Jeong lab:Projects

Laboratory of Drug Metabolism and Pharmacokinetics

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Role of gut microbiota in drug elimination and toxicity Intestines harbor trillions of microbes that have evolved in the milieu of a diverse diet-derived small molecules. Gut microbiome (the collection of genetic materials harbored by the gut microbes) contains thousands of distinct genes with an enormous capacity to catalyze chemical reactions. Their functions, however, remains largely unknown. Jeong and Lee lab has been investigating the gut microbiota as (1) a drug-metabolizing organ and (2) a modulator of host response to drugs. Based on the expertise of Dr Jeong (a pharmacologist) and Dr Lee (a microbiologist), we identify and characterize the microbial factors involved in drug metabolism as well as host-microbe interaction that leads to altered drug efficacy and toxicity. 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 [1]. 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 [2] Altered drug metabolism during pregnancy Medication use in pregnancy is prevalent due to pre-existing medical conditions or newly developing disorders. This unavoidable drug treatment requires accurate pharmacokinetic information because under- or over-exposure may result in detrimental clinical outcomes not only to the mother, but also to the fetus. Limited clinical evidence suggests that pharmacokinetic profiles of drugs are altered during pregnancy. Specifically, metabolic pathway-dependent changes have been reported for hepatic drug metabolism during pregnancy. Jeong lab is interested in identifying factors responsible for altered drug metabolism and elucidating the underlying molecular mechanisms. Koh KH, Pan X, Shen H, Arnold SLM, Yu A, Gonzalez FJ, Isoherranen N, Jeong H. 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 [3] Koh KH, Jurkovic S, Yang K, Choi S, 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 [4] "Druggability" of drug candidates Preclinical characterization of pharmacokinetics of a drug candidate is essential in drug development processes. Jeong lab provides our expertise in preclinical pharmacokinetics for development of antiviral and antibiotic agents. 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 [5]