王纲

发布时间：2021-06-27浏览次数：4349

教师基本信息：

姓名：王纲（WANG Gang）

职称：正高级

职务：复旦大学生命科学学院特聘教授，副院长（Distinguished Professor and Vice Dean）

电子邮箱：gwang_fd@fudan.edu.cn

办公地点：复旦大学生命科学学院E座201室


研究方向：

本实验室长期专注于转录中介体的分子调控机理及其在发育（成体干细胞分化等）和疾病（代谢疾病、神经相关疾病、癌症等）中的功能研究。发现转录中介体（Mediator）在mRNA剪切加工、转录延伸、以及DNA损伤修复过程中的非经典功能；首次提出平滑肌与脂肪细胞的“双向调控”及其共同起源；发现Mediator不同亚基在胚胎干细胞干性维持及多谱系细胞分化中的不同功能；发现转录中介体亚基MED23参与调控间充质干细胞向成骨细胞分化过程并影响成骨的发育；揭示Mediator作为表观遗传调控因子,调控癌症与肌肉细胞分化之间的拮抗作用等。

We have long been committed to the study of epigenetic transcription regulation and molecular mechanisms of development and diseases, heavily focusing on the Mediator co-factor complex.

The Mediator complex function as a molecular bridge linking signaling molecules and DNA-binding regulators with the Pol II machinery, which is responsible for transducing developmental and environmental signals into nucleus to generate various mRNA outputs. The key question here is how the transcription output is regulated in a gene- or cell type-specific manner. Therefore, one of our major research goals is to determine how the Mediator works with the general transcription machinery to generate the temporal- and spatial-specific gene expression under various developmental and physiological settings. Another important issue is that Mediator was often found to be dysregulated or mutated in numerous diseases such as developmental defects and cancers, therefore how the dysregulated Mediator causes diseases is an important research topic in our lab. In addition to the canonical function of Mediator in transcription initiation, we are also keen in discovering the non-canonical roles of Mediator in transcription regulation, such as in transcription elongation, mRNA processing, termination, and chromatin changes, etc.


个人简介：

王纲，复旦大学生命科学学院特聘教授，长期研究发育与疾病的转录及表观遗传调控；作为通讯作者在Mol Cell，Dev Cell，Genes Dev，EMBO J，PNAS，Nature Comm，PloS Biol等杂志发表论文。多项工作作为Mol Cell，EMBO J等重要学术期刊的封面文章发表，获同期专评，以及Faculty1000, Nature Asia-AIMBN, BioArt,“知识分子”的亮点评论。现任中国细胞生物学学会资深理事、Asian Transcription Conference 国际组委、JBC、TRANSCRIPTION学术期刊编委，获“百人计划”和“上海浦江人才计划”及“国务院特殊津贴”支持，作为首席科学家先后主持国家重大科学研究计划、国家重点研发计划项目及国家自然科学基金重点项目。

Dr. Gang Wang received his B.S. in Psychology from Peking University in 1988, M.S. in Psychology from University of North Carolina in 1993, and Ph.D. in Molecular and Cellular Biology from Tulane University in 1998. From 1999 to 2005, he was a Postdoctoral fellow and then an Assistant Researcher in the Molecular Biology Institute at the University of California, Los Angeles. He was recruited to the Institute of Biochemistry and Cell Biology by the Chinese Academy of Science "Hundred Talent Program" in 2006. He joined Fudan University School of Life Sciences as the Distinguished Professor in 2019.


授课情况：《分子生物学》（本科）、《干细胞与发育》（本科）、《科研之道》（研究生、本科生）

招生专业：生物化学；细胞与发育生物学；遗传学；生物与医药

科研项目：

在研项目包括：国家自然科学基金重点项目、面上项目及科技部国家重点研发计划

获奖情况：中科院“百人计划”、“浦江人才计划”、国务院特殊津贴、中科院朱李月华优秀教师奖（2013）、中科院优秀研究生指导教师奖（2013）

代表性论文和论著：

  1. Xiaobo Fu#, Siming Liu#, Dan Cao, Chonghui Li, Hongbin Ji, Gang Wang*. Med23 deficiency reprograms the tumor microenvironment to promote lung tumorigenesis. British Journal of Cancer 2023; In press

  2. Yenan Yang#, Chonghui Li#, Ziying Chen, Yiyang Zhang, Qing Tian, Meiling Sun, Shuai Zhang, Miao Yu*, Gang Wang*. An intellectual disability-related MED23 mutation dysregulates gene expression by altering chromatin conformation and enhancer activities. Nucleic Acids Research 2023, 51(5), 2137-2150.

