Photo of Guocheng Yuan,  PhD

Guocheng Yuan, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 582-8532


gcyuan@jimmy.harvard.edu

Guocheng Yuan, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Associate Professor, Biostatistics, Harvard T.H. Chan School Of Public Health
  • Associate Professor, Biostatistics and Computational Biology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

We develop computational biology methodologies for genomic data analysis and integration, with the aim to understand systems-level gene regulatory mechanisms. Since virtually all the cells in a living organism share the same genome, epigenetic information provides an essential role in regulating cell-type specific gene expression patterns. Our long-term goal is to systematically investigate the structure and dynamics of the gene regulatory network and its role in maintenance of cell-type specificity. To this end, we have developed integrated approaches to identify the chromatin state organization, to determine the targeting mechanism for epigenetic factors, and to reconstruct the gene regulatory network from integration of multiple data-types. We have applied these approaches to stem cells and cancer biology. We actively participate in the ENCODE consortium. We collaborate closely with a number of basic scientists and clinical physicians at Harvard and affiliated hospitals.

 

Publications

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  • Hu T, Yeh JE, Pinello L, Jacob J, Chakravarthy S, Yuan GC, Chopra R, Frank DA. Impact of the N-terminal domain of STAT3 in STAT3-dependent transcriptional activity. Mol Cell Biol 2015. PubMed
  • Xu J, Shao Z, Li D, Xie H, Kim W, Huang J, Taylor JE, Pinello L, Glass K, Jaffe JD, Yuan GC, Orkin SH. Developmental control of polycomb subunit composition by GATA factors mediates a switch to non-canonical functions. Mol Cell 2015; 57:304-16. PubMed
  • Glass K, Quackenbush J, Spentzos D, Haibe-Kains B, Yuan GC. A network model for angiogenesis in ovarian cancer. BMC Bioinformatics 2015; 16:115. PubMed
  • Lao T, Glass K, Qiu W, Polverino F, Gupta K, Morrow J, Mancini JD, Vuong L, Perrella MA, Hersh CP, Owen CA, Quackenbush J, Yuan GC, Silverman EK, Zhou X. Haploinsufficiency of Hedgehog interacting protein causes increased emphysema induced by cigarette smoke through network rewiring. Genome Med 2015; 7:12. PubMed
  • Marco E, Karp RL, Guo G, Robson P, Hart AH, Trippa L, Yuan GC. Bifurcation analysis of single-cell gene expression data reveals epigenetic landscape. Proc Natl Acad Sci U S A 2014; 111:E5643-50. PubMed
  • Chipumuro E, Marco E, Christensen CL, Kwiatkowski N, Zhang T, Hatheway CM, Abraham BJ, Sharma B, Yeung C, Altabef A, Perez-Atayde A, Wong KK, Yuan GC, Gray NS, Young RA, George RE. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell 2014; 159:1126-39. PubMed
  • Wu C, Wang Z, Song X, Feng XS, Abnet CC, He J, Hu N, Zuo XB, Tan W, Zhan Q, Hu Z, He Z, Jia W, Zhou Y, Yu K, Shu XO, Yuan JM, Zheng W, Zhao XK, Gao SG, Yuan ZQ, Zhou FY, Fan ZM, Cui JL, Lin HL, Han XN, Li B, Chen X, Dawsey SM, Liao L, Lee MP, Ding T, Qiao YL, Liu Z, Liu Y, Yu D, Chang J, Wei L, Gao YT, Koh WP, Xiang YB, Tang ZZ, Fan JH, Han JJ, Zhou SL, Zhang P, Zhang DY, Yuan Y, Huang Y, Liu C, Zhai K, Qiao Y, Jin G, Guo C, Fu J, Miao X, Lu C, Yang H, Wang C, Wheeler WA, Gail M, Yeager M, Yuenger J, Guo ET, Li AL, Zhang W, Li XM, Sun LD, Ma BG, Li Y, Tang S, Peng XQ, Liu J, Hutchinson A, Jacobs K, Giffen C, Burdette L, Fraumeni JF, Shen H, Ke Y, Zeng Y, Wu T, Kraft P, Chung CC, Tucker MA, Hou ZC, Liu YL, Hu YL, Liu Y, Wang L, Yuan G, Chen LS, Liu X, Ma T, Meng H, Sun L, Li XM, Li XM, Ku JW, Zhou YF, Yang LQ, Wang Z, Li Y, Qige Q, Yang WJ, Lei GY, Chen LQ, Li EM, Yuan L, Yue WB, Wang R, Wang LW, Fan XP, Zhu FH, Zhao WX, Mao YM, Zhang M, Xing GL, Li JL, Han M, Ren JL, Liu B, Ren SW, Kong QP, Li F, Sheyhidin I, Wei W, Zhang YR, Feng CW, Wang J, Yang YH, Hao HZ, Bao QD, Liu BC, Wu AQ, Xie D, Yang WC, Wang L, Zhao XH, Chen SQ, Hong JY, Zhang XJ, Freedman ND, Goldstein AM, Lin D, Taylor PR, Wang LD, Chanock SJ. Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations. Nat Genet 2014; 46:1001-6. PubMed
