Xiaole (Shirley) Liu

Professor
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Liu Lab Website

 

Research

My research focuses on computational models of transcription and epigenetic regulation by integrating data from genome-wide ChIP-chip / ChIP-Seq, nucleosome occupancy and histone modifications, gene expression microarray / RNA-sequencing, genomic sequence and conservation. To this end, we focus on the following areas of studies:

 

First, we developed a number of algorithms widely used and cited for transcription factor motif discovery from promoters of gene expression clusters (BioProspector, Liu et al, PSB2001, cited by 419), ChIP-chip (MDscan, Liu et al, Nature Biotech 2002), gene expression perturbation experiments (Motif Regressor, Conlon et al, PNAS 2003), and using comparative genomics (CompareProspector, Liu et al, Genome Res 2004). These tools are also available as a web server (Liu et al, NAR 2004). We are currently developing a tool to find sequence motifs from ChIP-seq and nucleosome sequencing.

 

Second, we design computational algorithm for ChIP-chip and ChIP-seq data analysis. We published the 3rd ever ChIP-chip paper and the first to integrate ChIP-chip with transcription factor motif discovery (Lieb et al, Nat Genet 2001). We also published the 2nd ever genome-wide ChIP-chip study in human, which is the first to systematically study genome-wide enhancer binding function (Carroll et al, Nat Genet 2006). We developed widely used ChIP-chip (MAT, Johnson et al, PNAS 2006; MA2C, Song et al, Genome Biol 2007) and ChIP-seq analysis algorithms (MACS, Zhang et al, Genome Biol 2008), and downstream analysis pipeline (CEAS, Ji et al, NAR 2006). I also coordinated a study in the NIH ENCODE consortium (involving all the ChIP-chip pioneers) to systematically evaluate the effect of DNA amplification method, tiling array platforms and analysis algorithms on ChIP-chip results (Johnson et al, Genome Res 2008). I am currently organizing a similar study in the NIH mod/ENCODE consortiums comparing different algorithms and high throughput sequencing platforms.

 

My third area of interest is on epigenetic regulation. We published the 1st high throughput nucleosome positioning study in human (Oszolak et al, Nat Biotech 2007). We also designed algorithms to identify positioned nucleosomes from nucleosome-resolution histone modification ChIP-seq data (Zhang et al, BMC Genomics, 2008) and use nucleosome positioning and histone modification to predict miRNA promoters (Oszolak et al, Gene Dev, in press). I am currently working on finding differential nucleosome positions between different conditions, and comparing the intrinsic nucleosome positioning with in vivo positioning. I am also a co-PI for the worm chromatin group at the NIH modENCODE consortium.

 

Finally, we integrate the tools and data for ChIP-chip/seq to understandings to study trasncription and epigenetic regulatory network in cancer, aging, diabetes and stem cell differentiation. Through genome-wide ChIP-chip analysis, we discovered important transcriptional and epigenetic regulation mechanisms of estrogen receptor (ER) in breast cancer (Carroll et al, Cell 2005; Carroll et al, Nat Genet 2006), androgen receptor (AR) in prostate cancer (Wang et al, Mol Cell 2006), ER and AR’s collaborating transcription factor and chromatin remodeler FoxA1 in breast and prostate cancers (Lupien et al, Cell 2008), and peroxisome proliferator-activated receptor gamma (PPAR?) in adipose tissues (Lefterova et al, Gene Dev 2008). We are currently directing bench and computational experiments to identify the epigenetic signature and infer the transcription regulatory network of hormone independent breast and prostate cancers.

 

Biography

X. Shirley Liu graduated summa cum laude from Smith College and received her PhD from Stanford University. Her research focuses on computational models of transcription and epigenetic regulation by integrating data from genome-wide ChIP-chip / Seq, gene expression microarray / sequencing, genomic sequence and nucleosome occupancy. She has developed a number of widely used transcription factor motif finding and ChIP-chip/Seq analysis algorithms, and has collaborated widely with pioneers in ChIP technology, transcription and epigenetic regulation.

