学习经历

1995-1998  武汉大学，生物物理化学，博士

1985-1988  武汉大学，生物物理化学，硕士

1981-1985  武汉大学，化学，学士

主要工作经历与任职情况

2001-至今  武汉大学生命科学学院，教授

2022-至今  武汉大学泰康生命医学中心，实验室负责人

2013-2013  美国密歇根大学医学院，高级访问学者

2008-2008  美国国立健康研究院（NIH，高级访问学者

2006-2007  美国国立健康研究院（NIH），高级访问学者

2001-2002  法国Louis Pasteur大学，高级访问学者

2001-2001  武汉大学生命科学学院，副教授

1998-2000  中国科学院生物物理研究所，博士后

1996-1998  武汉工程大学化工与制药学院，副教授

1988-1995  武汉工程大学化工与制药学院，讲师

主要社会兼职

2014/08-至今  中国生物化学与分子生物学会，理事

2021/08-至今  中国生物物理学会生物微量元素分会，副会长

2015/08-至今  中国生物物理学会分子生物物理分会，理事

2006/12-至今  Acta Biochimica et Biophysica Sinica（SCI源刊），编委

2020/08-至今  《生命的化学》，编委

2013/06-至今  湖北省生物化学与分子生物学学会，副理事长

主要科研奖励和个人荣誉

“体外和生理拥挤环境中蛋白质折叠和错误折叠机制研究”，湖北省自然科学奖二等奖，第一完成人，2010年

“大分子拥挤环境中朊蛋白错误折叠机制研究”，湖北省优秀博士学位论文指导教师，2011年

研究内容

Prion疾病是一类可传染的致死性神经退行性疾病，其主要病理特征为朊蛋白（PrP）由细胞型PrP^C转变为病理型PrP^Sc；肌萎缩侧索硬化症（ALS）是一种涉及大脑皮层、脑干和脊髓等主要运动神经元的神经退行性疾病，其病理特征之一是铜锌超氧化物歧化酶（SOD1）和TAR DNA结合蛋白43（TDP-43）在中枢神经系统的运动神经元中形成纤维；阿尔茨海默病等神经退行性疾病的病理特征之一是神经细胞内病理磷酸化修饰的微管结合蛋白Tau错误折叠形成的神经纤维缠结。梁毅实验室近年来运用生命科学及医学前沿技术研究金属离子、分子伴侣、病理突变、翻译后修饰和液-液相分离在神经退行性疾病发病过程中的作用，开展以致病蛋白质为靶标的药物设计和新药研发，在神经退行性疾病相关重要蛋白质朊蛋白、Tau蛋白、SOD1和TDP-43及其病理突变体淀粉样纤维的冷冻电镜结构测定及功能研究领域取得一系列成果，解析全长PrP纤维和全长SOD1纤维的冷冻电镜结构，发现散发型ALS病人脑脊液样本中的次磺酸化修饰SOD1水平显著高于对照组，提出在PrP和SOD1错误折叠过程中，PrP^C C端的两个a-螺旋转变成PrP纤维的b-折叠结构，脱辅基SOD1亚基的一个a-螺旋和b-桶状结构转变成SOD1纤维的b-折叠结构，揭示了PrP和SOD1由生理型向病理型结构转变及病理聚集多态性的分子机制。

