Tianwei LIN, Ph.D.
1983, B.Sc., Xiamen University, China;
1992, Ph.D., University of Alberta, Canada.
1991-1995, Postdoctoral Fellow at the department of Biological Sciences, Purdue University, USA;
1995-2000, Senior Research Associate, The Scripps Research Institute, USA;
2000-2005, Assistant Professor, The Scripps Research Institute, USA;
2004-2007, Adjunct Professor, Institute of Biophysics, Chinese Academy of Sciences;
2004-2007, Visiting Professor, Xiamen University;
2005-2006, Associate Professor, The Scripps Research Institute, USA;
2006-2007, Adjunct Associate Professor, The Scripps Research Institute, USA;
2006-2008, Visiting Associate Professor, University of Hong Kong;
2008-2010, Honorary Associate Professor, University of Hong Kong;
2007-Present, Professor, School of Life Sciences, Xiamen University.
Our research interests are on unraveling the structural and molecular basis of diseases and characterizing the therapeutic targets to atomic details for the search of cure and prevention. Besides cancer and metabolic diseases, a special interest is on the research of viral infectious diseases, caused by influenza A viruses and picornaviruses, among others. For example, enteroviruses 71 (EV71) is 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. Eneterovirus 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 b strands. The open cleft provides an accessible template for docking chemical compounds. Hits were identified by virtual screening and leads were generated by structure-based design as well as fragment-based methods for the development of therapeutics to treat the associated diseases.
1. Wang† W-J., Wang† Y., Hou† P-p, Li†FW.,Zhou B, Chen HZ, Bian XL, Cai QX,Xing YZ, He JP, Zhang HK, Huang PQ, Lin TW* and Wu Q*. (2015). Induction of Autophagic Death in Cancer Cells by Agonizing TR3 and Attenuating Akt2 Activity. Chem. Biol. 22(8):1040-51.
2. 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 p38reduces Lps-induced inflammation. Nat. Chem. Biol.11:339–346.
3. Wang† W-J., Wang† Y., Chen† H-Z., Xing† Y-Z., Li† F-W., Zhang Q.,Zhou B., Zhang H-k., Zhang J., Bian X-l., Li L., Liu Y., Zhao B-x.,Chen Y., Wu R., Li A-z., Yao L-m., Chen P., Zhang Y., Tian Y-y.,Beermann F., Wu M., HanJ.,Huang P-q., Lin T.* & Wu Q.*(2014).Orphan nuclear receptor TR3 acts in autophagic cell death viamitochondrial signaling pathway. Nat. Chem. Biol. 10:133-140.
4. Cai† Q., Yameen† M., Liu† W., Gao Z., Li Y., Peng X., Cai Y., Wu C., Zheng Q., Li* J., Lin* T.. (2013). Conformational Plasticity of 2A Proteinase from Enterovirus 71. J. Virol. 87, 7348-7356.
5. Wu† C., Cai† Q., Chen C., Li N., Peng X., Cai Y., Yin K., Chen X., Wang X., Zhang R., Liu L., Chen S., Li* J., and Lin* T. (2013). Crystal Structures of an Enterovirus 71 3C Proteinase (strain: E2004104-TW-CDC) and Its Complex with Rupintrivir. Acta Cryst. D,69, 866–871
6. Zhan† Y.Y., Chen† Y., Zhang† Q., Zhuang J.J., Tian M., Chen H.Z., Zhang L.R., Zhang H.K., He J.P., Wang W.J., Wu R., Wang Y., Shi C., Yang K., Li A.Z., Xin Y.Z., Li T.Y., Yang J.Y., Zheng Z.H., Yu C.D., Lin S.C., Chang C., Huang P.Q., Lin* T., Wu* Q.. (2012). The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK. Nat Chem Biol. 8, 897-904
7. Lin* T., Wang G., Li A., Zhang Q., Wu C., Zhang R., Cai Q., Song W., Yuen KY.(2009). The hemagglutinin structure of an H1N1 influenza A virus. Virology. 392, 73-81.
8. Lin T. (2006). Structural and Molecular Genesis of the Chemical Addressability of a Viral Nanoblock. J. Mat. Chem. 16, 3673 - 3681.
9. Lin T., and Johnson JE. (2003). Structures of Picorna-like plant viruses: implications and applications. Adv. Virus Res. 62, 167-239.