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Research

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Highlighted

Open collaborative writing with Manubot
Open collaborative writing with Manubot
Daniel S. Himmelstein, Vincent Rubinetti, David R. Slochower, Dongbo Hu, Venkat S. Malladi, Casey S. Greene, Anthony Gitter
PLOS Computational Biology  ·  24 Jun 2019  ·  doi:10.1371/journal.pcbi.1007128

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2025

Balancing heterochromatin: ASB7-mediated proteasomal control of H3K9me3 homeostasis
Balancing heterochromatin: ASB7-mediated proteasomal control of H3K9me3 homeostasis
Xinyu Zhou, Jonathan M. G. Higgins, Fangwei Wang
Science China Life Sciences  ·  14 Nov 2025  ·  doi:10.1007/s11427-025-3136-4
Chronic stress in cancer development and progression
Chronic stress in cancer development and progression
Xin Niu, Ting Wu, Linghui Zeng, Fangwei Wang, Weiguo Lv, Long Zhang, Fangfang Zhou
Science Bulletin  ·  01 Nov 2025  ·  doi:10.1016/j.scib.2025.09.034
DNA binding and mitotic phosphorylation: native mechanisms preventing polyglutamine protein aggregation
DNA binding and mitotic phosphorylation: native mechanisms preventing polyglutamine protein aggregation
Haiyan Yan, Xinyu Zhou, Junyue Tao, Fangwei Wang
Science China Life Sciences  ·  23 Sep 2025  ·  doi:10.1007/s11427-025-3058-6
FOXM1 condensate: a therapeutic target for breast tumor growth and metastasis
FOXM1 condensate: a therapeutic target for breast tumor growth and metastasis
Haiyan Yan, Fangwei Wang, Weiguo Lu
Science Bulletin  ·  01 Sep 2025  ·  doi:10.1016/j.scib.2025.04.043
The cAMP-PKA signaling initiates mitosis by phosphorylating Bora
The cAMP-PKA signaling initiates mitosis by phosphorylating Bora
Min Zhu, Shinan Zhou, Yingqi Zhang, Qinfu Chen, Xueying Yuan, Long Zhang, Haiyan Yan, Fangwei Wang
Nature Communications  ·  24 Aug 2025  ·  doi:10.1038/s41467-025-63352-y
Scalable data harmonization for single-cell image-based profiling with CytoTable
Scalable data harmonization for single-cell image-based profiling with CytoTable
Dave Bunten, Jenna Tomkinson, Erik Serrano, Michael J. Lippincott, Kenneth I. Brewer, Vince Rubinetti, Faisal Alquaddoomi, Gregory P. Way
openRxiv  ·  25 Jun 2025  ·  doi:10.1101/2025.06.19.660613
A chromatin-remodeling-independent role for ATRX in protecting centromeric cohesion
A chromatin-remodeling-independent role for ATRX in protecting centromeric cohesion
Lei Zhao, Xueying Yuan, Qinfu Chen, Haiyan Yan, Fangwei Wang
The EMBO Journal  ·  28 May 2025  ·  doi:10.1038/s44318-025-00465-6
Targeting a key disulfide linkage to regulate RIG-I condensation and cytosolic RNA-sensing
Targeting a key disulfide linkage to regulate RIG-I condensation and cytosolic RNA-sensing
Bin Wang, Yongqiang Wang, Ting Pan, Lili Zhou, Yu Ran, …, Ting Liu, Huasong Lu, Bing Yang, Fangfang Zhou, Long Zhang
Nature Cell Biology  ·  14 Apr 2025  ·  doi:10.1038/s41556-025-01646-5
Decoding Mitotic Chromosome Assembly: Three Rules Governing Condensin Cohesin Engagement
Decoding Mitotic Chromosome Assembly: Three Rules Governing Condensin–Cohesin Engagement
Haiyan Yan, Xinyu Zhou, Fangwei Wang
Research  ·  01 Jan 2025  ·  doi:10.34133/research.0812
Actin Takes the Steering Wheel: A New Mitotic Safeguard in the Early Embryo
Actin Takes the Steering Wheel: A New Mitotic Safeguard in the Early Embryo
Yingqi Zhang, Shukai Zhu, Fangwei Wang
Research  ·  01 Jan 2025  ·  doi:10.34133/research.1050

