biography
Dr.Lai is a Sr. Principal Scientist at BMS Pharmaceutical Candidate Optimization Department. His current role in BMS is to lead the transporter labs, to implement drug transporter strategies in drug discovery and development, to conduct in vitro/in vivo transporter investigations for regulatory filings. Dr Lai holds an Adjunct Professor faculty position in the Department of Pharmacy of the University of Rhode Island. He received his M.D from Fujian Medical University in China and his Ph.D. (Toxicology) from Sapporo Medical University in Japan in 1998. From 1998 to 2001, he was a research fellow of Japanese Society for Promotion (JSPS) in Department of Physiopathology, Graduate School of Medicine of Hokkaido University, followed by a position as Research Associate in Department of Pharmaceutics, University of Washington. In 2004, he Joined PDM, PGRD St. Louis and then moved to Groton in 2010, Pfizer Inc. and has been serving as a PDM representative (PI), postdoc supervisor and lab head for drug transporter research. In 2013, he joined BMS. He has had a significant role in translational researches in transporter associated ADME-PK-Tox. He is a patent inventor and the author of a book, book chapters and over 110 original publications in peer-reviewed journals.
Area of Interest
Current research interests include proteomics analysis for absolute differences of transporters across species, structure-activity relationship and the evaluation of in vitro/in vivo models to predict human PK and toxicity.
top publication
1. Mitochondrial expression of the human equilibrative nucleoside transporter 1 (hENT1) results in enhanced mitochondrial toxicity of antiviral drugs. Y Lai, CM Tse, JD Unadkat Journal of Biological Chemistry 279 (6), 4490-4497
2. Mechanistic pharmacokinetic modeling for the prediction of transporter-mediated disposition in humans from sandwich culture human hepatocyte data. HM Jones, HA Barton, Y Lai, Y Bi, E Kimoto, S Kempshall, SC Tate, ...Drug Metabolism and Disposition 40 (5), 1007-1017
3. In situ hybridization and immunolocalization of concentrative and equilibrative nucleoside transporters in the human intestine, liver, kidneys, and placenta. R Govindarajan, AH Bakken, KL Hudkins, Y Lai, FJ Casado, ...American Journal of Physiology-Regulatory, Integrative and Comparative ...
4. Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug–drug interactions. M Karlgren, A Vildhede, U Norinder, JR Wisniewski, E Kimoto, Y Lai, ...Journal of medicinal chemistry 55 (10), 4740-4763
5. A single glycine mutation in the equilibrative nucleoside transporter gene, hENT1, alters nucleoside transport activity and sensitivity to nitrobenzylthioinosine. DJ SenGupta, PY Lum, Y Lai, E Shubochkina, AH Bakken, G Schneider, ...Biochemistry 41 (5), 1512-1519
6. Simultaneous Expression of hCNT1-CFP and hENT1-YFP in Madin-Darby Canine Kidney Cells LOCALIZATION AND VECTORIAL TRANSPORT STUDIES. Y Lai, AH Bakken, JD Unadkat Journal of Biological Chemistry 277 (40), 37711-37717
7. Development of a new permeability assay using lowâ€efflux MDCKII cells. L Di, C Whitneyâ€Pickett, JP Umland, H Zhang, X Zhang, DF Gebhard, ...Journal of pharmaceutical sciences 100 (11), 4974-4985
8. Identification of interspecies difference in efflux transporters of hepatocytes from dog, rat, monkey and human. M Li, H Yuan, N Li, G Song, Y Zheng, M Baratta, F Hua, A Thurston, ... european journal of pharmaceutical sciences 35 (1), 114-126
9. LC− MS/MS mediated absolute quantification and comparison of bile salt export pump and breast cancer resistance protein in livers and hepatocytes across species. N Li, J Palandra, OV Nemirovskiy, Y Lai Analytical chemistry 81 (6), 2251-2259
10. Absolute difference of hepatobiliary transporter multidrug resistance-associated protein (MRP2/Mrp2) in liver tissues and isolated hepatocytes from rat, dog, monkey, and human. N Li, Y Zhang, F Hua, Y Lai Drug Metabolism and Disposition 37 (1), 66-73
11. Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver. X Chu, K Korzekwa, R Elsby, K Fenner, A Galetin, Y Lai, P Matsson, ...Clinical Pharmacology & Therapeutics 94 (1), 126-141
12. Absolute quantification of multidrug resistance-associated protein 2 (MRP2/ABCC2) using liquid chromatography tandem mass spectrometry. N Li, OV Nemirovskiy, Y Zhang, H Yuan, J Mo, C Ji, B Zhang, TG Brayman, ...Analytical biochemistry 380 (2), 211-222
13. Identification of the Mitochondrial Targeting Signal of the Human Equilibrative Nucleoside Transporter 1 (hENT1) IMPLICATIONS FOR INTERSPECIES DIFFERENCES IN MITOCHONDRIAL TOXICITY OF FIALURIDINE. EW Lee, Y Lai, H Zhang, JD Unadkat Journal of Biological Chemistry 281 (24), 16700-16706
14. In vitro methods to support transporter evaluation in drug discovery and development. KLR Brouwer, D Keppler, KA Hoffmaster, DAJ Bow, Y Cheng, Y Lai, ...Clinical Pharmacology & Therapeutics 94 (1), 95-112
15.Physiologically based modeling of pravastatin transporter-mediated hepatobiliary disposition and drug-drug interactions. MVS Varma, Y Lai, B Feng, J Litchfield, TC Goosen, A Bergman Pharmaceutical research 29 (10), 2860-2873
16. Characterization of organic anion transporting polypeptide (OATP) expression and its functional contribution to the uptake of substrates in human hepatocytes. E Kimoto, K Yoshida, LM Balogh, Y Bi, K Maeda, A El-Kattan, Y Sugiyama, ...Molecular pharmaceutics 9 (12), 3535-3542
17. Quantitative expression profile of hepatobiliary transporters in sandwich cultured rat and human hepatocytes. N Li, YA Bi, DB Duignan, Y Lai Molecular pharmaceutics 6 (4), 1180-1189
18. Improved extrapolation of hepatobiliary clearance from in vitro sandwich cultured rat hepatocytes through absolute quantification of hepatobiliary transporters. N Li, P Singh, KM Mandrell, Y Lai Molecular pharmaceutics 7 (3), 630-641
19. Regulation of MRP2/ABCC2 and BSEP/ABCB11 expression in sandwich cultured human and rat hepatocytes exposed to inflammatory cytokines TNF-α, IL-6, and IL-1β. L Diao, N Li, TG Brayman, KJ Hotz, Y Lai Journal of Biological Chemistry 285 (41), 31185-31192
20. In vitro evaluation of hepatic transporter-mediated clinical drug-drug interactions: hepatocyte model optimization and retrospective investigation. Y Bi, E Kimoto, S Sevidal, HM Jones, HA Barton, S Kempshall, ...Drug Metabolism and Disposition 40 (6), 1085-1092