Joseph Bentz
Professor
Department of Biology
Drexel University
United States of America
Biography
His primary project is the study of Multidrug resistance transporters. We have long-standing collaboration with GlaxoSmithKline to develop a quantitative kinetic model of transcellular transport mediated by the multidrug resistance protein P-gp. This transporter is found in many human tissues, where it is responsible for inhibiting uptake of foreign molecules, e.g. the colon, the kidney, the liver, gonads a nd the b picks up amphiphilic compounds from the inner apical membrane, which faces the “outside†world, and uses the energy of ATP hydrolysis to eject the compound back to the “outside†world. However, many cancer cells have acquired or amplified the gene for this transporter since it will also inhibit their uptake of chemotherapeutic agents. It is thought that this acquired resistance is responsible for much of the failure of cancer chemotherapy
Research Interest
Biophysics of Cell Membrane Function - Membrane Transport by Multidrug Resistance Proteins, chanisms of Membrane Fusion, Peptide/Protein-Membrane Interactions
Publications
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If the KI is defined by the free energy of binding to P-gp, what kinetic parameters define the IC50 for the MDCKII-hMDR1 confluent cell monolayer? AA Lumen, P Acharya, JW Polli, A Ayrton, H Ellens &Â J Bentz. Drug Met Disp, 38:260-9 (2010).
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Fitt ing the of P-gp mediated transport across the hMDR1-MDCK confluent cell monolayer using a Particle Swarm algorithm and establishing the functional properties of other substrate-specific transporters. D Agnani, P Acharya, E Martinez, T Tran, F Abraham, F Tobin, H Ellens & J Bentz. Submitted (2011)
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Kinetic identification of membrane transporters that assist transcellular transport of many P-gp substrates through a confluent monolayer of cells expressing hMDR1. AA Lumen, L Li, J Li, AD Owen, IJ Hidalgo, H Ellens & J Bentz. Drug Metab. Disp. submitted (2011).
