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Laboratory of Drug Metabolism and Pharmacokinetics

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Bold: corresponding author Hyunyoung Jeong (2016-2020) Guo Y, Lee H, Edusei E, Albakry S, Jeong H, Lee JR (2020) Blood profiles of gut bacterial tacrolimus metabolite in kidney transplant recipients. Transplant Direct 6(10): e601 [1]. Guo Y, Lee H, Jeong H. Gut microbiota in reductive drug metabolism. Progress in Molecular Biology and Translational Science. 2020 171;61-93 [2] Jeong H, Stika CS. Methods to study mechanisms underlying altered hepatic drug elimination during pregnancy. Semin Perinatol. 2020 Jan 25;151228 [3] Cho S, Won K-J, Yang X, Leone V, Hubert N, Chang EB, Chung E, Park J-S, Lee H, Jeong H. Phenylpropionic acid produced by gut microbiota alleviates acetaminophen-induced hepatotoxicity. bioRxiv [4]. Zhong G, Kirkwood J, Won K-J, Tjota N, Jeong H, Isoherranen N. Characterization of vitamin A metabolome in human livers with and without nonalcoholic fatty liver disease. J Pharmacol Exp Ther. 2019;370(1):92-103. [5]. Ning M, Duarte JD, Stevison F, Isoherranen N, Rubin LH, Jeong H. Determinants of cytochrome P450 2D6 mRNA levels in healthy human liver tissue. Clin Transl Sci. 2019 [6]. Won K-J, Park J-S, Jeong H. Repression of hepatocyte nuclear factor 4 alpha by AP-1 underlies dyslipidemia associated with retinoic acid J Lipid Res. 2019;60(4):794-804 [7]. Guo Y, Crnkovic CM, Won K-J, Yang X, Lee JR, Orjala J, Lee H, Jeong H. Commensal gut bacteria convert the immunosuppressant tacrolimus to less potent metabolites. Drug Metab Disp. 2019;47(3):194-202 [8]. Oguri T, Kwon Y, Woo JKK, Prehna G, Lee H, Ning M, Won K-J, Lee J, Mei S, Shi Y, Jeong H, Lee H. A family of small intrinsically disordered proteins involved in flagellum-dependent motility in Salmonella enterica. J Bacteriol. 2018;201(2):1 [9] Gaedigk A, Dinh JC, Jeong H, Prasad B, Leeder JS. Ten years’ experience with the CYP2D6 activity score: a perspective on future investigations to improve clinical predictions for precision therapeutics. J Pers Med. 2018; 8(2): 15. [10] Morgan ET, Dempsey JL, Mimche SM, Lamb TJ, Kulkarni S, Cui JY, Jeong H, Slitt AL. Physiological regulation of drug metabolism and transport: pregnancy, microbiome, inflammation, infection, and fasting. Drug Metab Disp. 2018;46(5):503-513 [11] Yeo WS, Arya R, Kim KK, Jeong H, Cho KH, Bae T. The FDA-approved anti-cancer drugs, streptozotocin and floxuridine, reduce the virulence of Staphylococcus aureus. Sci Rep. 2018;8(1):2521. [12] Ning M, Duarte JD, Rubin LH, Jeong H. CYP2D6 protein level is the major contributor to inter-individual variability in CYP2D6-mediated drug metabolism in healthy human liver tissue. Clin Pharmacol Ther 2018;104(5):974-982 [13] Nobutani K, Miyoshi J, Musch MW, Nishiyama M, Watanabe J, Kaneko A, Yamamoto M, Yoshida M, Kono T, Jeong H, Chang EB. Daikenchuto (TU-100) alters murine hepatic and intestinal drug metabolizing enzymes in an in vivo dietary model: effects of gender and withdrawal. Pharmacol Res Perspect [14] Cho S*, Tripathi A*, Chlipala G, Green S, Lee H, Chang EB, Jeong H (*, equal