Xiaoguang Lei, Ph.D.

Principal Investigator

Biography：

Prof. Dr. Xiaoguang Lei was born and raised in Beijing, China. He obtained BSc degree in chemistry at Peking University in 2001. He then moved to Boston and conducted his PhD research studies on complex natural product synthesis and chemical biology from 2001 to 2006 under the supervision of Prof. John. A. Porco at Boston University. After two years (2006-2008) as a postdoctoral fellow in the group of Prof. Samuel J. Danishefsky at Columbia University and Memorial Sloan-Kettering Cancer Center, Dr. Lei joined the faculty at the National Institute of Biological Sciences (NIBS) as a Principal Investigator and Director of Chemistry Center. He also holds a joint professorship in the college of pharmaceutical science and technology at Tianjin University. In January 2014, Dr. Lei moved back to Peking University and joined the faculty in Department of Chemical Biology. He is also a member of Synthetic and Functional Biomolecules Center (SFBC) as well as the Center for Life Sciences (CLS) at Peking University.

Awards：

§ Young Investigator Award by Chinese Chemical Society, 2013

§ Young Chemical Biologist Award by the International Chemical Biology Society (ICBS), 2013

§ Servier Young Investigator Award by Chinese Pharmaceutical Association, 2013

§ Thieme Chemistry Journal Award, 2013

§ Asian Core Program Lectureship Award, 2012

§ Outstanding Young Investigator Award by National Natural Science Foundation of China, 2012

§ New Century Excellent Talents in University Award, 2010

§ WuXi PharmaTech 2010 Life Science and Chemistry Award, 2010

§ IUPAC Young Chemist Award, 2009

§ NESACS-JCF/GDCh Exchange Scholarship to Germany, 2005

§ Sugata Ray Memorial Award for Excellence in Research and Teaching at Boston University, 2005

Research Interests：

Many critical biological processes are conducted by small molecules and so they can arguably be regarded as another essential component of the “central dogma” of molecular biology. Biologically meaningful small molecules may be natural products, which are discovered by nature through many cycles of diversity generation and natural selection, or they may be prepared through organic synthesis for the development of drug candidates or chemical probes to study life’s processes. New small molecules are needed to function as probes to further study the known biological pathways, to discover novel pathways and interactions, to validate potential drug targets, and to treat unmet medical needs as drugs. Accordingly, the central theme of our research focuses on the efficient synthesis of these small molecules, as well as the subsequent biological evaluations of these molecules applying medicinal chemistry and chemical biology approaches.

One of our major research interests is to discover chemical probes against novel cancer targets. We aim to accelerate the development of more efficacious anti-cancer drugs by discovering novel small-molecule probes of candidate cancer targets which have not been modulated by small molecules. The goal is to identify these gaps and to undertake collaborative probe-development projects involving high-throughput chemical screening, synthetic and medicinal chemistry, and mechanism-of-action studies. Currently we are particularly interested in projects involving challenging targets such as protein-protein interactions, transcription factors, and epigenetic targets.

Selected Publications：

1.  Li, Q.; Dong, T.; Liu, X.; Lei, X.* “A Bioorthogonal Ligation Enabled by Click Cycloaddition of o-Quinolinone Quinone Methide and Vinyl Thioether” J. Am. Chem. Soc. 2013, 135, 4996-4999. (News story describing this work was highlighted in Chem. & Eng. News 2013, 14, 37).

2.  Li, T.; Chen, J.; Li, X.; Ding, X.; Wu, Y.; Zhao, L.; Chen, S.; Lei, X.*; Dong, M.* “Absolute Quantification of a Steroid Hormone that Regulates Development in Caenorhabditis elegans” Anal. Chem. 2013, 85, 9281-9287.

3.  Li, C.; Dong, T.; Dian, L.; Zhang, W.; Lei, X.* “Biomimetic Syntheses and Structural Elucidation of the Apoptosis-Inducing Sesquiterpenoid Trimers: (-)-Ainsliatrimers A and B” Chem. Sci. 2013, 4, 1163-1167.

4.   Wang, G.;* Wang, X.; Yu, H.; Wei, S.; Williams, N.; Holmes, D. L.; Halfmann, R.; Naidoo, J.; Wang, L.; Li, L.; Chen, S.; Harran, P.; Lei, X.*; Wang, X.* “Small Molecule Activation of the TRAIL Receptor DR5 in Human Cancer Cells” Nat. Chem. Biol. 2013, 2, 84-90. (News stories describing this work were highlighted in Chem. & Eng. News 2013, 2, 37; Nature Asia 2012, December 24).

5.   Li, H.; Wang, X.; Hong, B.; Lei, X.* “Collective Synthesis of Lycopodium Alkaloids and Tautomer Locking Strategy for the Total Synthesis of (-)-Lycojapodine A” J. Org. Chem. 2013, 78, 800-821. (Featured and Cover Article).

