Research interests

小RNA的调控机制研究

研究哺乳动物中非编码小RNA (miRNA、siRNA、piRNA) 和RNA代谢调控的分子机制。主要成果包括： ①发现miRNA加速mRNA降解的机制，并且证明该途径也是siRNA引起的RNAi脱靶效应的机制；②发现Ago蛋白家族的各个成员对RNAi的on-target和off-target的贡献差异，是影响RNAi效率和专一性的重要因素，并且翻译抑制对RNAi也有重要贡献，在此基础上研发了更为安全高效的单链saiRNA；③鉴定了miRNA引起mRNA降解的关键脱腺苷酸化酶CCR4和Caf1，并且证明该酶对siRNA引起的RNAi脱靶效应也发挥了重要作用；④发现CCR4-NOT1复合物加速m6A修饰RNA的3′端poly(A)尾和降解的分子机制；⑤发现miRNA负责清除无义突变mRNA的新功能； ⑥建立了高灵敏的单细胞小RNA测序技术，在哺乳动物精子和卵子中发现了多种新类型的小RNA。

小RNA和mRNA的调控机制与药物开发

研究mRNA和非编码小RNA调控的分子机制、理性设计和转化应用。运用生物化学、分子生物学手段，结合高通量测序和生物信息学方法，从分子水平和RNA组学水平，研究mRNA和非编码小RNA在细胞命运决定、生殖细胞生成过程中的生物学功能和分子机制;运用获得的知识指导RNA分子机器的理性设计，开发新技术新方法，用于临床疾病诊治和工业化生产。

Group members

吴立刚

研究组长，博士生导师

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徐蓓英

实验室管家，高级实验师

研究方向: 行政事务，高通量测序

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张宏道

副研究员

研究方向: 单细胞测序、小RNA药物

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张瑞雯

研究助理

研究方向: 动物实验

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肖雅丽

研究助理

研究方向: 小RNA与细胞周期

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吕小龙

博士后

研究方向: 金黄地鼠PIWI蛋白功能

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黎硕珂

博士后

研究方向: mRNA序列、修饰优化

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李志学

博士研究生（2021级）

研究方向: CLIP分析、mRNA和小RNA药物设计

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高世琦

博士研究生

研究方向: 小RNA药物开发

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张一凡

博士研究生（2022级）

研究方向: 小RNA药物开发

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郑玉丽

博士研究生（2022级）

研究方向: 高通量测序开发及应用

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刘思雨

博士研究生（2023级）

研究方向: mRNA与衰老

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董心扬

硕士研究生（2024级）

研究方向: 辅助生殖技术对后代影响

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王周铭

硕士研究生（2025级）

研究方向: 新方法开发

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史广用

博士研究生（2026已毕业-西湖大学博士后）

研究方向: 干细胞转分化研究、mRNA疫苗

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常允建

博士研究生（2026已毕业）

研究方向: 单细胞及空间转录组、肿瘤新生抗原设计

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赵震

研究助理（2026已离职）

研究方向: 蛋白结构研究

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朱懿文

研究生（2025已毕业）

研究方向: 金黄地鼠PIWI蛋白功能

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李玉玺

研究生（2025已毕业）

研究方向: 自动化实验

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孟祥凯

研究生（2026已毕业）

研究方向: 高通量测序开发及应用

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蒋程熙

研究生（2026已毕业）

研究方向: 金黄地鼠PIWI蛋白功能

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• Alumni

Publications

Fengjuan Zhang (张凤娟)#, Hongdao Zhang (张宏道)#*, Yali xiao (肖雅丽)#, Miao Liu (刘淼)#, Aimin Ren (任爱民), Suying Liu (刘素英)* & Ligang Wu (吴立刚)* Integrated small and long RNA sequencing reveals piRNA mediated transposon repression during human oogenesis, Nature Communications, 2026 (17)