主持课题项目

1. 国家自然科学基金面上项目，32271326，Hsp70调控朊病毒蛋白相分离、聚集和毒性的分子机制研究，2023.01-2026.12，主持；

2. 国家自然科学基金面上项目，32071212，全长朊蛋白淀粉样纤维的冷冻电镜结构测定及功能研究，2021.01-2024.12，主持；

3. 国家自然科学基金面上项目，31770833，病理过氧化氢对超氧化物歧化酶致病结构形成的调控，2018.01-2021.12，主持；

4. 国家自然科学基金青年科学基金项目，32201040，超氧化物歧化酶病理聚集多态性的分子机制研究，2023.01-2025.12，本室王利强博士后主持；

5. 国家自然科学基金面上项目，31570779，人Tau蛋白纤维结构传递的机制研究，2016.01-2019.12，主持；

6. 国家自然科学基金面上项目，31370774，翻译后修饰对人朊蛋白致病结构形成的调控，2014.01-2017.12，主持；

7. 国家科技部973项目，2013CB910700，退行性疾病相关重要蛋白质翻译后修饰的化学生物学研究，2013.1-2017.12，课题负责人；

8. 国家科技部973项目，2012CB911000，蛋白质的生成、修饰与质量控制，2012.1-2016.12，学术骨干；

9. 国家自然科学基金面上项目，31170744，锌离子对人Tau蛋白致病结构形成的调控，2012.01-2015.12，主持；

10. 国家自然科学基金面上项目，30970599，模拟生理环境中朊蛋白错误折叠与聚集的机制，2010.01-2012.12，主持；

11. 国家自然科学基金面上项目，30770421，大分子拥挤环境中溶菌酶错误折叠与聚集的机制，2008.01-2010.12，主持；

12. 国家科技部973项目，2006CB910300，蛋白质生成、折叠、组装和降解的规律及其质量控制，2006.1-2010.12，课题负责人；

13. 教育部“新世纪优秀人才支持计划”资助项目，NCET-04-0670，G蛋白偶联受体激酶与钙调蛋白相互作用及调控机制的研究，2005.01-2007.12，主持；

14. 国家自然科学重大研究计划“真核生物重要生命活动的信息基础”资助项目，90408012，钙调蛋白与靶蛋白相互作用及调控机制的信息基础，2005.01-2007.12，主持；

15. 国家自然科学基金面上项目，30370309，大分子拥挤环境中蛋白质相互作用的机制，2004.01-2006.12，主持；

16. 国家科技部863课题，2004AA404260，非硅MEMS加工技术及其应用研究，2004.10-2005.06，学术骨干；

17. 国家自然科学基金面上项目，39970164，单抗探针探测蛋白质折叠机制的微量热研究，2000.01-2002.12，主持；

18. 武汉大学人才引进启动基金资助项目，00029，分子伴侣帮助蛋白质折叠机制的微量热学研究，2001.01-2005.12，主持。

发表的论文（^#并列第一作者，^*通讯作者）

1. Li-Qiang Wang#, Kun Zhao#, Han-Ye Yuan, Qiang Wang, Zeyuan Guan, Jing Tao, Xiang-Ning Li, Yunpeng Sun, Chuan-Wei Yi, Jie Chen, Dan Li, Delin Zhang, Ping Yin, Cong Liu*, Yi Liang*. Cryo-EM structure of an amyloid fibril formed by full-length human prion protein. Nature Structural & Molecular Biology 2020 Jun, 27(6), 598-602.

2. Li-Qiang Wang#, Kun Zhao#, Han-Ye Yuan#, Xiang-Ning Li, Hai-Bin Dang, Yeyang Ma, Qiang Wang, Chen Wang, Yunpeng Sun, Jie Chen, Dan Li, Delin Zhang, Ping Yin, Cong Liu*, Yi Liang*. Genetic prion disease-related mutation E196K displays a novel amyloid fibril structure revealed by cryo-EM. Science Advances 2021 Sep 10, 7(37), eabg9676.

3. Li-Qiang Wang#, Yeyang Ma#, Han-Ye Yuan#, Kun Zhao, Mu-Ya Zhang, Qiang Wang, Xi Huang, Wen-Chang Xu, Bin Dai, Jie Chen, Dan Li, Delin Zhang, Zhengzhi Wang, Liangyu Zou, Ping Yin, Cong Liu*, Yi Liang*. Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion. Nature Communications 2022 Jun 17, 13(1), 3491.

4. Wen-Chang Xu#, Jin-Zhao Liang, Cheng Li, Zhi-Xin He, Han-Ye Yuan, Ben-Yan Huang, Xiao-Ling Liu, Bo Tang, Dai-Wen Pang, Hai-Ning Du, Yi Yang, Jie Chen, Lei Wang, Min Zhang*, Yi Liang*. Pathological hydrogen peroxide triggers the fibrillization of wild-type SOD1 via sulfenic acid modification of Cys-111. Cell Death Dis. 2018 Jan 22, 9(2), 67.

5. Kan Wang#, Jia-Qi Liu#, Tao Zhong, Xiao-Ling Liu, Yan Zeng, Xinhua Qiao, Ting Xie, Yuzhe Chen, Ying-Ying Gao, Bo Tang, Jia Li, Jun Zhou, Dai-Wen Pang, Jie Chen, Chang Chen, Yi Liang*. Phase separation and cytotoxicity of Tau are modulated by protein disulfide isomerase and S-nitrosylation of this molecular chaperone. J. Mol. Biol. 2020 Mar 27, 432(7), 2141-2163.

