王綱

發布時間：2021-06-29瀏覽次數：9110

教師基本信息：

姓名：王綱（WANG Gang）

職稱：正高級

職務：万博英超狼队网官方网 特聘教授，副院長（Distinguished Professor and Vice Dean）

電子郵箱：gwang_fd@fudan.edu.cn

辦公地點：万博英超狼队网官方网 E座201室


研究方向：

本實驗室長期專注於轉錄中介體的分子調控機理及其在發育（成體幹細胞分化等）和疾病（代謝疾病、神經相關疾病、癌症等）中的功能研究。發現轉錄中介體（Mediator）在mRNA剪切加工、轉錄延伸、以及DNA損傷修複過程中的非經典功能；首次提出平滑肌與脂肪細胞的“雙向調控”及其共同起源；發現Mediator不同亞基在胚胎幹細胞幹性維持及多譜係細胞分化中的不同功能；發現轉錄中介體亞基MED23參與調控間充質幹細胞向成骨細胞分化過程並影響成骨的發育；揭示Mediator作為表觀遺傳調控因子,調控癌症與肌肉細胞分化之間的拮抗作用等。

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.


個人簡介：

王綱，万博英超狼队网官方网 特聘教授，長期研究發育與疾病的轉錄及表觀遺傳調控；作為通訊作者在Mol Cell，Dev Cell，Genes Dev，EMBO J，PNAS，Nature Comm，PloS Biol等雜誌發表論文。多項工作作為Mol Cell，EMBO J等重要學術期刊的封麵文章發表，獲同期專評，以及Faculty1000, Nature Asia-AIMBN, BioArt,“知識分子”的亮點評論。現任中國細胞生物學學會資深理事、Asian Transcription Conference 國際組委、JBC、TRANSCRIPTION學術期刊編委，獲“百人計劃”和“上海浦江人才計劃”及“國務院特殊津貼”支持，作為首席科學家先後主持國家重大科學研究計劃、國家重點研發計劃項目及國家自然科學基金重點項目。

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.


授課情況：《分子生物學》（本科）、《幹細胞與發育》（本科）、《科研之道》（研究生、本科生）

招生專業：生物化學；細胞與發育生物學；遺傳學；生物與醫藥

科研項目：

在研項目包括：國家自然科學基金重點項目、麵上項目及科技部國家重點研發計劃

獲獎情況：中科院“百人計劃”、“浦江人才計劃”、國務院特殊津貼、中科院朱李月華優秀教師獎（2013）、中科院優秀研究生指導教師獎（2013）

代表性論文和論著：

  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.



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