contribution). Fructose diet alleviates acetaminophen-induced hepatotoxicity in mice. PlosOne 2017;12(8):e0182977 [15] Gautam J, Ku JM, Regmi SC, Jeong H, Wang Y, Banskota S, Park MH, Nam TG, Jeong BS, Kim JA. Dual inhibition of NOX2 and receptor tyrosine kinase by BJ-1301 enhances anticancer therapy efficacy via suppression of autocrine stimulatory factors in lung cancer. Mol Cancer Ther. [16] Ning M, Jeong H. High fat diet feeding alters expression of hepatic drug-metabolizing enzymes in mice. Drug Metab Dispos. 2017;45(7):707-711 [17] Pan X, Kent R, Won KJ, Jeong H. Cholic acid feeding leads to increased CYP2D6 expression in CYP2D6-humanized mice. Drug Metab Dispos. 2017;45(4):346-352 [18] Pan X, Ning M, Jeong H. Transcriptional regulation of CYP2D6 expression. Drug Metab Dispos. 2017;45(1):42-48 [19] Yu AM, Ingelman-Sundberg M, Cherrington NJ, Aleksunes LM, Zanger UM, Xie W, Jeong H, Morgan ET, Turnbaugh PJ, Klaassen CD, Bhatt AP, Redinbo MR, Hao P, Waxman DJ, Wang L, Zhong XB. Regulation of drug metabolism and toxicity by multiple factors of genetics, epigenetics, lncRNAs, gut microbiota, and diseases: a meeting report of the 21st International Symposium on Microsomes and Drug Oxidations (MDO). Acta Pharm Sin B. 2017;7(2):241-248.[20] Wisner KL, Jeong H, Chambers C. Use of antipsychotics during pregnancy: pregnant women get sick-sick women get pregnant. JAMA Psychiatry. 2016;73(9):901-3 [21] Gautam J, Banskota S, Regmi SC, Ahn S, Jeon YH, Jeong H, Kim SJ, Nam TG, Jeong BS, Kim JA. Tryptophan hydroxylase 1 and 5-HT7 receptor preferentially expressed in triple-negative breast cancer promote cancer progression through autocrine serotonin signaling. Mol Cancer 2016;15:75 [22] Cho S, Ning M, Zhang Y, Rubin LH, Jeong H. 17β-Estradiol up-regulates UGT1A9 expression via ERα Acta Pharmaceutica Sinica B 2016;6:504–509 [23] Tracy TS, Chaudhry AS, Prasad B, Thummel KE, Schuetz EG, Zhong X, Tien Y, Jeong H, Pan X, Shireman LM, Tay-Sontheimer J, Lin YS. Interindividual variability in cytochrome P450-mediated drug metabolism. Drug Metab Dispos. 2016;44:343-51 [24] Koh K, Jeong H. Electrophoretic mobility shift assay (EMSA) and supershift assay of cytochrome P450 2B6 in response to estrogen. Methods Mol Biol 2016;1366:41-51. [25] Hyunyoung Jeong (2011-2015) Zhang N, Liu Y, Jeong H. Drug-Drug interaction potentials of tyrosine kinase inhibitors via inhibition of UDP-glucuronosyltransferases. Scientific Reports 2015;5:17778 [26] Ao L, Reichel DA, Hu D, Jeong H, Kim KB, Bae Y, Lee W. Polymer Micelle Formulations of Proteasome Inhibitor Carfilzomib for Improved Metabolic Stability and Anti-Cancer Efficacy in Human Multiple Myeloma and Lung Cancer Cell Lines. J Pharmacol Exp Ther 2015;355(2):168-73 [27] McClay K, Mehboob S, Yu J, Santarsiero B, Deng J, Cook JL, Jeong H, Johnson ME, Steffan RJ. Indole trimers with antibacterial activity against Gram-positive organisms produced using combinatorial biocatalysts. AMB Express. 2015;5(1):125 [28] Pan X, Jeong H. Estrogen-induced cholestasis leads to repressed CYP2D6 expression in CYP2D6-humanized mice. Mol Pharmacol. 