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刘定祥

发布者: 发布时间:2022-06-26浏览次数:173


  长期从事冠状病毒病原生物学、病毒-宿主互作、复制和致病机制研究,取得了一系列开创性成果,包括率先鉴定E蛋白为冠状病毒的结构蛋白,阐明其独特的核糖体内进入翻译机制和离子通道活性;IBV非结构多聚蛋白切割图谱和新型产物的鉴定及功能研究;第二个弗林样酶切点对激活S蛋白膜介导融合的关键作用。近年来,根据全基因组水平筛选结果,鉴定和阐明了一系列宿主因子对冠状病毒复制和致病机理的调控、影响及机制,包括nsp13-DNA复制酶δ催化亚基、nsp14-DDX1、M蛋白-actin和病毒RNA-Madp1等的互作,VCP在冠状病毒感染早期的关键作用,多种应激反应相关基因和信号通路的激活及调控作用等。


研究领域:

分子病毒学;动物RNA病毒;复制机理和致病机制;病毒-宿主相互作用;宿主抗病毒反应机制;新型疫苗和诊断技术开发


学习经历:

1988.10-1991.09英国剑桥大学分子生物学专业  博士   


1983.09-1986.06  四川大学(原华西医科大学)医学微生物学专业  硕士


1978.11-1981.07  湖北理工学院(原黄石卫生学校)医学检验专业  检验士文凭课程


工作经历:

2017.01-             教授

2010.06-2018.08    新加坡南洋理工大学生物科学学院    副教授、访问教授

2003.09-2010.05   新加坡分子与细胞生物学研究院分子病毒学和病毒致病机理研究室   首席研究员

2002.02-2003.09     新加坡南洋理工大学生物科学学院   副教授

1996.01-2002.01    新加坡国立大学分子农业生物学研究院动物病毒学研究室 首席研究员

1991.10-1996.01    英国剑桥大学医学系和病理学系病毒学专业  博士后

1986.07-1988.09    四川大学(原华西医科大学)微生物学和免疫学系  助教、讲师

1981.07-1983.08    湖北省黄石市中心医院(原黄石市第三医院)检验科检验士


社会兼职:

2009.10-2017.08   兰州兽医研究所,客座教授, 博士生导师 

2006.03-2015.12   四川大学客座教授 

2004.05-2010.05   新加坡南洋理工大学生物科学学院兼职副教授 

2003.09-2010.05   新加坡国立大学生物科学系兼职副教授 

2008-2016        PLoS ONE学术编委

2010-2017        World Journal of Virology编辑委员会成员

2019年-现在      Frontiers in Genetics客座编委

2019年-现在      Infection, Genetics and Evolution编委, 

 


荣誉与奖励:

1. 剑桥海外信托奖学金,1988-1991.

2. 新加坡卫生部五年服务奖,2015年10月。


近期发表的论文:(2017年-现在,* 通讯作者)

1. To J, Surya W, Fung TS, Li Y, Verdià-Bàguena C, Queralt-Martin M, Aguilella VM, D. X. Liu*, Torres J. (2017). Channel inactivating mutations and their revertant mutants in the envelope protein of the infectious bronchitis virus. Journal of Virology 2017 Feb 14;91(5). pii: e02158-16.

2.Guo H, Huang M, Yuan Q, Wei Y, Gao Y, Mao L, Gu L, Tan YW, Zhong Y, D. X. Liu*, Sun S*. (2017). The Important Role of Lipid Raft-Mediated Attachment in the Infection of Cultured Cells by Coronavirus Infectious Bronchitis Virus Beaudette Strain.  PLoS One. 2017 Jan 12;12(1):e0170123. doi: 10.1371/journal.pone.0170123.

3.Yanquan Wei, Yanhong Ji, Huichen Guo, Xiaoying Zhi, Shichong Han, Yuan Gao, Yun Zhang, D. X. Liu*, Shiqi Sun*. (2017). CD59 Association protects Infectious Bronchitis Virus against complement-mediated destruction. Journal of General Virology 98, 2725-2730. 2017 Oct 25. doi: 10.1099/jgv.0.000962. [Epub ahead of print].

4.To Sing Fung and D. X. Liu*. (2017). Activation of the c-Jun NH2-terminal kinase pathway by coronavirus infectious bronchitis virus promotes apoptosis independently of c-Jun. Cell Death and Disease 8, 3215.

5.Jie Zheng, Yoshiyuki Yamada,To Sing Fung, Raymond Chia, Mei Huang, and D. X. Liu*. (2018). Identification of N–linked glycosylation sites in the spike protein and their functional impact on the replication and infectivity of coronavirus infectious bronchitis virus in cell culture. Virology 513, 65-74.

