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., 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)
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.
Alka, K. and Casey J.R. (2014) Bicarbonate Transport in health and disease, IUBMB Life, 2014 Sep;66(9):596-615.
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.
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.
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 CHED2 Nature Genetics, 38, 755-7.
The Casey Laboratory is a member of The Team to Prevent Blindness , the Membrane Protein Disease Research Group and the International Research Training Group in Membrane Biology