6. Jun-Jie Huang#, Xiang-Ning Li#, Wan-Li Liu, Han-Ye Yuan, Yuan Gao, Kan Wang, Bo Tang, Dai-Wen Pang, Jie Chen, Yi Liang*. Neutralizing mutations significantly inhibit amyloid formation by human prion protein and decrease its cytotoxicity. J. Mol. Biol. 2020 Feb 14, 432(4), 828-844.

7. Xinxin Zuo#, Jie Zhou#, Yinming Li#, Kai Wu, Zonggui Chen, Zhiwei Luo, Xiaorong Zhang, Yi Liang, Miguel A. Esteban, Yu Zhou*, Xiang-Dong Fu*. TDP-43 aggregation induced by oxidative stress causes global mitochondrial imbalance in ALS. Nature Structural & Molecular Biology 2021 Feb, 28(2), 132-142.

8. Bin Dai#, Tao Zhong, Zhi-Xian Chen, Wang Chen, Na Zhang, Xiao-Ling Liu, Li-Qiang Wang, Jie Chen, Yi Liang*. Myricetin slows liquid-liquid phase separation of Tau and activates ATG5-dependent autophagy to suppress Tau toxicity. J. Biol. Chem. 2021 Oct, 297(4), 101222.

9. Ying-Ying Gao#, Tao Zhong#, Li-Qiang Wang, Na Zhang, Yan Zeng, Ji-Ying Hu, Hai-Bin Dang, Jie Chen, Yi Liang*. Zinc enhances liquid-liquid phase separation of Tau protein and aggravates mitochondrial damages in cells. Int. J. Biol. Macromol. 2022 Jun 1, 209(Pt A), 703-715.

10. Tianxin Xie#, Yuying Li, Chuan Tian, Chang Yuan, Bin Dai, Shubo Wang, Kaixiang Zhou, Jiaqi Liu, Hongwei Tan, Yi Liang*, Jiapei Dai, Baian Chen*, Mengchao Cui*. Fused cycloheptatriene–BODIPY is a high-performance near-infrared probe to image Tau tangles. J. Med. Chem. 2022 Nov 10, 65(21), 14527-14538.

11. Kaixiang Zhou#, Chang Yuan, Bin Dai, Kan Wang, Yimin Chen, Denglei Ma, Jiapei Dai, Yi Liang*, Hongwei Tan*, Mengchao Cui*. Environment-sensitive near-infrared probe for fluorescent discrimination of Ab and Tau fibrils in AD brain. J. Med. Chem. 2019 Jul 25, 62(14), 6694-6704.

12. Fan Yang#, Kan Wang, Kaixiang Zhou, Bin Dai, Jiapei Dai, Yi Liang*, Mengchao Cui*. Synthesis and bioevaluation of technetium-99 m / rhenium labeled phenylquinoxaline derivatives as Tau imaging probes. Eur. J. Med. Chem. 2019 Sep 1, 177, 291-301.

13. Ji-Ying Hu#, De-Lin Zhang, Xiao-Ling Liu, Xue-Shou Li, Xiao-Qing Cheng, Jie Chen, Hai-Ning Du, Yi Liang*. Pathological concentration of zinc dramatically accelerates abnormal aggregation of full-length human Tau and thereby significantly increases Tau toxicity in neuronal cells. Biochim. Biophys. Acta-Mol. Basis Dis. 2017 Feb, 1863(2), 414-427.

14. Ting Zhang#, Jing Li#, Yong-Zhong Jiang, Jun-Qiang Xu, Xu-Hua Guan, Li-Qiang Wang, Jie Chen, Yi Liang* (2022). Genotype distribution and evolutionary analysis of rotavirus associated with acute diarrhea outpatients in Hubei, China, 2013–2016. Virol. Sin. 37(4), 503-512.

15. Yuying Li#, Kan Wang, Kaixiang Zhou, Wentao Guo, Bin Dai, Yi Liang*, Jiapei Dai, Mengchao Cui* (2018). Novel D-A-D based near-infrared probes for the detection of beta-amyloid and Tau fibrils in Alzheimer's disease. Chem. Commun. 54(63), 8717-8720.

16. 王利强，袁菡烨，陶菁，郝苗苗，陈杰，朱海丽，梁毅* (2023). 全长朊粒蛋白淀粉样纤维引发细胞毒性的机制研究. 生物化学与生物物理进展 50(5), 1195-1205.