  3. Yenan Yang#, Qi Xiao#, Jingwen Yin, Chonghui Li, Decai Yu, Yulong He, Zhongzhou Yang*, Gang Wang*. Med23 supports angiogenesis and maintains vascular integrity through negative regulation of angiopoietin2 expression. Communications Biology 2022, 5: 374.

  4. Yangyang Li#, Ying Lu#, Shuhai Lin, Ning Li, Yichao Han, Qianru Huang, Yi Zhao, Feng Xie, Yixian Guo, Biaolong Deng, Andy Tsuna, Juan Du, Dan Li, Joanne Sun, Guochao Shi, Fang Zheng, Xiao Su, Shengzhong Duan, Song Guo Zheng, Gang Wang*, Xuemei Tong* & Bin Li*.Insulin signaling establishes a developmental trajectory of adipose Treg cells. Nature Immunology 2021, 22(9):1175-1185.

  5. Xiaoli Sun#, Jing-wen Yin#, Yan Liang, Chonghui Li, Pingjin Gao, Ying Yu, Gang Wang*. Mediator Med23 deficiency in smooth muscle cells prevents neointima formation after arterial injury. Cell Discovery 2021, 7(1):59.

  6. Yenan Yang, Xiaoli Zhu, Xiang Jia, Wanwan Hou, Guoqiang Zhou, Zhangjing Ma, Bin Yu, Yan Pi, Xumin Zhang, Jingqiang Wang, and Gang Wang*. Phosphorylation of Msx1 promotes cell proliferation through the Fgf9/18-MAPK signaling pathway during embryonic limb development. Nucleic Acids Research 2020, 48(20): 11452-11467.

  7. Zhichao Wang#, Dan Cao#, Chonghui Li, Lihua Min, Gang Wang*. Mediator MED23 regulates inflammatory responses and liver fibrosis. PLoS Biology 2019;17(12): e3000563.

  8. Min Xia, Kun Chen,Xiao Yao, Yichi Xu,Jiaying Yao, Jun Yan, ZhenShao, andGang Wang*. Mediator subunit MED23 links pigmentation and DNA repair through the transcription factor MITF. Cell Reports 2017; 20(8):1794-1804.

  9. Zhen Liu, Xiao Yao, Guang Yan, Yichi Xu, Jun Yan, Weiguo Zou*, Gang Wang*. Mediator MED23 cooperates with RUNX2 to drive osteoblast differentiation and bone development. Nat Commun 2016; 7:11149.

  10. Xiao Yao, Zhanyun Tang, Jingwen Yin, Yan Liang, Xing Fu, Robert G. Roeder,Gang Wang*. The Mediator subunit MED23 couples H2B mono-ubiquitination to transcriptional control and cell fate determination. EMBO J 2015; 34(23):2885-902. (Cover story with commentary)

  11. Wanqu Zhu, Xiao Yao, Yan Liang, Dan Liang, Lu Song, Naihe Jing, Jinsong Li, Gang Wang*. Mediator Med23-deficiency Enhances Neural Differentiation of Embryonic Stem Cells through Modulating BMP Signaling. Development 2015; 142(3):465-76.

  12. Yang Sun, Xiaoyan Zhu, Xufeng Chen, Haifeng Liu, Yu Xu, Yajing Chu, Gang Wang*, Xiaolong Liu*. The mediator subunit Med23 contributes to controlling T-cell activation and prevents autoimmunity. Nat Communs 2014; 5:5225.

  13. Jingwen Yin, and Gang Wang*. The Mediator complex: a master coordinator of transcription and cell lineage development. Development 2014; 141:977-987. (Invited review)

  14. Yajing Chu, Leonardo Gomez Rosso, Ping Huang, Zhichao Wang, Yichi Xu, Xiao Yao, Menghan Bao, Jun Yan, Haiyun Song, Gang Wang*. Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity. Cell Res 2014; 24:1250-1265.

  15. Yong Yu, Dan Liang, Qing Tian, Xiaona Chen, Bo Jiang, Binkuan Chou, Ping Hu, Linzhao Cheng, Ping Gao, Jinsong Li, Gang Wang*. Stimulation of somatic cell reprogramming by ERas-Akt-FoxO1 signaling axis. Stem Cells 2014; 32:349-363.

  16. Meng Zhao, Xu Yang, Yu Fu, Haifang Wang, Yuanheng Ning, Jun Yan, Ye-Guang Chen, Gang Wang*. Mediator MED15 modulates transforming growth factor beta (TGFβ)/Smad signaling and breast cancer cell metastasis. J Mol Cell Biol2013 Feb;5(1):57-60.

