RESEARCH



Decoding the central dogma

How do cells accurately synthesize a complex proteome from a genome with 98% noncoding DNA?


1) A unified model for the surveillance of translation in noncoding sequences.
See Kesner et al., 2023 Nature
2) A widespread role of RNA structures in controlling mRNA 3' end processing and stability.
See Wu & Bartel, 2017 Cell
3) How cells suppress pervasive noncoding transcription and how noncoding transcription drives the evolution of new genes.
See Wu & Sharp, 2013 Cell, Almada & Wu et al. 2013 Nature

CRISPR technology & therapy

We use CRISPR to control RNAs and proteins for therapeutic applications.


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^

2024


Jian Ge, Hongxu Ding, Hongxia Shao, Yuefeng Huang, Xuebing Wu, Jie Sun, Jianwen Que#
Single cell analysis of lung lymphatic endothelial cells and lymphatic responses during influenza infection.
Journal of Respiratory Biology and Translational Medicine, 2024, in press

2023


Yingyu Zhang, Wanwei Zhang, Jingyao Zhao, Takamasa Ito, Jiacheng Jin, Alexis O. Aparicio, Junsong Zhou, Vincent Guichard, Yinshan Fang, Jianwen Que, Joseph F. Urban Jr, Jacob H. Hanna, Sankar Ghosh, Xuebing Wu, Lei Ding, Uttiya Basu & Yuefeng Huang
m6A RNA modification regulates innate lymphoid cell responses in a lineage-specific manner.
Nature Immunology , 2023, 24:1256–1264

Jordan S Kesner*, Ziheng Chen*, Peiguo Shi, Alexis O Aparicio, Michael R. Murphy, Yang Guo, Aditi Trehan, Jessica E. Lipponen, Yocelyn Recinos, Natura Myeku, Xuebing Wu
Noncoding translation mitigation.
Nature, 2023, 617:395–402
See related preprint

Peiguo Shi^, Michael R Murphy, Alexis O Aparicio, Jordan S Kesner, Zhou Fang, Ziheng Chen, Aditi Trehan, Yang Guo, Xuebing Wu^
Collateral activity of the CRISPR/RfxCas13d system in human cells.
Communications Biology, 2023 6:334
See related preprint

2022


Jordan S Kesner*, Ziheng Chen*, Alexis A Aparicio, Xuebing Wu
A unified model for the surveillance of translation in diverse noncoding sequences.
bioRxiv, 2022.07.20.500724; doi: https://doi.org/10.1101/2022.07.20.500724

2021


Peiguo Shi^, Michael R Murphy, Alexis O Aparicio, Jordan S Kesner, Zhou Fang, Ziheng Chen, Aditi Trehan, Xuebing Wu^
RNA-guided cell targeting with CRISPR/RfxCas13d collateral activity in human cells.
bioRxiv, 2021, 2021.11.30.470032; doi: https://doi.org/10.1101/2021.11.30.470032

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







2023/09/29


Xuebing Wu


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

Michael Murphy


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

Peiguo Shi


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

Aditi Trehan


PhD student, Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University
MS in Biotechnology, Johns Hopkins University
BS in Neurobiology & Physiology and Cell, Molecular & Developmental Systems Biology, Purdue University

Yang Guo


Postdoc Research Scientist
PhD in Biochemistry, Zhejiang University, China

Feiyue Yang


Rotation student, Systems Biology
BS in Biological Science (major) and Data Science and Big Data Technology (minor), China Agricultural University

Sebastian Ho


Rotation student, Nutritional and Metabolic Biology
BS in Biochemistry, University of Pittsburgh

Sikandar Azam


Associate Research Scientist
PhD in Biochemistry and Molecular Biology, Dalian Medical University



Lab Alumni


Jordan Kesner 8/1/2020-10/1/2023, PhD student -> Postdoc

Katherine Da 9/1/2023-11/30/2023, Visiting undergraduate student, Dartmouth College

Yue Yin 11/01/2021-07/01/2022, Barnard Summer Research Institute, undergraduate student

Alexis Aparicio 02/19/19-08/19/2022, Technician B

Jonathan Algoo 9/20/21-12/14/2021, Rotation student, integrated program

Zhou "Zanis" Fang 11/01/19-12/06/2021, DSI Scholar -> Postdoc

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



Funding





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


2/7/24 Xuebing was selected as a 2024 Schaefer Research Scholar

2/1/24 We received our first R01 grant from NHLBI!

1/8/24 We welcomed rotation students Feiyue Yang (Systems Biology) and Sebastian Ho (Nutritional & Metabolic Bio)

12/20/23 We received a grant from the Million Dollar Bike Ride (MDBR) Grant Program to dissect STXBP1 3’ UTR regulation for therapeutic development

12/19/23 We received a grant from the Ines Mandl Research Foundation (IMRF) to develop an off-the-shelf gene editing therapy for Marfan Syndrome

11/17/23 We received a grant from the Cure Alzheimer’s Fund to study noncoding translation and feedback loops in Alzheimer's disease!

