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Xiaobing Shi, Ph.D.

Present Title & Affiliation

Primary Appointment

Assistant Professor, Department of Biochemistry and Molecular Biology, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

Our lab is interested in the epigenetic regulation of chromatin and transcription. Epigenetics is termed as heritable changes in phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence. One of the mechanisms is through covalent post-translational modifications-such as methylation-of histones that wound by DNA to form chromatin in the eukaryotic cells. Histone methylation is dynamically regulated by enzymes, namely lysine methyltransferase (KMT) and lysine demethylase (KDM), that add and remove the methyl marks, respectively. These histone methyl marks are then recognized by “reader” domains or proteins, which in turn dictate the “on” or “off” states of the underlying genes. We have previously identified the Plant HomeoDomain (PHD finger) as a novel reader of methylated histones. There are more than 200 PHD fingers in the human proteome. Currently we are focusing on elucidating the roles of the PHD fingers present in the recently identified JmjC domain-containing KDMs in the regulation of chromatin dynamics. Recently we developed a histone peptide array for a high-throughput screen to identify novel reader proteins that recognize distinct histone methylation.   

 

We are also interested in understanding the broader roles of KMTs and KDMs in modulating not only histones, but also non-histone proteins in a variety of biological processes and disease models, with the focus on breast cancer, cancer stem cells and mouse embryonic stem cells. We employ a combination of approaches including conventional biochemistry, molecular and cellular biology as well as the cutting-edge high-throughput sequencing technology (ChIP-seq and RNA-seq) to address these questions. Our long-term goal is to understand the molecular mechanisms of epigenetic regulation during normal development, and how disruption of the chromatin homeostasis leads to pathological development.

 

Lab page: http://www.mdanderson.org/education-and-research/departments-programs-and-labs/labs/shi-laboratory/index.html.

Office Address

The University of Texas MD Anderson Cancer Center
1515 Holcombe Blvd
Unit Number: Unit 1000
Houston, TX 77030
Room Number: BSRB, Rm. S9.8316A
Phone: 713-834-6293
Fax: 713-792-0346
Email: xbshi@mdanderson.org

Education & Training

Degree-Granting Education

2001 Chinese Academy of Sciences, Shanghai, China, PHD, Biology
1996 Wuhan University, Wuhan, China, BS, Biology

Postgraduate Training

2005-2008 Research Fellowship, Molecular and Cell Biology, Stanford University, Stanford, CA, Or Gozani
2001-2004 Research Fellowship, Biochemistry, Stanford University, Stanford, CA, Arthur Kornberg

Experience/Service

Academic Appointments

Member, The University of Texas Graduate School of Biomedical Sciences, Houston, TX, 11/2008-present

Honors and Awards

2010-2012 Kimmel Scholar, Sidney Kimmel Foundation for Cancer Research
2009-2010 CCSG Scholar, UT M.D. Anderson Cancer Center
2001 Pengyingang Award, Chinese Academy of Sciences
2000 Baoijie Award, Chinese Academy of Sciences
1996 Graduated with honors, Wuhan University