17. Haibin Dang#, Zhixian Chen, Wang Chen, Xudong Luo, Pan Liu, Liqiang Wang, Jie Chen, Xuhai Tang, Zhengzhi Wang, Yi Liang* (2022). The residues 4 to 6 at the N-terminus in particular modulate fibril propagation of b₂-microglobulin. Acta Biochim. Biophys. Sin. 54(2), 187-198.

18. Xu-Dong Luo#, Fan-Lou Kong, Hai-Bin Dang, Jie Chen, Yi Liang* (2016). Macromolecular crowding favors the fibrillization of beta2-microglobulin by accelerating the nucleation step and inhibiting fibril disassembly. Biochim. Biophys. Acta 1864(11), 1609-1619.

19. Xiao-Ling Liu#, Ji-Ying Hu, Meng-Yun Hu, Yi Zhang, Zheng-Yuan Hong, Xiao-Qing Cheng, Jie Chen, Dai-Wen Pang, Yi Liang* (2015). Sequence-dependent abnormal aggregation of human Tau fragment in an inducible cell model. Biochim. Biophys. Acta-Mol. Basis Dis. 1852(8), 1561-1573.

20. Kai Pan#, Chuan-Wei Yi, Jie Chen, Yi Liang* (2015). Zinc significantly changes the aggregation pathway and the conformation of aggregates of human prion protein. Biochim. Biophys. Acta 1854(8), 907-918.

21. Qian Ma#, Ji-Ying Hu, Jie Chen, Yi Liang* (2013). The role of crowded physiological environments in prion and prion-like protein aggregation. Int. J. Mol. Sci. 14(11), 21414-21427.

22. Chuan-Wei Yi#, Wen-Chang Xu, Jie Chen, Yi Liang* (2013). Recent progress in prion and prion-like protein aggregation. Acta Biochim. Biophys. Sin. 45(6), 520-526.

23. De-Lin Zhang#, Ling-Jia Wu, Jie Chen, Yi Liang* (2012). Effects of macromolecular crowding on the structural stability of human alpha-lactalbumin. Acta Biochim. Biophys. Sin. 44(8), 703-711.

24. Zheng Zhou#, Jun-Ming Liao, Peng Zhang, Jun-Bao Fan, Jie Chen, Yi Liang* (2011). Parkinson disease drug screening based on the interaction between D2 dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis. Protein Cell 2(11), 899-905.

25. Zheng Zhou#, Xu Yan, Kai Pan, Jie Chen, Zheng-Sheng Xie, Geng-Fu Xiao, Fu-Quan Yang, Yi Liang* (2011). Fibril formation of the rabbit/human/bovine prion proteins. Biophys. J. 101(6), 1483-1492.

26. Fan-Lou Kong#, Wei Cheng, Jie Chen, Yi Liang* (2011). D-ribose glycates beta2-microglobulin to form aggregates with high cytotoxicity through a ROS-mediated pathway. Chem.-Biol. Interact. 194(1), 69-78.

27. Hai-Li Zhu#, Cristina Fernández, Jun-Bao Fan, Frank Shewmaker, Jie Chen, Allen P. Minton, Yi Liang* (2010). Quantitative characterization of heparin binding to Tau protein: Implication for inducer mediated Tau filament formation. J. Biol. Chem. 285(6), 3592-3599.

28. Ming Jiao#, Hong-Tao Li, Jie Chen, Allen P. Minton*, Yi Liang* (2010). Attractive protein-polymer interactions markedly alter the effect of macromolecular crowding on protein association equilibria. Biophys. J. 99(3), 914-923.

29. Zhong-Ying Mo#, Ying-Zhu Zhu, Hai-Li Zhu, Jun-Bao Fan, Jie Chen, Yi Liang* (2009). Low micromolar zinc accelerates the fibrillization of human Tau via bridging Cys-291 and Cys-322. J. Biol. Chem. 284(50), 34648-34657.

30. Zheng Zhou#, Jun-Bao Fan#, Hai-Li Zhu, Frank Shewmaker, Xu Yan, Xi Chen, Jie Chen, Geng-Fu Xiao, Lin Guo, Yi Liang* (2009). Crowded cell-like environment accelerates the nucleation step of amyloidogenic protein misfolding. J. Biol. Chem. 284(44), 30148-30158.

31. Min Zhang#, Fang Yang (Jr.), Fang Yang, Jie Chen, Cong-Yi Zheng, Yi Liang* (2009). Cytotoxic aggregates of alpha-lactalbumin induced by unsaturated fatty acid induce apoptosis in tumor cells. Chem.-Biol. Interact. 180(2), 131-142.

