null John Hanrahan, PhD
airway epithelia • CFTR • cystic fibrosis • COPD • COVID-19 • drug development
We examine the epithelial cells that line the respiratory tract. The goal is to understand how salt and water are transported and how they are altered in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The main focus is ion channels, especially CFTR, the chloride and bicarbonate channel that is mutated in CF. Lately we have become interested in mechanisms of innate immunity and how the epithelial cells defend against infection by bacteria (Pseudomonas aeruginosa) and viruses (SARS-CoV-2). We are also engaged in the preclinical development of candidate drugs that target CFTR and SARS-CoV-2.
Kim D, Liao J, Scales NB, Martini C, Luan X, Abu-Arish 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):e20201831. doi: 10.1084/jem.20201831. PMID: 33533914.
Turner MJ, Sato Y, Thomas DY, Abbott-Banner K, Hanrahan JW. 2021. Phosphodiesterase 8A Regulates CFTR Activity in Airway Epithelial Cells. Cell Physiol Biochem. 55(6):784-804. doi: 10.33594/000000477. PMID: 34936285.
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. Sci Rep. 11(1):23256. doi: 10.1038/s41598-021-02420-x. PMID: 34853321.
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. doi: 10.1124/jpet.120.000080. PMID: 33012706.
Abu-Arish A, Pandžic E, Kim D, Tseng HW, Wiseman PM, Hanrahan JW. (2019). Agonists that stimulate secretion promote CFTR recruitment into membrane lipid microdomains. J. Gen Physiol. 151(6):834-849.doi: 10.1085/jgp.201812143. PMID: 31048413.