2024

Molecular mechanism and functional significance of Wapl interaction with the Cohesin complex
Molecular mechanism and functional significance of Wapl interaction with the Cohesin complex
Xueying Yuan, Lu Yan, Qinfu Chen, Shukai Zhu, Xinyu Zhou, …, Jun Huang, Weiguo Lu, Long Zhang, Haiyan Yan, Fangwei Wang
Proceedings of the National Academy of Sciences  ·  07 Aug 2024  ·  doi:10.1073/pnas.2405177121
A non-canonical role of the inner kinetochore in regulating sister-chromatid cohesion at centromeres
A non-canonical role of the inner kinetochore in regulating sister-chromatid cohesion at centromeres
Lu Yan, Xueying Yuan, Mingjie Liu, Qinfu Chen, Miao Zhang, …, Jun Huang, Weiguo Lu, Xiaojing He, Haiyan Yan, Fangwei Wang
The EMBO Journal  ·  07 May 2024  ·  doi:10.1038/s44318-024-00104-6

2023

The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species
The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species
Tim E Putman, Kevin Schaper, Nicolas Matentzoglu, Vincent P Rubinetti, Faisal S Alquaddoomi, …, Damian Smedley, Peter N Robinson, Christopher J Mungall, Melissa A Haendel, Monica C Munoz-Torres
Nucleic Acids Research  ·  24 Nov 2023  ·  doi:10.1093/nar/gkad1082
Integration of 168,000 samples reveals global patterns of the human gut microbiome
Integration of 168,000 samples reveals global patterns of the human gut microbiome
Richard J. Abdill, Samantha P. Graham, Vincent Rubinetti, Frank W. Albert, Casey S. Greene, Sean Davis, Ran Blekhman
openRxiv  ·  11 Oct 2023  ·  doi:10.1101/2023.10.11.560955
The RPA RNF20 SNF2H cascade promotes proper chromosome segregation and homologous recombination repair
The RPA–RNF20–SNF2H cascade promotes proper chromosome segregation and homologous recombination repair
Jimin Li, Jingyu Zhao, Xiaoli Gan, Yanyan Wang, Donghao Jiang, …, Fangwei Wang, Jingyan Xu, Huadong Pei, Jun Huang, Xuefeng Chen
Proceedings of the National Academy of Sciences  ·  08 May 2023  ·  doi:10.1073/pnas.2303479120
MyGeneset.info: an interactive and programmatic platform for community-curated and user-created collections of genes
MyGeneset.info: an interactive and programmatic platform for community-curated and user-created collections of genes
Ricardo Avila, Vincent Rubinetti, Xinghua Zhou, Dongbo Hu, Zhongchao Qian, Marco Alvarado Cano, Everaldo Rodolpho, Ginger Tsueng, Casey Greene, Chunlei Wu
Nucleic Acids Research  ·  18 Apr 2023  ·  doi:10.1093/nar/gkad289
The cGAS-STING pathway: a therapeutic target in chromosomally unstable cancers
The cGAS-STING pathway: a therapeutic target in chromosomally unstable cancers
Haiyan Yan, Weiguo Lu, Fangwei Wang
Signal Transduction and Targeted Therapy  ·  30 Jan 2023  ·  doi:10.1038/s41392-023-01328-4
Hetnet connectivity search provides rapid insights into how two biomedical entities are related
Hetnet connectivity search provides rapid insights into how two biomedical entities are related
Daniel S. Himmelstein, Michael Zietz, Vincent Rubinetti, Kyle Kloster, Benjamin J. Heil, …, David N. Nicholson, Yun Hao, Blair D. Sullivan, Michael W. Nagle, Casey S. Greene
openRxiv  ·  07 Jan 2023  ·  doi:10.1101/2023.01.05.522941