  • Yang G, Yuan G, Li X, Liu P, Chen Z, Fan M. BMP-2 induction of Dlx3 expression is mediated by p38/Smad5 signaling pathway in osteoblastic MC3T3-E1 cells. J Cell Physiol 2014; 229:943-54. PubMed
  • Riddell J, Gazit R, Garrison BS, Guo G, Saadatpour A, Mandal PK, Ebina W, Volchkov P, Yuan GC, Orkin SH, Rossi DJ. Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors. Cell 2014; 157:549-64. PubMed
  • Pinello L, Xu J, Orkin SH, Yuan GC. Analysis of chromatin-state plasticity identifies cell-type-specific regulators of H3K27me3 patterns. Proc Natl Acad Sci U S A 2014; 111:E344-53. PubMed
  • Das PP, Shao Z, Beyaz S, Apostolou E, Pinello L, De Los Angeles A, O'Brien K, Atsma JM, Fujiwara Y, Nguyen M, Ljuboja D, Guo G, Woo A, Yuan GC, Onder T, Daley G, Hochedlinger K, Kim J, Orkin SH. Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity. Mol Cell 2014; 53:32-48. PubMed
  • Saadatpour A, Guo G, Orkin SH, Yuan GC. Characterizing heterogeneity in leukemic cells using single-cell gene expression analysis. Genome Biol 2014; 15:525. PubMed
  • Pulakanti K, Pinello L, Stelloh C, Blinka S, Allred J, Milanovich S, Kiblawi S, Peterson J, Wang A, Yuan GC, Rao S. Enhancer transcribed RNAs arise from hypomethylated, Tet-occupied genomic regions. Epigenetics 2014; 8:1303-20. PubMed
  • Pinello L, Lo Bosco G, Yuan GC. Applications of alignment-free methods in epigenomics. 2013. PubMed
  • Bauer DE, Kamran SC, Lessard S, Xu J, Fujiwara Y, Lin C, Shao Z, Canver MC, Smith EC, Pinello L, Sabo PJ, Vierstra J, Voit RA, Yuan GC, Porteus MH, Stamatoyannopoulos JA, Lettre G, Orkin SH. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science 2013; 342:253-7. PubMed
  • Guo G, Luc S, Marco E, Lin TW, Peng C, Kerenyi MA, Beyaz S, Kim W, Xu J, Das PP, Neff T, Zou K, Yuan GC, Orkin SH. Mapping cellular hierarchy by single-cell analysis of the cell surface repertoire. Cell Stem Cell 2013; 13:492-505. PubMed
  • Walker SR, Nelson EA, Yeh JE, Pinello L, Yuan GC, Frank DA. STAT5 outcompetes STAT3 to regulate the expression of the oncogenic transcriptional modulator BCL6. Mol Cell Biol 2013; 33:2879-90. PubMed
  • Larson JL, Huttenhower C, Quackenbush J, Yuan GC. A tiered hidden Markov model characterizes multi-scale chromatin states. Genomics 2013. PubMed
  • Baena E, Shao Z, Linn DE, Glass K, Hamblen MJ, Fujiwara Y, Kim J, Nguyen M, Zhang X, Godinho FJ, Bronson RT, Mucci LA, Loda M, Yuan GC, Orkin SH, Li Z. ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients. Genes Dev 2013; 27:683-98. PubMed
  • Ku WL, Girvan M, Yuan GC, Sorrentino F, Ott E. Modeling the dynamics of bivalent histone modifications. PLoS ONE 2013; 8:e77944. PubMed
  • Nag A, Savova V, Fung HL, Miron A, Yuan GC, Zhang K, Gimelbrant AA. Chromatin signature of widespread monoallelic expression. Elife 2014; 2:e01256. PubMed
  • Glass K, Huttenhower C, Quackenbush J, Yuan GC. Passing messages between biological networks to refine predicted interactions. PLoS ONE 2013; 8:e64832. PubMed