 

Recent Publications

Gao W, Li W, Xiao T, Liu XS, Kaelin WG Jr. 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 Jan 31;114(5):1027-1032.

 

Zhu S, Li W, Liu J, Chen CH, Liao Q, Xu P, Xu H, Xiao T, Cao Z, Peng J, Yuan
P, Brown M, Liu XS, Wei W. 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.

 

Ma J, Köster J, Qin Q, Hu S, Li W, Chen C, Cao Q, Wang J, Mei S, Liu Q, Xu H,
Liu XS. CRISPR-DO for genome-wide CRISPR design and optimization. Bioinformatics. 2016 Nov 1;32(21):3336-3338.

 

Zhang J, Wang C, Chen X, Takada M, Fan C, Zheng X, Wen H, Liu Y, Wang C,
Pestell RG, Aird KM, Kaelin WG Jr, Liu XS, Zhang Q. EglN2 associates with the
NRF1-PGC1α complex and controls mitochondrial function in breast cancer. EMBO J. 2015 Dec 2;34(23):2953-70.

 

Fei Q, Yang X, Jiang H, Wang Q, Yu Y, Yu Y, Yi W, Zhou S, Chen T, Lu C, Atadja
P, Liu XS, Li E, Zhang Y, Shou J. SETDB1 modulates PRC2 activity at developmental genes independently of H3K9 trimethylation in mouse ES cells. Genome Res. 2015 Sep;25(9):1325-35.

 

Jiang P, Freedman ML, Liu JS, Liu XS. Inference of transcriptional regulation
in cancers. Proc Natl Acad Sci U S A. 2015 Jun 23;112(25):7731-6.

 

Yashiro-Ohtani Y, Wang H, Zang C, Arnett KL, Bailis W, Ho Y, Knoechel B,
Lanauze C, Louis L, Forsyth KS, Chen S, Chung Y, Schug J, Blobel GA, Liebhaber
SA, Bernstein BE, Blacklow SC, Liu XS, Aster JC, Pear WS. 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.

 

Ho JW, Jung YL, Liu T, Alver BH, Lee S, Ikegami K, Sohn KA, Minoda A,
Tolstorukov MY, Appert A, Parker SC, Gu T, Kundaje A, Riddle NC, Bishop E,
Egelhofer TA, Hu SS, Alekseyenko AA, Rechtsteiner A, Asker D, Belsky JA, Bowman SK, Chen QB, Chen RA, Day DS, Dong Y, Dose AC, Duan X, Epstein CB, Ercan S, Feingold EA, Ferrari F, Garrigues JM, Gehlenborg N, Good PJ, Haseley P, He D, Herrmann M, Hoffman MM, Jeffers TE, Kharchenko PV, Kolasinska-Zwierz P, Kotwaliwale CV, Kumar N, Langley SA, Larschan EN, Latorre I, Libbrecht MW, Lin X, Park R, Pazin MJ, Pham HN, Plachetka A, Qin B, Schwartz YB, Shoresh N, Stempor P, Vielle A, Wang C, Whittle CM, Xue H, Kingston RE, Kim JH, Bernstein BE, Dernburg AF, Pirrotta V, Kuroda MI, Noble WS, Tullius TD, Kellis M, MacAlpine DM, Strome S, Elgin SC, Liu XS, Lieb JD, Ahringer J, Karpen GH, Park PJ. Comparative analysis of metazoan chromatin organization. Nature. 2014 Aug 28;512(7515):449-52.

 

Zheng X, Zhao Q, Wu HJ, Li W, Wang H, Meyer CA, Qin QA, Xu H, Zang C, Jiang P, Li F, Hou Y, He J, Wang J, Wang J, Zhang P, Zhang Y, Liu XS. MethylPurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes. Genome Biol. 2014 Aug 7;15(8):419.

 

Hsieh CL, Fei T, Chen Y, Li T, Gao Y, Wang X, Sun T, Sweeney CJ, Lee GS, Chen
S, Balk SP, Liu XS, Brown M, Kantoff PW. 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.

 

Related Links

Liu Lab at DFCI