6.Yong Wah Tan, To Sing Fung, Hongyuang Shen, Mei Huang, and D. X. Liu*.  (2018). Coronavirus Infectious Bronchitis Virus Non-structural Proteins 8 and 12 Form Stable Complex Independent of the Non-translated Regions of Viral RNA and Other Viral Proteins. Virology 513, 75-84.

7.Ru Ying Puah, Huan Jia, Manikantha Maraswami, Desiree-Faye Kaixin Toh, Rya Ero, Lixia Yang, Kiran M. Patil, Ruimin Sun, Cailing Tong, Mei Huang, Xin Chen, Teck Peng Loh, Yong-Gui Gao, D. X. Liu* and Gang Chen*. (2018). Selective Binding to mRNA Duplex Regions by Chemically Modified PNAs Stimulates Ribosomal Frameshift. Biochemistry 57(1), 149-159.

8.Hui Hui Wong, To Sing Fung, Shouguo Fang, Mei Huang, My Tra Le, and D. X. Liu*. (2018). Severe Acute Respiratory Syndrome Coronvirus Proteins 8b and 8ab Suppress the Interferon Signaling Pathway by Mediating Ubiquitin-Dependent Rapid Degradation of Interferon Regulatory Factor 3. Virology 515, 165-175.

9.To Sing Fung and D. X. Liu*. (2018). Post-translational modifications of coronavirus proteins: roles and function. Future Virology  13, 405-430. Published online: 21 May 2018.

10. Si Min Zhang, Ying Liao, Tuan Ling Neo, Yanning Lu, D. X. Liu, Anders Vahlne, James P. Tam*. (2018). Identification and Application of Self-binding Zipper-like Sequences in SARS-CoV Spike Protein. International Journal of Biochemistry and Cell Biology 2018 Aug;101:103-112. doi: 10.1016/j.biocel.2018.05.012. Epub 2018 May 22.

11.Hongliu An, Zhichao Cai, Yuying Yang, Zhaoxiong Wang, D. X. Liu*, Shouguo Fang*. (2019). Identification and formation mechanism of a novel noncoding RNA produced by avian infectious bronchitis virus. Virology  528, 176-180.

12.Jia Qi Liang, Shouguo Fang, Quan Yuan, Mei Huang, Rui Ai Chen, To Sing Fung*, D. X. Liu*. (2019). N-Linked Glycosylation of the Membrane Protein Ectodomain Regulates Infectious Bronchitis Virus-Induced ER Stress Response, Apoptosis and Pathogenesis. Virology 531, 48-56.                                

13.To Sing Fung and D. X. Liu*. (2019). The ER stress sensor IRE1 and MAP kinase ERK modulate autophagy induction in cells infected with coronavirus infectious bronchitis virus. Virology 533,34-44.

14. To Sing Fung and D. X. Liu*. (2019). Human Coronavirus: Host-Pathogen Interaction. Annual Review of Microbiology 73, 529-557. 

15.Liu DX*, Ng YL, Fung TS. Infectious Bronchitis Virus. In Avian Virology: Current Research and Future Trends. (Ed. S. K. Samal). 133-178. Caister Academic Press. 2019; https://doi.org/10.21775/9781912530106.05.

16.Shumin Li, Lixia Yuan, Guo Dai, Rui Ai Chen, D. X. Liu* and To Sing Fung*. (2020). Regulation of the ER Stress Response by the Ion Channel Activity of the Infectious Bronchitis Coronavirus Envelope Protein Modulates Virion Release, Apoptosis, Viral Fitness, and Pathogenesis. Frontiers in Microbiology 10, 3022.

17.Chengwei Xiang, Mei Huang, Ting Xiong, Fang Rong, Linyu Li, D. X. Liu* and Rui Ai Chen*. (2020). Transcriptomic Analysis and Functional Characterization Reveal the Duck Interferon Regulatory Factor 1 as an Important Restriction factor in the Replication of Tembusu Virus. Frontiers in Microbiology 11, 2069.

18.Xiao Ying Liang, Qing Chun Zhu, Jia Qi Liang, Si Ying Liu,  D. X. Liu* and To Sing Fung*. (2020). Development of HiBiT-tagged recombinant infectious bronchitis coronavirus for efficient in vitro and in vivo viral quantification. Frontiers in Microbiology 11, 2100.

19.Nan Nan Wang, Mei Huang, Qiong Luo, Jun Xian Yie, Qianru Du, D. X. Liu* and Rui Ai Chen*. (2020). Rapid Development of an Efficacious Vaccine Candidate by Construction of an Infectious Cloning System and Attenuation of a Genotype VII Velogenic Newcastle Disease Virus Isolate. Frontiers in Veterinary Science 7, 648. 

