肖鵬(山東大學基礎醫學院生物化學與分子生物學系主任)

肖鵬，男，40歲（2024年），山東大學基礎醫學院教授，博士生導師 國家自然科學基金優秀青年基金獲得者；山東省“泰山學者”青年專家，山東省 優秀青年基金獲得者；山東大學傑出中青年；山東大學“齊魯青年學者”；山東 大學“未來學者”，山東大學基礎醫學院生物化學與分子生物學系主任。

基本介紹

• 中文名：肖鵬
• 國籍：中國

人物經歷

教育經歷

2006/7–2012/6，山東大學（UW-Madison美國威斯康星大學麥迪遜分校聯合培養），生化與分子生物學，博士，導師：汪天虹/JaeHyuk Yu

2002/9–2006/7，山東大學，生命科學， 學士， 導師：汪天虹

科研與學術工作經歷

2020/09-至今，山東大學基礎醫學院，研究員

2019/09-2020/09，山東大學基礎醫學院，副教授

2012/7-2018/08，山東大學基礎醫學院，講師

山東大學基礎醫學院生物化學與分子生物學系主任。

科研情況

研究方向

重大疾病靶標G蛋白偶聯受體（GPCR）進行結構與功能研究及天然產物篩選

創新成果

目前取得了系列創新性學術成績：1）闡明 重要神經遞質多巴胺受體的配體識別及激活機制，建立了GPCR調控Arrestin的 “碼頭分選”模型（Cell, 2021；Nat Chem Biol, 2018；Nat Commun, 2021）；2） 解析了具有神經活性脂類（固醇類和脂肪酸類）激素的識別機制，發現神經系 統疾病治療的GPCR新靶點（Proc Natl Acad Sci USA, 2022; Nature, 2021; Nature, 2020; Sci Adv, 2021）；3）開發了靶向GPCR和下游磷酸化網路治療神經系統疾病 的干預策略（Nature, 2022a; Nature, 2022b；J Neurochem, 2019; J Cell Mol Med, 2020; J Biol Chem, 2018;等）。迄今為止，在Cell、Nature (4篇)、Nat Chem Biol、PNAS等高水平期刊共發表學術論文32篇（含已接收）。其中以第一或通訊 作者（含共）發表論文19篇，包括4篇Nature (2022a; 2022b; 2021; 2020)，1篇Cell (2021)，2篇Nat Chem Biol (2018, 2022)，1篇Nature Commun (2021)，1篇Sci Adv (2021)。共主持國家自然科學基金項目2項，國家重點研發計畫子課題2項 （項目骨幹），山東省自然科學基金3項；擔任中國藥理學會生化與分子藥理學專 業委員會委員，山東生物化學與分子生物學會理事。

主持科研項目

1. 國家自然科學基金優秀青年基金，32222038, 神經系統GPCR結構與功能, 2023.01.01-2025.12.31，200萬元，課題負責人
2. 國家重點研發計畫，2019YFA0904200，基於基因密碼子擴展技術的非天然 真核系統的構建及其套用，2020.01.01-2024.12.31，45.32萬元，項目骨幹。
3. 國家自然科學基金面上項目, 31971195, CRHR2偏向性配體的發展和信號轉 導複合物的結構基礎, 2020.01.01-2023.12.31，63.51萬元，課題負責人。
4. 國家重點研發計畫青年項目，2019YFA0508801，組胺H3R精準調控神經乾 細胞特化的機制研究及其藥物發現，2019.11.01-2024.10.31，75.2萬元，項目 骨幹。
5. 國家自然科學基金青年項目，31700692，酪氨酸磷酸酶PTP1B和LYP催化活 性中心第二層胺基酸的功能研究，2018/01-2020/12，25萬元，課題負責人；
6. 山東省重點研發計畫，2018GSF118147，磷酸酶Slingshot催化機制、結構基 礎的研究和抑制劑的篩選，2018.04.01-2020.12.31，10萬元，課題負責人；
7. 山東省自然科學基金委，ZR2021YQ18，G蛋白偶聯受體信號轉導複合物結 構和功能研究，2022.01.01-2024.12.31，45萬元，課題負責人；
8. 山東大學齊魯青年學者建設經費，2022.01.01-2026.12.31，60萬，課題負責人；
9. 山東大學未來學者建設經費，2019.01.01-2021.12.31，50萬，課題負責人；

