RNA-centric gene regulation

We study mechanisms of gene regulation, focusing on mRNAs in mammalian systems. Our current efforts include: 1) functions and mechanisms of mRNA structures; 2) molecular and cellular consequences of translation in noncoding regions of mRNAs.

1) A widespread role of RNA structures in controlling mRNA 3' end processing and stability.
See Wu & Bartel, 2017 Cell
2) A model of how noncoding transcription shapes genome evolution.
See Wu & Sharp, 2013 Cell
3) A mechanism of how RNA processing signals suppress pervasive transcription and control promoter directionality.
See Almada & Wu et al. 2013 Nature

CRISPR technology & therapy

We characterize CRISPR/Cas technologies using genomic assays and develop CRISPR/Cas-based methods for interrogating and manipulating the genome, epigenome, transcriptome, and translatome. We are also exploring the therapeutic potential of CRISPR/Cas13-based mRNA targeting therapeutics for human diseases.

1) The first genome-wide analysis of Cas9 targeting in mammalian cells.
See Wu et al. 2014 Nature Biotechnology
2) CRISPR/Cas-based technologies for editing the genome, epigenome, and transcriptome.
See Cong et al. 2013 Science, Ran et al. 2015 Nature, Liu et al. 2016 Cell, Liu et al. 2018 Cell, Zhang et al. 2018 Cell

Computational biology

We develop new quantitative models, machine learning approaches, and computational tools when necessary to analyze data generated in our lab. We also analyze publicly available data set to uncover principles of gene regulation and evolution.

1) A web server called kpLogo for position-specific short motif analysis.
See Wu & Bartel 2017 Nucleic Acids Research
2) Network-based global prediction of human disease genes.
See Wu et al. 2008 Molecular Systems Biology
3) Network alignment-based identification of disease families and associated gene modules.
See Wu et al. 2009 Bioinformatics


Google Scholar Citations

co-first author*, co-corresponding author^


Cheng Zhang, Silvana Konermann, Nicholas J. Brideau, Peter Lotfy, Xuebing Wu, Scott J. Novick, Timothy Strutzenberg, Patrick R. Griffin, Patrick D. Hsu, Dmitry Lyumkis
Structural basis for the RNA-guided ribonuclease activity of CRISPR-Cas13d.
Cell, 2018, 175:212-223

Josh Tycko, Luis A Barrera, Nicholas Huston, Ari E Friedland, Xuebing Wu, Jonathan S Gootenberg, Omar O Abudayyeh, Vic E Myer, Christopher J Wilson, Patrick D Hsu
Pairwise library screen systematically interrogates Staphylococcus aureus Cas9 specificity in human cells.
Nature Communications, 2018, 9:2962

Wei Jiang*, Yuehua Wei*, Yong Long*, Arthur Owen, Bingying Wang, Xuebing Wu, Shuo Luo, Yongjun Dang, Dengke K. Ma
A genetic program mediates cold-warming response and promotes stress-induced phenoptosis in C. elegans
eLife, 2018, 7:e35037

X Shawn Liu, Hao Wu, Marine Krzisch, Xuebing Wu, John Graef, Julien Muffat, Denes Hnisz, Charles H. Li, Bingbing Yuan, Chuanyun Xu, Yun Li, Dan Vershkov, Angela Cacace, Richard A. Young, Rudolf Jaenisch
Rescue of fragile X syndrome neurons by DNA methylation editing of the FMR1 gene
Cell, 2018, 172:979–992

Anthony C. Chiu*, Hiroshi I. Suzuki*, Xuebing Wu, Dig B. Mahat, Andrea J. Kriz, Phillip A. Sharp
Transcriptional Pause Sites Delineate Stable Nucleosome-Associated Premature Polyadenylation Suppressed by U1 snRNP
Molecular Cell, 2018, 69:648–663


Xuebing Wu, David P. Bartel
Widespread influence of 3′-end structures on mammalian mRNA processing and stability
Cell, 2017, 169: 905–917

Xuebing Wu^, David P. Bartel^ (^co-corresponding author)
kpLogo: positional k-mer analysis reveals hidden specificity in biological sequences
Nucleic Acids Research, gkx323


