Joe Casey
Joe Casey (PhD, University of Toronto)
Director
Department of Biochemistry
Faculty of Medicine & Dentistry
University of Alberta
4020E Katz Group Rexall Building
Edmonton, Alberta, Canada
T6G 2E1
Tel: 780-492-7203
Lab: 780-492-1080
Fax: 780-492-0886
Research Description
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. 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. Understanding how bicarbonate transport contributes to the serious heart disease, cardiac ischemia and cardiac hypertrophy.
3. How do defects in the transport protein called BTR1 (SLC4A11) cause the serious eye diseases Fuch's endothelial dystrophy and congenital hereditary endothelial dystrophy?
Selected publications
Loganathan, S.K., Schneider, H.P., Morgan, P.E., Deitmer, J.W., and Casey, J.R. (2016) Functional Assessment of SLC4A11, an Integral Membrane Protein Mutated in Corneal Dystrophies, Am. J. Physiol., In Press.
Reithmeier, R.A.F., Casey, J. R., Kalli, A., Sansom, M.S.P. Alguel, Y., and Iwata, S. (2016) Band 3, the Human Red Cell Chloride/Bicarbonate Anion Exchanger (AE1, SLC4A1), in a Structural Context Biochim. Biophys. Acta, 1858, 1507-32
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.
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.
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.
Zoccola, D., Ganot, P., Bertucci, A., Caminiti-Segonds, N., Techer, N., Voolstra, C., Aranda, M., Tambutté, E., Allemand, D., Casey, J.R. and Sylvie Tambutté (2015) Bicarbonate Family Transporters In A Scleractinian Coral, Scientific Reports. 5, 2204-08.
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.
Okawa, Y., Li, J., Basu, A., Casey, J.R. and Reinhart A.F. Reithmeier (2014) Differential Roles of Tryptophan Residues in the Functional Expression of Human Anion Exchanger 1 (AE1, Band 3, SLC4A1) Molecular Membrane Biology, 26, 1-17.
Sowah, D., Brown, B.F., Quon, A., Alvarez, B.V., and Casey, J.R. (2014) Resistance to Cardiomyocyte Hypertrophy in ae3-/- Mice, Deficient in the AE3 Cl-/HCO3- Exchanger, BMC Cardiovascular Disorders, 14:89.
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)
Soumittra, N., Loganathan, S.K., Madhavan, D., Ramprasad, V.L., Arokiasamy, T., Sumathi, S., Karthiyayini, T., Rachapalli, S.R., Kumaramanicakvel, G., Casey, J.R., and Rajagopal, R. (2014), Biosynthetic and functional defects in newly-identified SLC4A11 mutants and absence of COL8A2 mutations in Fuchs endothelial corneal dystrophy, J. Human Genetics, 59, 444-53.
Shnitsar, V., Li, J., Li, X., Calmettes, C., Basu, A., Casey, J.R., Moraes, T.F. and Reithmeier, R.A.F. (2013) Structural and Functional Analysis of a Putative Substrate Access Tunnel in the Cytosolic Domain of Human Anion Exchanger 1 (AE1, Band 3, SLC4A1), J. Biol. Chem. 288, 33848-60.
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.
Alvarez, B.V., Quon, A., Mullen, J. and Casey, J.R. (2013) Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart, BMC- Cardiovascular Disorders, 13:2.
Brown, B., Quon, A., Dyck, J. and Casey, J.R. (2012) Carbonic Anhydrase II Promotes Cardiomyocyte Hypertrophy, Can. J. Physiol. Pharmacol. 90, 1599-610.
Vilas, G.L., Loganathan, S., Quon, A.,, Sundaresan, P., Vithana, E.N and Casey, J.R. (2012) Oligomerization of SLC4A11 protein and the severity of FECD and CHED2 corneal dystrophies caused by SLC4A11 mutations, Human Mutation, 33, 419-428.