代表性論文

第一作者或共同一作文章 ( #第一作者, *通訊作者)

1. An W# , Lin H# , Ma L# , Zhang C, Zheng Y, Cheng Q, Ma C, Wu X, Zhang Z, Zhong Y, Wang M, He D, Yang Z, Du L, Feng S, Wang C, Yang F, Xiao P*, Zhang P*, Yu X *, Sun JP*. Progesterone activates GPR126 to promote breast cancer development via the Gi pathway. Proc Natl Acad Sci USA 2022 119(15):e2117004119.
2. Xiao P# , Yan W# , Gou L# , Zhong YN# , Kong L# , Wu C, Wen X, Yuan Y, Cao S, Qu C, Yang X, Yang CC, Xia A, Hu Z, Zhang Q, He YH, Zhang DL, Zhang C, Hou GH, Liu H, Zhu L, Fu P, Yang S, Rosenbaum D, Sun JP*, Du Y*, Zhang L*, Yu X*, Shao Z*. Ligand recognition and allosteric regulation of DRD1-Gs signaling complexes. Cell 2021 Feb 18;184(4):943-956. (IF: 38.83, 封面文章; Nature Reviews Drug Discovery 推薦)
3. Xiao P# , Guo SC# , Wen X# , He QT# , Lin H# , Huang SM# , Gou L# , Zhang C, Yang Z, Zhong YN, Yang CC, Li Y, Li SL, Tao XN, Yang ZS, Lu Y, He JY, Wang CX, Zhang L*, Kong LL*, Sun JP*, Yu X*. Tethered peptide activation mechanism of adhesion GPCRs ADGRG2 and ADGRG4. Nature 2022 604(7907):771-778(Nature 雜誌同期評 述).
4. Ping Y# , Xiao P# , Yang F# , Zhao RJ# , Guo SC# , Wu X# , Yan X# , Yang Z, An WT, Shen DD, Yang F, Zhang H, Qu C, Li ZJ, Shen Q, Tian C, Li S, Wang GY, Tao X, Wen X, Zhong YN, Yang J, Yi F, Yu X, Xu HE*, Zhang Y*, Sun JP*. Structural basis for the tethered peptide activation of adhesion GPCRs. Nature 2022 604(7907):763-770 (Nature 雜誌同期評述).
5. Yuqi Ping# , Chunyou Mao# , Peng Xiao# , Ru-Jia Zhao# , Yi Jiang# , Zhao Yang, Wen-Tao An, Dan-Dan Shen, Fan Yang, Huibing Zhang, Changxiu Qu, Zi-jian Li, Qingya Shen, Caiping Tian, Shaolong Li, Guang-Yu Wang, Xiaona Tao, Xin Wen, Ya-Ni Zhong, Jing Yang, Fan Yi, Xiao Yu, H. Eric Xu, Yan Zhang, Jin-Peng Sun. Structures of glucocorticoid-bound adhesion receptor GPR97-Go complex. Nature. 2021 Jan;589 (7843):620-626. (IF: 42.778；Faculty 1000 推薦)
6. Fan Yang# , Chunyou Mao# , Lulu Guo# , Jingyu Lin# , Qianqian Ming# , Peng Xiao# , Xiang Wu# , Qingya Shen, Shimeng Guo, Dan-Dan Shen, Ruirui Lu, Linqi Zhang, Shenming Huang, Yuqi Ping, Chenlu Zhang, Cheng Ma, Kai Zhang, Xiaoying Liang, Yuemao Shen, Fajun Nan, Fan Yi, Vincent C Luca, Jiuyao Zhou, Changtao Jiang, Jin-Peng Sun*, Xin Xie*, Xiao Yu*, Yan Zhang*. Structural basis of GPBAR activation and bile acid recognition. Nature. 2020 Nov;587(7834):499-504 (IF: 42.778)
7. Fan Yang# , Peng Xiao# , Chang-xiu Qu# , Qi Liu# , Liu-yang Wang, Zhi-xin Liu, Qing-tao He, Chuan Liu, Jian-ye Xu, Rui-rui Li, Meng-jing Li, Qing Li, Xu-zhen Guo, Dong-fang He, Fan Yi, Ka-Young Chuang, Ke Ruan, Yue-mao Shen, Xiao Yu, Jin-peng Sun* & Jiang-yun Wang*. Allosteric mechanisms underlie GPCR signalling to SH3-domain proteins through arrestin. Nature Chemical Biology. 2018, 14(9):876-886. (IF: 12.587)
8. Hui Lin# , Peng Xiao# , Rui-Qian Bu# , Shengchao Guo# , Zhao Yang# , Daopeng Yuan# , Zhong-Liang Zhu, Chuan-Xin Zhang, Qing-Tao He, Chao Zhang, Yu-Qi Ping, Ru-Jia Zhao, Chuan-Shun Ma, Chang-Hao Liu, Xiao-Ning Zhang, Dan Jiang, Shaohui Huang, Yue-Tong Xi, Dao-Lai Zhang, Chen-Yang Xue, Bai-Sheng Yang, Jian-Yuan Li, Hao-Cheng Lin, Xu-Hui Zeng, Han Zhao, Wen-Ming Xu, Fan Yi* , Zhongmin Liu* , Jin-Peng Sun* , Xiao Yu* Structures of the ADGRG2-Gs complex in apo and ligand bound forms. Nature Chemical Biology. 2022(Accepted)
