Mengyue (Melody) Yin is the Drug Metabolism and Disposition Highlighted Trainee Author for the September 2022 issue. She is a predoctoral trainee at the University of Washington. Her mentor is Dr. Jashvant D. Unadkat. The DMD article that earned her selection as a Highlighted Trainee Author is titled “Is the Protein-Mediated Uptake of Drugs by OATPs A Real Phenomenon or An Artifact?” and is available at https://doi.org/10.1124/dmd.122.000849.
Ms. Yin’s primary research areas focuses on in vitro to in vivo extrapolation (IVIVE) of transporter-mediated drug disposition. She is currently working on optimizing and validating the proteomics-informed relative expression factor (REF) approach to predict drug clearance and tissue drug concentrations. Underprediction of transporter-mediated hepatic clearance (CL), using IVIVE, is widely reported for OATP substrate drugs. Using the proteomics-informed REF approach, IVIVE of hepatic uptake CL of rosuvastatin (obtained by PET imaging) is improved but still underpredicted.
Her research project is to optimize and validate the REF approach for IVIVE of hepatic CL of drugs. Numerous investigators have suggested that inclusion of plasma proteins can improve the IVIVE of the hepatic uptake CL of statins when using hepatocytes or OATP-expressing cells. This phenomenon is called the protein-mediated uptake effect (PMUE). However, Ms. Yin found that this so-called PMUE on statin uptake by plated OATP1B1-overexpressing HEK293 cells can be an experimental artifact that is due to the non-specific binding of the statin-protein complex that is not completely washed off when the statin uptake is terminated. Her next step is to investigate if the PMUE on statin uptake CL by plated or suspended hepatocytes is a real phenomenon or an artifact.
The anticipated impact of Ms. Yin’s research is that if the PMUE is an artifact, then there is no need to add plasma proteins to uptake assays to improve the IVIVE of hepatic CL of drugs. In that case, other underlying mechanisms should be investigated to bridge the gap in IVIVE of transporter-mediated hepatic uptake CL of drugs.
When not in the lab, Melody enjoys singing, reading, and writing. She also enjoys watching movies.