The University of Arizona

Department of Physiology - The University of Arizona

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Steve Wright
Steve Wright

Stephen Wright

Professor

Contact Information

Address: P.O. Box 245051
Tucson, AZ 85724
Phone: (520) 626-4253
Email: shwright@u.arizona.edu


Website: http://www.physiology.arizona.edu/labs/mcprtlabs/Index/Index.htm

Research Interests


Membrane Transport; Energetics and Kinetics of Transport; Molecular Basis of Transporter-Substrate Interaction



Our work is focused on understanding the molecular and cellular physiology of organic electrolyte transport in the kidney. The kidney, particularly the proximal tubule, actively secretes a wide array of organic ions, largely derived from dietary or pharmaceutical sources. Many of these compounds are toxic and renal secretion of these ‘xenobiotic’ compounds plays a critical role in protecting the body from these agents. However, this task also places the kidney ‘in harm’s way,’ and the development of nephrotoxicity is one consequence of the renal secretion of what are typically referred to as ‘organic anions’ and organic cations.’



We are currently studying the renal transport of organic anions and cations at several different levels of biological organization.


Molecular Level: We clone individual transport proteins for use in studies that gauge the effect of protein and substrate structure on the transport process.

Cellular Level: We use cultured cells (including primary renal cells, continuous renal cell lines, and ‘generic’ cells lines for the expression of cloned transport proteins) in studies of the activity and regulation of transport activity.

Tissue Level: We use isolated, intact renal proximal tubules, including single non-perfused and perfused tubules, to study the process of organic electrolyte secretion as it occurs in the native renal epithelium.



Our studies employ a wide array of methodologies, including

· molecular cloning, site-directed mutagenesis, construction of fusion proteins

· kinetic assessment of membrane transport in cultured cells, suspensions of isolated renal tubules and in single tubule segments using radiometric and real-time optical approaches

· computationally-based assessment of transporter and substrate structure and 3D distribution of cell type distribution along the renal nephron



Graduate Program Affiliations

Physiological Sciences


Publications

Pelis RM, Hartman RC, Wright SH, Wunz TM, Groves CE. Nov 2007. Influence of estrogen and xenoestrogens on basolateral uptake of tetraethylammonium by opossum kidney cells in culture. J Pharmacol Exp Ther, 323:555-61

Zhang X, Cherrington NJ, Wright SH. Jul 2007. Molecular identification and functional characterization of rabbit MATE1 and MATE2-K. Am J Physiol Renal Physiol, 293:F360-70

Pelis RM, Dangprapai Y, Wunz TM, Wright SH. May 2007. Inorganic mercury interacts with cysteine residues (C451 and C474) of hOCT2 to reduce its transport activity. Am J Physiol Renal Physiol, 292:F1583-91

Pelis RM Zhang X Dangprapai Y Wright SH. Nov 2006. Cysteine accessibility in the hydrophilic cleft of human organic cation transporter 2. J Biol Chem, 281:35272-80

Aavula BR, Ali MA, Bednarczyk D, Wright SH, Mash, EA. Mar 2006. Synthesis and fluorescence of n,n,n-trimethyl-2-[methyl(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino]ethanaminium iodide, a ph-insensitive reporter of organic cation transport. Synthetic Comm, 36:701-705

Pelis RM, Suhre WM, Wright SH. Dec 2005. Functional influence of N-glycosylation in OCT2-mediated tetraethylammonium transport. Am J Physiol Renal Physiol,2005 Dec 20;

Groves CE, Suhre WB, Cherrington NJ, Wright SH. Oct 2005. Sex Differences in the mRNA, protein and functional Expression of Oat1, Oat3 and Oct2 in Rabbit Renal Proximal Tubules. J Pharmacol Exp Ther,2005 Oct 25;

Zhang X, Shirahatti NV, Mahadevan D, Wright SH. Aug 2005. A conserved glutamate residue in transmembrane helix 10 influences substrate specificity of rabbit OCT2 (SLC22A2). J Biol Chem,2005 Aug 8;

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