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

Hehuang Xie

Associate Professor



Okyere B, Giridhar K, Hazy A, et al. Endothelial-Specific EphA4 Negatively Regulates Native Pial Collateral Formation and Re-Perfusion following Hindlimb Ischemia. PLoS One. 2016;11:e0159930.  http://www.ncbi.nlm.nih.gov/pubmed/27467069

Sharif J, Endo TA, Nakayama M, et al. Activation of Endogenous Retroviruses in Dnmt1(-/-) ESCs Involves Disruption of SETDB1-Mediated Repression by NP95 Binding to Hemimethylated DNA. Cell Stem Cell. 2016;19:81–94.  http://www.ncbi.nlm.nih.gov/pubmed/27151458

Sun MA, Sun Z, Wu X, et al. Mammalian Brain Development is Accompanied by a Dramatic Increase in Bipolar DNA Methylation. Sci Rep. 2016;6:32298.  http://www.ncbi.nlm.nih.gov/pubmed/27585862

Tran H, Wu X, Tithi S, Sun MA, Xie H, Zhang L. A Bayesian Assignment Method for Ambiguous Bisulfite Short Reads. PLoS One. 2016;11:e0151826.  http://www.ncbi.nlm.nih.gov/pubmed/27011215

von Meyenn F, Iurlaro M, Habibi E, et al. Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells. Mol Cell. 2016;62:983.  http://www.ncbi.nlm.nih.gov/pubmed/27315559


He J, Sun MA, Wang Z, Wang Q, Li Q, Xie H. Characterization and machine learning prediction of allele-specific DNA methylation. Genomics. 2015;106:331–339.  http://www.ncbi.nlm.nih.gov/pubmed/26407641

Porter J, Sun MA, Xie H, Zhang L. Investigating bisulfite short-read mapping failure with hairpin bisulfite sequencing data. BMC Genomics. 2015;16 Suppl 11:S2.  http://www.ncbi.nlm.nih.gov/pubmed/26576456

Sun MA, Velmurugan KR, Keimig D, Xie H. HBS-Tools for Hairpin Bisulfite Sequencing Data Processing and Analysis. Adv Bioinformatics. 2015;2015:760423.  http://www.ncbi.nlm.nih.gov/pubmed/26798339

Wu X, Sun MA, Zhu H, Xie H. Nonparametric Bayesian clustering to detect bipolar methylated genomic loci. BMC Bioinformatics. 2015;16:11.  http://www.ncbi.nlm.nih.gov/pubmed/25592753


Luo Y, Lu X, Xie H. Dynamic Alu methylation during normal development, aging, and tumorigenesis. Biomed Res Int. 2014;2014:784706.  http://www.ncbi.nlm.nih.gov/pubmed/25243180

McErlean P, Favoreto S Jr., Costa FF, et al. Human rhinovirus infection causes different DNA methylation changes in nasal epithelial cells from healthy and asthmatic subjects. BMC Med Genomics. 2014;7:37.  http://www.ncbi.nlm.nih.gov/pubmed/24947756

Shao X, Zhang C, Sun MA, Lu X, Xie H. Deciphering the heterogeneity in DNA methylation patterns during stem cell differentiation and reprogramming. BMC Genomics. 2014;15:978.  http://www.ncbi.nlm.nih.gov/pubmed/25404570

Tran H, Porter J, Sun MA, Xie H, Zhang L. Objective and comprehensive evaluation of bisulfite short read mapping tools. Adv Bioinformatics. 2014;2014:472045.  http://www.ncbi.nlm.nih.gov/pubmed/24839440

Zhao L, Sun MA, Li Z, et al. The dynamics of DNA methylation fidelity during mouse embryonic stem cell self-renewal and differentiation. Genome Res. 2014;24:1296–1307.  http://www.ncbi.nlm.nih.gov/pubmed/24835587


He J, Sun X, Shao X, Liang L, Xie H. DMEAS: DNA methylation entropy analysis software. Bioinformatics. 2013.  http://www.ncbi.nlm.nih.gov/pubmed/23749987


Hoxha E, Lambers E, Xie H, et al. Histone deacetylase 1 deficiency impairs differentiation and electrophysiological properties of cardiomyocytes derived from induced pluripotent cells. Stem Cells. 2012;30:2412–2422.  http://www.ncbi.nlm.nih.gov/pubmed/22915496

Sittig LJ, Herzing LB, Xie H, Batra KK, Shukla PK, Redei EE. Excess folate during adolescence suppresses thyroid function with permanent deficits in motivation and spatial memory. Genes Brain Behav. 2012;11:193–200.  http://www.ncbi.nlm.nih.gov/pubmed/22050771

