Elaine Leslie
Professor
PhD, Queen’s University
Office: 7-08A Medical Sciences Building
Laboratory: 7-08/7-10 and 7-16 Medical Sciences Building
Telephone: 780-492-9250
Email Address: eleslie@ualberta.ca
Research Interests / Academic Activities
My general research interests are in the area of Cellular Physiology and Molecular Toxicology. The major focus of my research is the biotransformation and membrane transport of the environmental human carcinogen arsenic. Chronic arsenic exposure is a public health crisis affecting an estimated 92-220 million people world-wide. Arsenic is proven to cause tumours of the skin, lung and bladder and is associated with other cancers (liver and kidney). Exposure to arsenic has also been strongly associated with other adverse health effects including cardiovascular disease, diabetes, neurological disorders, and lung disease. Research in the Leslie laboratory includes investigating the role of ATP-binding cassette (ABC) and other transporter proteins as well as phase II conjugating enzymes in the detoxification and elimination of arsenic. Our approach is to use physiologically-relevant human models [e.g., sandwich cultured primary human hepatocytes, HepaRG cells, human red blood cells] in combination with heterologous expression of specific transporters and/or conjugating enzymes. These approaches are taken to first understand what is happening in a physiological context, then to understand the molecular processes involved for specific proteins. Currently, we are using these approaches to explore how selenium (a proposed palliative for chronic arsenic exposure) changes the metabolism and transport of arsenic in human liver and blood. The long-term goal of my research is to understand how genetic variation in transporters and phase II enzymes influence the inter-individual susceptibility to arsenic-induced carcinogenesis and response to therapeutic strategies.
Select Publications
Hafey, M.J., Aleksunes, L.M., Bridges, C.C., Brouwer, K.R., Chien, H-C., Leslie, E.M., Hu, S., Li, Y., Shen, J., Sparreboom, A., Sprowl, J., Tweedie, D., and Lai, Y. Transporters and Toxicity: Insights from the International Transporter Consortium Workshop 4. Clin. Pharmacol. Ther. 112: 527-539 (2022).
Zhou, J.R., Kaur, G., Ma, Y., Arutyunov, D., Lu, X., Le, X.C., and Leslie E.M. Biliary Excretion of Arsenic by Human HepaRG Cells is Stimulated by Selenide and Mediated by the Multidrug Resistance Protein 2 (MRP2/ABCC2). Biochemical Pharmacology. 193, 114799 (2021)
Kaur, G.*, Javed, W.*, Ponomarenko, O., Shekh, K., Swanlund, D.P., Zhou, J.R., Summers, K.L., Casini, A., Wenzel, M., Casey, J.R., Cordat, E., Pickering, I.J., George, G.N., Leslie, E.M. Human red blood cell uptake and sequestration of arsenite and selenite: Evidence of seleno-bis(S-glutathionyl) arsinium ion formation in human cells *Equally contributed to the work. Biochemical Pharmacology. 180: 114141(2020).
Kaur, G., Ponomarenko, O., Zhou, J.R., Swanlund, D.P., Summers, K.L., Dolgova, N.V., Antipova, O., Pickering, I.J., George, G.N., and Leslie, E.M. Studies of selenium and arsenic mutual protection in human HepG2 cells. Chemico-Biological Interactions. 109162, (2020).
Banerjee, M., Kaur, G., Whitlock, B.D., Carew, M.W., Le, X.C., and Leslie E.M. Multidrug Resistance Protein 1 (MRP1/ABCC1)-mediated cellular protection and transport of methylated arsenic metabolites differs between human cell lines. Drug Metab. Dispos. 46, 1096-1105 (2018).
Banerjee, M., Marensi, V., Conseil, G., Le, X.C., and Cole, S.P. and Leslie, E.M. Polymorphic variants of MRP4/ABCC4 differentially modulate the transport of methylated arsenic metabolites and physiological organic anions. Biochem. Pharmacol. 120:72-82 (2016).
Shukalek, C.B., Swanlund, D.P., Rousseau, R.K., Weigl, K.E., Marensi, V., Cole, S.P. and Leslie, E.M. Arsenic triglutathione [As(GS)3] transport by multidrug resistance protein 1 (MRP1/ABCC1) is selectively modified by phosphorylation of Tyr920/Ser921 and glycosylation of Asn19/Asn23. Mol. Pharmacol. 90: 127-139 (2016).
Roggenbeck, B.A., Banerjee, M. and Leslie, E.M. Cellular arsenic transport pathways in mammals. J. Environ. Sci.49:38-58. (2016) (invited review-Special Arsenic Issue for Dr. Bill Cullen).
Roggenbeck, B.A., Carew, M.W., Charrois, G., Douglas, D., Kneteman, N., Lu, X., Le, X.C., and Leslie, E.M. Characterization of Arsenic Hepatobiliary Transport Using Sandwich Cultured Human Hepatocytes. Toxicol. Sci. 145: 307-20 (2015). Editor’s Highlight
Banerjee, M.,* Carew, M.W.,* Roggenbeck, B.A., Whitlock, B.D., Naranmandura, H., Le, X.C., and Leslie, E.M. A Novel Pathway for Arsenic Elimination: Human Multidrug Resistance Protein 4 (MRP4/ABCC4) Mediates Cellular Export of Dimethylarsinic Acid (DMAV) and the Diglutathione Conjugate of Monomethylarsonous acid (MMAIII). Mol. Pharmacol. 86: 168-79 (2014). *Joint first authors.
Carew, M.W., Naranmandura, H., Shukalek, C.B., Le, X.C., and Leslie, E.M. Monomethylarsenic Diglutathione [MMAIII(GS)2] Transport by the Human Multidrug Resistance Protein 1 (MRP1/ABCC1). Drug Metab. Dispos. 39: 2298-304 (2011).
Carew, M.W. and Leslie, E.M. Selenium-dependent and Independent Transport of Arsenic by the Human Multidrug Resistance Protein 2 (MRP2/ABCC2): Implications for the Mutual Detoxification of Arsenic and Selenium. Carcinogenesis. 31: 1450-5 (2010).
Laboratory Members
Graduate Students
Serena Li
William Li
Technician
Xiaohua Song