Elaine Leslie

Elaine Leslie

Elaine Leslie (PhD, Queen's University)

Associate Professor

7-10A Medical Sciences Building
University of Alberta
Edmonton, Alberta
Canada T6G 2S2

Tel: 780.492.9250
eleslie@ualberta.ca

Research Description

The Role of Transport Proteins in Toxicology

Increasingly, transport proteins are recognized for their importance in the absorption, distribution, excretion and detoxification of drugs, dietary components and toxins. The multidrug resistance proteins (MRPs) are ATP-binding cassette (ABC) transporter proteins critical for the cellular efflux of a wide variety of drugs and toxins. MRP1 (ABCC1) and MRP2 (ABCC2) transport glutathione- (GSH/GS-), sulfate- and glucuronide- (gluc-) conjugated organic anions and can act synergistically with phase II conjugating enzymes, including the GSH S-transferases (GSTs) and UDP-glucuronosyl transferases (UGTs), to reduce the cellular burden of toxins. In contrast with efflux, uptake transporters and ion channels can increase toxin accumulation. Uptake in conjunction with efflux across polarized epithelia in excretory organs can result in elimination. In addition to direct transport of toxins, disruption of the physiological function of transport proteins such as the bile salt export pump (BSEP/ABCB11) and the Na+-taurocholate cotransporting polypeptide (NTCP/SLC10A1) can have toxicological consequences. The objectives of my research program are:

  • To characterize the metabolism and active cellular import/export of carcinogens including metals/metalloids (e.g., arsenic and cadmium) and tobacco constituents [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)].
  • To investigate how the disruption of liver transport processes (e.g., bile salt transport) contribute to drug and toxin induced hepatotoxicity.

Selected publications

 

 

Banerjee, M.*, Carew, M.W.*, Roggenbeck, B.A., Whitlock, B.D., Naranmandura, H., Le, X.C., and Leslie, E.M. (2014) A Novel Pathway for Arsenic Elimination: Human Multidrug Resistance Protein 4 (MRP4/ABCC4) Mediates Cellular Export of Dimethytlarsinic Acid (DMAV) and the Diglutathione Conjugate of Monomethylarsonous acid (MMAIII). Mol. Pharmacol., In Press. *co-first authors

Possamai, L.A., McPhail, M.J., Quaglia, A., Zingarela, V., Abeles, R.D., Tidswell, R., Puthucheary, Z., Rawal, J., Karvellas, C.J., Leslie, E.M., Hughes, R.D., Ma, Y., Yassem, W., Shawcross, D.L. Bernal, W., Dharwan, A., Heaton, N.D., Thursz, M., Wendon, J.A., Mitry, R.R., and Antoniades, C.G. (2013) Character and Temporal Evolution of Apoptosis in Acetaminophen-induced Acute Liver Failure. Crit. Care Med. 41:2543-2550.

 

Leslie, E.M. (2012) Arsenic Glutathione Conjugate Transport by the Human Multidrug Resistance Proteins (MRPs/ABCCs). J. Inorg. Biochem. 108:141-149 (invited review).

 

Naranmandura, H., Carew, M.W., Lee, J., Leslie, E.M., Weinfeld, M., and Le, X.C., (2011) Comparative Toxicity of Arsenic Metabolites in Human Bladder Cancer EJ-1 Cells. Chem. Res. Toxicol. 24:1586-1596.

 

Qazi, S.S., Osoria Pérez, A., Sam, M. and Leslie, E.M. (2011) Glutathione Transferase P1 (GSTP1) Interacts Strongly with the Inner Leaflet of the Plasma Membrane. Drug. Metab. Dispos. 39:1122-1126

 

Carew, M.W., Naranmandura, H., Shukalek, C.B., Le, X.C., and Leslie, E.M. (2011) Monomethylarsenic Diglutathione [MMAIII(GS)2] Transport by the Human Multidrug Resistance Protein 1 (MRP1/ABCC1). Drug Metab. Dispos. 39:2298-2304.