Photo of Kaifu Chen,  PhD

Kaifu Chen, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2348


kaifu.chen@childrens.harvard.edu

Kaifu Chen, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Associate Professor, Pediatrics, Harvard Medical School
  • Director, Faculty Member, Computational Biology Program, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Chen lab does bioinformatics research with a focus on cell identity regulation in prostate cancer and cardiovascular endothelium. Different cell types in a healthy body share the same genetic sequence. Difference in identity of these cell types is determined by epigenetic regulation of gene expression. Meanwhile, many genetic mutations in germ line or somatic cells were found to affect epigenetic factors and can cause disease due to cell identity dysregulation. To study cell identity dysregulation in disease, the lab is focused on prostate cancer. To study cell identity regulation in development, we are focused on the cardiovascular endothelial lineage. One major interest of the Lab is in how cell identity genes are transcriptionally regulated in a way different from the regulation of other genes. An important finding of the Lab is that cell identity genes are often regulated by a significantly larger number of transcription factors when compared to other genes. Many of theses cell identity genes play roles as tumor suppressors and oncogenes during tumorigenesis.

Publications from Harvard Catalyst Profiles

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  • Yi Y, Li Y, Li C, Wu L, Zhao D, Li F, Fazli L, Wang R, Wang L, Dong X, Zhao W, Chen K, Cao Q. Methylation-dependent and -independent roles of EZH2 synergize in CDCA8 activation in prostate cancer. Oncogene 2022; 41:1610-1621. PubMed
  • Terranova CJ, Tang M, Maitituoheti M, Raman AT, Ghosh AK, Schulz J, Amin SB, Orouji E, Tomczak K, Sarkar S, Oba J, Creasy C, Wu CJ, Khan S, Lazcano R, Wani K, Singh A, Barrodia P, Zhao D, Chen K, Haydu LE, Wang WL, Lazar AJ, Woodman SE, Bernatchez C, Rai K. Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy. Cell Rep 2021; 36:109410. PubMed
  • Wang G, Xia B, Zhou M, Lv J, Zhao D, Li Y, Bu Y, Wang X, Cooke JP, Cao Q, Gyu Lee M, Zhang L, Chen K. MACMIC Reveals A Dual Role of CTCF in Epigenetic Regulation of Cell Identity Genes. Genomics Proteomics Bioinformatics 2021. PubMed
  • Yi Y, Li Y, Meng Q, Li Q, Li F, Lu B, Shen J, Fazli L, Zhao D, Li C, Jiang W, Wang R, Liu Q, Szczepanski A, Li Q, Qin W, Weiner AB, Lotan TL, Ji Z, Kalantry S, Wang L, Schaeffer EM, Niu H, Dong X, Zhao W, Chen K, Cao Q. A PRC2-independent function for EZH2 in regulating rRNA 2'-O methylation and IRES-dependent translation. Nat Cell Biol 2021; 23:341-354. PubMed
  • Meng S, Lv J, Chanda PK, Owusu I, Chen K, Cooke JP. Reservoir of Fibroblasts Promotes Recovery From Limb Ischemia. Circulation 2020; 142:1647-1662. PubMed
  • Li Q, Liu KY, Liu Q, Wang G, Jiang W, Meng Q, Yi Y, Yang Y, Wang R, Zhu S, Li C, Wu L, Zhao D, Yan L, Zhang L, Kim JS, Zu X, Kozielski AJ, Qian W, Chang JC, Patnaik A, Chen K, Cao Q. Antihistamine Drug Ebastine Inhibits Cancer Growth by Targeting Polycomb Group Protein EZH2. Mol Cancer Ther 2020. PubMed
  • Xia B, Zhao D, Wang G, Zhang M, Lv J, Tomoiaga AS, Li Y, Wang X, Meng S, Cooke JP, Cao Q, Zhang L, Chen K. Machine learning uncovers cell identity regulator by histone code. Nat Commun 2020; 11:2696. PubMed
  • Wang G, Meng Q, Xia B, Zhang S, Lv J, Zhao D, Li Y, Wang X, Zhang L, Cooke JP, Cao Q, Chen K. TADsplimer reveals splits and mergers of topologically associating domains for epigenetic regulation of transcription. Genome Biol 2020; 21:84. PubMed
  • Zhu S, Zhao D, Li C, Li Q, Jiang W, Liu Q, Wang R, Fazli L, Li Y, Zhang L, Yi Y, Meng Q, Wang W, Wang G, Zhang M, Zu X, Zhao W, Deng T, Yu J, Dong X, Chen K, Cao Q. BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. Oncogene 2020; 39:17-29. PubMed
  • Zhao D, Zhang L, Zhang M, Xia B, Lv J, Gao X, Wang G, Meng Q, Yi Y, Zhu S, Tomoiaga AS, Lee MG, Cooke JP, Cao Q, Chen K. Broad genic repression domains signify enhanced silencing of oncogenes. Nat Commun 2020; 11:5560. PubMed
