Faculty

Ryan M. Pelis, PhD

Assistant Professor

BSc, MSc (U. of Massachusetts), PhD (U. of Connecticut)

Keywords

Pharmacokinetics; transport; metabolism; barrier epithelia; drug clearance; drug-drug interactions; adverse drug reactions

Current Research

My laboratory is broadly interested in the cellular and molecular mechanisms and regulation of epithelial drug transport. Drug transporters occur in numerous epithelial cells throughout the body; notable examples are intestinal enterocytes, brain capillary endothelial cells, hepatocytes and renal proximal tubule cells. In these locales drug transporters can profoundly influence drug absorption into the body, distribution to various tissue compartments, and elimination from the body. Thus, drug transporters have a level of control over plasma/tissue drug concentrations, which can impact drug efficacy and potential for toxicity. Research in my laboratory is currently focused on:

    1)    Understanding the transport and metabolic processes that
            control drug concentrations inside the eye.

    2)    The mechanisms and control of renal tubular drug secretion.

    3)    Structure-activity relationships in drug transporters.

A number of techniques are being used to investigate epithelial drug transport at the molecular, cellular, tissue and whole animal level. This includes cloning, site-directed mutagenesis, kinetic assessment of transport, transport measurement across epithelia in Ussing chambers, and pharmacokinetic assessment of drug clearance in vivo.

Selected Publications

Manuscripts

Cheng Y, Vapurcuyan A, Shahidullah M, Aleksunes LM and Pelis RM. Expression of organic anion transporter 2 in the kidney and its potential role in the renal tubular secretion of guanine-containing antivirals. Drug Metabolism Disposition 40: 617-624, 2012.

Astorga BO, Morales M, Wunz TM, Wright SH and Pelis RM. Differences in the substrate binding regions of renal organic anion transporters 1 and 3. Am J Physiol. Renal Physiol 301: F378-86, 2011.

Pelis RM, Shahidullah M, Ghosh S, Coca-Prados M, Wright SH and Delamere NA. Localization of MRP2 in the non-pigmented ciliary epithelium of the eye. J Pharmacol Exp Ther 329: 479-485, 2009.

Shahidullah M, To C-H, Pelis RM, and Delamere NA. Studies on bicarbonate transporters and carbonic anhydrase in porcine non-pigmented ciliary epithelium. Invest Ophthalmol Vis Sci 50: 1791-800, 2009.

Pelis RM, Hartman R, Wunz TW, Wright SH, and Groves CE. Influence of estrogen and xenoestrogens on basolateral uptake of TEA by Opossum kidney cells in culture. J Pharmacol Exp Ther. 323: 555-561, 2007.

Pelis RM, Wunz TW and Wright SH. Inorganic mercury interacts with cysteine residues (C451 and C474) of hOCT2 to reduce its transport activity. Am J Physiol Renal Physiol. 292: F1583-F1591, 2007.

Pelis RM, Zhang X, Dangprapai Y, and Wright SH. Cysteine accessibility in the hydrophilic cleft of the human organic cation transporter 2. J Biol Chem. 281: 35272-35280, 2006.

Pelis RM, Suhre WM, and Wright SH. Functional influence of N-glycosylation in OCT2-mediated TEA transport. Am J Physiol Renal Physiol 290: F1118F1126, 2006.

Dudas PL, Pelis RM, Braun EJ, and Renfro JL. Transepithelial urate transport by avian renal proximal tubule epithelium in primary culture. J Exp Biol 208: 4305-4315, 2005.

Book Chapters

Hanna I and Pelis RM. Drug transporters in drug interactions and drug disposition. In ADME-Enabling Technologies for Drug Design and Development, John Wiley & Sons, 2012.

Pelis RM and Wright SH. Renal handling of organic acids and bases. In: Comprehensive Physiology, John Wiley & Sons, Inc., 2011.

Contact Information

Department of Pharmacology
Dalhousie University
Sir Charles Tupper Medical Building, 5B1
5850 College Street
P.O. Box 15000
Halifax, NS, Canada B3H 4R2

Phone: 902-494-6058

Fax: 902-494-1388

Email: Ryan.Pelis@Dal.Ca