2015;88(1):106-12 [29] Pan X, Lee YK, Jeong H. Farnesoid X receptor agonist represses cytochrome P450 2D6 expression by upregulating small heterodimer partner. Drug Metab Dispos. 2015;43(7):1002-7 [30] Zhang S, Pan X, Jeong H. GW4064, an agonist of Farnesoid X Receptor (FXR), represses CYP3A4 expression in human hepatocytes. Drug Metab Dispos. 2015;43(5):743-8 [31] Miller Z, Kim KS, Lee DM, Kasam V, Baek SE, Lee KH, Zhang YY, Ao L, Carmony K, Lee NR, Zhou S, Zhao Q, Jang Y, Jeong H, Zhan CG, Lee W, Kim DE, Kim KB. Proteasome inhibitors with pyrazole scaffolds from structure-based virtual screening. J Med Chem. 2015;58(4):2036-41 [32] Ning M, Koh KH, Pan X, Jeong H. Hepatocyte nuclear factor (HNF) 4α transactivation of cytochrome P450 (Cyp) 2d40 promoter is enhanced during pregnancy in mice. Biochem Pharmacol. 2015;94(1):46-52 [33] Hernandez W, Aquino-Michaels K, Drozda K, Patel S, Jeong H, Takahashi H, Cavallari LH, Perera MA. Novel single nucleotide polymorphism in CYP2C9 is associated with changes in warfarin clearance and CYP2C9 expression levels in African Americans. Trans Res. 2015;165(6):651-7 [34] Koh KH*, Pan X*, Zhang W, McLachlan A, Urrutia R, Jeong H. (*, equally contributed) Kruppel-like Factor 9 (KLF9) promotes cytochrome P450 (CYP) 2D6 expression during pregnancy in CYP2D6-humanized mice. Mol Pharmacol. 2014;86(6):727-35 (selected for Journal Highlights) [35] Stone R, Hong J, Jeong H. Pharmacokinetics of monoclonal antibodies used for inflammatory bowel diseases in pregnant women. J Clin Toxicol 2014;4:209 [36] Zhang Y, Liu Y, Mehboob S, Song J, Boci T, Johnson ME, Ghosh AK, Jeong H. Metabolism-directed structure optimization of benzimidazole-based Francisella tularensis enoyl-reductase (FabI) inhibitors. Xenobiotica. 2014;44(5):404-16 [37] Li W, Ning M, Koh K, Kim H, Jeong H. 17β-Estradiol (E2) induces sulfotransferase (SULT) 2A1 expression through estrogen Receptor (ER) α. Drug Metab Dispos. 2014;42(4):796-802 [38] Lee JK, Chung HJ, Fischer L, Fischer J, Gonzalez FJ, Jeong H. Human placental lactogen induces CYP2E1 expression via PI 3-kinase pathway in female human hepatocytes. Drug Metab Dispos. 2014;42(4):492-9. [39] Koh KH*, Pan X*, Shen H, Arnold SLM, Yu AM, Gonzalez FJ, Isoherranen N, Jeong H. (*, equally contributed) Altered expression of small heterodimer partner governs cytochrome P450 (CYP) 2D6 induction during pregnancy in CYP2D6-humanized mice. J Biol Chem. 2014;289(6):3105-13 [40] Fischer J, Sarto GE, Hardman J, Endres L, Jenkins TM, Kilpatrick SJ, Jeong H, Geller S, Deyo K, Fischer PA, Rodvold KA. Influence of gestational age and body weight on the pharmacokinetics of labetalol in pregnancy. Clin Pharmacokinet. 2014;53(4):373-83 [41] Lee H, Zhu T, Patel K, Zhang Y, Truong L, Hevener KE, Gatuz JL, Subramanya G, Jeong H, Uprichard SL, Johnson ME. High-throughput screening (HTS) and hit validation to identify small molecule inhibitors with activity against NS3/4A proteases from multiple Hepatitis C Virus genotypes. PlosOne. 2013;8(10):e75144 [42] Zhang N, Seguin RP, Kunze KL, Zhang Y, Jeong H. Characterization of inhibition kinetics of (S)-warfarin hydroxylation by noscapine: Implications in warfarin therapy. Drug Metab Dispos. 