Photo of Yang Shi,  PhD

Yang Shi, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-3100
Fax: (617) 919-3200


yang_shi@hms.harvard.edu

Yang Shi, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Professor, Cell Biology, Harvard Medical School
  • Professor, Pediatrics, Harvard Medical School
  • Professor, Neonatology, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

We are interested in the biological function and mechanism of action of a number of transcriptional regulators that are targets of viral oncoproteins. These proteins include p300/CBP, CtBP and YY1. We are using both genetic (C. elegans and mouse) and biochemical approaches to address relevant questions.

Publications

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  • Laurent B, Ruitu L, Murn J, Hempel K, Ferrao R, Xiang Y, Liu S, Garcia BA, Wu H, Wu F, Steen H, Shi Y. A Specific LSD1/KDM1A Isoform Regulates Neuronal Differentiation through H3K9 Demethylation. Mol Cell 2015; 57:957-70. PubMed
  • Murn J, Zarnack K, Yang YJ, Durak O, Murphy EA, Cheloufi S, Gonzalez DM, Teplova M, Curk T, Zuber J, Patel DJ, Ule J, Luscombe NM, Tsai LH, Walsh CA, Shi Y. Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt. Genes Dev 2015; 29:501-12. PubMed
  • Alpatov R, Lesch BJ, Nakamoto-Kinoshita M, Blanco A, Chen S, Stützer A, Armache KJ, Simon MD, Xu C, Ali M, Murn J, Prisic S, Kutateladze TG, Vakoc CR, Min J, Kingston RE, Fischle W, Warren ST, Page DC, Shi Y. A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response. Cell 2014; 157:869-81. PubMed
  • Greer EL, Beese-Sims SE, Brookes E, Spadafora R, Zhu Y, Rothbart SB, Aristizábal-Corrales D, Chen S, Badeaux AI, Jin Q, Wang W, Strahl BD, Colaiácovo MP, Shi Y. A Histone Methylation Network Regulates Transgenerational Epigenetic Memory in C. elegans. Cell Rep 2014; 7:113-26. PubMed
  • Mosammaparast N, Kim H, Laurent B, Zhao Y, Lim HJ, Majid MC, Dango S, Luo Y, Hempel K, Sowa ME, Gygi SP, Steen H, Harper JW, Yankner B, Shi Y. The histone demethylase LSD1/KDM1A promotes the DNA damage response. J Cell Biol 2013; 203:457-70. PubMed
  • Lim HJ, Dimova NV, Tan MK, Sigoillot FD, King RW, Shi Y. The G2/M regulator histone demethylase PHF8 is targeted for degradation by the anaphase-promoting complex containing CDC20. Mol Cell Biol 2013; 33:4166-80. PubMed
  • Tan MK, Lim HJ, Bennett EJ, Shi Y, Harper JW. Parallel SCF adaptor capture proteomics reveals a role for SCFFBXL17 in NRF2 activation via BACH1 repressor turnover. Mol Cell 2013; 52:9-24. PubMed
  • Greer EL, Shi Y. What's the Mtrr with your grandparents? Cell Metab 2013; 18:457-9. PubMed
  • Medvedovic J, Ebert A, Tagoh H, Tamir IM, Schwickert TA, Novatchkova M, Sun Q, Huis In 't Veld PJ, Guo C, Yoon HS, Denizot Y, Holwerda SJ, de Laat W, Cogné M, Shi Y, Alt FW, Busslinger M. Flexible long-range loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire. Immunity 2013; 39:229-44. PubMed
  • Yang YJ, Baltus AE, Mathew RS, Murphy EA, Evrony GD, Gonzalez DM, Wang EP, Marshall-Walker CA, Barry BJ, Murn J, Tatarakis A, Mahajan MA, Samuels HH, Shi Y, Golden JA, Mahajnah M, Shenhav R, Walsh CA. Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation. Cell 2012; 151:1097-112. PubMed
