Chris Cheeseman, PhD
Office: 7-22A Medical Sciences Building
Mail: University of Alberta, Edmonton, AB, T6G 2H7
Professor, Department of Physiology
Vice Provost and Associate VP HR
The Physiology and Structure Function Studies of Facilitated Hexose Transporters.
The primary goal of our research is to gain a better understanding of how the GLUT family of transporters recognizes their substrates and then translocates them across the cell membrane. Currently, there is no definitive structural model of these proteins which would allow us to determine how hexoses or organic anions gain access to and then bind to elements of their translocation pore.
Current Research Activities
1) Structure Function Studies of GLUT proteins
Our previous studies of human GLUT7 a high affinity glucose/ fructose transporter found in the apical membrane of the distal small intestine focused on computer modelling and site directed mutagenesis of this protein. This led to the identification of a hydrophobic motif apparently responsible for determining the substrate specificity of GLUT proteins. We have now extended this approach to GLUT9, which we have shown is primarily a urate, not a hexose transporter. This organic anion allows us to employ electrophysiological techniques to study the role of hydrophobic residues in the determination of substrate access to the transporter’s translocation mechanism.
2) Development of Specific GLUT substrates for Use with PET Imaging
We are developing a series of hexose analogues as unique substrates for GLUT5 a fructose transporter found to be overexpressed in a number of human tumors. This work we hope will lead to new imaging modalities for breast and other cancers.
3) Laboratory Techniques
This laboratory employs a mixture of classical physiological techniques along with molecular biology to address the specific questions outlined above. These include isolated membrane vesicle preparations, oocyte and cultured cell expression systems. Molecular techniques include Western and Northern blotting, PCR, in situ hybridization, and expression cloning. We also use flow cytometry with fluorescence imaging to measure transport of different hexose analogues and we employ two electrode voltage clamp techniques with oocytes to measure organic ion transport characteristics.
Other Activities and Affiliations
Member of the Membrane Protein Research Group
- Post Doctoral fellow, University of Oxford.
- PhD Physiology, University of Sheffield
- BSc Honours Physiology, University of Sheffield
Witkowska K, Smith KM, Yao SY, Ng AM, O'Neill D, Karpinski E, Young JD, Cheeseman CI. Human SLC2A9a and SLC2A9b isoforms mediate electrogenic transport of urate with different characteristics in the presence of hexoses. Am J Physiol Renal Physiol. 2012, 303(4):F527-539
Wuest M, Trayner BJ, Grant TN, Jans HS, Mercer JR, Murray D, West FG, McEwan AJ, Wuest F, Cheeseman CI. Radiopharmacological evaluation of 6-deoxy-6-[18F]fluoro-D-fructose as a radiotracer for PET imaging of GLUT5 in breast cancer. Nucl Med Biol. 2011, 38(4):461-475
Trayner BJ, Grant TN, West FG, Cheeseman CI. Synthesis and characterization of 6-deoxy-6-fluoro-D-fructose as a potential compound for imaging breast cancer with PET. Bioorg Med Chem. 2009 17(15):5488-95.
Sterling KM Jr, Cheeseman CI, Ahearn GA. Identification of a novel sodium-dependent fructose transport activity in the hepatopancreas of the Atlantic lobster Homarus americanus. J Exp Biol. 2009, 212(Pt 12):1912-20
Cheeseman C. Solute carrier family 2, member 9 and uric acid homeostasis. Curr Opin Nephrol Hypertens. 2009, 18(5):428-32.
Mark J. Caulfield, Patricia B Munroe, Deb O'Neill, Kate Witkowska, Fadi J. Charchar, Manuel Doblado, Sarah Evans, Susana Eyheramendy, Abiodun Onipinla , Philip Howard, Sue Shaw-Hawkins , Richard J. Dobson, Chris Wallace, Morris Brown, John M. Connell, Anna Dominiczak, Martin Farrall, G. Mark Lathrop, Nilesh J. Samani, John Webster, Meena Kumari, Michael Marmot, Eric Brunner, Michael Brunner, John Chambers, Paul Elliott, Jaspal Kooner, Maris Laan, ,Elin Org, Gudrun Veldre, Margus Viigimaa,Francesco P. Cappuccio, Chen Ji, Roberto Iacone, Pasquale Strazzullo, Kelle H. Moley, Chris Cheeseman. (2008) SLC2A9 is a high capacity urate transporter in man. PLoS Medicine. 5(10):e197.
Cheeseman C. Fructose the odd man out. Why is the genomic control of intestinal GLUT5 expression different? J Physiol. 2008 Aug 1;586(Pt 15):3563.
Cheeseman C. GLUT7: a new intestinal facilitated hexose transporter. Am J Physiol Endocrinol Metab. 2008,295(2):E238-41. Epub 2008 May 13
Andrei Manolescu, Robert Augustin, Kelle H. Moley and Chris Cheeseman. (2007) Identification of a Highly Conserved Motif in the Exofacial Vestibule of Fructose Transporting SLC2A Proteins which Acts as a Critical Determinant of their Substrate Specificity. Mol. Mem. Biol. 24(5):455-63.
Andrei R. Manolescu, Robert Augustin, Kelle Moley, Chris Cheeseman (2007). A Highly Conserved Hydrophobic Motif in the Exofacial Vestibule of Fructose Transporting SLC2A Proteins Acts as a Critical Determinant of their Substrate Selectivity. Mol. Mem. Biol. 24(5):455-63.
C Keembiyehetty, R Augustin, MO Marayannopoulos, S Steer, A Manolescu, CI Cheeseman, KH Moley. Mouse glucose transporter 9 (mGLUT9) splice variants are expressed in adult liver and kidney and are upregulated in diabetes. Mol Endocrinol. 20(3):686-97, 2005.
Wentong Long, PhD candidate.
Website Links of Interest
The membrane Protein Disease Group