林天伟LIN Tianwei, Ph.D.

教授，博士生导师

结构病毒学/结构生物学（Structural Virology/Biology）

课题组组长

电话:+86-592-2184912

E-mail: twlin@xmu.edu.cn

1979-1983,厦门大学生物学系,获理学学士

1983-1984,厦门大学生物学系,助教

1985-1992,加拿大Alberta大学生物化学系,获博士学位

1991-1995,美国Purdue大学生物科学系,博士后

1995-2000,美国Scripps 研究所分子生物学部高级研究员

2000-2005,美国Scripps 研究所分子生物学部和联合分子生命科学中心助理教授

2004-2007,中国科学院生物物理研究所兼职教授

2004-2007,厦门大学访问教授

2005-2006,美国Scripps 研究所分子生物学部和联合分子生命科学中心副教授2006-2007,美国Scripps 研究所分子生物学部和联合分子生命科学中心兼职副教授

2006-2008,香港大学微生物学系访问教授

2008-2010, 香港大学微生物学系名誉副教授

2007年至今, 厦门大学生命科学学院特聘教授

研究领域 (Research Area)

u手足口病的结构和分子生物学

u病毒与宿主天然免疫系统的相互作用

u核受体的结构生物学

u以结构为基础的化学药物开发

u以结构为基础的大分子药物开发

u病毒结构在纳米化学、材料学及医学中的应用

Our research interests are on unraveling the structural and molecular bases of diseases and characterizing the therapeutic targets to atomic details for the search of cure and prevention. Besides cancer and inflammatory diseases, a special interest is on the research of viral infectious diseases, such as those caused by picornaviruses among others. For example, enteroviruses 71 (EV71) are emerging as the most significant neurotropic enterovirus in some area of the world in outbreaks and epidemics of hand, foot and mouth disease (HFMD). It has also been associated with a variety of other clinical diseases, including herpangina, aseptic meningitis, encephalitis, and even fatal pulmonary edema or hemorrhage. Eneteroviruses can also cause severe chronic diseases, such as dermatomyositis, polymyositis, dilated cardiomyopathy, and diabetes mellitus. Recently, we determined the structures of a key component in EV71 replication and antagonism to host defense, the 2A proteinase (2Apro), as well as its complex with the substrate. The structure revealed an open substrate-binding cleft. Comparative studies with other 2Apro and molecular dynamic simulation indicated that the open conformation could be closed with a hinge motion in the bII2 and cII  strands. The open cleft provides an accessible template for docking chemical compounds. Hits were identified by fragment-based drug discovery and leads were generated by structure-based design and medical chemistry for the development of therapeutics to treat the associated diseases.

代表性论文（Selected Publications）

1.    Lin TW., and Johnson, J. E. (2003).  Structures of Picorna-like plant viruses: implications and applications.  Adv. Virus Res. 62, 167-239.

2.    Lin TW. (2006). Structural and Molecular Genesis of the Chemical Addressability of a Viral Nanoblock.  J.  Mat. Chem. 16, 3673 - 3681.

3.    Lin TW*., Wang GY., Li AZ., Zhang Q., Wu CM., Zhang RF., Cai QX., Song WJ., Yuen KY.(2009). The hemagglutinin structure of an H1N1 influenza A virus. Virology. 392, 73-81.

4.    Zhan YY.#, Chen Y.#, Zhang Q.#, Zhuang JJ., Tian M., Chen HZ., Zhang LR, Zhang HK., He JP., Wang WJ., Wu R., Wang Y., Shi C., Yang K., Li AZ., Xin YZ., Li TY., Yang JY., Zheng ZH., Yu CD., Lin SC., Chang CS., Huang PQ., Lin TW*, Wu Q.* (2012). The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK. Nat Chem Biol. 8, 897-904.

5.   Wu CM.#, Cai QX.#, Chen C., Li N., Peng XJ., Cai YX., Yin K., Chen XS., Wang XL., Zhang RF., Liu LJ., Chen SH., Li J*.,Lin TW.*. (2013). Crystal Structures of an Enterovirus 71 3C Proteinase (strain: E2004104-TW-CDC) and Its Complex with Rupintrivir. Acta Cryst. D69, 866–871.

6.   Cai QX.#, Yameen M.#, Liu WH.#, Gao ZT., Li YZ., Peng XJ., Cai YX., Wu CM., Zheng Q., Li J.*, Lin TW.* (2013). Conformational Plasticity of 2A Proteinase from Enterovirus 71. J. Virol. 87, 7348-7356.

7.   Wang WJ.#, Wang Y.#, Chen HZ.#, Xing YZ.#, Li FW.#, Zhang Q., Zhou B., Zhang, HK., Zhang J., Bian XL., Li L., Liu Y., Zhao BX., Chen Y., Wu R., Li AZ., Yao LM., Chen P., Zhang Y., Tian XY., Beermann F., Wu M., Han JH., Huang PQ., Lin TW* , Wu Q.*.(2014).Orphan nuclear receptor TR3 acts in autophagic cell death viamitochondrial signaling pathway. Nat. Chem. Biol. 10:133-140.

8.   Li L#, Liu Y#, Chen HZ#, Li FW#, Wu JF, Zhang HK, He JP, Xing YZ, Chen Y, Wang WJ, Tian XY, Li AZ, Zhang Q, Huang PQ, Han JH, Lin TW* , Wu Q*. (2015). Impeding the interaction between nur77 and p38 reduces Lps-induced inflammation. Nat. Chem. Biol.11:339–346.

9.    Kong C., Srinivasa R. Penumutchu, Kuo-wei Hung, Huang HY., Lin TW*., Yu C*.(2015) .Backbone resonance assignments of the PRYSPRY domain of TRIM25. Biomol NMR Assign. 9:313-315.

10.  Wang WJ#., Wang Y. #, Hou PP. #, Li FW. #, Zhou B, Chen HZ, Bian XL, Cai QX, Xing YZ, He JP, Zhang HK, Huang PQ, Lin TW* ,Wu Q*. (2015). Induction of Autophagic Death in Cancer Cells by Agonizing TR3 and Attenuating Akt2 Activity. Chem. Biol. 22(8):1040-51.

11.  Wu CM#., Zhang LJ#., Li P#., Cai QX#., Peng XJ., Yin K., Chen XS., Ren HX., Zhong SL., Weng YW., Guan Y.,  Chen SH., Wu JZ. *, Li J. *, Lin TW*.(2016).Fragment-wise design of inhibitors to 3C proteinase from enterovirus 71. Biochimica et Biophysica Acta-General Subjects.1860(6):1299-1307.

12.  Zhang LJ#., Huang GL#., Cai QX#., Zhao C.,Tang LY., Ren HX., Li P., Li N., Huang JW., Chen XQ., Guan Y., You H., Chen SH., Li J*., Lin TW*.(2016) .Optimize the interactions at S4 with efficient inhibitors targeting 3C proteinase from enterovirus 71.Journal of Molecular Recognition.29(11):520~527.