个人简介

杨培国，吉林省临江市人，西湖大学生命科学学院研究员，博士生导师。2007毕业于北京师范大学，获得学士学位。2012年获得北京师范大学与北京生命科学研究所联合培养生物化学与分子生物学博士学位。2012-2020年先后于中国科学院生物物理研究所、哈佛医学院及St. Jude儿童医院从事博士后研究。2020年9月加入西湖大学生命科学学院，组建相分离与生物分子凝聚体实验室。

学术成果与未来研究方向

一、液-液相分离与生物分子凝聚体

细胞的区域化(compartmentalization）是细胞的一个典型特征。典型的有膜细胞器包括线粒体，溶酶体等；而典型的无膜细胞器包括核仁，应激颗粒(stress granule)等。许多无膜细胞器又被称为生物分子凝聚体，而其形成机制目前并不清楚。过去几年的研究将液-液相分离的概念引入生物系统，采用生物化学与生物物理学的手段来解释生物分子凝聚体的形成，加深了对其组装与功能的认识。实验室目前针对相分离在各类信号转导、酶活调控、病原微生物-宿主互作，及神经退行疾病方面的多种生物分子凝聚体展开研究，探讨其背后共同及特异性的调控机制。

二、应激颗粒

    各类RNP颗粒是广泛存在于细胞内的一大类生物分子凝聚体，其中，应激颗粒作为一类典型的无膜细胞器，具有广泛的生物学意义。先前的工作阐述了应激颗粒组装的关键蛋白及其相分离机制，而且建立了一套研究分子凝聚体的指导框架（Cell, 2020；Cell Rep, 2024）。应激颗粒在细胞胁迫应激和肿瘤、神经退行疾病中有密切联系，实验室将继续就应激颗粒在各种生理及病例情况的形成机制和功能展开研究。

三、生物分子凝聚体与人类疾病

    相分离在生理条件下生物分子凝聚体形成中的重要性，而且为研究各种人类疾病，尤其是神经退行疾病提供了新思路，包括阿尔茨海默病，帕金森病，渐冻症(ALS）等在内的神经退行疾病的一个典型特征是相关致病蛋白的聚集，相分离过程可能参与了疾病发生的各个阶段。寻找参与相变的核心组分并研究其发生相变的分子机制，将为疾病治疗提供新的干预手段。实验室将综合运用生物化学、分子生物学、细胞生物学及生物物理学的方法对生理与病理相关的生物分子凝聚体的形成机制与生理/病理功能展开研究，并基于对相关生物分子聚集体的认识设计与开发新的化学干预手段。

代表论文

  (*First and co-first author; # corresponding)

1. Zhiying Yao, Yi Liu, Qi Chen, Xiaoxin Chen, Zhenshuo Zhu, Sha Song, Xianjue Ma, Peiguo Yang#. The divergent effects of G3BP orthologs on human stress granule assembly imply a centric role for the core protein interaction network. Cell Rep. 2024 Aug 8;43(8):114617.

2. Yi Liu, Peiguo Yang#. eIF4G as a switch for heat shock mRNA translation. Mol Cell. 2024 May 2;84(9):1633-1634.

3. Ke Ruan#, Yi Lin#, Peiguo Yang#., Wen Zhou#. Condensation matters. Nat Chem Biol. 2023;19(10):1180-1182.

4. Zhenshuo Zhu, Peiguo Yang#. RNA repeats stall translation. Nat Chem Biol. 2023;19(11):1299-1300.

5. Yi Liu, Zhiying Yao, Guiwei Lian, Peiguo Yang#. Biomolecular phase separation in stress granule assembly and virus infection. Acta Biochim Biophys Sin (Shanghai). 2023;55(7):1099-1118.

6. Peiguo Yang*, Cécile Mathieu*, Regina M. Kolaitis, Peipei Zhang, James Messing, Ugur Yurtsever, Zemin Yang, Jinjun Wu, Yuxin Li, Qingfei Pan, Jiyang Yu, Erik W. Martin, Tanja Mittag, Hong Joo Kim, J. Paul Taylor. G3BP1 is a tunable switch that triggers phase separation to assemble stress granules. Cell 2020; 181: 325-345 (*equal contribution)

7. Peiguo Yang, Hong Zhang. You are what you eat: multifaceted functions of autophagy during C. elegans development. Cell Res 2014; 24: 80-91

8. Sihui Li*, Peiguo Yang*, E Tian, Hong Zhang. Arginine Methylation Modulates Autophagic Degradation of PGL Granules in C. elegans. Mol. Cell 2013; 52: 421-33. (*co-first author)

9. Yinyan Sun*, Peiguo Yang*, Yuxia Zhang*, Xin Bao, Jun Li, Wenru Hou, Xiangyu Yao, Jinghua Han, Hong Zhang. A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi. Protein Cell 2011; 2:918-39. (*co-first author) 

10. Peiguo Yang, Hong Zhang. The coiled-coil domain protein EPG-8 plays an essential role in the autophagy pathway in C. elegans. Autophagy 2011; 7: 159-65.

11. Yuxia Zhang*, Libo Yan*, Zhi Zhou*, Peiguo Yang*, E Tian, Kai Zhang, Yu Zhao, Zhipeng Li, Bing Song, Jinghua Han, Long Miao, Hong Zhang. SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy in C. elegans. Cell 2009; 136:308-21. (*co-first author)

12. Ting Qiu, Yichao Kong, Guifeng Wei, Kai Sun, Ruijie Wang, Yang Wang, Yiji Chen, Wenxin Wang, Yun Zhang, Caihong Jiang, Peiguo Yang, Tian Xie, Xiabin Chen. CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche. Proc Natl Acad Sci U S A. 2024 Jun 4;121(23):e2322359121.