2022

Hetnet connectivity search provides rapid insights into how biomedical entities are related
Hetnet connectivity search provides rapid insights into how biomedical entities are related
Daniel S Himmelstein, Michael Zietz, Vincent Rubinetti, Kyle Kloster, Benjamin J Heil, …, David N Nicholson, Yun Hao, Blair D Sullivan, Michael W Nagle, Casey S Greene
GigaScience  ·  28 Dec 2022  ·  doi:10.1093/gigascience/giad047
Role of pyroptosis in inflammation and cancer
Role of pyroptosis in inflammation and cancer
Xiang Wei, Feng Xie, Xiaoxue Zhou, Yuchen Wu, Haiyan Yan, Ting Liu, Jun Huang, Fangwei Wang, Fangfang Zhou, Long Zhang
Cellular & Molecular Immunology  ·  15 Aug 2022  ·  doi:10.1038/s41423-022-00905-x
Dissecting the roles of Haspin and VRK1 in histone H3 phosphorylation during mitosis
Dissecting the roles of Haspin and VRK1 in histone H3 phosphorylation during mitosis
Tyrell N. Cartwright, Rebecca J. Harris, Stephanie K. Meyer, Aye M. Mon, Nikolaus A. Watson, …, Agathe Marcelot, Fangwei Wang, Sophie Zinn-Justin, Paula Traktman, Jonathan M. G. Higgins
Scientific Reports  ·  01 Jul 2022  ·  doi:10.1038/s41598-022-15339-8
Microbiota in Tumors: From Understanding to Application
Microbiota in Tumors: From Understanding to Application
Yifan Xie, Feng Xie, Xiaoxue Zhou, Lei Zhang, Bing Yang, …, Fangwei Wang, Haiyan Yan, Linghui Zeng, Long Zhang, Fangfang Zhou
Advanced Science  ·  23 May 2022  ·  doi:10.1002/advs.202200470
MolEvolvR: A web-app for characterizing proteins using molecular evolution and phylogeny
MolEvolvR: A web-app for characterizing proteins using molecular evolution and phylogeny
Faisal S Alquaddoomi, Joseph T Burke, Lo Sosinski, David A Mayer, Evan P Brenner, …, Vincent P Rubinetti, Shaddai Amolitos, Kellen M Reason, John B Johnston, Janani Ravi
openRxiv  ·  22 Feb 2022  ·  doi:10.1101/2022.02.18.461833
SUMOylation in Viral Replication and Antiviral Defense
SUMOylation in Viral Replication and Antiviral Defense
Yao Fan, Xiang Li, Lei Zhang, Zhi Zong, Fangwei Wang, …, Linghui Zeng, Chong Zhang, Haiyan Yan, Long Zhang, Fangfang Zhou
Advanced Science  ·  21 Jan 2022  ·  doi:10.1002/advs.202104126

2021

ISGylation in Innate Antiviral Immunity and Pathogen Defense Responses: A Review
ISGylation in Innate Antiviral Immunity and Pathogen Defense Responses: A Review
Mengdi Zhang, Jingxian Li, Haiyan Yan, Jun Huang, Fangwei Wang, Ting Liu, Linghui Zeng, Fangfang Zhou
Frontiers in Cell and Developmental Biology  ·  25 Nov 2021  ·  doi:10.3389/fcell.2021.788410
Engineering Extracellular Vesicles Enriched with Palmitoylated ACE2 as COVID 19 Therapy
Engineering Extracellular Vesicles Enriched with Palmitoylated ACE2 as COVID‐19 Therapy
Feng Xie, Peng Su, Ting Pan, Xiaoxue Zhou, Heyu Li, …, Jun Huang, Haiyan Yan, Linghui Zeng, Long Zhang, Fangfang Zhou
Advanced Materials  ·  19 Oct 2021  ·  doi:10.1002/adma.202103471
Targeted Anti Tumor Immunotherapy Using Tumor Infiltrating Cells
Targeted Anti‐Tumor Immunotherapy Using Tumor Infiltrating Cells
Yifan Xie, Feng Xie, Lei Zhang, Xiaoxue Zhou, Jun Huang, Fangwei Wang, Jin Jin, Long Zhang, Linghui Zeng, Fangfang Zhou
Advanced Science  ·  18 Oct 2021  ·  doi:10.1002/advs.202101672
Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation
Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation
Qinfu Chen, Miao Zhang, Xuan Pan, Xueying Yuan, Linli Zhou, …, Jun Huang, Weiguo Lu, Tatsuo Fukagawa, Fangwei Wang, Haiyan Yan
Cell Reports  ·  01 Sep 2021  ·  doi:10.1016/j.celrep.2021.109740
A subcellular map of the human kinome
A subcellular map of the human kinome
Haitao Zhang, Xiaolei Cao, Mei Tang, Guoxuan Zhong, Yuan Si, …, Zongping Xia, Tingbo Liang, Huasong Lu, Xin-Hua Feng, Bin Zhao
eLife  ·  14 May 2021  ·  doi:10.7554/eLife.64943

