Contributions to the Research & Society
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.
-Back
to Faculty Directory-
|