2013;41(12):2114-23 [43] Cavallari LH, Vaynshteyn D, Freeman KM, Wang D, Perera MP, Takahashi H, Drozda K, Patel SR, Jeong H. CYP2C9 promoter region SNPs linked to the R150H polymorphism are functional suggesting their role in CYP2C9*8-mediated effects. Pharmacogenetics and Genomics. 2013;23(4):228-31. [44] Choi S, Koh KH, Jeong H. Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013;41(2):263-269. [45] Vaynshteyn D, Jeong H. Caffeine induces CYP1A2 expression in rat hepatocytes but not in human hepatocytes. Drug Metab Lett. 2012;6(2):116-9. [46] Koh KH, Jurkovic S, Yang K, Choi SY, Jung JW, Kim KP, Zhang W, Jeong H. Estradiol induces cytochrome P450 2B6 expression at high concentrations: Implication in estrogen-mediated gene regulation in pregnancy. Biochem Pharmacol. 2012;84(1):93-103 [47] Liu Y, Jeong H, Takahashi H, Drozda K, Patel SR, Shapiro NL, Nutescu EA, Cavallari LH. Decreased warfarin clearance associated with the CYP2C9 R150H (*8) polymorphism. Clin Pharmacol Ther. 2012; 91(4): 660-665 [48] Cavallari LH, Jeong H, Bress A. Role of cytochrome P450 genotype in the steps toward personalized drug therapy. Pharmacogenomics and Personalized Medicine. 2011 Nov;4:123-136. [49] Choi SY, Fischer L, Yang K, Chung H, Jeong H. Isoform-specific regulation of cytochrome P450 expression and activity by estradiol in female rats. Biochem Pharmacol. 2011 Mar 15;81(6):777-782. [50] Koh KH, Xie H, Yu AM, Jeong H. Altered cytochrome P450 expression in mice during pregnancy. Drug Metab Dispos. 2011 Feb;39(2):165-169. [51] Hyunyoung Jeong (before 2010) Della Torre M, Hibbard JU, Jeong H, Fischer JH. Betamethasone in pregnancy: influence of maternal body weight and multiple gestation on pharmacokinetics. Am J Obstet Gynecol. 2010 Sep;203(3):254.e1-12. [52] Yang K, Koh KH, Jeong H. Induction of CYP2B6 and CYP3A4 expression by 1-aminobenzotriazole (ABT) in human hepatocytes. Drug Metab Lett. 2010 Aug;4(3):129-133. [53] Shord S, Chan L, Camp JR, Vasquez EM, Jeong H, Molokie RE, Baum CL, Xie H. Effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam. Br J Clin Pharmacol. 2010 69:160-166. [54] Jeong H. Altered drug metabolism during pregnancy: Hormonal regulation of drug-metabolizing enzymes. Expert Opin Drug Metab Toxicol 2010; 6(6):1-11 Chen H, Yang K, Choi SY, Fischer JH, Jeong H. Up-regulation of UDP-glucuronosyltransferase (UGT) 1A4 by 17beta-estradiol: a potential mechanism of increased lamotrigine elimination in pregnancy. Drug Metab Dispos. 2009 Sep;37(9):1841-1847. [55] Shord SS, Cavallari LH, Gao W, Jeong HY, Deyo K, Patel SR, Camp JR, Labott SM, Molokie RE. The pharmacokinetics of codeine and its metabolites in Blacks with sickle cell disease. Eur J Clin Pharmacol. 2009 Jul;65(7):651-658. [56] Choi S, Sainz B Jr, Corcoran P, Uprichard S, Jeong H. Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells. Xenobiotica. 2009 Mar;39(3):205-217. [57] Jeong H, Choi SY, Song JW, Chen H, Fischer JH. Regulation of UDP-glucuronosyltransferase (UGT) 1A1 by progesterone and its impact on labetalol elimination. Xenobiotica. 2008 Jan;38(1):62-75. Jeong H and Kaplan B. Therapeutic monitoring of mycophenolate mofetil. Clin J Am Soc Nephrol. 