  • Xu J, Shao Z, Glass K, Bauer DE, Pinello L, Van Handel B, Hou S, Stamatoyannopoulos JA, Mikkola HK, Yuan GC, Orkin SH. Combinatorial Assembly of Developmental Stage-Specific Enhancers Controls Gene Expression Programs during Human Erythropoiesis. Dev Cell 2012; 23:796-811. PubMed
  • Shao Z, Zhang Y, Yuan GC, Orkin SH, Waxman DJ. MAnorm: a robust model for quantitative comparison of ChIP-Seq data sets. Genome Biol 2012; 13:R16. PubMed
  • Yuan GC. Linking genome to epigenome. 2012. PubMed
  • Larson JL, Yuan GC. Chromatin States accurately classify cell differentiation stages. PLoS ONE 2012; 7:e31414. PubMed
  • Van Rechem C, Black JC, Abbas T, Allen A, Rinehart CA, Yuan GC, Dutta A, Whetstine JR. The SKP1-Cul1-F-box and leucine-rich repeat protein 4 (SCF-FbxL4) ubiquitin ligase regulates lysine demethylase 4A (KDM4A)/Jumonji domain-containing 2A (JMJD2A) protein. J Biol Chem 2011; 286:30462-70. PubMed
  • Pinello L, Lo Bosco G, Hanlon B, Yuan GC. A motif-independent metric for DNA sequence specificity. BMC Bioinformatics 2012; 12:408. PubMed
  • Rao S, Zhen S, Roumiantsev S, McDonald LT, Yuan GC, Orkin SH. Differential roles of sall4 isoforms in embryonic stem cell pluripotency. Mol Cell Biol 2010; 30:5364-80. 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
  • Liu Y, Shao Z, Yuan GC. Prediction of Polycomb target genes in mouse embryonic stem cells. Genomics 2010; 96:17-26. PubMed
  • Chastanet A, Vitkup D, Yuan GC, Norman TM, Liu JS, Losick RM. Broadly heterogeneous activation of the master regulator for sporulation in Bacillus subtilis. Proc Natl Acad Sci U S A 2010; 107:8486-91. PubMed
  • Lantermann AB, Straub T, Strålfors A, Yuan GC, Ekwall K, Korber P. Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae. Nat Struct Mol Biol 2010; 17:251-7. PubMed
  • Larson JL, Yuan GC. Epigenetic domains found in mouse embryonic stem cells via a hidden Markov model. BMC Bioinformatics 2010; 11:557. PubMed
  • Shen X, Kim W, Fujiwara Y, Simon MD, Liu Y, Mysliwiec MR, Yuan GC, Lee Y, Orkin SH. Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells. Cell 2010; 139:1303-14. PubMed
  • Wippo CJ, Krstulovic BS, Ertel F, Musladin S, Blaschke D, Stürzl S, Yuan GC, Hörz W, Korber P, Barbaric S. Differential cofactor requirements for histone eviction from two nucleosomes at the yeast PHO84 promoter are determined by intrinsic nucleosome stability. Mol Cell Biol 2009; 29:2960-81. PubMed
  • Di Ges. A multi-layer method to study genome-scale positions of nucleosomes. Genomics 2009; 93:140-5. PubMed
  • Yuan GC. Targeted recruitment of histone modifications in humans predicted by genomic sequences. J Comput Biol 2009; 16:341-55. PubMed
  • Shen X, Liu Y, Hsu YJ, Fujiwara Y, Kim J, Mao X, Yuan GC, Orkin SH. EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol Cell 2008; 32:491-502. PubMed
  • Yuan GC, Liu JS. Genomic sequence is highly predictive of local nucleosome depletion. PLoS Comput Biol 2008; 4:e13. PubMed
  • Dennis JH, Fan HY, Reynolds SM, Yuan G, Meldrim JC, Richter DJ, Peterson DG, Rando OJ, Noble WS, Kingston RE. Independent and complementary methods for large-scale structural analysis of mammalian chromatin. Genome Res 2007; 17:928-39. PubMed
  • Yuan GC, Ma P, Zhong W, Liu JS. Statistical assessment of the global regulatory role of histone acetylation in Saccharomyces cerevisiae. Genome Biol 2006; 7:R70. PubMed
  • Yuan GC, Liu YJ, Dion MF, Slack MD, Wu LF, Altschuler SJ, Rando OJ. Genome-scale identification of nucleosome positions in S. cerevisiae. Science 2005; 309:626-30. PubMed
  • Yuan GC, Nam K, Antonsen TM, Ott E, Guzdar PN. Power spectrum of passive scalars in two dimensional chaotic flows. Chaos 2003; 10:39-49. PubMed
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