9. Qu C# , Mao C# , Xiao P# , Shen Q# , Zhong YN# , Yang F# , Shen DD, Tao X, Zhang H, Yan X, Zhao RJ, He J, Guan Y, Zhang C, Hou Guihua, Zhang PJ, Hou Guige, Li Z, Yu X, Chai RJ*, Guan YF,10 Sun JP*, Zhang Y*. Ligand recognition, unconventional activation and G protein coupling of the prostaglandin E2 receptor 2. Science Advances 2021, Apr 2;7(14):eabf1268. (IF: 14.09)
10. He QT, Xiao P# , Huang SM, Jia YL, Zhu ZL, Lin JY, Yang F, Tao XN, Zhao RJ, Gao FY, Niu XG, Xiao KH, Wang JY*, Jin CW*, Sun JP*, Yu X*. Structural studies of phosphorylation-dependent interactions between the V2R receptor and arrestin-2. Nature Commun 2021, Apr 22;12(1):2396. (IF 13.610).
11. Shen-Ming Huang# , Peng Xiao# . Structural basis of signaling of cannabinoids receptors: paving a way for rational drug design in controling mutiple neurological and immune diseases. Signal Transduct and Target Ther. 2020, 5(1):127. (IF: 13.195)
12. Zhiyuan Lu# , Peng Xiao# , Yuan Zhou, Zhenyu Li, Xiao Yu, Jin-Peng Sun, Yuemao Shen, Baobing Zhao. Identification of HN252 as a potent inhibitor of protein phosphatase PPM1B. J Cell Mol Med. 2020 doi: 10.1111/jcmm.15975.
13. Yang D# , Xiao P# , Li Q# , Fu X, Pan C, Lu D, Wen S, Xia W, He, Li H, Fang H, Shen Y, Xu X, Lin A, Wang C, Yu X, Wu J*, Sun J*. Allosteric modulation of the catalytic VYD loop in Slingshot by its N-terminal domain underlies both Slingshot auto-inhibition and activation. J Biol Chem. 2018, 293(42):16226-16241. (IF:4.238)
14. Qiu-Yu Gong# , Wenqing Qing# , Peng Xiao# . Internal standard fluorogenic probe based on vibration-induced emission for visualizing PTP1B in living cells. Chem Commun (Camb). 2019 56(1):58-61. (IF: 5.989)
15. Meisam Rostaminasab Dolatabad# , Lulu Guo# , Peng Xiao# , Zhongliang Zhu, Qingtao He, DuxiaoYang, Changxiu Qu, Shengchao Guo, Xiaolei Fu, Ruirui Li, Lin Ge, Kejia Hu, Hongda Liu, Yuemao Shen, Xiao Yu, Jinpeng Sun*, Pengju Zhang*. Crystal structure and catalytic activity of the PPM1K N94K mutant. J Neurochem. 2019, 148(4):550-560. (IF: 4.066)
16. Kang-shuai Li# , Peng Xiao# , Dao-lai Zhang, Xu-Ben Hou, Lin Ge, Du-xiao Yang, Hong-da Liu, Dong-fang He, Xu Chen, Ke-rui Han, Xiao-yuan Song, Xiao Yu, Hao Fang, Jin-peng Sun. Identification of para-Substituted Benzoic Acid Derivatives as Potent Inhibitors of the Protein Phosphatase Slingshot. ChemMedChem. 2015 Dec;10(12):1980-7.
17. Peng Xiao# , Xiao Wang# , Hong-Mei Wang, Xiao-Lei Fu, Fu-ai Cui, Xiao Yu, Shi-shuai Wen, Wen-Xiang Bi*, Jin-Peng Sun*. The second-sphere residue T263 is important for the function and catalytic activity of PTP1B via interaction with the WPD-loop. Int J Biochem Cell Biol. 2014, 57:84-95. (IF: 3.673)
18. Peng Xiao, Shin KS, Wang T*, Yu JH*. Aspergillus fumigatus flbB encodes two basic leucine zipper domain (bZIP) proteins required for proper asexual development and gliotoxin production, Eukaryot Cell. 2010, 9(11):1711-1723.
19. 肖鵬, 孫金鵬, 裴鋼, 新生物學年鑑 2013（G 蛋白偶聯受體結構分析的近年進展）