2007 Jan;2(1):184-191 Jeong H and Chiou WL. Role of P-glycoprotein in hepatic metabolism of tacrolimus. Xenobiotica. 2006 Jan;36(1):1-13. Chiou WL, Ma C, Wu TC, Jeong H. Unexpected lack of effect of the rifampin-induced P-glycoprotein on the oral bioavailability of its substrate, talinolol, in humans: implication in phenotyping. J Pharm Sci. 2003 Jan;92(1):4-7 Wu TC, Ma C, Jeong H, Yao HM, Chiou WL. Comparison of gastrointestinal absorption between human and rat: the role of intestinal absorptive surface area and unstirred aqueous layer. Food Chem Toxicol. 2002 Nov;40(11):1727-1728. Chiou WL, Wu TC, Ma C, Jeong H. Enhanced oral bioavailability of docetaxel by coadministration of cyclosporine: quantitation and role of P-glycoprotein. J Clin Oncol. 2002 Apr 1;20(7):1951-1952 Chiou WL, Jeong H, Wu TC, Ma C. Use of erythromycin breath test for in vivo assessments of cytochrome P4503A activity and dosage individualization. Clin Pharmacol Ther. 2001 Oct;70(4):305-310 Chiou WL, Jeong H, Wu TC, Ma C. Erythromycin breath test. Clin Pharmacol Ther. 2001 Oct;70(4):395-399. Chiou WL, Jeong H, Chung SM, Wu TC. Evaluation of using dog as an animal model to study the fraction o f oral dose absorbed of 43 drugs in humans. Pharm Res. 2000 Feb;17(2):135-140 Chiou WL, Chung SM, Wu TC and Jeong H. Similarity in the linear and nonlinear oral absorption of drugs between human and rat. Int J Clin Pharmacol Ther. 2000 Nov;38(11):532-539 Hyunwoo Lee (2016-2020) Guo Y, Lee H, Jeong H (2020) Gut microbiota in reductive drug metabolism. Prog Mol Biol Transl Sci 171;61-93 [58]. Guo Y, Lee H, Edusei E, Albakry S, Jeong H, Lee JR (2020) Blood profiles of gut bacterial tacrolimus metabolite in kidney transplant recipients. Transplantation Direct[59]. Guo Y, Crnkovic CM, Won K-J, Yang X, Lee JR, Orjala J, Lee H, Jeong H (2019) Commensal gut bacteria convert the immunosuppressant tacrolimus to less potent metabolites. Drug Metab Dispos 47:194-202 [60]. Oguri T, Kwon Y, Woo KKJ, Prehna G, Lee H, Ning M, Won K-J, Lee J, Mei S, Shi Y, Jeong H, Lee H (2019) A family of small intrinsically disordered proteins involved in flagellum-dependent motility in Salmonella enterica. J. Bacteriology 201:e00415-18. [61] (Selected as Spotlight) Baek J, Lee J, Yoon K, Lee H (2017) Identification of unannotated small genes in Salmonella. G3 (Genes-Genomes-Genetics) (Bethesda) 7:983-989 [62]. Liu Q, Hu M, Yeo WS, He L, Li T, Zhu Y, Meng H, Wang Y, Lee H, Liu X, Li M, Bae T (2017) Rewiring of the FtsH regulatory network by a single nucleotide change in saeS of Staphylococcus aureus. Sci Rep 7:8456 [63]. Cho S, Tripathi A, Chlipala G, Green S, Lee H, Chang EB, Jeong H (2017) Fructose diet alleviates acetaminophen-induced hepatotoxicity in mice. PLoS One. 12:e0182977 [64]. Oguri T, W-S Yeo, T Bae, Lee H (2016) Identification of EnvC and its cognate amidases as novel determinants of intrinsic resistance to cationic antimicrobial peptides. Antimicrob Agents Chemother 60:2222-2231 [65]. Rice AJ, Woo JK, Khan A, Szypulinski MJ, Johnson ME, Lee H, Lee H (2016) Over-expression, purification, and confirmation of Bacillus anthracis transcriptional regulator NprR. Protein Exp Purif. 