We take a unique approach to the study of renal transport of the broad chemical classes of compounds referred to as ‘organic anions’ ‘and organic cations’ involves. Recognizing that the renal proximal tubule can coexpress a large number of transporters with overlapping specificity for these compounds, we first study the activity of individual cloned transporters in heterologous expression systems, and then use the data so obtained to design studies employing isolated single renal tubule segments.

This approach has permitted development of a a map of the functional distribution of individual transport proteins along the length of the proximal tubule, and an understanding of the relative role played by selected transport proteins in the overall secretion of selected drugs and toxins. In addition, we employ computational methods to develop quantitative structure activity relationships (QSARs) of the molecular determinants of substrate interaction with selected transport proteins, and are combining the information gained from this approach to parallel efforts to models of the 3D structure of these proteins.

The kidney plays a central role in clearing from the body toxic metabolites and xenobiotic compounds. This function is achieved through the concerted activity of a suite of transport proteins. However, these transport processes are also the site of dangerous drug interactions and can serve as avenues of entry into kidney cells of chemicals that can exert nephrotoxicity. Our studies are directed toward development of predictive models of drug and toxicant interaction with specific transport proteins, placed into the context of a map of their functional distribution within the kidney. These results are contributing to the design and application of drugs to treat a vast array of human diseases.