其他作者文章

20. Qi Liu, Qing-Tao He, Xiaoxuan Lyu, Fan Yang, Zhong-Liang Zhu, Peng Xiao, Zhao Yang, Feng Zhang, Zhao-Ya Yang, Xiao-Yan Wang, Peng Sun, Qian-Wen Wang, Chang-Xiu Qu, Zheng Gong, Jing-Yu Lin, Zhen Xu, Shao-le Song, Shen-Ming Huang, Sheng-Chao Guo, Ming-Jie Han, Kong-Kai Zhu, Xin Chen, Alem W Kahsai, Kun-Hong Xiao, Wei Kong, Fa-Hui Li, Ke Ruan, Zi-Jian Li, Xiao Yu, Xiao-Gang Niu, Chang-Wen Jin, Jiangyun Wang, Jin-Peng Sun. DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl 1H-NMR probe. Nat Commun. 2020 Sep 25;11(1):4857.

21. Xiao Liang, Huansheng Fu, Peng Xiao, Hao Fang, Xuben Hou. Design, synthesis and biological evaluation of imidazolidine-2,4-dione and 2-thioxothiazolidin-4-one derivatives as lymphoid-specific tyrosine phosphatase inhibitors. Bioorg Chem. 2020 Oct;103:104124.

22. Kangshuai Li, Xuben Hou, Ruirui Li, Wenxiang Bi, Fan Yang, Xu Chen, Peng Xiao, Tiantian Liu, Tiange Lu, Yuan Zhou, Zhaomei Tian, Yuemao Shen, Yingkai Zhang, Jiangyun Wang, Hao Fang, Jinpeng Sun, Xiao Yu. Identification and structure-function analyses of an allosteric inhibitor of the tyrosine phosphatase PTPN22.J Biol Chem.2019 May 24;294(21):8653-8663.

23. Xuben Hou, David Rooklin, Duxiao Yang, Xiao Liang, Kangshuai Li, Jianing Lu, Cheng Wang, Peng Xiao, Yingkai Zhang, Jin-Peng Sun, Hao Fang. Computational Strategy for Bound State Structure Prediction in Structure-Based Virtual Screening: A Case Study of Protein Tyrosine Phosphatase Receptor Type O Inhibitors.J Chem Inf Model.2018 Nov 26;58(11):2331-2342.

24. Hui Li, Duxiao Yang, Shanglei Ning, Yinghui Xu, Fan Yang, Rusha Yin, Taihu Feng, Shouqing Han, Lu Guo, Pengju Zhang, Wenjie Qu, Renbo Guo, Chen Song, Peng Xiao, Chengjun Zhou, Zhigang Xu, Jin-Peng Sun, Xiao Yu. Switching of the substrate specificity of protein tyrosine phosphatase N12 by cyclin-dependent kinase 2 phosphorylation orchestrating 2 oncogenic pathways. FASEB J. 2018 Jan;32(1):73-82.