Huanhuan Feng#, Zhixue Li#, Hongdao Zhang, Yuli Zheng, Beiying Xu, Yao Zhang, Lin Zou*, Ligang Wu* Characterization of gRNA-dependent and gRNA-independent off-target binding sites of PspCas13b and RfxCas13d in mammalian cells, Nucleic Acids Research, 2026 (54)

Wen Xiao (肖稳)#, Yuli Zheng (郑玉丽)#, Hongdao Zhang (张宏道)#*, Beiying Xu (徐蓓英)#, Ruiwen Zhang (张瑞雯) & Ligang Wu (吴立刚)* An absolute quantification atlas of small non-coding RNAs across diverse mammalian tissues and cell lines, Nature Communications, 2026 (7)

Xiaolong Lv#, Hongdao Zhang#, Ligang Wu* Advances in PIWI-piRNA function in female reproduction in mammals, Acta Biochim Biophys Sin, 2025 (57)

Yunjian Chang#, Ligang Wu* CapHLA: a comprehensive tool to predict peptide presentation and binding to HLA class I and class II, Briefings in Bioinformatics, 2025 (26)

Yuanyuan Li#, Ying Cao#, Wei Liu#, Fangzheng Chen, Hongdao Zhang, Haisheng Zhou, Aonan Zhao, Ningdi Luo, Jun Liu* & Ligang Wu* Candidate biomarkers of EV-microRNA in detecting REM sleep behavior disorder and Parkinson’s disease, npj parkinson's disease, 2024 (10)

Yanhong Li#, Yifei Sang#, Yunjian Chang#, Chunfang Xu#, Yikong Lin, Yao Zhang, Philip C.N. Chiu, William S.B. Yeung, Haisheng Zhou, Ningzheng Dong, Ling Xu, Jiajia Chen, Weijie Zhao, Lu Liu, Di Yu, Xingxing Zang, Jiangfeng Ye, Jinying Yang*, Qingyu Wu, Dajin Li*, Ligang Wu* and Meirong Du* A Galectin-9–Driven CD11chigh Decidual Macrophage Subset Suppresses Uterine Vascular Remodeling in Preeclampsia, Circulation, 2024 (0)

Xueqing Wang#, Quanlong Jiang#, Hongdao Zhang#, Zhidong He, Yuanyuan Song, Yifan Chen, Na Tang, Yifei Zhou, Yiping Li, Adam Antebi, Ligang Wu*, Jing-Dong Han*, Yidong Shen* Tissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans, Nature Communication, 2024 (15)

Li Hou#, Wei Liu#, Hongdao Zhang, Ronghong Li, Miao Liu, Huijuan Shi & Ligang Wu* Divergent composition and transposon-silencing activity of small RNAs in mammalian oocytes, Genome Biology, 2024 (25)

Yanwei Zhang#, Beibei Sun#, Yinghong Yu#, Jun Lu#, Yuqing Lou, Fangfei Qian, Tianxiang Chen, Li Zhang, Jiancheng Yang*, Hua Zhong*, Ligang Wu* & Baohui Han * Multimodal fusion of liquid biopsy and CT enhances differential diagnosis of early-stage lung adenocarcinoma, npj Precision Oncology, 2024 (8)

Qing Li#, Jiansen Lu#, Xidi Yin#, Yunjian Chang#, Chao Wang#, Meng Yan#, Li Feng, Yanbo Cheng, Yun Gao, Beiying Xu, Yao Zhang, Yingyi Wang, Guizhong Cui, Luang Xu, Yidi Sun, Rong Zeng, Yixue Li, Naihe Jing, Guo-Liang Xu*, Ligang Wu*, Fuchou Tang* & Jinsong Li* Base editing-mediated one-step inactivation of the Dnmt gene family reveals critical roles of DNA methylation during mouse gastrulation, Nature Communication, 2023 (14)