125:83-89 [66]. Hyunwoo Lee (2011-2015) Mullowney MW, Hwang CH, Newsome AG, Wei C, Tanouye U, Wan B, Carlson S, Barranis NJ,   hAinmhire E, Chen W-L, Krishnamoorthy K, White J, Blair R, Lee H, Burdette JE, Rathod PK, Parish T, Cho S, Franzblau SG, and Murphy BT. (2015) Diaza-anthracene antibiotics from a freshwater-derived Actinomycete with selective antibacterial activity toward Mycobacterium tuberculosis. ACS Infect. Dis. 1:168-174 [67]. Barendt S, Lee H, Birch C, Nakano MM, Jones M, Zuber P. (2013) Transcriptomic and phenotypic analysis of paralogous spx gene function in Bacillus anthracis Sterne. Microbiology Open 2:695-714 [68]. Kang SO, Tesorero RA, Lee H, and Cho KH. (2012) CvfA-mediated thermoregulation of capsule production in Streptococcus pyogenes. PLoS ONE 7:e37367 [69]. Jeong DW, Cho H, Lee H, Li C, Garza J, Fried M, Bae T (2011) Identification of the P3 promoter and distinct roles of the two promoters of the SaeRS two-component system in Staphylococcus aureus. J. Bacteriololgy 193:4672-84 [70]. Hyunwoo Lee (before 2010) Samant S, Hsu FF, Neyfakh AA, Lee H(2009) The Bacillus anthracis MprF is required for synthesis of lysylphosphatidylglycerols and for resistance to cationic antimicrobial peptides. J. Bacteriology 191:1311-1319 [71]. Samant S, Lee H, Ghassemi M, Chen J, Cook J, Mankin AS, and Neyfakh AA (2008) Nucleotide biosynthesis is critical for growth of bacteria in human blood. PLoS Pathogens 4:e37 [72]. Smith, KL, Gomez MJ, Shatalin KY, Lee H and Neyfakh AA (2007) Monitoring of gene knockouts: genome-wide profiling of conditionally essential genes in bacteria. Genome Biology 8: R87 [73]. Vazquez-Laslop N, Lee H, and Neyfakh AA (2006) Increased persistence in Escherichia coli caused by controlled expression of toxins or other unrelated proteins. J. Bacteriology 188:3494-97 [74]. Lee H, Hsu FF, Turk J, Groisman EA (2004) The PmrA-regulated pmrC gene mediates phosphoethanolamine modification of lipid A and polymyxin resistance in Salmonella enterica. J. Bacteriology 186:4124-33 [75]. Lee H, Vazquez-Laslop N, Klyachko KA, and Neyfakh AA (2003) Isolation of antibiotic hypersusceptibility mutants of Acinetobacter spp. by selection for DNA release. Antimicrobial Agents and Chemotherapy 47:1267-74 [76]. Vasquez-Laslop N, Lee H, Hu R, and Neyfakh AA (2001) Molecular sieve mechanism of selective release of cytoplasmic proteins by osmotically shocked Escherichia coli. J. Bacteriology 183:2399-404 [77]. Naqvi SM., Park KS, Yi SY, Lee H, Bok SH, and Choi D (1998) A glycine-rich RNA-binding protein gene is differentially expressed during acute hypersensitive response following tobacco mosaic virus infection in tobacco. Plant Molecular Biology 37:571-6 [78]. Kim YK, Lee H, Son KH, Kwon BM, Jeong TS, Lee DH, Shin JS, Seo YW, Kim SU, and Bok SH (1996) GERI-BP002-A, Novel Inhibitor of Acyl-CoA:Cholesterol Acyltransferase produced by Aspergillus fumigatus F93. J. Antibiotics 49:31-36 Son KH, Kim YK, Lee H, Lee WS, and Kim SU (1996) Amplication of farnesyl protein transferase inhibitory activity from Aspergillus fumigatus F93 by Plackett-Burman design. Biotechnology Letters 18:1297-1300