The Yue research program focuses on studying novel mechanisms involved in regulation of organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 transporter function. The long-term goal of the Yue laboratory is to establish a mechanistic model to predict OATP-mediated drug-drug interactions (DDIs) and inter-individual variability in drug response. Multi-disciplinary approaches are utilized in the Yue laboratory including: 1) Sandwich-cultured primary human hepatocytes model and gene-knockout models; 2) Physiologically based pharmacokinetic (PBPK) modeling and simulation; 3) Pharmacogenomics studies of drug transport proteins; 4) Post-translational regulation of OATP transporters; 5) Contemporary molecular and cell biology tools including confocal microscopy.
DDIs often lead to severe adverse drug events. It is a major concern in patients receiving multidrug therapy and during drug development. OATP1B1 and OATP1B3 are transport proteins expressed on plasma membrane of hepatocytes in human liver. They transport a diverse array of clinically important drugs, from the blood into the liver, for further clearance from the body. Dysfunction of OATP1B1 and OATP1B3 can lead to altered drug efficacy and toxicity. OATP1B1 and OATP1B3 are important determinants of transport protein-mediated DDIs, as highlighted in the FDA guidance for industry1 and recently published white paper2 on behalf of the International Transport Consortium.
1. In vitro drug interaction studies-cytochrome P450 enzyme- and transporter-mediated drug interactions: Guidance for industry, US FDA, 2020, https://www.fda.gov/media/134582/download
2. Brouwer, K., Evers, R., Hayden, E., Hu, S., Li, C., Meyer zu Schwabedissen, H., Neuhoff, S., Oswald, S., Piquette-Miller, M., Saran, C., Sjostedt, N., Sprowl, J., Stahl, S., and Yue, W., Regulation of drug transport proteins-from mechanisms to clinical impact: a white paper on behalf of the international transporter consortium, Clinical Pharmacology & Therapeutics, 2022, doi:10.1002/cpt.2605, https://www.ncbi.nlm.nih.gov/pubmed/35390174