We study epigenetic regulatory networks associated with cell specification and disease development. Toward this goal, we emphasize the development of novel high-throughput experimental approaches and the implementation of computational tools for -omics data analysis. Over the last decade, we have investigated the epigenetic programming mechanisms with stem cells and for tissues of the brain and blood.



Principal Investigators

Xie Hehuang

Hehuang Xie

Associate Professor




  • Tran H, Wu X, Tithi S, Sun M-A, Xie H, Zhang L. A Bayesian Assignment Method for Ambiguous Bisulfite Short Reads. PLOS ONE. 2016;11(3). https://doi.org/10.1371/journal.pone.0151826.
  • Sharif J, Endo TA, Nakayama M, Karimi MM, Shimada M, Katsuyama K, Goyal P, Brind’Amour J, Sun M-A, Sun Z, Ishikura T, Mizutani-Koseki Y, Ohara O, Shinkai Y, Nakanishi M, Xie H, Lorincz MC, Koseki H. Activation of Endogenous Retroviruses in Dnmt1 −/− ESCs Involves Disruption of SETDB1-Mediated Repression by NP95 Binding to Hemimethylated DNA. Cell Stem Cell. 2016;19(1):81–94. https://doi.org/10.1016/j.stem.2016.03.013.
  • Okyere B, Giridhar K, Hazy A, Chen M, Keimig D, Bielitz RC, Xie H, He J-Q, Huckle WR, Theus MH. Endothelial-Specific EphA4 Negatively Regulates Native Pial Collateral Formation and Re-Perfusion following Hindlimb Ischemia. PLOS ONE. 2016;11(7). https://doi.org/10.1371/journal.pone.0159930.
  • von Meyenn F, Iurlaro M, Habibi E, Liu NQ, Salehzadeh-Yazdi A, Santos F, Petrini E, Milagre I, Yu M, Xie Z, Kroeze LI, Nesterova TB, Jansen JH, Xie H, He C, Reik W, Stunnenberg HG. Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells. Molecular Cell. 2016;62(6):848–861. https://doi.org/10.1016/j.molcel.2016.04.025.
  • Sun M-A, Sun Z, Wu X, Rajaram V, Keimig D, Lim J, Zhu H, Xie H. Mammalian Brain Development is Accompanied by a Dramatic Increase in Bipolar DNA Methylation. SCIENTIFIC REPORTS. 2016;6. https://doi.org/10.1038/srep32298.


  • Porter J, Sun M-A, Xie H, Zhang L. Investigating bisulfite short-read mapping failure with hairpin bisulfite sequencing data. Presented at the 4th IEEE International Conference on Computational Advances in Bio and Medical Sciences (ICCABS), Miami Beach, FL; 2015. https://doi.org/10.1186/1471-2164-16-S11-S2.
  • He J, Sun M-A, Wang Z, Wang Q, Li Q, Xie H. Characterization and machine learning prediction of allele-specific DNA methylation. GENOMICS. 2015;106(6):331–339. https://doi.org/10.1016/j.ygeno.2015.09.007.
  • Wu X, Sun M-A, Zhu H, Xie H. Nonparametric Bayesian clustering to detect bipolar methylated genomic loci. BMC BIOINFORMATICS. 2015;16. https://doi.org/10.1186/s12859-014-0439-2.
  • Sun M-A, Velmurugan KR, Keimig D, Xie H. HBS-Tools for Hairpin Bisulfite Sequencing Data Processing and Analysis. Advances in Bioinformatics. 2015;2015:1–4. https://doi.org/10.1155/2015/760423.


  • Zhao L, Sun M-A, Li Z, Bai X, Yu M, Wang M, Liang L, Shao X, Arnovitz S, Wang Q, He C, Lu X, Chen J, Xie H. The dynamics of DNA methylation fidelity during mouse embryonic stem cell self-renewal and differentiation. GENOME RESEARCH. 2014;24(8):1296–1307. https://doi.org/10.1101/gr.163147.113.
  • Shao X, Zhang C, Sun M-A, Lu X, Xie H. Deciphering the heterogeneity in DNA methylation patterns during stem cell differentiation and reprogramming. BMC Genomics. 2014;15(1):978–978. https://doi.org/10.1186/1471-2164-15-978.
  • Luo Y, Lu X, Xie H. Dynamic Alu methylation during normal development, aging, and tumorigenesis. BioMed research international. 2014;2014:784706. https://doi.org/10.1155/2014/784706.
  • McErlean P, Favoreto S, Costa FF, Shen J, Quraishi J, Biyasheva A, Cooper JJ, Scholtens DM, Vanin EF, Bonaldo MF de, Xie H, Soares MB, Avila PC. Human rhinovirus infection causes different DNA methylation changes in nasal epithelial cells from healthy and asthmatic subjects. BMC Medical Genomics. 2014;7(1). https://doi.org/10.1186/1755-8794-7-37.
  • Tran H, Porter J, Sun M-A, Sun M-A, Xie H, Zhang L. Objective and comprehensive evaluation of bisulfite short read mapping tools. Advances in bioinformatics. 2014;2014:472045. https://doi.org/10.1155/2014/472045.



  • Hoxha E, Lambers E, Xie H, De Andrade A, Krishnamurthy P, Wasserstrom JA, Ramirez V, Thal M, Verma SK, Soares MB, Kishore R. Histone Deacetylase 1 Deficiency Impairs Differentiation and Electrophysiological Properties of Cardiomyocytes Derived from Induced Pluripotent Cells. STEM CELLS. 2012;30(11):2412–2422. https://doi.org/10.1002/stem.1209.
  • Wang M, Xie H, Shrestha S, Sredni S, Morgan GA, Pachman LM. Methylation alterations of WT1 and homeobox genes in inflamed muscle biopsy samples from patients with untreated juvenile dermatomyositis suggest self-renewal capacity. Arthritis & Rheumatism. 2012;64(10):3478–3485. https://doi.org/10.1002/art.34573.
  • Zhang X, Wallace AD, Du P, Kibbe WA, Jafari N, Xie H, Lin S, Baccarelli A, Soares MB, Hou L. DNA methylation alterations in response to pesticide exposure in vitro. Environmental and Molecular Mutagenesis. 2012;53(7):542–549. https://doi.org/10.1002/em.21718.