RESEARCH



RNA-centric gene regulation

We study mammalian mRNA regulation. Current efforts include: 1) noncoding translation; 2) translation-independent functions of mRNAs; 3) functions of mRNA structures


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 technologies using unbiased genomic assays. 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 are currently developing interpretable deep learning models for alternative splicing and CRISPR targeting.


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 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

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

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

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

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.

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.



Xuebing's undergraduate publications


Xuebing Wu, Zhirong Sun, Rui Jiang
Logic motif of combinatorial control in transcriptional networks
Nature Precedings, 2008, https://doi.org/10.1038/npre.2008.2227.1

Zhirong Sun, Xuebing Wu
Systems biology: new interdisciplinary science
Communication of China Computer Society, 2006, 2 (3):56-65 (Cover story, review, in Chinese)

Xuebing Wu, Yuanjie Li, Huaiyu Wang
An intelligent transportation system based on virtual force
Physics and Engineering, 2005, 2 (in Chinese)

Lab members







2019/12/07


Xuebing Wu


Assistant Professor
Department of Medicine / Cardiology division
-- Cardiometabolic Genomics Program
Department of Systems Biology
Herbert Irving Comprehensive Cancer Center
Data Science Institute

Postdoc with David Bartel at Whitehead Institute
PhD with Phil Sharp and Chris Burge at MIT
BS/MS with Shao Li, Michael Q Zhang / Rui Jiang at Tsinghua University

Alexis Aparicio


Technician
BA in Biochemistry and Molecular Biology, Boston University

aoa2145@columbia.edu

Michael Murphy


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

mrm2267@cumc.columbia.edu

Peiguo Shi


Postdoc Research Scientist
Ph.D. in Cell Biology, University of the Chinese Academy of Sciences, Beijing, China

ps3008@cumc.columbia.edu

Katherine Liu


Undergraduate student (Biomedical Engineering)
Columbia University

liu.katherine@columbia.edu

Yixuan Li


Undergraduate student (Computer Science)
Columbia University

yl3803@columbia.edu

Zanis Fang


Postdoctoral Research Scientist
PhD in Genetics, Fudan University
MS in Biostatistics, Data Science Institute Scholar, 2019, Columbia University

zf2213@columbia.edu

Shruti Verma


Egleston Scholar, Class of 2023, Columbia Engineering
Data Science Institute Scholar, 2020

sv2611@columbia.edu

Jordan Kesner


PhD student (Systems Biology), Columbia University
MS in Biotechnology, Columbia University
BS in Molecular Biology, Cornell University

jk3755@cumc.columbia.edu



Lab Alumni


Ziheng "Calvin" Chen 1/15/19-8/10/2020, Master's student, Columbia BME

Qijin Yin 11/25/19-5/10/2020, Visiting PhD student from Tsinghua University

Ellen Alt 5/28/19-8/1/19, Barnard Summer Research Institute, undergraduate student





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


10/6/20 Lab receives NIH Director's New Innovator Award (DP2) . Also see CUIMC News

9/1/20 Zanis joined the lab as a Postdoc!

8/3/20 The Wu lab welcomes our first PhD student Jordan Kesner!

6/15/20 Xuebing is named a 2020 Pew-Stewart Scholar for Cancer Research. Also see Columbia HICCC News

4/1/20 Lab's COVID-19 research highlighted in HICCC news article Columbia University Cancer Researchers in the Fight Against COVID-19

2/21/20 Xuebing's faculty profile/interview article at Dept. Systems Biology and Cancer Center / HICCC

2/10/20 Shruti Verma joined the lab from Columbia Engineering

12/17/19 Xuebing is named Highly Cited Researcher in 2019 by Web of Science

12/03/19 Michael's AHA postdoc fellowship application was funded. Congratulations!

11/25/19 Qijin Yin started as a visiting scholar. Welcome Qijin!

11/01/19 Welcome four new members to the lab: Peiguo Shi (postdoc), Zanis Fang (MS/DSI Scholar), Katherine Liu and Yixuan Li (undergrad)

10/24/19 Lab moves to our permanent space in P&S

06/28/19 Xuebing gave a talk at the RNA therapeutics conference at UMass Med School.

06/14/19 Xuebing gave a video-taped talk at the RNA Society Annual Meeting in Krakow, Poland.

05/28/19 Ellen Alt joined the lab as a summer research student. Welcome Ellen!

03/01/19 Michael Murphy joined the lab as a staff associate. Welcome Michael!

02/19/19 Alexis Aparicio joined the lab as our first Technician. Welcome Alex!

01/15/19 Ziheng (Calvin) Chen, a graduate student in the BME Master of Science program joined the lab. Welcome Calvin!

12/07/18 Xuebing won the Scaringe Award from the RNA Society

11/01/18 Lab officially started!





Join us


We are seeking passionate researchers of all stages (postdocs, graduate students, undergraduates, and research associates) to join our team.

Graduate student looking for rotation or postdoc opportunity: please email me (xw2629@cumc.columbia.edu) directly.

Undergraduate students: If you are interested in becoming a graduate student in the lab, you need to first get admitted to one of the PhD programs at Columbia. Students with background in computational biology can apply to the systems biology track within the integrated program. Once you are here, you can choose to rotate or join the lab. We also welcome passionate and creative undergraduate students to work in the lab during summer or regular semesters. Dr. Xuebing Wu is a mentor of the Summer Undergraduate Research Fellowship (SURF) program.