Physiology and Biophysics Discipline

Center for Genetic Diseases

Research Projects

Dr. Bridges' primary area of research is on epithelial ion transport with a special focus on epithelial ion channels. His lab uses a wide range of electrophysiological methods and video imaging to study the regulation, pharmacology and biophysics of ion channels including CFTR, ENaC and various potassium channels. He collaborates with several pharmaceutical companies working toward the development of drugs for the treatment of Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.

Publications

Michaels W.E., Bridges R.J.,* Hastings M.L. (2020) Antisense oligonucleotide-mediated correction of CFTR splicing improves chloride secretion in cystic fibrosis patient-derived bronchial epithelial cells. Nucleic Acids Research, 2020 1–14 doi: 10.1093/nar/gkaa490

Clancy J.P., Cotton C.U., Donaldson S.H., Solomon G.M., VanDevanter D.R., Boyle M.P., Gentzsch M., Nick J.A., Illek B., Wallenburg J.C., Sorscher E.J., Amaral M.D., Beekman J.M., Naren A.P., Bridges R.J., Thomas P.J., Cutting G., Rowe S., Durmowicz A.G., Mense M., Boeck K.D., Skach W., et al. (2019) CFTR modulator theratyping: Current status, gaps and future directions. J Cyst Fibros. 2019 Jan;18(1):22-24. 
PMCID: PMC6301143

Bridges R.J. and Bradbury NA. (2018) Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator and Drugs: Insights from Cellular Trafficking. Handb Exp Pharmacol. 245:385-425.

Zeng M., Szymczak M., Ahuja M., Zheng C., Yin H., Swaim W., Chiorini J.A., Bridges R.J., and Muallem S. (2017) Restoration of CFTR Activity in Ducts Rescues Acinar Cell Function and Reduces Inflammation in Pancreatic and Salivary Glands of Mice. Gastroenterology. 153:1148-1159.

Xue X., Mutyam V., Thakerar A., Mobley J., Bridges R.J., Rowe S.M., Keeling K.M., and Bedwell D.M. (2017) Identification of the amino acids inserted during suppression of CFTR nonsense mutations and determination of their functional consequences. Hum Mol Genet. 26:3116-3129.

Vu C.B., Bridges R.J., Pena-Rasgado C., Lacerda A.E., Bordwell C., Sewell A., Nichols A.J., Chandran S., Lonkar P., Picarella D., Ting A., Wensley A., Yeager M., and Liu F. (2016) Fatty Acid Cysteamine Conjugates as Novel and Potent Autophagy Activators That Enhance the Correction of Misfolded F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). J Med Chem. 60:458-473.

Jai Y., Shah K., Bridges R.J., and Bradbury N.A. (2015) Evidence against resveratrol as a viable therapy for the rescue of defective ΔF508 CFTR. Biochim Biophys Acta. 1850:2377-2384.

Rasgado-Flores H., Krishna Mandava V., Siman H., Van Driessche W., Pilewski J.M., Randell S.H., and Bridges R.J. (2013) Effect of apical hyperosmotic sodium challenge and amiloride on sodium transport in human bronchial epithelial cells from cystic fibrosis donors. Am J Physiol Cell Physiol. 305:C1114-1122.

Bridges R.J. (2012) Mechanisms of bicarbonate secretion: lessons from the airways. Cold Spring Harb Perspect Med.2(8): a015016.

Kalid O., Mense M., Fischman S., Shitrit A., Bihler H., Ben-Zeev E., Schutz N., Pedemonte N., Thomas P.J., Bridges R.J., Wetmore D.R., Marantz Y., and Senderowitz H. (2010) Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening. J Comput Aided Mol Des. 24:971-991.

Young A., Gentzsch M., Abban C.Y., Jia Y., Meneses P.I., Bridges R.J., and Bradbury NA. (2009) Dynasore inhibits removal of wild-type and DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) from the plasma membrane. Biochem J. 421:377-385.

Coote K., Atherton-Watson H.C., Sugar R., Young A., MacKenzie-Beevor A., Gosling M., Bhalay G., Bloomfield G., Dunstan A., Bridges R.J., Sabater J.R., Abraham W.M., Tully D., Pacoma R., Schumacher A., Harris J., and Danahay H. (2009) Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease. J Pharmacol Exp Ther. 329:764-774.

Adebamiro, A., Cheng, Y., Rao, U.S., Danahay, H., and Bridges, R.J. (2007). A segment of g ENaC mediates elastase activation of Na+ transport. J Gen Physiol. 130(6):611-629.

Adebamiro, A., Cheng, Y., Johnson, J.P. and Bridges, R.J. (2005). Endogenous protease activation of ENaC: Effect of serine protease inhibition on ENaC single channel properties. J. Gen. Physiol. 126(4):339-352.

Kreindler, J.L., Jackson, A., Kemp, P., Bridges, R.J., Danahay, H. (2005). Inhibition of chloride secretion in human bronchial epithelial cells by cigarette smoke extract. Am J Physiol Lung Cell Mol Physiol. 288:L894-902.

Singh, A.K., Schultz, B.D., van Driessche, W., Bridges, R.J. (2004). Transepithelial fluctuation analysis of chloride secretion. J. Cyst Fibros. Suppl 2:127-132.

Bridges, R.J., Newton, B.B., Pilewski, J.M., Devor, D.C., Poll, C.T., and Hall, R.L. (2001). Na transport in normal and CF human bronchial epithelial cells is inhibited by BAY 39-9437. Am. J. Physiol. 281:L16-L23.

Devor, D.C., Bridges, R.J., and Pilewski, J.M. (2000). Pharmacological modulation of ion transport across wild-type and deltaF508-CFTR-expressing human bronchial epithelia. Am. J. Physiol. 279:C461-C479.

Schultz, B.D., Singh, A.K., Devor, D.C. and Bridges, R.J. (1999). Pharmacology of CFTR chloride channel activity. Physiological Reviews 79:S109-S144.

Devor, D. C., Singh, A.K., Lambert, L.C., DeLuca, A., Frizzell, R.A., and Bridges, R.J. (1999). Bicarbonate and chloride secretion in Calu-3 human airway epithelial cells. J. Gen Physiol. 113:743-760.