20.Liu DX*, Ng YL, Fung TS. Coronaviruses as vaccine vectors for veterinary pathogens. In Viral Vectors in Veterinary Vaccine Development: A Textbook (Ed. Thiru Vanniasinkam, Suresh Tikoo and Siba Samal). 149-168. Springer Nature 2020. https:doi.org/10.1007/978-3-030-51927-8_10.

21.Liu DX*, Liang JQ, Fung TS. Human Coronavirus-229E, -OC43, -NL63, and -HKU1. (2020). Reference Module in Life Sciences. 2020: B978-0-12-809633-8.21501-X. PMC | ID: covidwho-827842.

22.Guo Dai, Mei Huang, To Sing Fung* and D. X. Liu*. (2020). Research progress in the development of porcine reproductive and respiratory syndrome virus as a viral vector for foreign gene expression and delivery. Expert Review of Vaccine 19, 1041-1051.

23.Xiao-Yu Zhang, Jing Guo, Xin Wan, Jin-Ge Zhou, Jia Lu, Wei-Ping Jin, Wen-Hui Wang, An-Na Yang, D. X. Liu, Zheng-Li Shi, Zhi-Ming Yuan, Xin-Guo Li, Kai Duan, Sheng-Li Meng, Ze-Jun Wang, Xiao-Ming Yang, Shuo Shen. (2020). Biochemical and antigenic characterization of the structural proteins and their post-translational modifications in purified SARS-CoV-2 virions of an inactivated vaccine candidate. Emerging Microbes & Infections 9, 2653-2662. 

24.Li Xia Yuan, Jia Qi Liang, QingChun Zhu, Guo Dai, Shumin Li, To Sing Fung* and D. X. Liu*. (2021). A gammacoronavirus, avian infectious bronchitis virus, and an alphacoronavirus, porcine epidemic diarrhea virus, exploit a cell-survival strategy via upregulation of cFOS to promote viral replication. Journal of Virology 95, e02107-20.

25. To Sing Fung and D. X. Liu*. (2021). Similarities and Dissimilarities of COVID-19 and Other Coronavirus Diseases. Annual Review of Microbiology 75,19-47. https://doi.org/10.1146/annurev-micro-110520-023212.

26.Liu DX*, Liang JQ, Fung TS. Human Coronavirus-229E, -OC43, -NL63, and -HKU1 (Coronaviridae).  Encyclopedia of Virology. 2021: 428–440. Published online 2021 Mar 1. doi: 10.1016/B978-0-12-809633-8.21501-X. Guest Editor (s): Dennis H. Bamford and Mark Zuckerman.

27.Jiahao Zhang, Kaixiong Ma, Bo Li, Yiqun Chen, Ziwen Qiu, Jinchao Xing, Jinyu Huang, Chen Hu, Yifan Huang, Huanan Li, D. X. Liu, Ming Liao*, and Wenbao Qi*. (2021). A risk marker of tribasic hemagglutinin cleavage site in influenza A (H9N2) virus. Communications Biology (2021) 4:71 | https://doi.org/10.1038/s42003-020-01589-7 | www.nature.com/commsbio.

28.Huan Wang, D. X. Liu, Yingjie Sun, Chunchun Meng, Lei Tan, Cuiping Song, Xusheng Qiu, Weiwei Liu, Chan Ding, Ying Liao. (2021). Upregulation of DUSP6 impairs infectious bronchitis virus replication by negatively regulating ERK pathway and promoting apoptosis. Veterinary Research 52, 7.

29.Qing Chun Zhu, ShuMin Li, Li Xia Yuan, Rui Ai Chen, D. X. Liu* and To Sing Fung*. (2021). Induction of the proinflammatory chemokine interleukin-8 is regulated by integrated stress response and AP-1 family proteins activated during infectious bronchitis coronavirus infection. International Journal of Molecular Sciences 22, 5646.

30. Shumin Li, Siying Liu, Rui Ai Chen, Mei Huang, To Sing Fung, D. X. Liu* (2022). Activation of the MKK3-p38-MK2-ZFP36 Axis by Coronavirus Infection Restricts the Upregulation of AU-Rich Element-Containing Transcripts in Proinflammatory Responses. Journal of Virology 96 (5) e02086-21.

31.Yu Shi, Xiaobei Yang, Xiaoxin Ye, Jiaying Feng, Tianfang Cheng, Xiaofan Zhou, D. X. Liu, Linghui Xu*, Junxia Wang*. (2022). The methyltransferase HemK regulates the virulence and nu-trient utilization of the phytopathogenic bacterium Xanthomo-nas citri subsp. citri. International Journal of Molecular Sciences 23, 3931.



