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Xiaole Shirley Liu, PhD


Researcher

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Researcher

  • Director, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute
  • Professor of Biostatistics and Computational Biology, Harvard T.H. Chan School of Public Health

Contact Information

  • Office Phone Number(617) 632-2472
  • Fax(617) 632-2444

Bio

Dr. X. Shirley Liu graduated summa cum laude from Smith College double majoring in Biochemistry and Computer Science in 1997, and received PhD in Biomedical Informatics and PhD minor in Computer Science from Stanford University in 2002. She is now Professor at the Department of Biostatistics and Computational Biology at the Dana-Farber Cancer Institute and Harvard School of Public Health. She is the Director of the Center of Functional Cancer Epigenetics at Dana-Farber Cancer Institute, and an associate member of the Broad Institute. Her research focuses on computational cancer epigenetics, and developing algorithms for big cancer data integration and mining. 

Recent Awards:

  • Claudia Adams Barr Award for Innovative Basic Cancer Research 2005
  • Department of Defense Prostate Cancer Research Program New Investigator Award 2006
  • Sloan Research Fellowship 2008

Research

Computational Cancer Epigenetics

Through genome-wide transcription factor binding, chromatin dynamics, and gene expression profiles, we try to model the specificity and function of transcription factors, chromatin regulators and lncRNAs in tumor development, progression, drug response and resistance. 