  • Ballaré C, Lange M, Lapinaite A, Martin GM, Morey L, Pascual G, Liefke R, Simon B, Shi Y, Gozani O, Carlomagno T, Benitah SA, Di Croce L. Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity. Nat Struct Mol Biol 2012. PubMed
  • Chen S, Shi Y. Small molecules that inhibit a specific subfamily of histone demethylases: A new horizon for epigenetic medicine? Cell Res 2012. PubMed
  • Blättler SM, Verdeguer F, Liesa M, Cunningham JT, Vogel RO, Chim H, Liu H, Romanino K, Shirihai OS, Vazquez F, Rüegg MA, Shi Y, Puigserver P. Defective mitochondrial morphology and bioenergetic function in mice lacking the transcription factor Yin Yang 1 in skeletal muscle. Mol Cell Biol 2012; 32:3333-46. PubMed
  • Kim HG, Kim HT, Leach NT, Lan F, Ullmann R, Silahtaroglu A, Kurth I, Nowka A, Seong IS, Shen Y, Talkowski ME, Ruderfer D, Lee JH, Glotzbach C, Ha K, Kjaergaard S, Levin AV, Romeike BF, Kleefstra T, Bartsch O, Elsea SH, Jabs EW, MacDonald ME, Harris DJ, Quade BJ, Ropers HH, Shaffer LG, Kutsche K, Layman LC, Tommerup N, Kalscheuer VM, Shi Y, Morton CC, Kim CH, Gusella JF. Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies. Am J Hum Genet 2012; 91:56-72. PubMed
  • Chen S, Ma J, Wu F, Xiong LJ, Ma H, Xu W, Lv R, Li X, Villen J, Gygi SP, Liu XS, Shi Y. The histone H3 Lys 27 demethylase JMJD3 regulates gene expression by impacting transcriptional elongation. Genes Dev 2012; 26:1364-75. PubMed
  • Iwase S, Shi Y. Histone and DNA modifications in mental retardation. Prog Drug Res 2010; 67:147-73. PubMed
  • Yu H, Mashtalir N, Daou S, Hammond-Martel I, Ross J, Sui G, Hart GW, Rauscher FJ, Drobetsky E, Milot E, Shi Y, Affar el B. The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1 and is a critical regulator of gene expression. Mol Cell Biol 2010; 30:5071-85. PubMed
  • Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY. Long noncoding RNA as modular scaffold of histone modification complexes. Science 2010; 329:689-93. PubMed
  • Fang R, Barbera AJ, Xu Y, Rutenberg M, Leonor T, Bi Q, Lan F, Mei P, Yuan GC, Lian C, Peng J, Cheng D, Sui G, Kaiser UB, Shi Y, Shi YG. Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation. Mol Cell 2010; 39:222-33. PubMed
  • Qi HH, Sarkissian M, Hu GQ, Wang Z, Bhattacharjee A, Gordon DB, Gonzales M, Lan F, Ongusaha PP, Huarte M, Yaghi NK, Lim H, Garcia BA, Brizuela L, Zhao K, Roberts TM, Shi Y. Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development. Nature 2010; 466:503-7. PubMed
  • Whitehouse JS, Xu H, Shi Y, Noll L, Kaul S, Jones DW, Pritchard KA, Oldham KT, Gourlay DM. Mesenteric nitric oxide and superoxide production in experimental necrotizing enterocolitis. J Surg Res 2010; 161:1-8. PubMed
  • Rujirabanjerd S, Nelson J, Tarpey PS, Hackett A, Edkins S, Raymond FL, Schwartz CE, Turner G, Iwase S, Shi Y, Futreal PA, Stratton MR, Gecz J. Identification and characterization of two novel JARID1C mutations: suggestion of an emerging genotype-phenotype correlation. Eur J Hum Genet 2010; 18:330-5. PubMed
