Abstract: Peter J. Meier, MD, a pioneer in the molecular characterization of hepatic bile acid transporters, and a major leader in translational and national science in Switzerland, passed away on May 27 2021. Dr. Meier was born on May 10, 1947 in Baden (AG), Switzerland and graduated in Medicine in 1974 from the University of Basel. He completed the Postgraduate Course in Experimental Medicine and Biology at the University Hospital and the Faculty of Medicine of the University of Zurich and continued as a research fellow until the end of 1976 in the Division of Clinical Pharmacology and Toxicology at the University Hospital Zurich. From 1977 to 1981 he was a resident in internal medicine at the University Hospitals in Basel and Zurich and qualified for the Swiss Speciality Board (FMH) in Internal Medicine in 1981. Dr. Meier began his research career as an undergraduate with Dr. Ph. Heitz in the Department of Pathology of the University of Basel in 1973, where he worked on uremic rat models with a special focus on mitochondria in the diseased kidney. He then joined the group of Dr. U.A. Meyer in 1974 in Zurich working in the area of hepatic drug metabolism with a focus on the biosynthesis of cytochrome P450 and the genetics of drug metabolism.[1]Meier P.J. Mueller H.K. Dick B. Meyer U.A. Hepatic monooxygenase activities in subjects with a genetic defect in drug oxidation.Gastroenterology. 1983; 85: 682-692Abstract Full Text PDF PubMed Google Scholar,[2]Meier P.J. Gasser R. Hauri H.P. Stieger B. Meyer U.A. Biosynthesis of rat liver cytochrome P-450 in mitochondria-associated rough endoplasmic reticulum and in rough microsomes in vivo.J Biol Chem. 1984; 259: 10194-10200Abstract Full Text PDF PubMed Google Scholar He completed his research training in the United States, where he worked as a Research Associate with Dr. J.L. Boyer in the Liver Study Unit of the Department of Medicine at the Yale University School of Medicine in New Haven CT between 1982 to 1984. This was the beginning of Dr. Meier's longstanding interest in physiology and pathophysiology of bile formation. At Yale, Dr. Meier developed a widely accepted method for the isolation of highly purified basolateral and canalicular membranes[3]Meier P.J. Sztul E.S. Reuben A. Boyer J.L. Structural and functional polarity of canalicular and basolateral plasma membrane vesicles isolated in high yield from rat liver.J Cell Biol. 1984; 98: 991-1000Crossref PubMed Google Scholar and characterized bile salt transport extensively in membrane vesicles.[4]Meier P.J. St Meier-Abt A. Barrett C. Boyer J.L. Mechanisms of taurocholate transport in canalicular and basolateral rat liver plasma membrane vesicles. Evidence for an electrogenic canalicular organic anion carrier.J Biol Chem. 1984; 259: 10614-10622Abstract Full Text PDF PubMed Google Scholar In 1985, he returned to Switzerland to establish his own laboratory at the University Hospital Zurich and to lead the Division of Clinical Pharmacology and Toxicology. In 1990 he received the Diploma of The Swiss Speciality Board (FMH) in Clinical Pharmacology & Toxicology and rose to the rank of full Professor in 1992. There he and his colleagues, Bruno Stieger and Bruno Hagenbuch, were the first to elucidate the molecular mechanisms of hepatocellular bile salt transport, initially cloning the sodium-dependent bile salt uptake transporter, NTCP (SLC10A1), a major milestone in the field of hepatobiliary transport mechanisms.[5]Hagenbuch B. Stieger B. Foguet M. Lubbert H. Meier P.J. Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system.Proc Natl Acad Sci U S A. 1991; 88: 10629-10633Crossref PubMed Google Scholar His team then identified the rat organic anion transporting polypeptide 1 (OATP1A1),[6]Jacquemin E. Hagenbuch B. Stieger B. Wolkoff A.W. Meier P.J. Expression cloning of a rat liver Na(+)-independent organic anion transporter.Proc Natl Acad Sci U S A. 1994; 91: 133-137Crossref PubMed Scopus (535) Google Scholar the founding member of the SLCO gene family,[7]Hagenbuch B. Stieger B. The SLCO (former SLC21) superfamily of transporters.Mol Aspects Med. 2013; 34: 396-412Crossref PubMed Scopus (223) Google Scholar followed by the identification of the canalicular bile salt export pump, BSEP,[8]Gerloff T. Stieger B. Hagenbuch B. Madon J. Landmann L. Roth J. et al.The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver.J Biol Chem. 1998; 273: 10046-10050Abstract Full Text Full Text PDF PubMed Scopus (800) Google Scholar thus defining all of the major bile salt transporters in hepatocytes at the molecular level. Further work revealed that the OATPs were also important drug transporters,[9]Bossuyt X. Muller M. Hagenbuch B. Meier P.J. Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver.J Pharmacol Exp Ther. 1996; 276: 891-896PubMed Google Scholar a concept that was met with skepticism for a considerable time.[10]Fenner K.S. Jones H.M. Ullah M. Kempshall S. Dickins M. Lai Y. et al.The evolution of the OATP hepatic uptake transport protein family in DMPK sciences: from obscure liver transporters to key determinants of hepatobiliary clearance.Xenobiotica. 