11/10/23 Xuebing is invited to give a seminar at Duke Biology and RNA Center @ Durham

11/9/23 Xuebing is invited to give a seminar at NIEHS @ Durham

10/17/23 Xuebing is invited to give a seminar at Koch Institute/MIT

10/14/23 Xuebing gave a talk at EMBL@Heidelberg, Germany, during the 2023 non-coding genome symposium

10/13/23 Xuebing is invited to give a seminar at Heidelberg University Hospital @ Heidelberg, Germany

10/11/23 Xuebing is invited to give a seminar at Max Planck Institute for Molecular Genetics @ Berlin, Germany

9/20/23 We received the inaugural Glenn Foundation Discovery Award !

9/18/23 Our NCI admin supplement grant with Que lab has been funded!

9/13/23 We welcome visiting student Katherine Da, Biology and CS @ Dartmouth College

9/4/23 We receive a 2nd grant from Longevity Impetus Grants !

8/28/23 We welcome graduate student Colin Kalicki for his 1st rotation

7/31/23 Xuebing gave a talk in the Basic Cardiovascular Sciences (BCVS) conference in Boston

7/3/23 Our collaborative work with Yuefeng Huang lab was published at Nature Immunology

7/1/23 We receive a grant from HICCC/Inter/Intra-Programmatic Pilot Program (IPPP) to target lung cancer using CRISPR/Cas13

5/30-6/4/23 Xuebing, Michael, and Jordan attended 2023 annual RNA meeting at Singapore. Michael won a poster award. Xuebing gave a talk on RPL3L ribosomes.

4/19/23 Xuebing was invited to visit U of Chicago by postdocs at the Department of Human Genetics

4/12/23 Our paper titled noncoding translation mitigation has been published online at Nature. See CUIMC news release Illuminating tumor cells with dark proteins

3/28/23 Our paper on Cas13 collateral activity has been published online at Communications Biology

3/21/23 Jordan has been selected as one of the two recipients of the 2023 Dean’s Award for Excellence in Research! Congratulations, Jordan!

10/14/22 Xuebing and Michael each gave an invited virtual talk to the Toronto RNA Club

9/29/22 Xuebing gave an invited virtual seminar at the University of Texas at Dallas

9/6-9/22 Xuebing and Michael each gave a talk at the 18th translational control conference at CSHL

8/31/22 Xuebing gave an invited talk at the first FASEB conference on RNA and immunity.

8/25/22 Congrats Dr. Jordan Kesner! First PhD from the lab!

7/21/22 Lab releases the 2nd bioRxiv preprint, led by Jordan, Ziheng, and Alex

6/4/22 Jordan gave a talk at RNA society meeting 2022

5/25/22 Congrats to Aditi for passing her qualifying exam!

5/4/22 Xuebing gave an invited talk at Weill Cornell and MSKCC

5/3/22 Xuebing gave an invited virtual talk at Prevail Therapeutics / Eli Lilly and Company

4/18/22 Lab welcomes Yang Guo as a postdoctoral research scientist !

11/30/21 First preprint from the lab, led by Peiguo: RNA-guided cell targeting with CRISPR/RfxCas13d collateral activity in human cells

11/16/21 Lab welcomes Barnard/Columbia undergraduate student Yue Yin!

10/14/21 Lab receives Longevity Impetus Grants to study aging!

9/20/21 Lab welcomes Jonathan Algoo as a rotation student in the Fall!

6/21/21 Lab receives 2021 Paul A. Marks Scholars Award , which provides unrestricted fund for 3 years

6/3/21 Lab receives Columbia Precision Medicine Pilot Grant , which supports our study on specialized ribosomes in the heart

5/27/21 Aditi Trehan became PhD student #2 of the Wu lab!

5/18/21 Lab receives the 2021 Pershing Square Sohn Prize for Young Investigators in Cancer Research, which supports our study on cancer-targeting using CRISPR/Cas13 and machine learning. Also see CUIMC News

4/12/21 Aditi Trehan started her rotation in the lab!

10/6/20 Lab receives NIH Director's New Innovator Award (DP2) for genome-scale study of mRNA noncoding functions using CRISPR/Cas13. 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, which will support our study of how cancer cells reprogram mRNA structures on a genome-scale. 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 The RNA Society/Scaringe Young Scientist Award 2019

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 (xuebing.wu@columbia.edu) directly.

Graduate programs we are affiliated with: Integrated Program in Cellular, Molecular, and Biomedical Studies (CMBS); Systems Biology (also a track in the CMBS program); Nutritional and Metabolic Biology.

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. Once you are admitted, you can choose to rotate or join the lab. We also welcome passionate and creative undergraduate students who can work in the lab full-time during summer or as a visiting student during regular semester. Dr. Xuebing Wu is a mentor of the Summer Undergraduate Research Fellowship (SURF) program and the Barnard Summer Research Institute.