6.  Li, C.; Dian, L.; Zhang, W.; Lei, X.* “Biomimetic Syntheses of (-)-Gochnatiolides A-C and (-)-Ainsliadimer B” J. Am. Chem. Soc. 2012, 134, 12414-12417.

7. Sun, L.; Wang, H.; Wang, Z.; He, S.; Chen, S.; Liao, D.; Wang, L.; Yan, J.; Liu, W.; Lei, X.*; Wang, X.* “Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase” Cell 2012, 148, 213-227. (News stories describing this work were highlighted in Chem. & Eng. News 2012, 5, 40; Nature China 2012, February 1; Asian Scientist 2012, January31; and Nature Reviews Molecular Cell Biology, 2012, Feb. 8).

8. Li, H.; Wang, X.; Lei, X.* “Total Syntheses of Lycopodium Alkaloids (+)-Fawcettimine, (+)-Fawcettidine and (-)-8-Deoxyserratinine” Angew. Chem. Int. Ed. 2012, 51, 491-495; Angew. Chem. 2012, 124, 506-510.

9. Liao, D.; Li, H.; Lei, X.* “Efficient Generation of ortho-Quinone Methide: Application to the Biomimetic Syntheses of (±)-Schefflone and Tocopherol Trimers” Org. Lett. 2012, 14, 18-21.

10. Li, C.; Tu, S.; Wen, S.; Li, S.; Chang, J.; Shao, F.; Lei, X.* “Total Synthesis of the G2/M DNA Damage Checkpoint Inhibitor Psilostachyin C” J. Org. Chem. 2011, 76, 3566-3570.

11. Chou, T.; Dong, H.; Zhang, X.; Lei, X.; Hartung, J.; Zhang, Y.; Lee, H. L.; Wilson, R. M.; Danishefsky, S. J. * “Multifaceted Cytoprotection by Synthetic Polyacetylenes Inspired by the Ginseng-derived Natural Product Panaxytriol” Proc. Natl. Acad. Sci. 2011, 108, 14336-14341.

12. Li, C.; Yu, X.; Lei, X.* “A Biomimetic Total Synthesis of (+)-Ainsliadimer A” Org. Lett. 2010, 12, 4284-4287.

13. Gong, Y.; Wang, X.; Wang, J.; Yang, Z.; Li, S.; Yang, J.; Liu, L.; Lei, X.*; Shao, F. * “Chemical Probing Reveals Insights into the Signaling Mechanism of Inflammasome Activation” Cell Res. 2010, 20, 1289-1305.

14. Han，Z.; Niu, T.; Chang, J.; Lei, X.; Zhao, M.; Wang, Q.; Cheng, W.; Wang, J.; Feng, Y.; Chai, J.* “Crystal structure of the FTO protein reveals basis for its substrate specificity” Nature 2010, 464, 1205-1209.

15. Lei, X.; Danishefsky, S. J.* “Efficient Synthesis of a Novel Resorcyclide as Anticancer Agent Based on Hsp90 Inhibition” Adv. Synth. Catal. 2008, 350, 1677-1681。

16. Lei, X.; Porco, J. A., Jr.* “Total Synthesis of the Diazobenzofluorene Antibiotic (-)-Kinamycin C.” J. Am. Chem. Soc. 2006, 128, 14790-14791. (News story describing this work was highlighted in Chem. & Eng. News 2006, 45, 9)

17. Porco, J. A., Jr.*; Su, S.; Lei, X.; Bardhan, S.; Rychnovsky, S. D. “Total Synthesis and Structure Assignment of (+)-Hexacyclinol” Angew. Chem. Int. Ed. 2006, 45, 5790-5792; Angew. Chem. 2006, 118, 5922-5924. (News stories describing this work were reported in Chem. & Eng. News 2006, 31, 11 and Nature 2006, 442, 492-493)

18. Lei, X.; Zaarur, N.; Sherman, M. Y.; Porco, J. A., Jr.* “Stereocontrolled Synthesis of a Complex Chemical Library via Elaboration of Angular Epoxyquinol Scaffolds.” J. Org. Chem. 2005, 70, 6474-6483.

19. Lei, X.; Porco, J. A., Jr.* “Synthesis of a Polymer-Supported Anthracene and Its Application as a Dienophile Scavenger.” Org. Lett. 2004, 6, 795-798.

20. Lei, X.; Johnson, R. P.; Porco, J. A., Jr.* “Total Synthesis of the Ubiquitin-Activating Enzyme Inhibitor (+)-Panepophenanthrin.” Angew. Chem. Int. Ed. 2003, 42, 3913-3917; Angew. Chem. 2003, 115, 4043-4047. (This publication was highlighted as a “Hot Paper”)