  • Amour J, Brzezinska AK, Jager Z, Sullivan C, Weihrauch D, Du J, Vladic N, Shi Y, Warltier DC, Pratt PF, Kersten JR. Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms. Anesthesiology 2010; 112:576-85. PubMed
  • Honda S, Lewis ZA, Huarte M, Cho LY, David LL, Shi Y, Selker EU. The DMM complex prevents spreading of DNA methylation from transposons to nearby genes in Neurospora crassa. Genes Dev 2010; 24:443-54. PubMed
  • Wang JK, Tsai MC, Poulin G, Adler AS, Chen S, Liu H, Shi Y, Chang HY. The histone demethylase UTX enables RB-dependent cell fate control. Genes Dev 2010; 24:327-32. PubMed
  • Horton JR, Upadhyay AK, Qi HH, Zhang X, Shi Y, Cheng X. Enzymatic and structural insights for substrate specificity of a family of jumonji histone lysine demethylases. Nat Struct Mol Biol 2010; 17:38-43. PubMed
  • Mosammaparast N, Shi Y. Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases. Annu Rev Biochem 2010; 79:155-79. PubMed
  • Wu S, Hu YC, Liu H, Shi Y. Loss of YY1 impacts the heterochromatic state and meiotic double-strand breaks during mouse spermatogenesis. Mol Cell Biol 2009; 29:6245-56. PubMed
  • Wang B, Li S, Qi HH, Chowdhury D, Shi Y, Novina CD. Distinct passenger strand and mRNA cleavage activities of human Argonaute proteins. Nat Struct Mol Biol 2009; 16:1259-66. PubMed
  • Falbo KB, Alabert C, Katou Y, Wu S, Han J, Wehr T, Xiao J, He X, Zhang Z, Shi Y, Shirahige K, Pasero P, Shen X. Involvement of a chromatin remodeling complex in damage tolerance during DNA replication. Nat Struct Mol Biol 2009; 16:1167-72. PubMed
  • Du J,Xu H,Wei N,Wakim B,Halligan B,Pritchard KA Jr,Shi Y. Identification of proteins interacting with GTP cyclohydrolase I. Biochem Biophys Res Commun 2009; 385:143-7. PubMed
  • Roelofs J, Park S, Haas W, Tian G, McAllister FE, Huo Y, Lee BH, Zhang F, Shi Y, Gygi SP, Finley D. Chaperone-mediated pathway of proteasome regulatory particle assembly. Nature 2009; 459:861-5. PubMed
  • Nottke A,Colaiacovo MP,Shi Y. Developmental roles of the histone lysine demethylases. Development 2009; 136:879-89. PubMed
  • Chen S,Whetstine JR,Ghosh S,Hanover JA,Gali RR,Grosu P,Shi Y. The conserved NAD(H)-dependent corepressor CTBP-1 regulates Caenorhabditis elegans life span. Proc Natl Acad Sci U S A 2009; 106:1496-501. PubMed
  • Shi Y,Mantuano E,Inoue G,Campana WM,Gonias SL. Ligand binding to LRP1 transactivates Trk receptors by a Src family kinase-dependent pathway. Sci Signal 2009; 2:ra18. PubMed
  • Mulligan P,Westbrook TF,Ottinger M,Pavlova N,Chang B,Macia E,Shi YJ,Barretina J,Liu J,Howley PM,Elledge SJ,Shi Y. CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation. Mol Cell 2008; 32:718-26. PubMed
  • Liu B,Ren Z,Shi Y,Guan C,Pan Z,Zong Z. Activation of signal transducers and activators of transcription 3 and overexpression of its target gene CyclinD1 in laryngeal carcinomas. Laryngoscope 2008; 118:1976-80. PubMed
  • Li F,Huarte M,Zaratiegui M,Vaughn MW,Shi Y,Martienssen R,Cande WZ. Lid2 is required for coordinating H3K4 and H3K9 methylation of heterochromatin and euchromatin. Cell 2008; 135:272-83. PubMed