X Shawn Liu*, Hao Wu*, Xiong Ji, Yonatan Stelzer, Xuebing Wu, Szymon Czauderna, Jian Shu, Chikdu S. Shivalila, Daniel Dadon, Richard A. Young, Rudolf Jaenisch
Editing DNA methylation in the mammalian genome
Cell, 2016, 167:233-247
     Journal highlight: Nature 

Xiaochang Zhang, Ming Hui Chen, Xuebing Wu, Andrew Kodani, Jean Fan, Ryan Doan, Manabu Ozawa, Jacqueline Ma, Nobuaki Yoshida, Jeremy F Reiter, Douglas L. Black, Peter V Kharchenko, Phillip A. Sharp, Christopher A. Walsh
Cell type-specific alternative splicing governs cell fate in the developing cerebral cortex
Cell, 2016, 166:1147-1162


F. Ann Ran*, Le Cong*, Winston X. Yan*, David A. Scott, Jonathan S. Gootenberg, Andrea J. Kriz, Bernd Zetsche, Ophir Shalem, Xuebing Wu, Kira S. Makarova, Eugene V. Koonin, Phillip A. Sharp, Feng Zhang
In vivo genome editing using Staphylococcus aureus Cas9
Nature, 2015, 520:186-191


Xuebing Wu, Andrea J. Kriz, Phillip A. Sharp
Target specificity of the CRISPR-Cas9 system
Quantitative Biology, 2014, 2:59-70

Xuebing Wu, David A. Scott, Andrea J. Kriz, Anthony C. Chiu, Patrick D. Hsu, Daniel B. Dadon, Albert W. Cheng, Alexandro E. Trevino, Silvana Konermann, Sidi Chen, Rudolf Jaenisch, Feng Zhang, Phillip A. Sharp
Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells
Nature Biotechnology, 2014, 32:670-676

Sidi Chen, Yuan Xue, Xuebing Wu, Le Cong, Arjun Bhutkar, Eric Bell, Feng Zhang, Robert Langer, Phillip A. Sharp
Global microRNA depletion suppresses tumor angiogenesis
Genes & Development, 2014, 28:1054-1067


Xuebing Wu, Phillip A. Sharp
Divergent transcription: a driving force for new gene origination?
Cell, 2013, 155:990-996
"Leading Edge Featured Article" in Cell

Albert E. Almada*, Xuebing Wu*, Andrea J. Kriz, Christopher B. Burge, Phillip A. Sharp (*equal contribution)
Promoter directionality is controlled by U1 snRNP and polyadenylation signals
Nature, 2013, 499:360–363
Access the recommendation on F1000Prime
    Journal highlight: Nature Reviews Genetics | Cell Research | Nature Structural Molecular Biology
MIT News | ScienceDaily | The Christian Science MonitorGenetic Engineering & Technology News

Le Cong, F Ann Ran, David Cox, Shuailiang Lin, Robert Barretto, Naomi Habib, Patrick D Hsu, Xuebing Wu, Wenyan Jiang, Luciano A Marraffini, Feng Zhang
Multiplex genome engineering using CRISPR/Cas systems
, 2013, 339 (6121):819-823.
     highlighted in Science  |  Nature Reviews Genetics  |  Nature Methods

Patrick D. Hsu, David A. Scott, Joshua A. Weinstein, F. Ann Ran, Silvana Konermann, Vineeta Agarwala, Yinqing Li, Eli J. Fine, Xuebing Wu, Ophir Shalem, Thomas J. Cradick, Luciano A. Marraffini, Gang Bao, and Feng Zhang
DNA Targeting Specificity of the RNA-guided Cas9 Nuclease
Nature Biotechnology
, 2013, 31:827-832

Anna Lyubimova, Shalev Itzkovitz, Jan Philipp Junker, Zi Peng Fan, Xuebing Wu, Alexander van Oudenaarden
Single-molecule mRNA detection and counting in mammalian tissue
Nature Protocols
, 2013, 8:1743–1758 (download software)

Yong Chen, Xuebing Wu, Rui Jiang
Integrating human omics data to prioritize candidate genes
BMC Medical Genomics, 2013, 6:57


Xuebing Wu, Shao Li
Cancer gene prediction using a network approach
Chapter 11 in: Cancer Systems Biology (Ed. Edwin Wang). Series: Chapman & Hall/CRC Mathematical & Computational Biology, USA: CRC Press 2010. [Amazon]