2020

Compressing gene expression data using multiple latent space dimensionalities learns complementary biological representations
Compressing gene expression data using multiple latent space dimensionalities learns complementary biological representations
Gregory P. Way, Michael Zietz, Vincent Rubinetti, Daniel S. Himmelstein, Casey S. Greene
Genome Biology  ·  11 May 2020  ·  doi:10.1186/s13059-020-02021-3
Mps1 dimerization and multisite interactions with Ndc80 complex enable responsive spindle assembly checkpoint signaling
Mps1 dimerization and multisite interactions with Ndc80 complex enable responsive spindle assembly checkpoint signaling
Ping Gui, Divine M Sedzro, Xiao Yuan, Sikai Liu, Mohan Hei, …, Felix O Aikhionbare, Xinjiao Gao, Dongmei Wang, Xuebiao Yao, Zhen Dou
Journal of Molecular Cell Biology  ·  26 Mar 2020  ·  doi:10.1093/jmcb/mjaa006

2019

Centromere-localized Aurora B kinase is required for the fidelity of chromosome segregation
Centromere-localized Aurora B kinase is required for the fidelity of chromosome segregation
Cai Liang, Zhenlei Zhang, Qinfu Chen, Haiyan Yan, Miao Zhang, Linli Zhou, Junfen Xu, Weiguo Lu, Fangwei Wang
Journal of Cell Biology  ·  23 Dec 2019  ·  doi:10.1083/jcb.201907092
Histone H2A phosphorylation recruits topoisomerase scp II scp α to centromeres to safeguard genomic stability
Histone H2A phosphorylation recruits topoisomerase II α to centromeres to safeguard genomic stability
Miao Zhang, Cai Liang, Qinfu Chen, Haiyan Yan, Junfen Xu, …, Xueying Yuan, Jingbo Liu, Shixian Lin, Weiguo Lu, Fangwei Wang
The EMBO Journal  ·  26 Nov 2019  ·  doi:10.15252/embj.2019101863
NudC-like protein 2 restrains centriole amplification by stabilizing HERC2
NudC-like protein 2 restrains centriole amplification by stabilizing HERC2
Min Li, Xiaoyang Xu, Jun Zhang, Min Liu, Wei Wang, …, Yunkun Lu, Fangwei Wang, Wei Liu, Tianhua Zhou, Yuehong Yang
Cell Death & Disease  ·  19 Aug 2019  ·  doi:10.1038/s41419-019-1843-3
Open collaborative writing with Manubot
Open collaborative writing with Manubot
Daniel S. Himmelstein, Vincent Rubinetti, David R. Slochower, Dongbo Hu, Venkat S. Malladi, Casey S. Greene, Anthony Gitter
PLOS Computational Biology  ·  24 Jun 2019  ·  doi:10.1371/journal.pcbi.1007128
Sequential compression of gene expression across dimensionalities and methods reveals no single best method or dimensionality
Sequential compression of gene expression across dimensionalities and methods reveals no single best method or dimensionality
Gregory P. Way, Michael Zietz, Vincent Rubinetti, Daniel S. Himmelstein, Casey S. Greene
openRxiv  ·  11 Mar 2019  ·  doi:10.1101/573782
Aurora B kinase activity dependent and independent functions of the chromosomal passenger complex in regulating sister chromatid cohesion
Aurora B kinase activity–dependent and –independent functions of the chromosomal passenger complex in regulating sister chromatid cohesion
Qi Yi, Qinfu Chen, Haiyan Yan, Miao Zhang, Cai Liang, Xingfeng Xiang, Xuan Pan, Fangwei Wang
Journal of Biological Chemistry  ·  01 Feb 2019  ·  doi:10.1074/jbc.RA118.005978
A positive feedback mechanism ensures proper assembly of the functional inner centromere during mitosis in human cells
A positive feedback mechanism ensures proper assembly of the functional inner centromere during mitosis in human cells
Cai Liang, Zhenlei Zhang, Qinfu Chen, Haiyan Yan, Miao Zhang, Xingfeng Xiang, Qi Yi, Xuan Pan, Hankun Cheng, Fangwei Wang
Journal of Biological Chemistry  ·  01 Feb 2019  ·  doi:10.1074/jbc.RA118.006046