  • Kim HG,Kurth I,Lan F,Meliciani I,Wenzel W,Eom SH,Kang GB,Rosenberger G,Tekin M,Ozata M,Bick DP,Sherins RJ,Walker SL,Shi Y,Gusella JF,Layman LC. Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet 2008; 83:511-9. PubMed
  • Qi HH,Ongusaha PP,Myllyharju J,Cheng D,Pakkanen O,Shi Y,Lee SW,Peng J,Shi Y. Prolyl 4-hydroxylation regulates Argonaute 2 stability. Nature 2008; 455:421-4. PubMed
  • Tsai WW,Nguyen TT,Shi Y,Barton MC. p53-targeted LSD1 functions in repression of chromatin structure and transcription in vivo. Mol Cell Biol 2008; 28:5139-46. PubMed
  • Lan F, Nottke AC, Shi Y. Mechanisms involved in the regulation of histone lysine demethylases. Curr Opin Cell Biol 2008; 20:316-25. PubMed
  • Westbrook TF, Hu G, Ang XL, Mulligan P, Pavlova NN, Liang A, Leng Y, Maehr R, Shi Y, Harper JW, Elledge SJ. SCFbeta-TRCP controls oncogenic transformation and neural differentiation through REST degradation. Nature 2008; 452:370-4. PubMed
  • Ongusaha PP,Qi HH,Raj L,Kim YB,Aaronson SA,Davis RJ,Shi Y,Liao JK,Lee SW. Identification of ROCK1 as an upstream activator of the JIP-3 to JNK signaling axis in response to UVB damage. Sci Signal 2008; 1:ra14. PubMed
  • Matthews AG, Kuo AJ, Ramon-Maiques S, Han S, Champagne KS, Ivanov D, Gallardo M, Carney D, Cheung P, Ciccone DN, Walter KL, Utz PJ, Shi Y, Kutateladze TG, Yang W, Gozani O, Oettinger MA. RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature 2007; 450:1106-10. PubMed
  • Wu S, Shi Y, Mulligan P, Gay F, Landry J, Liu H, Lu J, Qi HH, Wang W, Nickoloff JA, Wu C, Shi Y. A YY1-INO80 complex regulates genomic stability through homologous recombination-based repair. Nat Struct Mol Biol 2007; 14:1165-72. PubMed
  • Shi Y, He B, Kuchenbecker KM, You L, Xu Z, Mikami I, Yagui-Beltran A, Clement G, Lin YC, Okamoto J, Bravo DT, Jablons DM. Inhibition of Wnt-2 and galectin-3 synergistically destabilizes beta-catenin and induces apoptosis in human colorectal cancer cells. Int J Cancer 2007; 121:1175-81. PubMed
  • Shi Y, Liu YW, Gao PJ, Gao YH, Tan Y. [Identification of the beta(2)GPI-binding receptor on hepatocyte membrane] Zhonghua Yi Xue Za Zhi 2007; 87:2429-31. PubMed
  • Liu L, Ning X, Sun L, Shi Y, Han S, Guo C, Chen Y, Sun S, Yin F, Wu K, Fan D. Involvement of MGr1-Ag/37LRP in the vincristine-induced HIF-1 expression in gastric cancer cells. Mol Cell Biochem 2007; 303:151-60. PubMed
  • Han Y, Shi Y, Han Z, Sun L, Fan D. Detection of potassium currents and regulation of multidrug resistance by potassium channels in human gastric cancer cells. Cell Biol Int 2007; 31:741-7. PubMed
  • Liang J, Pan Y, Zhang D, Guo C, Shi Y, Wang J, Chen Y, Wang X, Liu J, Guo X, Chen Z, Qiao T, Fan D. Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS. FASEB J 2007; 21:2247-56. PubMed
  • Bai F, Guo X, Yang L, Wang J, Shi Y, Zhang F, Zhai H, Lu Y, Xie H, Wu K, Fan D. Establishment and Characterization of a High Metastatic Potential in the Peritoneum for Human Gastric Cancer by Orthotopic Tumor Cell Implantation. Dig Dis Sci 2007; 52:1571-1578. PubMed
