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Xiaobing Shi, Ph.D.

Present Title & Affiliation

Primary Appointment

Associate Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX
Member, The University of Texas Graduate School of Biomedical Sciences, Houston, TX

Research Interests

Posttranslational modifications on histones play animportant role in modulating chromatin dynamics and the accessibility of theunderlying DNA, thus regulating all chromatin-associated processes, such astranscription. Dysregulation of the homeostasis of histone modifications leadsto pathogenesis of developmental disorders and genetic diseases, includingcancer. However, despite the biological and clinical importance, it remainslargely unknown how the modifications on the histone tails dictate gene expressionprofiles. The long-term goal of my research is to understand the molecularmechanisms by which histone modifications, particularly lysine methylation andacetylation, regulate chromatin and transcription and how dysregulation of thehomeostasis of histone modifications leads to human cancer.

The current research focus of my laboratory is to identifyand characterize novel epigenetic readers and to elucidate their roles incancer. One of the principal functions of histone methylation and acetylation isbelieved to be to recruit or repel “reader” proteins that recognize the methylor acetyl moiety on specific residues and transduce the epigenetic signals todistinct outcomes. Therefore, identification of reader proteins is critical forunderstanding the mechanistic and functional consequences of histonemodifications. Preciously we have identified the PHD finger as a novel readermodule for histone lysine methylation (Shi et al Nature 2006). Recently wedeveloped a histone peptide array for high throughput screening and identifiedseveral novel readers for histone methylation and acetylation, including ahistone variant H3.3-specific reader of H3K36 methylation (Wen et al Nature 2014) and a new family reader of histone acetylation (Li et al Cell 2014). Global alterations of histone modifications occur frequently in manytypes of human cancers. The identification of potent inhibitors including JQ1targeting BRD4 and other BET family Bromodomain-containing proteins suggeststhat epigenetic readers are attractive therapeutic targets for cancertreatment. Ongoing projects in the lab aim to elucidate the biological functionsof the new epigenetic readers that we identified using diverse biologicalsystems and to develop and characterize small molecules targeting theseepigenetic readers for the treatment of diverse human cancers.

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

Assistant Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX, 9/2014-9/2015
Assistant Professor, Department of Biochemistry and Molecular Biology, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX, 10/2008-8/2014

Honors and Awards

2014-present R. Lee Clark Fellow, UT M.D. Anderson Cancer Center
2013-present American Cancer Society Research Scholar
2010-2012 Kimmel Scholar, Sidney Kimmel Foundation for Cancer Research
2009-2010 MD Anderson Faculty Development Award - CCSG

Selected Publications

Peer-Reviewed Original Research Articles

1. Chen K, Chen Z, Wu D, Zhang L, Lin X, Su J, Rodriguez B, Xi Y, Xia Z, Chen X, Shi X, Wang Q, Li W. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes. Nat Genet. e-Pub 8/2015.
2. Li Y, Wen H, Xi Y, Tanaka K, Wang H, Peng D, Ren Y, Jin Q, Dent SY, Li W, Li H, Shi X. AF9 YEATS Domain Links Histone Acetylation to DOT1L-Mediated H3K79 Methylation. Cell 159(3):558-71, 10/2014. e-Pub 10/2014. PMCID: PMC4344132.
3. Guo R, Zheng L, Park JW, Lv R, Chen H, Jiao F, Xu W, Mu S, Wen H, Qiu J, Wang Z, Yang P, Wu F, Hui J, Fu X, Shi X, Shi YG, Xing Y, Lan F, Shi Y. BS69/ZMYND11 Reads and Connects Histone H3.3 Lysine 36 Trimethylation-Decorated Chromatin to Regulated Pre-mRNA Processing. Mol Cell 56(2):298-310, 10/2014. e-Pub 9/2014. PMCID: PMC4363072.
4. Jiang Y, Trescott L, Holcomb J, Zhang X, Brunzelle J, Sirinupong N, Shi X, Yang Z. Structural Insights into Estrogen Receptor α Methylation by Histone Methyltransferase SMYD2, a Cellular Event Implicated in Estrogen Signaling Regulation. J Mol Biol 426(pii: S0022-2836(14)00101-6):3413-25, 10/2014. e-Pub 3/2014. PMID: 24594358.
5. Poplawski A, Hu K, Lee W, Natesan S, Peng D, Carlson S, Shi X, Balaz S, Markley JL, Glass KC. Molecular Insights into the Recognition of N-Terminal Histone Modifications by the BRPF1 Bromodomain. J Mol Biol 426(8):1661-76, 4/2014. e-Pub 12/2013. PMCID: PMC3969779.
6. Wen H, Li Y, Xi Y, Jiang S, Stratton S, Peng D, Tanaka K, Ren Y, Xia Z, Wu J, Li B, Barton MC, Li W, Li H, Shi X. ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression. Nature 508(7495):263-8, 4/2014. e-Pub 3/2014. PMCID: PMC4142212.
7. Klein BJ, Piao L, Xi Y, Rincon-Arano H, Rothbart SB, Peng D, Wen H, Larson C, Zhang X, Zheng X, Cortazar MA, Peña PV, Mangan A, Bentley DL, Strahl BD, Groudine M, Li W, Shi X, Kutateladze TG. The Histone-H3K4-Specific Demethylase KDM5B Binds to Its Substrate and Product through Distinct PHD Fingers. Cell Rep 6(2):325-35, 1/30/2014. e-Pub 1/9/2014. PMCID: PMC3918441.
8. 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.
9. 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.
10. 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, 2/1/2013. e-Pub 12/10/2012. PMCID: PMC3561539.
11. 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, 12/15/2012. PMCID: PMC3533079.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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, 3/2010. e-Pub 2/2010. PMCID: PMC2843180.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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, Huang Y, Shi X. Emerging roles of lysine methylation on non-histone proteins. Cell Mol Life Sci. e-Pub 7/2015.
2. Wen H, Li Y, Li H, Shi X. ZMYND11: An H3.3-specific reader of H3K36me3. Cell Cycle 13(14):2153-4, 2014. e-Pub 6/2014. PMID: 24963723.
3. Zhang X, Wen H, Shi X. Lysine methylation: Beyond histones. Acta Biochim Biophys Sin (Shanghai) 44(1):14-27, 1/2012. PMID: 22194010.
4. Shi X, Gozani O. The fellowships of the INGs. J Cell Biochem 96(6):1127-36, 12/15/2005. PMID: 16167330.

Last updated: 9/1/2015