Cross-Site Concordance Evaluation of Tumor DNA and RNA Sequencing Platforms for the CIMAC-CIDC Network. Clin Cancer Res. 2021 Sep 15; 27(18):5049-5061.
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Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer. Cancer Res. 2021 01 01; 81(1):158-173.
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Inhibition of MAN2A1 Enhances the Immune Response to Anti-PD-L1 in Human Tumors. Clin Cancer Res. 2020 11 15; 26(22):5990-6002.
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Evaluation of immune repertoire inference methods from RNA-seq data. Nat Biotechnol. 2018 11 09; 36(11):1034.
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Topological analysis reveals a PD-L1-associated microenvironmental niche for Reed-Sternberg cells in Hodgkin lymphoma. Blood. 2017 11 30; 130(22):2420-2430.
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Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proc Natl Acad Sci U S A. 2017 06 27; 114(26):E5207-E5215.
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Transcriptional landscape of the human cell cycle. Proc Natl Acad Sci U S A. 2017 03 28; 114(13):3473-3478.
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Applications of Immunogenomics to Cancer. Cell. 2017 02 09; 168(4):600-612.
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Inactivation of the PBRM1 tumor suppressor gene amplifies the HIF-response in VHL-/- clear cell renal carcinoma. Proc Natl Acad Sci U S A. 2017 01 31; 114(5):1027-1032.
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Genome-scale deletion screening of human long non-coding RNAs using a paired-guide RNA CRISPR-Cas9 library. Nat Biotechnol. 2016 Dec; 34(12):1279-1286.
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Cistrome Data Browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse. Nucleic Acids Res. 2017 01 04; 45(D1):D658-D662.
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ChiLin: a comprehensive ChIP-seq and DNase-seq quality control and analysis pipeline. BMC Bioinformatics. 2016 Oct 03; 17(1):404.
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Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol. 2016 08 22; 17(1):174.
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Modeling cis-regulation with a compendium of genome-wide histone H3K27ac profiles. Genome Res. 2016 10; 26(10):1417-1429.
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NF-E2, FLI1 and RUNX1 collaborate at areas of dynamic chromatin to activate transcription in mature mouse megakaryocytes. Sci Rep. 2016 07 26; 6:30255.
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CRISPR-DO for genome-wide CRISPR design and optimization. Bioinformatics. 2016 11 01; 32(21):3336-3338.
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Landscape of tumor-infiltrating T cell repertoire of human cancers. Nat Genet. 2016 07; 48(7):725-32.
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Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles. Nat Med. 2016 06; 22(6):685-91.
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High-dimensional genomic data bias correction and data integration using MANCIE. Nat Commun. 2016 Apr 13; 7:11305.
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Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer. Nat Commun. 2016 Mar 15; 7:10982.
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An Integrative Pharmacogenomic Approach Identifies Two-drug Combination Therapies for Personalized Cancer Medicine. Sci Rep. 2016 Feb 26; 6:22120.
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Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature. 2016 Jan 21; 529(7586):413-417.
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Quality control, modeling, and visualization of CRISPR screens with MAGeCK-VISPR. Genome Biol. 2015 Dec 16; 16:281.
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Integrative Analysis Reveals the Transcriptional Collaboration between EZH2 and E2F1 in the Regulation of Cancer-Related Gene Expression. Mol Cancer Res. 2016 Feb; 14(2):163-172.
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Network analysis of gene essentiality in functional genomics experiments. Genome Biol. 2015 Oct 30; 16:239.
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EglN2 associates with the NRF1-PGC1a complex and controls mitochondrial function in breast cancer. EMBO J. 2015 Dec 02; 34(23):2953-70.
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SETDB1 modulates PRC2 activity at developmental genes independently of H3K9 trimethylation in mouse ES cells. Genome Res. 2015 Sep; 25(9):1325-35.
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Sequence determinants of improved CRISPR sgRNA design. Genome Res. 2015 Aug; 25(8):1147-57.
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Inference of transcriptional regulation in cancers. Proc Natl Acad Sci U S A. 2015 Jun 23; 112(25):7731-6.
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The role of Notch receptors in transcriptional regulation. J Cell Physiol. 2015 May; 230(5):982-8.
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Lysine-specific demethylase 1 has dual functions as a major regulator of androgen receptor transcriptional activity. Cell Rep. 2014 Dec 11; 9(5):1618-1627.
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Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T cell leukemia. Proc Natl Acad Sci U S A. 2014 Nov 18; 111(46):E4946-53.
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Identifying and mitigating bias in next-generation sequencing methods for chromatin biology. Nat Rev Genet. 2014 Nov; 15(11):709-21.
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Comparative analysis of metazoan chromatin organization. Nature. 2014 Aug 28; 512(7515):449-52.
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Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells. Genes Dev. 2014 Aug 15; 28(16):1827-39.
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Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma. Cancer Discov. 2014 Oct; 4(10):1154-67.
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MethylPurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes. Genome Biol. 2014 Aug 07; 15(8):419.
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JARID1B is a luminal lineage-driving oncogene in breast cancer. Cancer Cell. 2014 Jun 16; 25(6):762-77.
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Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation. Proc Natl Acad Sci U S A. 2014 May 20; 111(20):7319-24.
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XBP1 promotes triple-negative breast cancer by controlling the HIF1a pathway. Nature. 2014 Apr 03; 508(7494):103-107.
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Targeting epigenetic regulators for cancer therapy. Ann N Y Acad Sci. 2014 Feb; 1309:30-6.
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MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens. Genome Biol. 2014; 15(12):554.
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NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers. Proc Natl Acad Sci U S A. 2014 Jan 14; 111(2):705-10.
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An integrative analysis reveals functional targets of GATA6 transcriptional regulation in gastric cancer. Oncogene. 2014 Dec 04; 33(49):5637-48.
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Refined DNase-seq protocol and data analysis reveals intrinsic bias in transcription factor footprint identification. Nat Methods. 2014 Jan; 11(1):73-78.
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Canonical nucleosome organization at promoters forms during genome activation. Genome Res. 2014 Feb; 24(2):260-6.
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Target analysis by integration of transcriptome and ChIP-seq data with BETA. Nat Protoc. 2013 Dec; 8(12):2502-15.
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A systematic approach identifies FOXA1 as a key factor in the loss of epithelial traits during the epithelial-to-mesenchymal transition in lung cancer. BMC Genomics. 2013 Oct 04; 14:680.
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Protein kinase C a is a central signaling node and therapeutic target for breast cancer stem cells. Cancer Cell. 2013 Sep 09; 24(3):347-64.
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Molecular profiling of human mammary gland links breast cancer risk to a p27(+) cell population with progenitor characteristics. Cell Stem Cell. 2013 Jul 03; 13(1):117-30.
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Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer. Nat Struct Mol Biol. 2013 Jul; 20(7):908-13.