科研创新 :

1.Yoon Ho Sup, D. X. Liu and Nguyen Quoc Toan. (2014). Anti-viral methods and the use of an anti-viral agent. PCT Patent Application No. PCT/SG2013/000329. 

2.冯涛声,刘定祥,陈瑞爱,李淑敏,李延鹏,梁佳琪,袁丽霞,朱庆春,罗琼,熊挺。(2018)。 一株缺失E蛋白离子通道活性的传染性支气管炎病毒的构建和回复突变体的分离纯化及应用。授权专利号:201811449640.5。

3.陈瑞爱,黄梅,刘定祥,李延鹏,王楠楠,叶俊贤,罗琼,杨小云,董楠。(2019)。一种针对II类VII型流行NDV株 DHN3的感染性重组克隆方法。授权专利号:2019108947549。

4.陈瑞爱,黄梅,李延鹏,刘定祥,闫园园,方倪冉,杨小云,董楠。(2019)。一种具有高拷贝能力的棒状杆菌和大肠杆菌双表达载体及其构建方法。授权专利号:2019113794030。

5.刘定祥,冯涛声,陈瑞爱,梁佳琪,李延鹏,李淑敏,袁丽霞,朱庆春,罗琼,熊挺。(2018)。一株M蛋白糖基化位点突变的传染性支气管炎病毒的构建及应用。专利申请号:201811389187.3。

6.刘定祥, 黄梅,冯涛声, 代过。(2019)。 一株猪繁殖与呼吸综合征病毒重组疫苗株PRRSV-SP及其制备方法与应用。专利申请号:201911119406.0。

7.冯涛声, 刘定祥,朱庆春,梁潇颖,李淑敏,梁佳琪。(2019)。一株S蛋白融合HiBiT的传染性支气管炎重组病毒及制备方法与应用。专利申请号:201910910558.6。

8.陈瑞爱,黄梅,王楠楠,李延鹏,刘定祥,叶俊贤,罗琼,董楠,杨小云。(2019)。一种全基因组表达载体pBR322-DHN3的制备方法。专利申请号:2019108935537。

9.陈瑞爱,黄梅,刘定祥,李延鹏,闫园园,董楠,杨小云。(2019)。一种可有效表达外源蛋白的棒状杆菌ATCC 13032改良菌种以及构建方法。专利申请号:2019111635311。

10.陈瑞爱,闫园园,刘定祥,黄梅。(2019)。一种具有较高棒状杆菌复制能力的表达质粒及其构建方法。专利申请号:2019113676960。

11.陈瑞爱,王楠楠,刘定祥,黄梅,杜倩茹,叶俊贤,罗琼,董楠。(2020)。一株经过密码子替换的基因Ⅶ型新城疫病毒的拯救方法。专利申请号:2020103466102。

12.陈瑞爱,黄梅,刘定祥,王楠楠,叶俊贤,罗琼,杨小云,董楠。一种NDVVIId突变型感染性克隆病毒DHN3-mF及其制备方法和疫苗。专利申请号:2020104998794。

13.陈瑞爱,杜倩茹,刘定祥,黄梅,王楠楠,叶俊贤,罗琼,任广彩。(2020)。一株表达传染性法氏囊强毒株VP2蛋白的基因Ⅶ型新城疫重组病毒和疫苗。专利申请号:2020107308697。

14.陈瑞爱,黄梅,刘定祥,向成威,叶俊贤,董楠,杨小云。(2020)。VIPERIN功能缺失的细胞系的构建方法及其应用。专利申请号:2020107436892。

15.冯涛声, 刘定祥,李淑敏。(2020)。一种利用KIE噬菌体RNA聚合酶/启动子的双质粒系统在真核细胞质内高效表达冠状病毒S蛋白和非结构蛋白的方法。专利申请号:202011145191.2。

16.刘定祥, 黄梅,冯涛声, 代过。(2021)。一株表达ASFV结构囊膜蛋白的PRRS病毒及其构建方法与应用。专利申请号:202110102802.3。


科研项目: 

1.鸡传染性支气管炎病毒宿主嗜性及新型细胞疫苗的合作研究。人民币175万,2014年4月-2017年3月,国家国际科技合作专项项目(2014DFA31890), 申请人:孙世祺 (中方) , 刘定祥 (外方)。

2.国家自然科学基金面上项目,名称: 冠状病毒调控细胞周期以创造适于病毒复制微环境策略的分子细胞生物学研究,编号: 31972660,59 万元, 2020年1月-2023年12月, 申请人: 刘定祥。


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