis JB, Dumut DC, Shah J, Peña MJ, Youssef M, Petrof BJ, Kopriva F, Hanrahan JW, Hajduch M, Radzioch D. (2020). Fenretinide favorably affects mucins (MUC5AC/MUC5B) and fatty acid imbalance in a manner mimicking CFTR-induced correction. Biochim Biophys Acta - Mol Cell Biol Lipids. 1865(2): 158538.
Link to Dr. Hanrahan's publications