Xuebing Wu, Qifang Liu, Rui Jiang
Align human interactome with phenome to identify causative genes and networks underlying disease families
Bioinformatics, 2009, 25 (1): 98-104 [Data]

Wanwan Tang, Xuebing Wu, Rui Jiang, Yanda Li
Epistatic module detection for case-control studies: A Bayesian model with a Gibbs sampling strategy
PLoS Genetics, 2009, (5):e1000464

Rui Jiang, Wanwan Tang, Xuebing Wu, Wenhui Fu
A random forest approach to the detection of epistatic interactions in case-control studies
BMC Bioinformatics, 2009, 10 (Suppl 1):S65


Xuebing Wu, Rui Jiang, Michael Q. Zhang, Shao Li
Network-based global inference of human disease genes
Molecular Systems Biology, 2008, 4:189.

Lab members

Xuebing Wu

Assistant Professor of Medicine and Systems Biology (CV)

Postdoc, David Bartel lab, Whitehead Institute
PhD in Computational and Systems Biology, MIT (Phil Sharp and Chris Burge lab)
BS/MS in Control Science and Engineering, Tsinghua University, Beijing

Ziheng (Calvin) Chen

Master of Science Program, Department of Biomedical Engineering, Columbia University
BSc Biochemistry, University of Liverpool, Liverpool

Alexis Aparicio

BA in Biochemistry and Molecular Biology, Boston University

Michael Murphy

Postdoc Research Scientist
Ph.D. in Molecular, Cellular, and Developmental Biology, City University of New York

Ellen Alt

Undergraduate student (Cellular and Molecular Biology)
Barnard College of Columbia University

Ziqiang Wang

Postdoc Research Scientist
PhD in Cell Biology, Tsinghua University




A webserver for positional k-mer analysis
Wu & Bartel (2017) Nucleic Acids Res, gkx323


CIPHER, which stands for Correlating interactome and phenome networks to predict disease genes, is a computational framework we proposed to prioritize human disease genes. It was one of the first studies to explore interactome-phenome wide gene-disease relationships, and generated the first comprehensive genetic landscape of human disease, connecting 5080 human disease phenotypes with 14433 human genes.

Links: Click here to Download dataset or Explore predictions (try mirror at CSHL )

Citation: Wu X, Jiang R, Zhang MQ, Li S (2008) Network-based global inference of human disease genes. Molecular Systems Biology, 4:189


AlignPI is the abbreviation of "Align Phenome & Interactome." We have performed the first alignment of human phenome and interactome network, and identified 39 bi-modules and made predictions of candidate genes for 70 diseases. Bi-module consists of two inter-connected modules: a network of diseases and a network of genes. 

Links: The
AlignPI website provides a search interface for all identified bi-modules and candidate gene predictions, and corresponding functional enrichment analysis. 

Citation: Wu X, Liu Q, Jiang R (2009) Align human interactome with phenome to identify causative genes and networks underlying disease families. Bioinformatics, 25 (1): 98-104


4sU-2P-Seq and DIM-2P-seq protocol (Mar 2017) (PDF)

Lab news

June 1, 2019 Ziqiang Wang joined the lab as a postdoc research scientist. Welcome Ziqiang!

May 28, 2019 Ellen Alt joined the lab as a summer research student. Welcome Ellen!

Mar 1, 2019 Michael Murphy joined the lab as a staff associate. Welcome Michael!

Feb 19, 2019 Alexis Aparicio joined the lab as our first Technician. Welcome Alex!

Jan, 2019 Ziheng (Calvin) Chen, a graduate student in the BME Master of Science program joined the lab. Welcome Calvin!

Dec 7, 2018 Xuebing won the Scaringe Award from the RNA Society

Nov 1, 2018 Lab officially starts!

Join us

We are seeking passionate researchers of all stages (postdocs, graduate students, undergraduates, and research associates) to join our team. Please email me ( directly if you are interested in joining our team.

Columbia University undergraduate students: We welcome passionate and creative students to work in the lab. Dr. Xuebing Wu is also a mentor of the Summer Undergraduate Research Fellowship (SURF) program.