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
  • C.H. Waddington Professor of Pediatrics, Pediatrics, Harvard Medical School
  • Professor, Neonatology, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

We are interested in identifying key epigenetic regulators in cancer, elucidate their mechanism of action and provide the conceptual basis for translating our basic findings to the clinic and for developing new therapeutic strategies.

Publications

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  • Jambhekar A, Dhall A, Shi Y. Roles and regulation of histone methylation in animal development. Nat Rev Mol Cell Biol 2019. PubMed
  • Zhang J, Lee YR, Dang F, Gan W, Menon AV, Katon JM, Hsu CH, Asara JM, Tibarewal P, Leslie NR, Shi Y, Pandolfi PP, Wei W. PTEN Methylation by NSD2 Controls Cellular Sensitivity to DNA Damage. 2019. PubMed
  • Byrum AK, Carvajal-Maldonado D, Mudge MC, Valle-Garcia D, Majid MC, Patel R, Sowa ME, Gygi SP, Harper JW, Shi Y, Vindigni A, Mosammaparast N. Mitotic regulators TPX2 and Aurora A protect DNA forks during replication stress by counteracting 53BP1 function. J Cell Biol 2019. PubMed
  • Sheng W, LaFleur MW, Nguyen TH, Chen S, Chakravarthy A, Conway JR, Li Y, Chen H, Yang H, Hsu PH, Van Allen EM, Freeman GJ, De Carvalho DD, He HH, Sharpe AH, Shi Y. LSD1 Ablation Stimulates Anti-tumor Immunity and Enables Checkpoint Blockade. Cell 2018. PubMed
  • Li H, Liefke R, Jiang J, Kurland JV, Tian W, Deng P, Zhang W, He Q, Patel DJ, Bulyk ML, Shi Y, Wang Z. Polycomb-like proteins link the PRC2 complex to CpG islands. Nature 2017; 549:287-291. PubMed
  • Murn J, Shi Y. The winding path of protein methylation research: milestones and new frontiers. Nat Rev Mol Cell Biol 2017. PubMed
  • Iberg-Badeaux A, Collombet S, Laurent B, van Oevelen C, Chin KK, Thieffry D, Graf T, Shi Y. A Transcription Factor Pulse Can Prime Chromatin for Heritable Transcriptional Memory. Mol Cell Biol 2016. PubMed
  • Jambhekar A, Anastas JN, Shi Y. Histone Lysine Demethylase Inhibitors. Cold Spring Harb Perspect Med 2017. PubMed
  • Xiang Y, Laurent B, Hsu CH, Nachtergaele S, Lu Z, Sheng W, Xu C, Chen H, Ouyang J, Wang S, Ling D, Hsu PH, Zou L, Jambhekar A, He C, Shi Y. RNA m(6)A methylation regulates the ultraviolet-induced DNA damage response. Nature 2017; 543:573-576. PubMed
  • Liefke R, Karwacki-Neisius V, Shi Y. EPOP Interacts with Elongin BC and USP7 to Modulate the Chromatin Landscape. Mol Cell 2016; 64:659-672. PubMed
  • Greer EL, Becker B, Latza C, Antebi A, Shi Y. Mutation of C. elegans demethylase spr-5 extends transgenerational longevity. Cell Res 2016; 26:229-38. PubMed
  • Cheloufi S, Elling U, Hopfgartner B, Jung YL, Murn J, Ninova M, Hubmann M, Badeaux AI, Euong Ang C, Tenen D, Wesche DJ, Abazova N, Hogue M, Tasdemir N, Brumbaugh J, Rathert P, Jude J, Ferrari F, Blanco A, Fellner M, Wenzel D, Zinner M, Vidal SE, Bell O, Stadtfeld M, Chang HY, Almouzni G, Lowe SW, Rinn J, Wernig M, Aravin A, Shi Y, Park PJ, Penninger JM, Zuber J, Hochedlinger K. The histone chaperone CAF-1 safeguards somatic cell identity. Nature 2015; 528:218-24. PubMed
  • Murn J, Teplova M, Zarnack K, Shi Y, Patel DJ. Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal protein Unkempt. Nat Struct Mol Biol 2015. PubMed
  • Luo GZ, Blanco MA, Greer EL, He C, Shi Y. DNA N(6)-methyladenine: a new epigenetic mark in eukaryotes? Nat Rev Mol Cell Biol 2015; 16:705-10. PubMed
  • Chen M, Zhu N, Liu X, Laurent B, Tang Z, Eng R, Shi Y, Armstrong SA, Roeder RG. JMJD1C is required for the survival of acute myeloid leukemia by functioning as a coactivator for key transcription factors. Genes Dev 2015; 29:2123-39. PubMed
  • van Oevelen C, Collombet S, Vicent G, Hoogenkamp M, Lepoivre C, Badeaux A, Bussmann L, Sardina JL, Thieffry D, Beato M, Shi Y, Bonifer C, Graf T. C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis. Stem Cell Reports 2015; 5:232-47. PubMed
  • Lan F, Shi Y. Histone H3.3 and cancer: A potential reader connection. Proc Natl Acad Sci U S A 2015. PubMed
  • Greer EL, Blanco MA, Gu L, Sendinc E, Liu J, Aristizábal-Corrales D, Hsu CH, Aravind L, He C, Shi Y. DNA Methylation on N6-Adenine in C. elegans. Cell 2015; 161:868-78. PubMed
  • 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
  • Tsai CL, Shi Y, Tainer JA. How substrate specificity is imposed on a histone demethylase--lessons from KDM2A. Genes Dev 2014; 28:1735-8. 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
  • Brookes E, Shi Y. Diverse epigenetic mechanisms of human disease. Annu Rev Genet 2014. 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
  • Chen S, Shi Y. A new horizon for epigenetic medicine? Cell Res 2013. 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Mosammaparast N, Shi Y. Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases. Annu Rev Biochem 2010; 79:155-79. 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Shi YJ, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y. . Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 Cell 2004; 119:941-953.
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