  • Lan M, Shi Y, Sun L, Liu L, Guo X, Lu Y, Wang J, Liang J, Fan D. KCl Depolarization Increases HIF-1 Transcriptional Activity via the Calcium-Independent Pathway in SGC7901 Gastric Cancer Cells. Tumour Biol 2007; 28:173-180. PubMed
  • Horwitz AA, Affar el B, Heine GF, Shi Y, Parvin JD. A mechanism for transcriptional repression dependent on the BRCA1 E3 ubiquitin ligase. Proc Natl Acad Sci U S A 2007; 104:6614-9. PubMed
  • Lin YC, You L, Xu Z, He B, Yang CT, Chen JK, Mikami I, Cl. Wnt inhibitory factor-1 gene transfer inhibits melanoma cell growth. Hum Gene Ther 2007; 18:379-86. PubMed
  • Lin M, Xie HL, Su Q, Zhou JG, Tan H, Yi L, Tang HL, Huang Y, Shi Y. [Effects of Diallyl Disulfide on Differential Expression of Apoptosis-associated Genes in Leukemia Cell Line HL-60.] Ai Zheng 2007; 26:351-6. PubMed
  • Iwase S, Lan F, Bayliss P, de la Torre-Ubieta L, Huarte M, Qi HH, Whetstine JR, Bonni A, Roberts TM, Shi Y. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 2007; 128:1077-88. PubMed
  • Niu Y, Yu Q, Yu Y, Ding XM, Shi YR. [Clonality of the peripheral papilloma and cancerous cells of breast] Zhonghua Yi Xue Za Zhi 2007; 87:542-5. PubMed
  • Donohoe ME, Zhang LF, Xu N, Shi Y, Lee JT. Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch. Mol Cell 2007; 25:43-56. PubMed
  • Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, Mukherjee C, Shi Y, G. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 2006; 10:51-64. PubMed
  • Chen Z, Zang J, Whetstine J, Hong X, Davrazou F, Kutateladze TG, Simpson M, Mao Q, Pan CH, Dai S, Hagman J, Hansen K, Shi Y, Zhang G. Structural insights into histone demethylation by JMJD2 family members. Cell 2006; 125:691-702. PubMed
  • Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 2006; 125:467-81. PubMed
  • Rosendorff A, Sakakibara S, Lu S, Kieff E, Xuan Y, DiBacco A, Shi Y, Shi Y, Gill G. NXP-2 association with SUMO-2 depends on lysines required for transcriptional repression. Proc Natl Acad Sci U S A 2006; 103:5308-13. PubMed
  • Sui GC, Affar EB, Shi YJ, Wall N, Brignone C, Yin P, Dohonoe M, Calvo D, Grossman S, Shi Y. Yin Yang 1 is a negative regulator of p53 Cell 2004; 117:859-872.
  • Chen J, Wall NR, Kocher K, Duclos N, Fabbro D, Neuberg D, Griffin JD, Shi Y, Gilliland DG. Stable expression of small interfering RNA sensitizes TEL-PDGFbetaR to inhibition with imatinib or rapamycin. J Clin Invest 2004; 113:1784-91. PubMed
  • Shi YJ, Sawada JI, Su GC, Affar EB, Whetstine J, Lan F, Ogawa H, Luke M, Nakatani Y, Shi, Y.. Coordinated histone modifications mediated by a CtBP co-repressor complex Nature 2003; 422:735-738.
  • Gay F, Calvo D, Lo MC, Ceron J, Maduro M, Lin R, Shi Y. Acetylation regulates subcellular localization of the Wnt signaling nuclear effector POP-1. Genes Dev 2003; 17:717-22. PubMed
  • Sui G, Soohoo C, Affar el B, Gay F, Shi Y, Forrester WC, Shi Y. A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc Natl Acad Sci U S A 2002; 99:5515-20. PubMed
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