Xiaolong Lv#, Wen Xiao#, Yana Lai#, Zhaozhen Zhang#, Hongdao Zhang#, Chen Qiu, Li Hou, Qin Chen, Duanduan Wang, Yun Gao, Yuanyuan Song, Xinjia Shui, Qinghua Chen, Ruixin Qin, Shuang Liang, Wentao Zeng, Aimin Shi*, Jianmin Li*, Ligang Wu* The non-redundant functions of PIWI family proteins in gametogenesis in golden hamsters, NATURE COMMUNICATIONS[J], 2023 (14)

Yanwei Zhang#, Wei Liu#, Hongdao Zhang#, Beibei Sun, Tianxiang Chen, Minjuan Hu, Haisheng Zhou, Ying Cao, Baohui Han*, Ligang Wu* Extracellular vesicle long RNA markers of early-stage lung adenocarcinoma, INTERNATIONAL JOURNAL OF CANCER[J], 2023 (152)

Xueqing Wang, Quanlong Jiang, Yuanyuan Song, Zhidong He, Hongdao Zhang, Mengjiao Song, Xiaona Zhang, Yumin Dai, Oezlem Karalay, Christoph Dieterich, Adam Antebi, Ligang Wu*, Jing-Dong J Han*, Yidong Shen* Ageing induces tissue-specific transcriptomic changes in Caenorhabditis elegans, EMBO JOURNAL[J], 2022 (41)

Guannan Zhou, Yuanyuan Gu, Zhongyi Zhu, Hongdao Zhang, Wei Liu, Beiying Xu, Fangyue Zhou, Menglei Zhang, Keqin Hua*, Ligang Wu*, Jingxin Ding* Exosome Mediated Cytosolic Cisplatin Delivery Through Clathrin-Independent Endocytosis and Enhanced Anti-cancer Effect via Avoiding Endosome Trapping in Cisplatin-Resistant Ovarian Cancer, FRONTIERS IN MEDICINE[J], 2022 (9)

Minghua Liu#, Peiru Liu#, Yunjian Chang#, Beiying Xu, Nengzhuang Wang, Lina Qin, Jufen Zheng*, Yun Liu*, Ligang Wu* & Hongli Yan* Genome-wide DNA methylation profiles and small noncoding RNA signatures in sperm with a high DNA fragmentation index, Journal of Assisted Reproduction and Genetics, 2022 (39)

Hongdao Zhang, Fengjuan Zhang, Qinghua Chen, Mingzhe Li, Xiaolong Lv, Yali Xiao, Zhaozhen Zhang, Li Hou, Yana Lai, Ying Zhang, Aihua Zhang, Shiqi Gao, Heling Fu, Wen Xiao, Jianli Zhou, Feiyang Diao, Aimin Shi, You-Qiang Su, Wentao Zeng*, Ligang Wu*, Jianmin Li* The piRNA pathway is essential for generating functional oocytes in golden hamsters, NATURE CELL BIOLOGY[J], 2021 (23)

Yuanyuan Li, Ying Cao, Wei Liu, Hongdao Zhang, Aonan Zhao, Ningdi Luo, Jun Liu*, Ligang Wu* MicroRNA Candidate Biomarkers for Parkinson’s Disease and Idiopathic REM Sleep Behavior Disorder, PREPRINT, 2021 (0)

Yao Zhang, Yilan Teng,Wangwen Xiao,Beiying Xu,Ya Zhao, Weihua Li, Ligang Wu* Identifying Cleaved and Noncleaved Targets of Small Interfering RNAs and MicroRNAs in Mammalian Cells by SpyCLIP, MOLECULAR THERAPY-NUCLEIC ACIDS[J], 2020 (22)

Zhongyi Zhu, Yijing Zhang, Ligang Wu*, Keqin Hua*, Jingxin Ding* Regeneration-Related Functional Cargoes in Mesenchymal Stem Cell-Derived Small Extracellular Vesicles, STEM CELLS AND DEVELOPMENT[J], 2020 (29)