25. Huatang Zhang, Peng Xiao, Yin Ting Wong, Wei Shen, Mohit Chhabra, Raoul Peltier, Yin Jiang, Yonghe He, Jun He, Yi Tan, Yusheng Xie, Derek Ho, Yun-Wah Lam, Jinpeng Sun, Hongyan Sun. Construction of an alkaline phosphatase-specific two-photon probe and its imaging application in living cells and tissues. Biomaterials. 2017 Sep;140:220-229.

26. Zhao Yang, Fan Yang, Daolai Zhang, Zhixin Liu, Amy Lin, Chuan Liu, Peng Xiao, Xiao Yu, Jin-Peng Sun. Phosphorylation of G Protein-Coupled Receptors: From the Barcode Hypothesis to the Flute Model. Mol Pharmacol. 2017 Sep;92(3):201-210.

27. Chun-Hua Liu, Zheng Gong, Zong-Lai Liang, Zhi-Xin Liu, Fan Yang, Yu-Jing Sun, Ming-Liang Ma, Yi-Jing Wang, Chao-Ran Ji, Yu-Hong Wang, Mei-Jie Wang, Fu-Ai Cui, Amy Lin, Wen-Shuai Zheng, Dong-Fang He, Chang-Xiu Qu, Peng Xiao, Chuan-Yong Liu, Alex R B Thomsen, Thomas Joseph Cahill 3rd, Alem W Kahsai, Fan Yi, Kun-Hong Xiao, Tian Xue, Zhuan Zhou, Xiao Yu, Jin-Peng Sun. Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling. Nat Commun. 2017 Feb 9;8:14335.

28. Lin Ge, Kang-Shuai Li, Meng-Meng Li, Peng Xiao, Xu-Ben Hou, Xu Chen, Hong-da Liu, Amy Lin, Xiao Yu, Gui-Jie Ren, Hao Fang, Jin-Peng Sun. Identification of a benzo imidazole thiazole derivative as the specific irreversible inhibitor of protein tyrosine phosphatase. Bioorg Med Chem Lett. 2016 Oct 1;26(19):4795-4798.

29. Hui Li, Fan Yang, Chunhua Liu, Peng Xiao, Yunfei Xu, Zonglai Liang, Chuan Liu, Hongmei Wang, Wenjun Wang, Wenshuai Zheng, Wei Zhang, Xiaoyun Ma, Dongfang He, Xiaoyuan Song, Fuai Cui, Zhigang Xu, Fan Yi, Jin-Peng Sun, Xiao Yu. Crystal Structure and Substrate Specificity of PTPN12. Cell Rep. 2016 May 10;15(6):1345-58.

30. Chang Pan, Jun-yi Tang, Yun-fei Xu, Peng Xiao, Hong-da Liu, Hao-an Wang, Wen-bo Wang, Fan-guo Meng, Xiao Yu, Jin-peng Sun. The catalytic role of the M2 metal ion in PP2Cα. Sci Rep. 2015 Feb 24;5:8560.

31. Yanmei Zhang, Jiwei Zhang, Peng Xiao, Tianhong Wang, Yinbo QuImproved cellulase production via disruption of PDE01641 in cellulolytic fungus Penicillium decumbens. Bioresour Technol. 2012 Nov;123:733-7.

32. Jiwei Zhang, Yinbo Qu, Peng Xiao, Xiaoyan Wang, Tianhong Wang, Feng HeImproved biomass saccharification by Trichoderma reesei through heterologous expression of lacA gene from Trametes sp. AH28-2. J Biosci Bioeng. 2012 Jun;113(6):697-703.

33. Yaohua Zhong, Xuan Liu, Peng Xiao, Songhuan Wei, Tianhong Wang. Expression and secretion of the human erythropoietin using an optimized cbh1 promoter and the native CBH I signal sequence in the industrial fungus Trichoderma reesei. Appl Biochem Biotechnol. 2011 Nov;165(5-6):1169-77.

學術獎勵

肖鵬 (3/5), 靶向 G 蛋白偶聯受體和磷酸酶的藥理學研究, 山東省教育廳, 山東 省高等學校優秀科研成果獎，一等獎，2015 (孫金鵬，於曉，肖鵬, 龐琦，方浩）。

所獲榮譽

2024年8月，入選第三屆鐘南山青年科技創新獎擬授獎人選名單（套用學科類）。