13. Zehua Shang, Sitao Zhang, Jinrui Wang, Lili Zhou, Xinyue Zhang, Daniel D Billadeau, Peiguo Yang, Lingqiang Zhang, Fangfang Zhou, Peng Bai, Da Jia. TRIM25 predominately associates with anti-viral stress granules. Nat Commun. 2024 May 15;15(1):4127.

14. Qinqin Cui, Hongyun Bi, Zhanyun Lv, Qigui Wu, Jianfeng Hua, Bokai Gu, Chanjuan Huo, Mingmin Tang, Yanqin Chen, Chongjiu Chen, Sihan Chen, Xinrui Zhang, Zhangrui Wu, Zhengkai Lao, Nengyin Sheng, Chengyong Shen, Yongdeng Zhang, Zhi-YingWu, Zhigang Jin, Peiguo Yang, Huaqing Liu, Jinsong Li, Ge Bai. Diverse CMT2 neuropathies are linked to aberrant G3BP interactions in stress granules. Cell 2023; 186(4):803-820.e25.

15. Brian D Freibaum, James Messing, Peiguo Yang, Hong Joo Kim, J. Paul Taylor.   High-fidelity reconstitution of stress granules and nucleoli in mammalian cellular lysate. J Cell Biol 2021; Mar 1;220(3):e202009079. 

16. Anna K. Lee, Jonathon Klein, Klementina Fon Tacer, Tessa Lord, Melissa J. Oatley, Jon M. Oatley, Shaina N. Porter, Shondra M. Pruett-Miller, Elena B. Tikhonova, Andrey L. Karamyshev, Yong-Dong Wang, Peiguo Yang, Ane Korff, Hong Joo Kim, J. Paul Taylor, and Patrick Ryan Potts. Translational Repression of G3BP in Cancer and Germ Cells Suppresses Stress Granules and Enhances Stress Tolerance. Mol. Cell 2020; 79: 645-59.

17. Cristina Batlle, Peiguo Yang, Maura Coughlin, James Messing, Mireia Pesarrodona, Elzbieta Szulc, Xavier Salvatella, Hong Joo Kim, J. Paul Taylor and Salvador Ventura. hnRNPDL phase separation is regulated by alternative splicing and disease-causing mutations accelerate its aggregation. Cell reports 2020; 30:1117–1128.

18. Peipei Zhang, Baochang Fan, Peiguo Yang, Jamshid Temirov, James Messing, Hong Joo Kim, J Paul Taylor. Chronic optogenetic induction of stress granules is cytotoxic and reveals the evolution of ALS-FTD pathology. eLife 2019;8:e39578

19. Yubing Liu, Wei Zou, Peiguo Yang, Li Wang, Yan Ma, Hong Zhang, Xiaochen Wang. Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development. eLife 2018;7:e36588

20. Ke Zhang, Gavin Daigle, Kathleen M. Cunningham, Alyssa N. Coyne, Kai Ruan, Jonathan C. Grima, Kelly E. Bowen, Harsh Wadhwa, Peiguo Yang, Frank Rigo, J. Paul Taylor, Aaron D. Gitler, Jeffrey D. Rothstein and Thomas E. Lloyd. Stress Granule Assembly Disrupts Nucleocytoplasmic Transport. Cell 2018; 173: 958-971.

21. Tommaso Poggioli*, Ana Vujic*, Peiguo Yang, Claudio Macias-Trevino, Aysu N Uygur, Francesco S    Loffredo, James R Pancoast, Miook Cho, Jill Goldstein, Rachel M Tandias, Emilia Gonzalez, Ryan G Walker, Thomas B Thompson, Amy J Wagers, Yick W Fong, Richard T Lee. Circulating Growth Differentiation Factor 11/8 Levels Decline with Age. Circ. Res 2015; 7442: 467-73.  (*co-first author)

22. Long Lin, Peiguo Yang, Xinxin Huang, Qun Lu, Hui Zhang, Hong Zhang. The scaffold protein EPG-7 links cargo/receptor complexes with the autophagic assembly machinery. J Cell Biol 2013; 201:113-129.

23. Qianqian Liang, Peiguo Yang, E Tian, Jinghua Han, Hong Zhang. The C. elegans ATG101 homolog EPG-9 directly interacts with EPG-1/Atg13 and is essential for autophagy. Autophagy 2012; 8:1426-33.

24. Qun Lu, Peiguo Yang, Xinxin Huang, Wanqiu Hu, Bin Guo, Fan Wu, Long Lin, Attila L. Kovács, Li Yu, Hong Zhang. The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates progression of omegasomes to autophagosomes. Dev Cell 2011; 21:343-357.

25. Ye Tian, Haiyan Ren, Yu Zhao, Qun Lu, Xinxin Huang, Peiguo Yang, Hong Zhang. Four metazoan autophagy genes regulate cargo recognition, autophagosome formation and autolysosomal degradation. Autophagy 2010; 6:984-5.

26. Ye Tian*, Zhipeng Li*, Wanqiu Hu*, Haiyan Ren*, E Tian, Yu Zhao, Qun Lu, Xinxin Huang, Peiguo Yang, Xin Li, Xiaochen Wang, Attila L. Kova ́cs, Li Yu, Hong Zhang. C. elegans Screen Identifies Autophagy Genes Specific to Multicellular Organisms. Cell 2010; 141:1042-55. (*co-first author)

联系方式

电子邮箱：yangpeiguo@westlake.edu.cn

本实验室常年招收博士新生轮转，欢迎感兴趣的同学通过电子邮件直接联系，同时也欢迎有意报考西湖大学的优秀本科生前来实验室完成毕业设计，实验室招聘科研助理（本科学位），博士后（博士学位），欢迎通过电子邮件联系。