Ya Zhao, Yao Zhang, Yilan Teng, Kai Liu, Yanqing Liu, Weihua Li, Ligang Wu* SpyCLIP: an easy-to-use and high-throughput compatible CLIP platform for the characterization of protein-RNA interactions with high accuracy, NUCLEIC ACIDS RESEARCH[J]., 2019 (47)

Minmin Hua, Wei Liu, Ying Chen, Fengjuan Zhang, Beiying Xu, Suying Liu, Guowu Chen*, Huijuan Shi* & Ligang Wu* Identification of small non-coding RNAs as sperm quality biomarkers for in vitro fertilization, CELL DISCOVERY[J], 2019 (5)

薛皖强, 侯丽, 李荣红, 吴立刚* NaIO4氧化–深度测序技术的优化用于检测微量RNA样品中小RNA 3′末端甲基化修饰, 中国细胞生物学学报[J], 2019 (41)

Fengjuan Zhang, Ying Zhang, Xiaolong Lv, Beiying Xu, Hongdao Zhang, Jun Yan, Haipeng Li, Ligang Wu* Evolution of an X-Linked miRNA Family Predominantly Expressed in Mammalian Male Germ Cells, MOLECULAR BIOLOGY AND EVOLUTION[J], 2019 (36)

Qiyuan Yang, Ronghong Li, Qifeng Lyu, Li Hou, Zhen Liu, Qiang Sun, Miao Liu, Huijuan Shi, Beiying Xu, Mingru Yin, Zhiguang Yan, Ying Huang, Mofang Liu*, Yiping Li* & Ligang Wu* Single-cell CAS-seq reveals a class of short PIWI-interacting RNAs in human oocytes, NATURE COMMUNICATIONS[J], 2019 (10)

Ling Peng, Fengjuan Zhang, Renfu Shang, Xueyan Wang, Jiayi Chen, James J. Chou, Jinbiao Ma, Ligang Wu*, Ying Huang* Identification of substrates of the small RNA methyltransferase Hen1 in mouse spermatogonial stem cells and analysis of its methyl-transfer domain, JOURNAL OF BIOLOGICAL CHEMISTRY[J], 2018 (293)

Yuhan Zhang, Weiwei Liu, Ronghong Li, Jiaqi Gu, Ping Wu, Chao Peng, Jinbiao Ma, Ligang Wu*, Yang Yu*, Ying Huang* Structural insights into the sequence-specific recognition of Piwi by Drosophila Papi, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA[J], 2018 (115)

Yang Qiu, Yanpeng Xu, Yao Zhang, Hui Zhou, Yong-Qiang Deng, Xiao-Feng Li, Meng Miao, Qiang Zhang, Bo Zhong, Yuanyang Hu, Fu-Chun Zhang, Ligang Wu*, Cheng-Feng Qin*, Xi Zhou* Human Virus-Derived Small RNAs Can Confer Antiviral Immunity in Mammals, IMMUNITY[J], 2017 (46)

Chencheng Yao, Qingqing Yuan, Minghui Niu, Hongyong Fu, Fan Zhou, Wenhui Zhang, Hong Wang, Liping Wen, Ligang Wu*, Zheng Li*, Zuping He* Distinct Expression Profiles and Novel Targets of MicroRNAs in Human Spermatogonia, Pachytene Spermatocytes, and Round Spermatids between OA Patients and NOA Patients, MOLECULAR THERAPY-NUCLEIC ACIDS[J], 2017 (9)

Xiaoxu Chen, Dongxue Che, Pengfei Zhang, Xueliang Li, Qingqing Yuan, Tiantian Liu, Jiayin Guo, Tongying Feng, Ligang Wu*, Minzhi Liao*, Zuping He*, Wenxian Zeng* Profiling of miRNAs in porcine germ cells during spermatogenesis, REPRODUCTION[J], 2017 (154)