Wang D, Liu X, Zhou Y, et al. Individual variation and longitudinal pattern of genome-wide DNA methylation from birth to the first two years of life. Epigenetics. 2012;7:594–605.  http://www.ncbi.nlm.nih.gov/pubmed/22522910

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 Rheum. 2012;64:3478–3485.  http://www.ncbi.nlm.nih.gov/pubmed/22674142

Zhang X, Wallace AD, Du P, et al. DNA methylation alterations in response to pesticide exposure in vitro. Environ Mol Mutagen. 2012;53:542–549.  http://www.ncbi.nlm.nih.gov/pubmed/22847954

Zhang X, Wallace AD, Du P, et al. Genome-wide study of DNA methylation alterations in response to diazinon exposure in vitro. Environ Toxicol Pharmacol. 2012;34:959–968.  http://www.ncbi.nlm.nih.gov/pubmed/22964155


de Andrade A, Wang M, Bonaldo MF, Xie H, Soares MB. Genetic and epigenetic variations contributed by Alu retrotransposition. BMC Genomics. 2011;12:617.  http://www.ncbi.nlm.nih.gov/pubmed/22185517

Wang M, Xie H, Stellpflug W, et al. BTECH: a platform to integrate genomic, transcriptomic and epigenomic alterations in brain tumors. Neuroinformatics. 2011;9:59–67.  http://www.ncbi.nlm.nih.gov/pubmed/21210251

Xie H, Wang M, de Andrade A, et al. Genome-wide quantitative assessment of variation in DNA methylation patterns. Nucleic Acids Res. 2011;39:4099–4108.  http://www.ncbi.nlm.nih.gov/pubmed/21278160


Hamm CA, Stevens JW, Xie H, et al. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors. BMC Cancer. 2010;10:471.  http://www.ncbi.nlm.nih.gov/pubmed/20809981

Xie H, Wang M, Bonaldo Mde F, et al. Epigenomic analysis of Alu repeats in human ependymomas. Proc Natl Acad Sci U S A. 2010;107:6952–6957.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20351280


Hamm CA, Xie H, Costa FF, et al. Global demethylation of rat chondrosarcoma cells after treatment with 5-aza-2'-deoxycytidine results in increased tumorigenicity. PLoS One. 2009;4:e8340.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20019818

Xie H, Wang M, Bischof J, Bonaldo Mde F, Soares MB. SNP-based prediction of the human germ cell methylation landscape. Genomics. 2009;93:434–440.  http://www.ncbi.nlm.nih.gov/pubmed/19442638

Xie H, Wang M, Bonaldo Mde F, et al. High-throughput sequence-based epigenomic analysis of Alu repeats in human cerebellum. Nucleic Acids Res. 2009;37:4331–4340.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19458156

Xie H, Wang M, Tange Y, Bonaldo Mde F, Soares MB. A primer design algorithm for global analysis of CpG methylation. International Joint Conference on System Biology, Bioinformatics and Intelligent Computing (IJCBS). . 2009:126–130.  

Yadav AK, Renfrow JJ, Scholtens DM, et al. Monosomy of chromosome 10 associated with dysregulation of epidermal growth factor signaling in glioblastomas. Jama. 2009;302:276–289.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19602687


Dvorak CM, Hardstedt M, Xie H, et al. Transcriptional profiling of stress response in cultured porcine islets. Biochem Biophys Res Commun. 2007;357:118–125.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17407763

Wang M, Xie H, Mi S, Chen J. Recent patents on the identification and clinical application of microRNAs and target genes. Recent Pat DNA Gene Seq. 2007;1:116–124.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19075924


Ma S, Kosorok MR, Huang J, Xie H, Manzella L, Soares MB. Robust semiparametric microarray normalization and significance analysis. Biometrics. 2006;62:555–561.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16918920


Wang D, Huang J, Xie H, Manzella L, Soares MB. A robust two-way semi-linear model for normalization of cDNA microarray data. BMC Bioinformatics. 2005;6:14.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15663789


Xie H, Chen S, Wang J, Ge X. Cloning and sequencing of the variable gene fragments of LC-1 McAb. Journal of cellular and molecular immunology. 1998;14:89–92.  


Xie H, Ge X. Recent advance in antibody engineering with functional genomic fragment transplant. Annual report of shanghai immunology society. 1997:1–3.  


Lu Y, Xie H, Ge X. Inhibition of tumor formation in vivo via increasing IL-2 level in microenvironment. Shanghai Journal of Immunology. 1996;5.