P.O. Box 245051
Tucson, AZ 85724
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