Joe Casey (PhD University of Toronto)
Director, Membrane Protein Disease Research Group
Director, International Research Training Group in Membrane Biology
Department of Biochemistry
Office: 4020E Katz Building
Lab: 4055 Katz Building
University of Alberta
Edmonton, Alberta T6G 2H7
Tel: 780 492-7203 (office)
Tel: 780 492-1050 (lab)
Lab Web site: http://www2.biochem.ualberta.ca/CaseyLab
Membrane Protein Disease Research Group: http://www.membranegroup.ualberta.ca/
IRTG in Membrane Biology: http://www.membranetraining.ualberta.ca/
The laboratory’s passion is membrane transport. How do integral membrane transport proteins function as micro-machines to move substances selectively across our cell’s membranes? How does disease arise when these processes go wrong?
Bicarbonate Transport proteins move bicarbonate (HCO3-) across the plasma membrane of our cells. This process is essential to control cell levels of the waste product carbon dioxide (CO2) and to regulate the pH (acid level) both inside and outside our cells. Bicarbonate transport is a simple yet central part of our body's normal functioning. Disruption of bicarbonate transport underlies many diseases. Our laboratory studies the role of bicarbonate transport in causing disease. Supported by two operating grants from the Canadian Institutes of Health Research, our major projects ongoing in our laboratory include:
1. Determining the structure and transport mechanism of the chloride/bicarbonate exchanger, AE1, which is central to red blood cell and kidney function.
2. How do defects in the transport protein called SLC4A11 cause blinding corneal diseases: Fuch's endothelial dystrophy and congenital hereditary endothelial dystrophy?
Loganathan, S.K., Lukowski, C.M. and Casey, J.R. (2016) The cytoplasmic domain is essential for transport function of the integral membrane transport protein SLC4A11, Am. J. Physiol., 310, C161-174.
Chiu, A.M., Mandziuk, J.J., Alka, K., Loganathan, S.K., and Casey, J.R. (2015) High Throughput Assay Identifies Glafenine as a Chemical Corrector for the Folding Defect in Corneal Dystrophy-Causing Mutants of SLC4A11, Invest. Opthal. and Vis. Sci., 56, 7739-53.
Krishnan, D., Liu, L., Wiebe S.A., Casey, J.R., Cordat, E. and Alexander, R.T. (2015) Carbonic anhydrase II binds to and increases the activity of the epithelial sodium proton exchanger, NHE3, Am. J. Physiol., 309, F383-92.
Vilas, G.L., Krishnan, D., Loganathan, S.K., Malhotra, D., Liu, L., Beggs, M., Gena, P., Calamita, G., Jung, M., Zimmermann, R., Tamma, G., Casey, J.R. and Alexander, R.T. (2015), Increased Water Flux Induced by an Aquaporin-1/Carbonic Anhydrase II interaction, Mol. Biol. of Cell., 26, 1106-18.
Loganathan, S.K., and Casey, J.R. (2014) Corneal Dystrophy-causing SLC4A11 Mutants: Suitability for Folding-Correction Therapy, Human Mutation, 35, 1082-91. (Article selected for a video highlight; See http://www.youtube.com/watch?v=rLvUicNtsoM)
Vilas, G.L., Loganathan, S., Liu J., Riau, A.K., Young, J.D., Mehta, J.S., Vithana, E.N. and Casey, J.R. (2013) Transmembrane water flux through SLC4A11: a route defective in corneal diseases, Human Mol. Genet., 22, 4579-90.
Bonar, P.T., Schneider, H.P., Becker, H.M., Deitmer, J.W., and Casey, J.R. (2013) Three-Dimensional Model for the Human Cl-/HCO3- Exchanger, AE1, by Homology to the E. coli ClC Protein J. Mol. Biol. 425, 2591-2608.
Johnson, D.E. and Casey, J.R. (2011) Cytosolic H+ Microdomain Developed Around AE1 During AE1-Mediated Cl-/HCO3- Exchange, J. Physiol., 589, 1551-69.
Vilas, G.L., Morgan, P.E., Loganathan, S., Quon, A., and Casey, J.R. (2011) Biochemical Framework for SLC4A11, the Plasma Membrane Protein Defective in Corneal Dystrophies Biochemistry, 50, 2157-69.
Casey, J.R., Orlowski, J. and Grinstein, S. (2010) Sensors and Regulators of the Intracellular pH Nature Reviews Molecular Cell Biology, 11, 50-61.
Vithana, E.N, Morgan, P.E., Ramprasad, V., Tan, D.T.H., Yong, V.H.K., Venkataraman, D., Venkatraman, A., Yam, G.H.F., Nagasamy, S., Law, R.W.K., Rajagopal, R., Pang, C.P., Kumaramanickevel, G., Casey, J.R, Aung, T. (2008) SLC4A11 Mutations in Fuchs Endothelial Corneal Dystrophy (FECD) Hum. Mol. Genet., 17, 656-666.
Vithana, E.N. Morgan, P.E., Sundaresan, P., Ebenezer, N., Tan, D.T.H., Anand, S., Khine, K.O., Venkataraman, D., Yong, V., Salto-Tellez, M., Venkataraman, A., Guo, K., Hemadevi, B., Mohamed, M.D., Srinivasan, M., Prajna, V., Khine, M., Casey, J.R., Inglehearn, C.F., & Aung, T. (2006) Mutations in Na+-borate co-transporter SLC4A11 cause recessive Congenital Hereditary Endothelial Dystrophy CHED 2 Nature Genetics, 38, 755-7.