  17. Jingwen Yin, Yan Liang, JiYeon Park, Dongrui Chen, Xiao Yao, Qi Xiao, Zhen Liu, Bo Jiang, Yu Fu, Menghan Bao, Yan Huang, Yuting Liu, Jun Yan, Minsheng Zhu, Zhongzhou Yang, Pingjin Gao, Bin Tian, Dangsheng Li, GangWang*. The Mediator MED23 plays opposing roles in directing smooth muscle cell and adipocyte differentiation. Genes & Dev 2012; 26(19):2192-2205. (Highlighted by Nature Asia – AIMBN)

  18. Xu Yang, Meng Zhao, Min Xia, Yuting Liu, Jun Yan, HongbinJi, and Gang Wang*. Selective Requirement for Mediator MED23 in Ras-active Lung Cancer. PNAS 2012; 109(41):E2813-22. (Highlighted by Nature Asia – AIMBN)

  19. Yan Huang, Wencheng Li, Xiao Yao, Qijiang Lin, Jingwen Yin, Yan Liang, Monika Heiner, Bin Tian, Jingyi Hui, and Gang Wang*. Mediator Complex Regulates Alternative mRNA Processing via the MED23 Subunit. Mol Cell 2012; 45:459-469. (Cover story with commentary; Highlighted in Faculty 1000)

  20. Wei Wang, Lu Huang, Yan Huang, Jingwen Yin, Arnold J. Berk, Jeffrey Friedman, Gang Wang*. Mediator MED23 links insulin signaling to the adipogenesis transcription cascade. Dev Cell 2009; 16:764-771.


Achievement & Future Work:

We have long been dedicated to research on the molecular mechanisms of development and diseases, with a particular focus on epigenetic regulation of gene transcription. Over the years, we have made a series of scientific achievements as following.

Mediator complex is an integrative hub for transcriptional regulation. We have identified multiple non-canonical roles beyond its classic function in transcription initiation, which include (i) the cross-talk between transcription, mRNA processing, and termination (Mol Cell, 2012; Wiley RNA, 2014), (ii) transcription elongation (Transcription, 2013), (iii) genetic & epigenetic regulation (EMBO J, 2015; NAR, 2023), and (iv) DNA damage repair and pigmentation (Cell Rep, 2017). Based on these findings, we proposed that Mediator can act as a key central conductor orchestrating diverse factors and machineries at multiple transcriptional stages for precise gene expression control (Wiley RNA, 2014).

It has also emerged that multiple pathways responsible for cell growth, differentiation, or tissue development were able to converge on one or more of the ~30 subunits of Mediator complex. We first demonstrated that Mediator MED23 can act as a “molecular switch” between adipogenesis and smooth muscle cell differentiation, thus providing the initial evidence for the possible common origin for adipocytes and smooth muscle cells (Dev Cell, 2009; Genes Dev, 2012). Utilizing stem cells and conditional knockout mouse model that we have generated, we have further analyzed the roles of Mediator in embryonic stem cell differentiation, T cell development, neural differentiation, osteogenesis, and bone development, adipose Treg plasticity, and angiogenesis (Nat Comm, 2014; Development, 2015; Nat Comm, 2016; NAR, 2020; Nat Immunol, 2021; Comm Bio, 2022).

Dys-regulation or genetic mutations of developmental regulators often leads to diseases. We observed that MED23 is selectively important for Ras-active lung cancer cells (PNAS, 2012), and MED15 is selectively important for breast cancer metastasis, correlate with the hyperactive TGFb signaling (JMCB, 2014). Mediator MED23 mediates liver glucose/lipid metabolism (Cell Res, 2014) and participates liver fibrosis and inflammatory responses (PLoS Biol, 2019). Our recent work showed that an intellectual disability-related MED23 mutation dysregulates gene expression by altering chromatin conformation and enhancer activities (NAR, 2023). Collectively, we proposed to consider Mediator as a master cofactor, coordinating diverse developmental signaling and sophisticated gene programs to direct distinct cell fates and diseases (Development, 2014).

In sum, we have published research papers in prominent journals such as Dev Cell, Mol Cell, Nature Immunol, Genes Dev, PNAS, EMBO J, Nat Comm, PLoS Biol, NAR, and Development. These findings were commented by Mol Cell, EMBO J and highlighted by academic web such as F1000, Nature Asia-AIMBN, and BioArt, etc. Our future research will continue using the combinatorial approaches including protein biochemistry, molecular biology, conditional knockout/knockin mouse models, gene editing, and various high throughput methodology, to address some most challenging issues in our field, such as the dynamic interplay between genetic and epigenetic factors, the complexity of genome and epigenome organization, non-coding regulatory elements & non-coding RNAs (ncRNAs), and the regulatory network underlying development and diseases. Successfully addressing these challenges will vastly enhance our understanding of gene regulation as well as its impact on human health and disease, and facilitate the development of novel therapeutic strategies.