Stephen H Wright
Investigator, Center for Toxicology
Professor, BIO5 Institute
Professor, Biochemistry/Molecular Biophysics
Professor, Physiological Sciences - GIDP
The kidney plays a critical role in clearing the body of potentially harmful compounds, including many commonly prescribed drugs. Unfortunately, this also sets the kidney up as a site where multiple drugs can interact in unwanted ways. We study the cellular transport processes responsible for renal drug clearance with the intent of developing predictive models that can assist clinicians, drug companies, and the Food & Drug Administration in their efforts to increase patient safety.
Stephen Wright, PhD, 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. Dr. Wright’s lab currently studies the renal transport of organic anions and cations at several different levels of biological organization.At the molecular level, they clone individual transport proteins for use in studies that gauge the effect of protein and substrate structure on the transport process. At the cellular level, Dr. Wright and his lab 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. At the tissue level, they 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.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. Keywords: Membrane Transport; Kidney; Drug Clearance