2018

NudCL2 is an Hsp90 cochaperone to regulate sister chromatid cohesion by stabilizing cohesin subunits
NudCL2 is an Hsp90 cochaperone to regulate sister chromatid cohesion by stabilizing cohesin subunits
Yuehong Yang, Wei Wang, Min Li, Ya Gao, Wen Zhang, …, Xiaoyi Yan, Wei Liu, Fangwei Wang, Dingwei Chen, Tianhua Zhou
Cellular and Molecular Life Sciences  ·  27 Oct 2018  ·  doi:10.1007/s00018-018-2957-y
HP1 cooperates with CAF-1 to compact heterochromatic transgene repeats in mammalian cells
HP1 cooperates with CAF-1 to compact heterochromatic transgene repeats in mammalian cells
Haiyan Yan, Xingfeng Xiang, Qinfu Chen, Xuan Pan, Hankun Cheng, Fangwei Wang
Scientific Reports  ·  20 Sep 2018  ·  doi:10.1038/s41598-018-32381-7
WAC Promotes Polo-like Kinase 1 Activation for Timely Mitotic Entry
WAC Promotes Polo-like Kinase 1 Activation for Timely Mitotic Entry
Feifei Qi, Qinfu Chen, Hongxia Chen, Haiyan Yan, Binbin Chen, …, Miao Zhang, Hankun Cheng, Zhenlei Zhang, Jun Huang, Fangwei Wang
Cell Reports  ·  01 Jul 2018  ·  doi:10.1016/j.celrep.2018.06.087
scp HP scp 1 links centromeric heterochromatin to centromere cohesion in mammals
HP 1 links centromeric heterochromatin to centromere cohesion in mammals
Qi Yi, Qinfu Chen, Cai Liang, Haiyan Yan, Zhenlei Zhang, Xingfeng Xiang, Miao Zhang, Feifei Qi, Linli Zhou, Fangwei Wang
EMBO reports  ·  28 Feb 2018  ·  doi:10.15252/embr.201745484

2017

A kinase dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion
A kinase‐dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion
Cai Liang, Qinfu Chen, Qi Yi, Miao Zhang, Haiyan Yan, …, Linli Zhou, Zhenlei Zhang, Feifei Qi, Sheng Ye, Fangwei Wang
EMBO reports  ·  14 Nov 2017  ·  doi:10.15252/embr.201744737
The N-Terminal Non-Kinase-Domain-Mediated Binding of Haspin to Pds5B Protects Centromeric Cohesion in Mitosis
The N-Terminal Non-Kinase-Domain-Mediated Binding of Haspin to Pds5B Protects Centromeric Cohesion in Mitosis
Linli Zhou, Cai Liang, Qinfu Chen, Zhenlei Zhang, Bo Zhang, …, Youchen Guan, Xingfeng Xiang, Xiaoqing Zhang, Sheng Ye, Fangwei Wang
Current Biology  ·  01 Apr 2017  ·  doi:10.1016/j.cub.2017.02.019
Aurora-A promotes the establishment of spindle assembly checkpoint by priming the Haspin-Aurora-B feedback loop in late G2 phase
Aurora-A promotes the establishment of spindle assembly checkpoint by priming the Haspin-Aurora-B feedback loop in late G2 phase
Fazhi Yu, Ya Jiang, Lucy Lu, Mimi Cao, Yulong Qiao, …, Terry Van Dyke, Fangwei Wang, Xuebiao Yao, Jing Guo, Zhenye Yang
Cell Discovery  ·  10 Jan 2017  ·  doi:10.1038/celldisc.2016.49

