Research work focuses on the cellular drug uptake mechanisms in normal and diseased livers. The goal of our research work is to enhance the efficiency with which a diseased liver maintains its function and whenever possible increase the liver's regenerative capacity through specific drug treatment regimens. To this end we are investigating the uptake process of lipophilic drugs and the influence of extracellular and intracellular binding proteins on this process. Drug uptake is being studied using hepatocytes isolated from normal and diseased female and male livers as well as cultured cells and isolated perfused livers. Our experimental studies are based on mathematical models of the uptake process. Our studies also are concerned with the role of inorganic ions (e.g., membrane potential) on the drug uptake process.
Cell cultures, cell suspensions, isolated perfused organs and anesthetized animals are used to study transmembrane drug flux at a fundamental biophysical level. The laboratory is extremely well equipped with state-of-the-art electrophysiological equipment that is interfaced with intracellular imaging instrumentation. Thus, our laboratory is equipped to study the role of cellular electrical activity and directly measure intracellular drug levels using fluorescent drugs. Analysis of intracellular pH utilizes microelectrodes and fluorescent indicators. Northern and Western blot analyses are used to determine cellular protein activity. Isolated perfused organs and anesthetized animals are used to study the effect of vasoactive drugs on organ perfusion and drug uptake. Anesthetized animals are used for orthotopic liver transplantation and hepatic regeneration studies.
Present studies focus on assessing the role of: a) extracellular and intracellular binding proteins on the drug uptake process; b) membrane potential on drug uptake. Further studies focus on preservation of donor livers; and increasing viability of transplanted livers.
Requests for further information should be directed to: F.J. Burczynski at above address.
Frank J. Burczynski
Area of Research: Biophysics of hepatic drug uptake