RESEARCH



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

Genomic technologies

We develop sequencing-based assays and CRISPR/Cas-based methods for interrogating and manipulating the structure and function of the genome, epigenome, and transcriptome. Current projects include nascent RNA structure probing and Cas13-based translation modulation.


1) Transcriptome-wide 3'-end RNA structure probing and high-throughput mutagenesis of endogenous RNA structures.
See Wu & Bartel, 2017 Cell
2) The first genome-wide analysis of Cas9 targeting in mammalian cells.
See Wu et al. 2014 Nature Biotechnology
3) 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



PUBLICATIONS


Google Scholar Citations

co-first author*, co-corresponding author^

2018


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 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
U1 snRNP suppresses premature polyadenylation at transcriptional pause sites associated with stable nucleosomes
Molecular Cell, 2018, 69:648–663

2017


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
http://kplogo.wi.mit.edu

2016


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


2015


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

2014


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

2013


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
           Media:
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
Science
, 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

2010


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]

2009


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

2008


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
xw2629@cumc.columbia.edu (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

You

Postdoc

email

You

Graduate student

email



Software

kpLogo


A webserver for positional k-mer analysis
Links: http://kplogo.wi.mit.edu
Citation:
Wu & Bartel (2017) Nucleic Acids Res, gkx323


CIPHER

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



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





Protocols


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





Lab news


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 (xw2629@cumc.columbia.edu) directly if you are interested in joining our team.

For postdoc position, please apply through http://pa334.peopleadmin.com/postings/2017 .

For technician position, please apply through https://jobs.columbia.edu/applicants/Central?quickFind=173130.

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.