2014

Polo like kinase 1 triggers histone phosphorylation by Haspin in mitosis
Polo‐like kinase‐1 triggers histone phosphorylation by Haspin in mitosis
Linli Zhou, Xiaoying Tian, Cailei Zhu, Fangwei Wang, Jonathan MG Higgins
EMBO reports  ·  13 Jan 2014  ·  doi:10.1002/embr.201338080

2013

Histone modifications and mitosis: countermarks, landmarks, and bookmarks
Histone modifications and mitosis: countermarks, landmarks, and bookmarks
Fangwei Wang, Jonathan M.G. Higgins
Trends in Cell Biology  ·  01 Apr 2013  ·  doi:10.1016/j.tcb.2012.11.005

2012

Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation
Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation
Fangwei Wang, Natalia P. Ulyanova, John R. Daum, Debasis Patnaik, Anna V. Kateneva, Gary J. Gorbsky, Jonathan M.G. Higgins
Journal of Cell Biology  ·  15 Oct 2012  ·  doi:10.1083/jcb.201205106
Molecular basis for phosphospecific recognition of histone H3 tails by Survivin paralogues at inner centromeres
Molecular basis for phosphospecific recognition of histone H3 tails by Survivin paralogues at inner centromeres
Ewa Niedzialkowska, Fangwei Wang, Przemyslaw J. Porebski, Wladek Minor, Jonathan M. G. Higgins, P. Todd Stukenberg
Molecular Biology of the Cell  ·  15 Apr 2012  ·  doi:10.1091/mbc.E11-11-0904

2011

A Positive Feedback Loop Involving Haspin and Aurora B Promotes CPC Accumulation at Centromeres in Mitosis
A Positive Feedback Loop Involving Haspin and Aurora B Promotes CPC Accumulation at Centromeres in Mitosis
Fangwei Wang, Natalia P. Ulyanova, Maike S. van der Waal, Debasis Patnaik, Susanne M.A. Lens, Jonathan M.G. Higgins
Current Biology  ·  01 Jun 2011  ·  doi:10.1016/j.cub.2011.05.016

2010

A phospho methyl switch at histone H3 regulates TFIID association with mitotic chromosomes
A phospho/methyl switch at histone H3 regulates TFIID association with mitotic chromosomes
Radhika A Varier, Nikolay S Outchkourov, Petra de Graaf, Frederik M A van Schaik, Henk Jan L Ensing, Fangwei Wang, Jonathan M G Higgins, Geert J P L Kops, HTh Marc Timmers
The EMBO Journal  ·  15 Oct 2010  ·  doi:10.1038/emboj.2010.261
Histone H3 Thr-3 Phosphorylation by Haspin Positions Aurora B at Centromeres in Mitosis
Histone H3 Thr-3 Phosphorylation by Haspin Positions Aurora B at Centromeres in Mitosis
Fangwei Wang, Jun Dai, John R. Daum, Ewa Niedzialkowska, Budhaditya Banerjee, P. Todd Stukenberg, Gary J. Gorbsky, Jonathan M. G. Higgins
Science  ·  08 Oct 2010  ·  doi:10.1126/science.1189435

2009

Structure and functional characterization of the atypical human kinase haspin
Structure and functional characterization of the atypical human kinase haspin
Jeyanthy Eswaran, Debasis Patnaik, Panagis Filippakopoulos, Fangwei Wang, Ross L. Stein, James W. Murray, Jonathan M. G. Higgins, Stefan Knapp
Proceedings of the National Academy of Sciences  ·  01 Dec 2009  ·  doi:10.1073/pnas.0901989106

2006

The Assembly and Maintenance of Heterochromatin Initiated by Transgene Repeats Are Independent of the RNA Interference Pathway in Mammalian Cells
The Assembly and Maintenance of Heterochromatin Initiated by Transgene Repeats Are Independent of the RNA Interference Pathway in Mammalian Cells
Fangwei Wang, Naoki Koyama, Hiroko Nishida, Tokuko Haraguchi, Walter Reith, Toshiro Tsukamoto
Molecular and Cellular Biology  ·  01 Jun 2006  ·  doi:10.1128/MCB.02189-05