  • Zhu M, Deng G, Tan P, Xing C, Guan C, Jiang C, Zhang Y, Ning B, Li C, Yin B, Chen K, Zhao Y, Wang HY, Levine B, Nie G, Wang RF. Beclin 2 negatively regulates innate immune signaling and tumor development. J Clin Invest 2020; 130:5349-5369. PubMed
  • Chanda PK, Meng S, Lee J, Leung HE, Chen K, Cooke JP. Nuclear -Nitrosylation Defines an Optimal Zone for Inducing Pluripotency. Circulation 2019; 140:1081-1099. PubMed
  • Gu Q, Yang X, Lv J, Zhang J, Xia B, Kim JD, Wang R, Xiong F, Meng S, Clements TP, Tandon B, Wagner DS, Diaz MF, Wenzel PL, Miller YI, Traver D, Cooke JP, Li W, Zon LI, Chen K, Bai Y, Fang L. AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate. Science 2019; 363:1085-1088. PubMed
  • Long Z, Li Y, Gan Y, Zhao D, Wang G, Xie N, Lovnicki JM, Fazli L, Cao Q, Chen K, Dong X. Roles of the HOXA10 gene during castrate-resistant prostate cancer progression. Endocr. Relat. Cancer 2019; 26:279-292. PubMed
  • Liu Q, Wang G, Li Q, Jiang W, Kim JS, Wang R, Zhu S, Wang X, Yan L, Yi Y, Zhang L, Meng Q, Li C, Zhao D, Qiao Y, Li Y, Gursel DB, Chinnaiyan AM, Chen K, Cao Q. Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer. Int. J. Cancer 2019; 145:415-426. PubMed
  • Zhu S, Zhao D, Yan L, Jiang W, Kim JS, Gu B, Liu Q, Wang R, Xia B, Zhao JC, Song G, Mi W, Wang RF, Shi X, Lam HM, Dong X, Yu J, Chen K, Cao Q. BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1. Nat Commun 2018; 9:500. PubMed
  • Meng S, Gu Q, Yang X, Lv J, Owusu I, Matrone G, Chen K, Cooke JP, Fang L. TBX20 Regulates Angiogenesis Through the Prokineticin 2-Prokineticin Receptor 1 Pathway. Circulation 2018; 138:913-928. PubMed
  • Yu Y, Pham N, Xia B, Papusha A, Wang G, Yan Z, Peng G, Chen K, Ira G. Dna2 nuclease deficiency results in large and complex DNA insertions at chromosomal breaks. Nature 2018; 564:287-290. PubMed
  • Dhar SS, Zhao D, Lin T, Gu B, Pal K, Wu SJ, Alam H, Lv J, Yun K, Gopalakrishnan V, Flores ER, Northcott PA, Rajaram V, Li W, Shilatifard A, Sillitoe RV, Chen K, Lee MG. MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes. Mol Cell 2018; 70:825-841.e6. PubMed
  • Matrone G, Meng S, Gu Q, Lv J, Fang L, Chen K, Cooke JP. Lmo2 (LIM-Domain-Only 2) Modulates Sphk1 (Sphingosine Kinase) and Promotes Endothelial Cell Migration. Arterioscler Thromb Vasc Biol 2017; 37:1860-1868. PubMed
  • Wong WT, Matrone G, Tian X, Tomoiaga SA, Au KF, Meng S, Yamazoe S, Sieveking D, Chen K, Burns DM, Chen JK, Blau HM, Cooke JP. Discovery of novel determinants of endothelial lineage using chimeric heterokaryons. Elife 2017. PubMed
  • Lv J, Chen K. Broad H3K4me3 as A Novel Epigenetic Signature for Normal Development and Disease. Genomics Proteomics Bioinformatics 2016; 14:262-264. PubMed
  • Meng S, Matrone G, Lv J, Chen K, Wong WT, Cooke JP. LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration. J Am Heart Assoc 2016. PubMed
  • Lee SH, Chen TY, Dhar SS, Gu B, Chen K, Kim YZ, Li W, Lee MG. A feedback loop comprising PRMT7 and miR-24-2 interplays with Oct4, Nanog, Klf4 and c-Myc to regulate stemness. Nucleic Acids Res 2016; 44:10603-10618. PubMed
  • Li N, Li Y, Lv J, Zheng X, Wen H, Shen H, Zhu G, Chen TY, Dhar SS, Kan PY, Wang Z, Shiekhattar R, Shi X, Lan F, Chen K, Li W, Li H, Lee MG. ZMYND8 Reads the Dual Histone Mark H3K4me1-H3K14ac to Antagonize the Expression of Metastasis-Linked Genes. Mol Cell 2016; 63:470-84. PubMed
  • Dhar SS, Lee SH, Chen K, Zhu G, Oh W, Allton K, Gafni O, Kim YZ, Tomoiga AS, Barton MC, Hanna JH, Wang Z, Li W, Lee MG. An essential role for UTX in resolution and activation of bivalent promoters. Nucleic Acids Res 2016; 44:3659-74. PubMed
  • 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 2015; 47:1149-57. PubMed
  • Chen K, Xi Y, Pan X, Li Z, Kaestner K, Tyler J, Dent S, He X, Li W. DANPOS: dynamic analysis of nucleosome position and occupancy by sequencing. Genome Res 2013; 23:341-51. PubMed
  • 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 2011; 44:609-20. PubMed
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