My research is focused on a family of membrane proteins that are involved in the transport of nucleosides such as adenosine. Not only are these transporters important in the general homeostatis of all cells, they are also of critical clinical importance in the treatment of cancer and systemic viral infection since they are the routes of entry of many therapeutic nucleoside analogue drugs such as AZT and ddC. In addition, one isoform from this family of proteins appears to be involved in the cascade of events leading to cellular tolerance to alcohol. Despite their fundamental biological and clinical importance, very little is known about the structure of these proteins, their mRNAs or genes. My research involves fully characterising this protein family at the molecular level. We have recently cloned one isoform from human normal and tumour tissue and I am now in the process of isolating other forms from other tissues, tumour cell lines and species. I am also investigating the temporal and spatial expression and regulation of these proteins in tissues and cell lines.
The long term goal of my research is to understand how nucleoside transporters are regulated at the cellular level in terms of intracellular signalling pathways. My research involves using both indirect and direct methods to study the role of cAMP-dependent kinase (PKA) and protein kinase C(PKC) in regulating this protein. In particular, I am interested at the possible regulation of expression, subcellular localisation and/or activity of these proteins by hormones and growth factors. Since these transporters are the means of entry of synthetic nucleoside analogues into cells for treatment of a number of conditions, and understanding of their molecular structure, regulation and activity is crucial in maximizing the effectiveness of anti-cancer and anti-viral treatments.
Reyes G, Coe IR. 2005. Genomics and proteomics of nucleoside transporters. Current Pharmacogenomics 3, 281-287.
Eltzschig HK, Abdulla P, Hoffman E, Hamilton KE, Daniels D, Schonfeld C, Loffler M, Reyes G, Duszenko M, Karhausen J, Robinson A, Westerman KA, Coe IR, Colgan SP. 2005. HIF-1-dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia. The Journal of Experimental Medicine 202(11) 1493-1505.
Chaudary N, Naydenova Z, Shuralyova I, Coe IR, 2004. The adenosine transporter, mENT1, is a target for adenosine receptor signling and protein kinase Ce in hypoxic and pharmacological preconditioning in the mouse cardiomyocyte cell line, HL-1. The Journal of Pharmacology and Experimental Therapeutics 310(3) 1190-1198.
Chaudary N, Naydenova Z, Shuralyova I, Coe IR, 2004. Hypoxia regulates the adenosine transporter, mENT1, in the murine cardiomyocyte cell line, HL-1. Cardiovascular Research 61(4) 780-8.
Tajmir P, Ceddia RB, Li RK, Coe IR, Sweeney G, 2004. Leptin increases cardiomyocytes hyperplasia via extracellular signal-regulated kinase-and phosphatidylinositol 3-kinase-dependent signaling pathways. Endocrinology 145(4) 1550-5.
Shuralyova I, Tajmir P, Bilan PJ, Sweeney G, Coe IR, 2004. Inhibition of glucose uptake in murine cardiomyocyte cell line HL-1 by cardioprotective drugs dilazep and dipyridamole. Am J Physiol Heart Circ Physiol 286 H627-32.
Sankar, N., Machado, J., Abdulla, P., Hilliker, A.J. and Coe, I.R. 2002. Comparative genomic analysis of equilibrative nucleoside transporters suggests conserved protein structure despite limited sequence identity. Nucleic Acids Research, 30 (20) 4339-4350.
Acimovic, Y., and Coe, I.R. 2002 Molecular Evolution of the Equilibrative Nucleoside Transporter Family: Identification of novel forms in Eukaryotes and Prokaryotes. Molecular Biology and Evolution. 19 (12), 2199-2210.
Chaudary, N, Shuralyova, I., Liron, T., Sweeney, G. and Coe, I.R. 2002. Transport characteristics of HL-1 cells; a new model for the study of adenosine physiology in cardiomyocytes. Biochem. Cell Biol. 80, 655-665.