Biochemistry

Joe Casey

Joe Casey

Ph.D, University of Toronto

Professor
Office: 780-492-7203
Lab: 780-492-1080
Fax: 780-492-0886
joe.casey@ualberta.ca

Research:

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?

 

Selected Publications:

Corneal dystrophy-causing SLC4A11 mutants: suitability for folding-correction therapy.
Loganathan SK, Casey JR.
Hum Mutat. (2014) Sep;35(9):1082-91. (Article selected for a video highlight)

Resistance to Cardiomyocyte Hypertrophy in ae3-/- Mice, Deficient in the AE3 Cl-/HCO3- Exchanger.
Sowah D, Brown BF, Quon A, Alvarez BV, Casey JR.
BMC Cardiovasc Disord. (2014) Jul 21;14:89.

Bicarbonate Transport in health and disease. 
Alka K, Casey JR.
IUBMB Life. (2014) Sep;66(9):596-615.

Transmembrane water flux through SLC4A11: a route defective in corneal diseases
Vilas GL, Loganathan SK, Liu J, Riau AK, Young JD, Mehta JS, Vithana EN, Casey JR
Human Mol. Genet., 22, 4579-90.

Three-Dimensional Model for the Human Cl-/HCO3- Exchanger, AE1, by Homology to the E. coli ClC Protein
Bonar P, Schneider HP, Becker HM, Deitmer JW, Casey JR.
J Mol Biol. (2013) Jul 24;425(14):2591-608.

Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart.
Alvarez BV, Quon AL, Mullen J, Casey JR.
BMC Cardiovasc Disord. (2013) Jan 8;13:2.

Oligomerization of SLC4A11 protein and the severity of FECD and CHED2 corneal dystrophies caused by SLC4A11 mutations.
Vilas GL1, Loganathan SK, Quon A, Sundaresan P, Vithana EN, Casey J.
Human Mutation (2012) 33, 419-428.

Cytosolic H+ Microdomain Developed Around AE1 During AE1-Mediated Cl-/HCO3- Exchange
Johnson DE, Casey JR
J. Physiol. (2011) 589, 1551-69.

Biochemical Framework for SLC4A11, the Plasma Membrane Protein Defective in Corneal Dystrophies
Vilas GL, Morgan PE, Loganathan SK, Quon A, Casey JR
Biochemistry (2011) 50, 2157-69.

Sensors and Regulators of the Intracellular pH.
Casey JR, Grinstein S, Orlowski J.
Nat Rev Mol Cell Biol. (20101) 11, 50-61.

SLC4A11 Mutations in Fuchs Endothelial Corneal Dystrophy (FECD)
Vithana EN, Morgan PE, Ramprasad V, Tan DT, Yong VH, Venkataraman D, Venkatraman A, Yam GH, Nagasamy S, Law RW, Rajagopal R, Pang CP, Kumaramanickevel G, Casey JR, Aung T.
Hum. Mol. Genet. (2008) 17, 656-666.

Mutations in Na+-borate co-transporter SLC4A11 cause recessive Congenital Hereditary Endothelial Dystrophy CHED2
Vithana EN, Morgan P, Sundaresan P, Ebenezer ND, Tan DT, Mohamed MD, Anand S, Khine KO, Venkataraman D, Yong VH, Salto-Tellez M, Venkatraman A, Guo K, Hemadevi B, Srinivasan M, Prajna V, Khine M, Casey JR, Inglehearn CF, Aung T.
Nature Genetics (2006) 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