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Amplitude modulation of androgen signaling by c-MYC. Genes Dev. 2013 Apr 01; 27(7):734-48.
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CistromeFinder for ChIP-seq and DNase-seq data reuse. Bioinformatics. 2013 May 15; 29(10):1352-4.
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ERG induces androgen receptor-mediated regulation of SOX9 in prostate cancer. J Clin Invest. 2013 Mar; 123(3):1109-22.
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EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent. Science. 2012 Dec 14; 338(6113):1465-9.
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Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding. Mol Cell Biol. 2013 Jan; 33(2):281-92.
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Estrogen receptor prevents p53-dependent apoptosis in breast cancer. Proc Natl Acad Sci U S A. 2012 Oct 30; 109(44):18060-5.
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Identifying ChIP-seq enrichment using MACS. Nat Protoc. 2012 Sep; 7(9):1728-40.
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Minireview: applications of next-generation sequencing on studies of nuclear receptor regulation and function. Mol Endocrinol. 2012 Oct; 26(10):1651-9.
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The histone H3 Lys 27 demethylase JMJD3 regulates gene expression by impacting transcriptional elongation. Genes Dev. 2012 Jun 15; 26(12):1364-75.
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Differential DNase I hypersensitivity reveals factor-dependent chromatin dynamics. Genome Res. 2012 Jun; 22(6):1015-25.
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Computational inference of mRNA stability from histone modification and transcriptome profiles. Nucleic Acids Res. 2012 Aug; 40(14):6414-23.
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Androgen receptor gene expression in prostate cancer is directly suppressed by the androgen receptor through recruitment of lysine-specific demethylase 1. Cancer Cell. 2011 Oct 18; 20(4):457-71.
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A comprehensive view of nuclear receptor cancer cistromes. Cancer Res. 2011 Nov 15; 71(22):6940-7.
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Cistrome: an integrative platform for transcriptional regulation studies. Genome Biol. 2011 Aug 22; 12(8):R83.
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Targeting androgen receptor in estrogen receptor-negative breast cancer. Cancer Cell. 2011 Jul 12; 20(1):119-31.
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The JAK2/STAT3 signaling pathway is required for growth of CD44?CD24? stem cell-like breast cancer cells in human tumors. J Clin Invest. 2011 Jul; 121(7):2723-35.
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BINOCh: binding inference from nucleosome occupancy changes. Bioinformatics. 2011 Jul 01; 27(13):1867-8.
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Epigenetic regulation of cell type-specific expression patterns in the human mammary epithelium. PLoS Genet. 2011 Apr; 7(4):e1001369.
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Essential and redundant functions of caudal family proteins in activating adult intestinal genes. Mol Cell Biol. 2011 May; 31(10):2026-39.
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MM-ChIP enables integrative analysis of cross-platform and between-laboratory ChIP-chip or ChIP-seq data. Genome Biol. 2011; 12(2):R11.
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Altered antisense-to-sense transcript ratios in breast cancer. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):2820-4.
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Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2. Dev Cell. 2010 Nov 16; 19(5):713-26.
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Gene expression profiling of human breast tissue samples using SAGE-Seq. Genome Res. 2010 Dec; 20(12):1730-9.
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CaSNP: a database for interrogating copy number alterations of cancer genome from SNP array data. Nucleic Acids Res. 2011 Jan; 39(Database issue):D968-74.
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Growth factor stimulation induces a distinct ER(alpha) cistrome underlying breast cancer endocrine resistance. Genes Dev. 2010 Oct 01; 24(19):2219-27.
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TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions. Proc Natl Acad Sci U S A. 2010 Aug 24; 107(34):15157-62.
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8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC. Proc Natl Acad Sci U S A. 2010 May 25; 107(21):9742-6.
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Chromatin signature of embryonic pluripotency is established during genome activation. Nature. 2010 Apr 08; 464(7290):922-6.
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Nucleosome dynamics define transcriptional enhancers. Nat Genet. 2010 Apr; 42(4):343-7.
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MYC regulation of a "poor-prognosis" metastatic cancer cell state. Proc Natl Acad Sci U S A. 2010 Feb 23; 107(8):3698-703.
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Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen. Nature. 2010 Jan 21; 463(7279):374-8.
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Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery. Genome Res. 2009 Nov; 19(11):1963-73.
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Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell. 2009 Jul 23; 138(2):245-56.
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Coactivator function defines the active estrogen receptor alpha cistrome. Mol Cell Biol. 2009 Jun; 29(12):3413-23.
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Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis. Proc Natl Acad Sci U S A. 2009 Mar 17; 106(11):4260-5.
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Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers. Genome Res. 2009 Mar; 19(3):372-80.
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ChIP-Chip: algorithms for calling binding sites. Methods Mol Biol. 2009; 556:165-75.
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Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008; 9(9):R137.
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Nkx3-1 and LEF-1 function as transcriptional inhibitors of estrogen receptor activity. Cancer Res. 2008 Sep 15; 68(18):7380-5.
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Target gene-specific regulation of androgen receptor activity by p42/p44 mitogen-activated protein kinase. Mol Endocrinol. 2008 Nov; 22(11):2420-32.
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FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell. 2008 Mar 21; 132(6):958-70.
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Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets. Genome Res. 2008 Mar; 18(3):393-403.
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xMAN: extreme MApping of OligoNucleotides. BMC Genomics. 2008; 9 Suppl 1:S20.
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Getting started in tiling microarray analysis. PLoS Comput Biol. 2007 Oct; 3(10):1842-4.
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A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth. Mol Cell. 2007 Aug 03; 27(3):380-92.
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Genome-wide analysis of estrogen receptor binding sites. Nat Genet. 2006 Nov; 38(11):1289-97.
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Model-based analysis of tiling-arrays for ChIP-chip. Proc Natl Acad Sci U S A. 2006 Aug 15; 103(33):12457-62.
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Genomic localization of RNA binding proteins reveals links between pre-mRNA processing and transcription. Genome Res. 2006 Jul; 16(7):912-21.
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Genomic mapping of RNA polymerase II reveals sites of co-transcriptional regulation in human cells. Genome Biol. 2005; 6(8):R64.
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Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell. 2005 Jul 15; 122(1):33-43.
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A hidden Markov model for analyzing ChIP-chip experiments on genome tiling arrays and its application to p53 binding sequences. Bioinformatics. 2005 Jun; 21 Suppl 1:i274-82.
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Defining a centromere-like element in Bacillus subtilis by Identifying the binding sites for the chromosome-anchoring protein RacA. Mol Cell. 2005 Mar 18; 17(6):773-82.
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