Xiaobo Zhong, Ph.D.

 

Ph.D., Wageningen University, The Netherlands, 1998

Curriculum Vitae

Research Interests

Pharmacogenomics, pharmacoepigenomics, and developmental pharmacology.

My long-term research goals are to better understand how genetic polymorphisms and epigenetic alterations result in varied responses to drugs. Presently, I am proposing researches to systematically examine genetic polymorphisms and epigenetic alterations (DNA methylation, histone modifications, and chromatin dynamic alterations) in the genes involved in drug metabolism.

I have a NIH grant focusing on identification of the mechanisms controlling the developmental switch of the Cyp3a gene expression in liver by using mouse as a model. This study uses RNA-seq, ChIP-seq, and FISH approaches to test a hypothesis that the developmental switch of the Cyp3a genes in mouse liver is controlled by transcription factors which change epigenetic modifications at the target chromatin, and place the Cyp3a genes in distinct nuclear positions, allowing the Cyp3a genes to be turned on or off at different developmental stages.

I have another NIH grant using genome-wide approaches to elucidate how alterations of hormones and transcription factors modulate epigenetic signatures and hepatic ontogenic expression of drug processing genes, with main focus on Phase I metabolizing enzymes.

Technologies used in my laboratory include RNA-seq, ChIP-seq, fluorescence in situ hybridization, and RT-PCR.

Selected Publications

Sugimura R, He XC, Venkatraman A, Arai F, Box A, Semerad C, Haug JS, Peng L, Zhong XB, Suda T, and Li L. Non-canonical Wnt signaling maintains hematopoietic stem cells through flamingo and frizzled8 interaction in the niche. Cell, 2012, in press.

Peng L, Yoo B, Gunewardena SS, Lu H, Klaassen CD, and Zhong XB. RNA-Seq reveals dynamic changes of mRNA abundance of cytochrome P450s and their alternative transcripts during liver development. Drug Metabolism and Disposition, 2012, doi:10.1124/dmd.112.045088. PMID:22434873.

Cui JY, Gunewardena SS, Yoo B, Liu J, Renaud HJ, Lu H, Zhong XB, and Klaassen CD. RNA-Seq reveals different mRNA abundance of transporters and their alternative transcript isoforms during liver development. Toxicological Sciences, 2012, doi:10.1093/toxsci/kfs107. PMID:22454430.

Cui JY, Aleksunes LM, Tanaka Y, Fu ZD, Guo Y, Guo GL, Lu H, Zhong XB, and Klaassen CD. Bile acids via FXR initiate the expression of major transporters involved in the enterohepatic circulation of bile acids in newborn mice. American Journal of Physiology: Gastrointestinal and Liver Physiology, 2012, doi:10.1152/ajpgi.00370.2011. PMID:22268101.

Li Y and Zhong XB. Epigenetic regulation of developmental expression of Cyp2d genes in mouse liver. Acta Pharmaceutica Sinica B. 2012; 2(2):144-156.

Li D, Gaedigk R, Hart SN, Leeder JS, and Zhong XB. The role of CYP3A4 mRNA transcript with shortened 3’-UTR in hepatocyte differentiation, liver development, and response to drug induction. Molecular Pharmacology, 2012; 81(1): 86-96. PMID:21998292. PMCID:PMC3250109.

Li H, Wolfe A, Septer S, Edwards G, Zhong XB, Abdulkarim AB, Ranganathan S, and Apte U. Deregulation of hippo kinase signaling in human hepatic malignancies. Liver International, 2012; 32(1):38-47. PMID:22098159.

Rodova M, Lu Q, Li Y, Woodbury B, Crist J, Gardner B, Yost J, Zhong XB, Anderson HC, and Wang J. Nfat1 regulates adult articular chondrocyte function through its age-dependent expression mediated by epigenetic histone modifications. Journal of Bone and Mineral Research, 2011; 26(8):1974-1986. PMID:21452283.

Wang L, Li F, Lu J, Li G, Li D, Zhong XB, Guo GL, Ma X. The Chinese herbal medicine sophora flavescens activates pregnane X receptor. Drug Metabolism and Disposition, 2010. PMID:20736322.

Li GD, Thomas AM, Hart SN, Zhong XB, Wu D, and Guo GL. Novel insight of transcriptional activation of SHP by FXR: chromatin looping of promoter and downstream FXR response elements in Nr0b2 gene. Molecular Endocrinology, 2010, 24(7):1404-1412. PMID:20444884. PMCID:PMC2903909.

Hart SN, Li Y, Nakamoto K, Subileau E, Steen D, and Zhong XB. A comparison of whole genome gene expression profiles of HepaRG cells and HepG2 cells to primary human hepatocytes and human liver tissues. Drug Metabolism and Disposition, 2010, 38(6):988-994. PMID: 20228232. PMCID:PMC2879958.

Thomas AM, Hart SN, Kong B, Fang J, Zhong XB, Guo GL.. Genome-wide tissue-specific farnesoid X receptor binding in mouse liver and intestine. Hepatology, 2010, 51(4):1410-1419. PMID: 20091679.

