Shanghai Institute of Material Medical Chinese Academy of Sciences

Biography

Liu Dongxiang was graduated with Ph.D. degree from SIMM in 1998 and received the postdoctoral training at Thomas Jefferson University from 1998 to 2001. Currently, his research interest is the structure and function of proteins involved in the occurrence and development of tumor, diabetes and neurodegenerative diseases, and molecular design targeting these proteins. He developed Bcl-2 inhibitor HA14-1, Bcl_xL inhibitor DCBL55, and determined that DCBL55 bound to Bcl-xL in R-configuration, induced cancer cell death by decreasing mitochondrial membrane potential, activating caspase-9 and caspase-3 (Journal of Medical Chemistry, 2010,53:3465-79). In addition, he designs molecules to modulate the enzyme activities of sirtuins, and developed a novel SIRT1 activator and elucidated its function mechanism (Journal of Medical Chemistry, 2013,56:761-80). Targeting the intermediate conformations in the aggregation process of amyloid beta peptide (Aβ), he designed small molecules to inhibit Aβ aggregation and fibrosis (Biochemistry, 2006, 45:10963-72; Journal of Medical Chemistry, 2010,53:5449-66)

Education

1987.9-1992.8 B.S. in Chemistry Tong-Ji University, China

1992.9-1995.8 M.S. in Chemistry Tong-Ji University, China

1995.9-1998.8 Ph.D. in Chemistry Chinese Academy of Sciences, China

Work Experience

Postdoctor 1998.8-2001.12 Thomas Jefferson University, Philadelphia, U.S.A.

Research Scientist 2002.1-2004.5 University of Illinois at Urbana-Champaign, Illinois, U.S.A.

Research Assistant Professor 2004.6-2005.5 The Burnham Institute, California, U.S.A.

Principle Investigator 2005.6-Present Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China

Research Directions

Chemical Biology, Molecular Pharmacology

Grants & Research Projects

1.Ministry ofScience and Technology, China,Collection of natural products that regulate the differentiation of stem cells,Project Leader,2009/1– 2013/12

2.Science and Technology Commission of Shanghai Municipality，Structure study and drug molecule design of SIRT1,Project Leader,2008/10– 2010/9

3.State key Laboratoryof Drug Research, Chinese Academy of Sciences，Design and mechanism study of HN peptides that protect neural cells ,Project Leader,2014/5-2015/5

Achievements

1. Structure-activity relationship and interaction study of novel Aβ inhibitor
2. We developed an ELISA to compare the affinity of compounds with monomeric Aβ
3. We discovered a pan Bcl-2 inhibitor that induces the apoptosis of cancer cells
4. Discovery and activation mechanism of a new SIRT1 activator
5. Discovery and interaction study of a new SIRT1 inhibitor
6. Integration and oligomerization of Bax in lipid membrane

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Social Titles

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Awards & Honors

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Pubilcations

Full Publication List

Selected Publications

1. Shen Z, Jiang X, Yan L, Chen Y, Wang W, Shi Y, Shi L*, Liu D*, Zhou N*. Structural basis for the interaction of diapause hormone with its receptor in the silkworm, Bombyx mori. FASEB J. 2018; 32(3):1338-1353. doi: 10.1096/fj.201700931R.

2. Ma ZW, Liu DX*. Humanin decreases mitochondrial membrane permeability by inhibiting the membrane association and oligomerization of Bax and Bid proteins. Acta Pharmacol Sin. 2018; 39(6):1012-1021. doi: 10.1038/aps.2017.169.

3. Zhou Y, Liu J, Zheng M, Zheng S, Jiang C, Zhou X, Zhang D, Zhao J, Ye D, Zheng M, Jiang H, Liu D*, Cheng J*, Liu H*. Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase. Acta Pharm Sin B. 2016; 6(1):32-45. doi: 10.1016/j.apsb.2015.11.004.

4. Luo L, Yang J, Liu D* Integration and oligomerization of Bax protein in lipid bilayers characterized by single molecule fluorescence study. J Biol Chem. 2014; 289(46):31708-18. doi: 10.1074/jbc.M114.583393.

5. Wu J, Li Y, Chen K, Jiang H, Xu MH, Liu D*. Identification of benzofuran-3-yl(phenyl)methanones as novel SIRT1 inhibitors: binding mode, inhibitory mechanism and biological action. Eur. J. Med. Chem. 2013; 60:441-50.

6. Wu J, Zhang D, Chen L, Li J, Wang J, Ning C, Yu N, Zhao F, Chen D, Chen X, Chen K, Jiang H, Liu H, Liu D*. Discovery and mechanism study of SIRT1 activators that promote the deacetylation of fluorophore-labeled substrate. J. Med. Chem. 2013; 56(3):761-80

7. Zhou Y, Jiang C, Zhang Y, Liang Z, Liu W, Wang L, Luo C, Zhong T, Sun Y, Zhao L, Xie X, Jiang H, Zhou N, Liu D*, Liu H*. Structural Optimization and Biological Evaluation of Substituted Bisphenol A Derivatives as Beta-Amyloid Peptide Aggregation Inhibitors. J. Med. Chem. 2010; 53(15):5449-66.

8. Feng Y, Ding X, Chen T, Chen L, Liu F, Jia X, Luo X, Shen X, Chen K, Jiang H, Wang H*, Liu H*, Liu D*. Design, Synthesis and Interaction Study of Quinazoline- 2(1H)-Thione Derivatives as Novel Potential Bcl-xL Inhibitors. J. Med. Chem. 2010; 53:3465-79.

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