Lan-Tao Gou, Jun-Yan Kang, Peng Dai, Xin Wang, Feng Li, Shuang Zhao, Man Zhang, Min-Min Hua, Yi Lu, Yong Zhu, Zheng Li, Hong Chen, Li-Gang Wu, Dangsheng Li, Xiang-Dong Fu, Jinsong Li, Hui-Juan Shi, Mo-Fang Liu* Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis, CELL[J], 2017 (169)

Juanjuan Long, Chenhui Huang, Yanyan Chen, Ying Zhang, Shaohua Shi, Ligang Wu*, Yie Liu*, Chengyu Liu*, Jian Wu & Ming Lei* Telomeric TERB1-TRF1 interaction is crucial for male meiosis, NATURE STRUCTURAL & MOLECULAR BIOLOGY[J], 2017 (24)

Qiyuan Yang, Jimin Lin, Miao Liu, Ronghong Li, Bin Tian, Xue Zhang, Beiying Xu, Mofang Liu*, Xuan Zhang*, Yiping Li*, Huijuan Shi*, Ligang Wu* Highly sensitive sequencing reveals dynamic modifications and activities of small RNAs in mouse oocytes and early embryos, SCIENCE ADVANCES[J], 2016 (2)

Hao Du, Ya Zhao, Jinqiu He, Yao Zhang, Hairui Xi, Mofang Liu, Jinbiao Ma, Ligang Wu* YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex, NATURE COMMUNICATIONS[J], 2016 (7)

Yuxuan Wu, Hai Zhou, Xiaoying Fan, Ying Zhang, Man Zhang, Yinghua Wang, Zhenfei Xie, Meizhu Bai, Qi Yin, Dan Liang, Wei Tang, Jiaoyang Liao, Chikai Zhou, Wujuan Liu, Ping Zhu, Hongshan Guo, Hong Pan, Chunlian Wu, Huijuan Shi, Ligang Wu*, Fuchou Tang* & Jinsong Li* Correction of a genetic disease by CRISPR-Cas9-mediated gene editing in mouse spermatogonial stem cells, CELL RESEARCH[J], 2015 (25)

Renfu Shang, Fengjuan Zhang, Beiying Xu, Hairui Xi, Xue Zhang, Weihua Wang* & Ligang Wu* Ribozyme-enhanced single-stranded Ago2-processed interfering RNA triggers efficient gene silencing with fewer off-target effects, NATURE COMMUNICATIONS[J], 2015 (6)

Ya Zhao, Jimin Lin, Beiying Xu, Sida Hu, Xue Zhang, Ligang Wu* MicroRNA-mediated repression of nonsense mRNAs, ELIFE[J], 2014 (3)

Xianghua Piao, Xue Zhang, Ligang Wu* & Joel G. Belasco* CCR4-NOT deadenylates RISC-associated mRNA in human cells, MOL CELL BIOL[J], 2010 (30)

Ligang Wu, Joel G. Belasco* Examining the influence of microRNA on translation and mRNA decay, METHODS IN ENZYMOLOGY[J], 2008 (449)

Ligang Wu, Joel G. Belasco* Let me count the ways: Mechanisms of gene regulation by miRNAs and siRNAs, MOLECULAR CELL[J], 2008 (29)

Ligang Wu, Jihua Fan, Joel G. Belasco* Importance of translation and non-nucleolytic Ago proteins for on-target RNA interference, CURRENT BIOLOGY[J], 2008 (18)

Ligang Wu, Jihua Fan, Joel G. Belasco* MicroRNAs direct rapid deadenylation of mRNA, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA[J], 2006 (103)

Ligang Wu, Joel G. Belasco* Micro-RNA regulation of the mammalian lin-28 gene during neuronal differentiation of embryonal carcinoma cells, MOLECULAR AND CELLULAR BIOLOGY[J], 2005 (25)

吴立刚, 尚仁福. 可诱导型siRNA表达载体及其制备和应用, CN107557363A, 2018

吴立刚, 杨其元. 测序文库构建中5’和3’接头连接副产物的去除方法, CN107488655A, 2017

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