Sim SC, Miller WL, Zhong XB, Arlt W, Ogata T, Ding XX, Wolf R. Pandey AV, Henderson C, Porter T, Masters BS, Daly AK, Nebert DW, and Ingelman-Sundberg M.
Nomenclature for alleles of the cytochrome P450 oxidoreductase gene. Pharmacogenetics and Genomics, 2009, 19:565-566. PMID:19535965. PMCID:PMC2753199.

Li Y, Buckley D, Wang S, Klaassen CD, and Zhong XB. Genetic polymorphisms in the TATA box and upstream phenobarbital responsive enhancer module of the UGT1A1 promoter have combined effects on UDP-glucuronosyltransferase 1A1 transcription mediated by constitutive androstane receptor, pregnane X receptor, or glucocorticoid receptor in human liver. Drug Metabolism and Disposition, 2009, 37(9):1978-1986. PMID:19541828, PMCID:PMC2729330.

Cui JY, Leager RL, Zhong XB, and Klaassen CD. Ontogenic expression of hepatic Ahr mRNA is associated with histone H3K4 dimethylation during mouse liver development. Toxicology Letters, 2009, 189(3):184-190. PMID:19481593, PMCID:PMC2762423.

Li Y, Cui Y, Hart SN, Klaassen CD, and Zhong XB. Dynamic patterns of histone methylation are associated with ontogenic expression of Cyp3a genes during mouse liver maturation. Molecular Pharmacology, 2009, 75:1171-1179. PMID:19188337. PMCID: PMC2672803.

Hart SN, Cui Y, Klaassen CD, and Zhong XB. Three patterns of cytochrome P450 gene expression during liver maturation in mice. Drug Metabolism and Disposition, 2009, 37(1): 116-121. PMID:18845660. PMCID: PMC2683655.

Hart SN and Zhong XB. P450 oxidoreductase: genetic polymorphisms and implications to drug metabolism and toxicity. Expert Opinion on Drug Metabolism and Toxicology, 2008, 4(4):439-452. Review. PMID:18433346.

Hart SN, Wang S, Nakamoto K, Wesselman C, Li Y, and Zhong XB. Genetic polymorphisms in cytochrome P450 oxidoreductase influence microsomal P450-catelyzed drug metabolism. Pharmacogenetics and Genomics, 2008, 18(1):11-24. PMID:18216718.

Hart SN, Li Y, Nakamoto K, Wesselman C, and Zhong XB. Novel SNPs in cytochrome P450 oxidoreductase. Drug Metabolism and Pharmacokinetics, 2007, 22(4):322-326. PMID:17827787.

Nakamoto K, Kidd JR, Jenison RD, Klaassen CD, Wan YJ, Kidd KK, and Zhong XB. Genotyping and haplotyping of CYP2C19 functional alleles on thin-film biosensor chips. Pharmacogenetics and Genomics, 2007, 17(2):103-114. PMID:17301690.

Bai SL, Zhong XB, Ma LG, Zheng WJ, Fan LM, Wei N, and Deng XW. A simple and reliable assay for detecting specific nucleotide sequence variations in plants using optical thin-film biosensor chips. The Plant Journal, 2007, 49:354-366. PMID:17156412.

Nakamoto K, Wang S, Jenison RD, Guo GL, Klaassen CD, Wan YJ, and Zhong XB. Linkage disequilibrium blocks, haplotype structure, and htSNPs of human CYP7A1 gene. BMC Genetics, 2006, 7:29-37. PMID:16709249. PMCID: PMC1488870.

Zhong XB, Leng L, Beitin A, Chen R, McDonald C, Hsiao B, Jenison RD, Kang I, Park SH, Lee A, Gregersen P, Thuma P, Bray-Ward P, Ward DC, Bucala R. Simultaneous detection of microsatellite repeats and SNPs in the macrophage migration inhibitory factor (MIF) gene by thin-film biosensor chips and application to rural field studies. Nucleic Acids Research, 2005, 33 (13): e121. PMID:16077028. PMCID: PMC1182331.

Zhong XB, Reynolds R, Kidd JR, Kidd KK, Jenison R, Marlar RA, and Ward DC. Single-nucleotide polymorphism genotyping on optical thin-film biosensor chips. Proceedings of the National Academy of Sciences USA, 2003, 100(20):11559-11564. PMID:12975525. PMCID: PMC208797.

Zhong, XB, Lizardi PM, Huang XH, Bray-Ward PL, and Ward DC. Visualization of oligonucleotide probes and point mutations in interphase nuclei and DNA fibers using rolling circle DNA amplification. Proceedings of the National Academy of Sciences USA, 2001, 98(7):3940-3945. PMID:11274414. PMCID: PMC31158.

Grichtchenko II, Choi IY, Zhong XB, Bray-Ward P, Russell JM, Boron WF. Cloning, characterization, and chromosomal mapping of a human electroneutral Na+-driven Cl-NCO3 exchanger. Journal of Biological Chemistry, 2001, 276 (11):8358-8363. PMID: 11133997.

Contact Information

Xiao-bo Zhong, Ph.D.
Associate Professor
Department of Pharmacology, Toxicology, & Therapeutics
The University of Kansas Medical Center
4065 HLSIC; MS 1018
3901 Rainbow Blvd.
Kansas City, KS 66160
Phone:  (913) 588-0401
Fax:  (913) 588-7501
E-mail address:  xzhong@kumc.edu

Updated 5/1/12