Selected Publications

Peer-Reviewed Original Research Articles

1. Zhang X, Tanaka K, Yan J, Li J, Peng D, Jiang Y, Yang Z, Barton MC, Wen H, Shi X. Regulation of estrogen receptor α by histone methyltransferase SMYD2-mediated protein methylation. Proc Natl Acad Sci U S A 110(43):17284-9, 10/22/2013. e-Pub 10/7/2013. PMCID: PMC3808627.
2. Zhang H, Ma ZY, Zeng L, Tanaka K, Zhang CJ, Ma J, Bai G, Wang P, Zhang SW, Liu ZW, Cai T, Tang K, Liu R, Shi X, He XJ, Zhu JK. DTF1 is a core component of RNA-directed DNA methylation and may assist in the recruitment of Pol IV. Proc Natl Acad Sci U S A 110(20):8290-5, 5/2013. e-Pub 5/2013. PMCID: PMC3657815.
3. Wang J, Leung JW, Gong Z, Feng L, Shi X, Chen J. PHF6 regulates cell cycle progression by suppressing ribosomal RNA synthesis. J Biol Chem 288(5):3174-83, 2/2013. e-Pub 12/2012. PMCID: PMC3561539.
4. Brien GL, Gambero G, O'Connell DJ, Jerman E, Turner SA, Egan CM, Dunne EJ, Jurgens MC, Wynne K, Piao L, Lohan AJ, Ferguson N, Shi X, Sinha KM, Loftus BJ, Cagney G, Bracken AP. Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation. Nat Struct Mol Biol 19(12):1273-81, 12/2012. e-Pub 11/2012. PMID: 23160351.
5. Dhar SS, Lee SH, Kan PY, Voigt P, Ma L, Shi X, Reinberg D, Lee MG. Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4. Genes Dev 26(24):2749-62, 12/2012. PMCID: PMC3533079.
6. Calnan DR, Webb AE, White JL, Stowe TR, Goswami T, Shi X, Espejo A, Bedford MT, Gozani O, Gygi SP, Brunet A. Methylation by Set9 modulates FoxO3 stability and transcriptional activity. Aging (Albany NY) 4(7):462-79, 7/2012. PMCID: PMC3433933.
7. Qian W, Miki D, Zhang H, Liu Y, Zhang X, Tang K, Kan Y, La H, Li X, Li S, Zhu X, Shi X, Zhang K, Pontes O, Chen X, Liu R, Gong Z, Zhu JK. A histone acetyltransferase regulates active DNA demethylation in Arabidopsis. Science 336(6087):1445-8, 6/2012. PMCID: PMC3575687.
8. Kuo AJ, Cheung P, Chen K, Zee BM, Kioi M, Lauring J, Xi Y, Park BH, Shi X, Garcia BA, Li W, Gozani O. NSD2 Links Dimethylation of Histone H3 at Lysine 36 to Oncogenic Programming. Mol Cell 44(4):609-20, 11/2011. PMCID: PMC3222870.
9. Levy D, Kuo AJ, Chang Y, Schaefer U, Kitson C, Cheung P, Espejo A, Zee BM, Liu CL, Tangsombatvisit S, Tennen RI, Kuo AY, Tanjing S, Cheung R, Chua KF, Utz PJ, Shi X, Prinjha RK, Lee K, Garcia BA, Bedford MT, Tarakhovsky A, Cheng X, Gozani O. Lysine methylation of the NF-?B subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-?B signaling. Nat Immunol 12(1):29-36, 1/2011. e-Pub 12/2010. PMCID: PMC3074206.
10. Tsai WW, Wang Z, Yiu TT, Akdemir KC, Xia W, Winter S, Tsai CY, Shi X, Schwarzer D, Plunkett W, Aronow B, Gozani O, Fischle W, Hung MC, Patel DJ, Barton MC. TRIM24 links a non-canonical histone signature to breast cancer. Nature 468(7326):927-32, 12/16/2010. PMCID: PMC3058826.
11. West LE, Roy S, Lachmi-Weiner K, Hayashi R, Shi X, Appella E, Kutateladze TG, Gozani O. The MBT repeats of L3MBTL1 link SET8-mediated p53 methylation at lysine 382 to target gene repression. J Biol Chem 285(48):37725-32, 11/26/2010. e-Pub 9/24/2010. PMCID: PMC2988377.
12. Kleine-Kohlbrecher D, Christensen J, Vandamme J, Abarrategui I, Bak M, Tommerup N, Shi X, Gozani O, Rappsilber J, Salcini AE, Helin K. A Functional Link between the Histone Demethylase PHF8 and the Transcription Factor ZNF711 in X-Linked Mental Retardation. Mol Cell 38(2):1-14, 4/23/2010. e-Pub 3/25/2010. PMCID: PMC2989439.
13. Wen H, Li J, Song T, Lu M, Kan PY, Lee MG, Sha B, Shi X. Recognition of histone H3K4 trimethylation by the PHD finger of PHF2 modulates histone demethylation. J Biol Chem 285(13):9322, 3/26/2010. e-Pub 2/2/2010. PMCID: PMC2843180.