2012; 42: 28-45Crossref PubMed Scopus (46) Google Scholar OATP's substrate specificities are now routinely assessed during drug development and testing of OATPs and other SLC transporters are often requested by the FDA or EMA.[11]Tweedie D. Polli J.W. Berglund E.G. Huang S.M. Zhang L. Poirier A. et al.Transporter studies in drug development: experience to date and follow-up on decision trees from the International Transporter Consortium.Clin Pharmacol Ther. 2013; 94: 113-125Crossref PubMed Scopus (97) Google Scholar Subsequently, Dr. Meier's research interests broadened to investigate the contribution of genetics to transporter defects in inherited and acquired cholestatic liver diseases.12Pauli-Magnus C. Kerb R. Fattinger K. Lang T. Anwald B. Kullak-Ublick G.A. et al.BSEP and MDR3 haplotype structure in healthy Caucasians, primary biliary cirrhosis and primary sclerosing cholangitis.Hepatology. 2004; 39: 779-791Crossref PubMed Scopus (151) Google Scholar, 13Noe J. Kullak-Ublick G.A. Jochum W. Stieger B. Kerb R. Haberl M. et al.Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis.J Hepatol. 2005; 43: 536-543Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar, 14Meier Y. Pauli-Magnus C. Zanger U.M. Klein K. Schaeffeler E. Nussler A.K. et al.Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver.Hepatology. 2006; 44: 62-74Crossref PubMed Scopus (196) Google Scholar He also pursued other scholarly endeavors in clinical pharmacology, including the interaction of drugs15Stieger B. Fattinger K. Madon J. Kullak Ublick G.A. Meier P.J. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver.Gastroenterology. 2000; 118: 422-430Abstract Full Text Full Text PDF PubMed Google Scholar, 16Durr D. Stieger B. Kullak-Ublick G.A. Rentsch K.M. Steinert H.C. Meier P.J. et al.St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4.Clin Pharmacol Ther. 2000; 68: 598-604Crossref PubMed Scopus (556) Google Scholar, 17Fattinger K. Funk C. Pantze M. Weber C. Reichen J. Stieger B. et al.The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions.Clin Pharmacol Ther. 2001; 69: 223-231Crossref PubMed Scopus (412) Google Scholar or toxins[18]Kröncke K.D. Fricker G. Meier P.J. Gerok W. Wieland T. Kurz G. alpha-Amanitin uptake into hepatocytes. Identification of hepatic membrane transport systems used by amatoxins.J Biol Chem. 1986; 261: 12562-12567Abstract Full Text PDF PubMed Google Scholar,[19]Kontaxi M. Echkardt U. Hagenbuch B. Stieger B. Meier P.J. Petzinger E. Uptake of the mycotoxin ochratoxin A in liver cells occurs via the cloned organic anion transporting polypeptide.J Pharmacol Exp Ther. 1996; 279: 1507-1513PubMed Google Scholar with the liver. He also established the importance of uptake transporters at the blood brain barrier.[20]Gao B. Stieger B. Noe B. Fritschy J.M. Meier P.J. Localization of the organic anion transporting polypeptide 2 (Oatp2) in capillary endothelium and choroid plexus epithelium of rat brain.J Histochem Cytochem. 1999; 47: 1255-1264Crossref PubMed Google Scholar He pursued all of this work in considerable detail, and with a high degree of scientific accuracy. He had a keen sense of the most important questions to pursue, which enabled significant advances in the field of hepatocellular bile salt transport, as well as the role of transport systems in drug and xenobiotic disposition. He received many international awards for this body of work including the Adolf Windaus Prize from the Falk Foundation in 1990 (Freiburg Germany); the 3rd Kanto-Koshinetsu Bile Acid Prize in 1991 (Tokyo, Japan); and the Paul-Martini Prize in 1992 (Wiesbaden, Germany). In Switzerland, his awards included the Georg Friedrich Götz-Prize in 1990 and the Award of the Cloëtta-Foundation, both from the Faculty of Medicine in Zurich; Membership in the Swiss Academy of Medicine in 2000 and the Hartman-Müller Prize and Lecture from the University of Zurich in 2005. Later in his career, in recognition of his scientific prominence and administrative ability, he was recruited to the University of Basel as Vice-Rector for Research & Talent Promotion from 2005 to 2011. He held leadership positions in several Swiss Scientific organizations including President of the Swiss National Science Foundation - Section III for Biology and Medicine in 2003/2004; President of the Swiss Clinical Trial Organization from 2009-2015; President of the Swiss Academy of Medical Sciences from 2011-2016; and Founding President of the Swiss Personalized Health Network from 2016 to 2018. Towards the end of his career, he served as President of the Ethics Commission, for the Canton Zurich from 2011 until retirement in 2020. On a personal note, Peter was known to his friends and family as a warm and caring physician scientist, husband, father and grandfather. He loved skiing, hiking in the mountains and classical music and learned to play the organ at a young age. He was often seen accompanied by his dogs Coffee and Aria and doted on his grandson. Peter is survived by his wife Andrée, daughters Fabiene and Carol, son in-law Alex and grandson Thomas. He will be greatly missed.