32. Jun-Bao Fan#, Jie Chen, Yi Liang* (2008). Oxidative refolding of reduced, denatured lysozyme in AOT reverse micelles. J. Colloid Interface Sci. 322(1), 95-103.

33. Jun-Ming Liao#, Zhong-Ying Mo, Ling-Jia Wu, Jie Chen, Yi Liang* (2008). Binding of calcium ions to Ras promotes Ras guanine nucleotide exchange under emulated physiological conditions. Biochim. Biophys. Acta 1784(11), 1560-1569.

34. Bing-Rui Zhou#, Zheng Zhou, Qing-Lian Hu, Jie Chen, Yi Liang* (2008). Mixed macromolecular crowding inhibits amyloid formation of hen egg white lysozyme. Biochim. Biophys. Acta 1784(3), 472-480.

35. Fang Yang#, Bing-Rui Zhou, Peng Zhang, Yan-Feng Zhao, Jie Chen, Yi Liang* (2007). Binding of ferulic acid to cytochrome c enhances stability of the protein at physiological pH and inhibits cytochrome c-induced apoptosis. Chem.-Biol. Interact. 170(3), 231-243.

36. Fen Du#, Zheng Zhou, Zhong-Ying Mo, Jun-Zhi Shi, Jie Chen, Yi Liang* (2006). Mixed macromolecular crowding accelerates the refolding of rabbit muscle creatine kinase: Implications for protein folding in physiological environments. J. Mol. Biol. 364(3), 469-482.

37. Fang Yang (Jr.)#, Min Zhang, Bing-Rui Zhou, Jie Chen, Yi Liang* (2006). Oleic acid inhibits amyloid formation of the intermediate of alpha-lactalbumin at moderately acidic pH. J. Mol. Biol. 362(4), 821-834.

38. Yu-Ling Zhou#, Jun-Ming Liao, Jie Chen, Yi Liang* (2006). Macromolecular crowding enhances the binding of superoxide dismutase to xanthine oxidase: Implications for protein-protein interactions in intracellular environments. Int. J. Biochem. Cell Biol. 38(11), 1986-1994.

39. Jin Xiang#, Jun-Bao Fan, Nan Chen, Jie Chen, Yi Liang* (2006). Interaction of cellulase with sodium dodecyl sulfate at critical micelle concentration level. Colloids Surf. B: Biointerfaces 49(2), 175-180.

40. Fang Yang (Jr.)#, Min Zhang, Jie Chen, Yi Liang* (2006). Structural changes of alpha-lactalbumin induced by low pH and oleic acid. Biochim. Biophys. Acta 1764(8), 1389-1396.

41. Nan Chen#, Jun-Bao Fan, Jin Xiang, Jie Chen, Yi Liang* (2006). Enzymatic hydrolysis of microcrystalline cellulose in reverse micelles. Biochim. Biophys. Acta 1764(6), 1029-1035.

42. Jun Wu#, Fen Du, Peng Zhang, Izhar Ahmed Khan, Jie Chen, Yi Liang* (2005). Thermodynamics of the interaction of aluminum ions with DNA: Implications for the biological function of aluminum. J. Inorg. Biochem. 99(5), 1145-1154.

43. Hong Xu#, Yi Liang*, Peng Zhang, Fen Du, Bing-Rui Zhou, Jun Wu, Jian-Hong Liu, Zhi-Gang Liu, Liang-Nian Ji (2005). Biophysical studies of a ruthenium(II) polypyridyl complex binding to DNA and RNA prove that nucleic acid structure has significant effects on binding behaviors. J. Biol. Inorg. Chem. 10(5), 529-538.

44. Bing-Rui Zhou#, Yi Liang*, Fen Du, Zheng Zhou, Jie Chen (2004). Mixed macromolecular crowding accelerates the oxidative refolding of reduced, denatured lysozyme: Implications for protein folding in intracellular environments. J. Biol. Chem. 279(53), 55109-55116.

45. Yi Liang#*, Fen Du, Sarah Sanglier, Bing-Rui Zhou, Yi Xia, Alain Van Dorsselaer, Clarisse Maechling, Marie-Claude Kilhoffer, Jacques Haiech (2003). Unfolding of rabbit muscle creatine kinase induced by acid. A study using electrospray ionization mass spectrometry, isothermal titration calorimetry, and fluorescence spectroscopy. J. Biol. Chem. 278(32), 30098-30105.