14. McCord RA, Michishita E, Hong T, Berber E, Boxer LD, Kusumoto R, Guan S, Shi X, Gozani O, Burlingame AL, Bohr VA, Chua KF. SIRT6 stabilizes DNA-dependent Protein Kinase at chromatin for DNA double-strand break repair. Aging (Albany NY) 1(1):109-121, 1/2009. e-Pub 1/15/2009. PMCID: PMC2815768.
15. Kachirskaia I, Shi X, Yamaguchi H, Tanoue K, Wen H, Wang EW, Appella E, Gozani O. Role for 53BP1 Tudor domain recognition of p53 dimethylated at lysine 382 in DNA damage signaling. J Biol Chem 283(50):34660-6, 12/12/2008. e-Pub 10/7/2008. PMCID: PMC2596381.
16. Zhang H, Gómez-García MR, Shi X, Rao NN, Kornberg A. Polyphosphate kinase 1, a conserved bacterial enzyme, in a eukaryote, Dictyostelium discoideum, with a role in cytokinesis. Proc Natl Acad Sci U S A 104(42):16486-91, 10/16/2007. e-Pub 10/10/2007. PMCID: PMC2034253.
17. Shi X, Kachirskaia I, Yamaguchi H, West LE, Wen H, Wang EW, Dutta S, Appella E, Gozani O. Modulation of p53 function by SET8-mediated methylation at lysine 382. Mol Cell 27(4):636-46, 8/17/2007. PMCID: PMC2693209.
18. Lan F, Collins RE, De Cegli R, Alpatov R, Horton JR, Shi X, Gozani O, Cheng X, Shi Y. Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression. Nature 448(7154):718-22, 8/9/2007. PMCID: PMC2702779.
19. Huang W, Zhang H, Davrazou F, Kutateladze TG, Shi X, Gozani O, Prestwich GD. Stabilized phosphatidylinositol-5-phosphate analogues as ligands for the nuclear protein ING2: chemistry, biology, and molecular modeling. J Am Chem Soc 129(20):6498-506, 5/23/2007. e-Pub 5/1/2007. PMCID: PMC2553394.
20. Shi X, Kachirskaia I, Walter KL, Kuo JH, Lake A, Davrazou F, Chan SM, Martin DG, Fingerman IM, Briggs SD, Howe L, Utz PJ, Kutateladze TG, Lugovskoy AA, Bedford MT, Gozani O. Proteome-wide analysis in Saccharomyces cerevisiae identifies several PHD fingers as novel direct and selective binding modules of histone H3 methylated at either lysine 4 or lysine 36. J Biol Chem 282(4):2450-5, 1/26/2007. e-Pub 12/1/2006. PMCID: PMC2735445.
21. Martin DG, Baetz K, Shi X, Walter KL, MacDonald VE, Wlodarski MJ, Gozani O, Hieter P, Howe L. The Yng1p plant homeodomain finger is a methyl-histone binding module that recognizes lysine 4-methylated histone H3. Mol Cell Biol 26(21):7871-9, 11/2006. e-Pub 8/21/2006. PMCID: PMC1636756.
22. Shi X, Hong T, Walter KL, Ewalt M, Michishita E, Hung T, Carney D, Peña P, Lan F, Kaadige MR, Lacoste N, Cayrou C, Davrazou F, Saha A, Cairns BR, Ayer DE, Kutateladze TG, Shi Y, Côté J, Chua KF, Gozani O. ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature 442(7098):96-9, 7/6/2006. e-Pub 5/21/2006. PMCID: PMC3089773.
23. Peña PV, Davrazou F, Shi X, Walter KL, Verkhusha VV, Gozani O, Zhao R, Kutateladze TG. Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2. Nature 442(7098):100-3, 7/6/2006. e-Pub 5/21/2006. PMCID: PMC3190580.
24. Shi X, Kornberg A. Endopolyphosphatase in Saccharomyces cerevisiae undergoes post-translational activations to produce short-chain polyphosphates. FEBS Lett 579(9):2014-8, 3/2005. PMID: 15792812.
25. Shi X, Rao NN, Kornberg A. Inorganic polyphosphate in Bacillus cereus: motility, biofilm formation, and sporulation. Proc Natl Acad Sci U S A 101(49):17061-5, 12/7/2004. e-Pub 11/30/2004. PMCID: PMC535361.

Invited Articles

1. Zhang X, Wen H, Shi X. Lysine methylation: Beyond histones. Acta Biochim Biophys Sin (Shanghai) 44(1):14-27, 1/2012. PMID: 22194010.
2. Shi X, Gozani O. The fellowships of the INGs. J Cell Biochem 96(6):1127-36, 12/15/2005. PMID: 16167330.

Last updated: 12/7/2013