Shanghai Institute of Material Medical Chinese Academy of Sciences

Biography

Dr. Shiyu Chen is a professor of chemical biology and molecular biology at Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Chen’s primary research focuses on resolving health related issues by developing innovative chemical and biological tools and generating next-generation antibody-mimicking therapeutics. His current research includes engineering novel formats of polypeptides, advancing directed evolution selection platforms and exploring the potential to develop biological therapeutics for treating infection, cancer and immunity related diseases. His achievement in developing peptide cyclization linkers led to the development of several first-in-class antibody-mimicking cyclic peptides and the clinic trial of several anti-tumor agents.

Chen was initially trained in Nanjing University and performed medicinal chemistry research on studying HIV integrate inhibitors at SIMM. During his Ph.D. research with Dr. Christian Heinis at EPFL and postdoctoral research with Dr. Matthew Bogyo at Stanford University, Chen pioneered the technologies of applying phage display to evolve bicyclic/cyclic peptides with antibody mimicking functionality and applied them in developing medication tools. He became a professor of the department of biological medicine at SIMM in April 2020.

Chen’s research was funded by diverse institutions. He was the primary executor of a professorship grant from Swiss National Science Foundation and a National Institutes of Health (NIH) Research Project Grant (R01). He was also awarded the advanced postdoc fellowship by Swiss National Science Foundation. His current research is supported by the Shanghai Science and Technology Committee (STCSM) and Chinese Academy of Sciences (CAS) with several grants.

Education:

2009.04–2014.12 Dr. Christian Heinis group, EPFL, Switzerland (Ph.D. degree) Develop new linkers and non-natural amino acids for generating novel formats of bicyclic peptides and apply them in phage display.

2005.09–2008.07 Dr. Hong Liu group, Shanghai Institute of Materia Medica, CAS, Shanghai (M.S. degree) Study the structure？activity relationship of inhibitors of HIV integrase.

2001.09–2005.07 Study in chemistry, major in analytical chemistry. Nanjing University, China.

Work Experience:

2020.04–Now Professor, Principle Investigator Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

2015.01–2020.03 Postdoc, Dr. Matthew Bogyo group, School of Medicine, Stanford University, USA

Research Directions

The development of novel formats of antibody and antibody-mimics, and their application in directed evolution methods to develop biological therapeutics.

Grants & Research Projects

Achievements

Several bicyclic peptides in clinic trial

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Social Titles

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Awards & Honors

2001 – 2005 People’s scholarship of Nanjing University - Awarded 3 times

2007 Outstanding student award of graduate school of Chinese Academy of Science

2012 SCNAT/SCS award

2015 – 2017 Swiss National Science Foundation Advanced.Postdoc fellowship

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Pubilcations

Full Publication List

Selected Publications

1 S. Chen, S. Lovell, S. Lee, M. Fellne, P. Mace and M. Bogyo. A phage display approach to identify highly selective covalent binders, Nature Biotechnology, 2020, Online (DOI: 10.1038/s41587-020-0733-7).

2 S. Chen, R. Gopalakrishnan, T. Schaer, F. Marger, R. Hovius, D. Bertrand, F. Pojer, C. Heinis, Synthetic di-thiol containing amino acids for structurlly shaping polypeptides and enhancing target-ligand binding interactions, Nature Chemistry, 2014, 6, 1009–1016.

3 S. Chen, D. Bertoldo, A. Angelini, F. Pojer, C. Heinis, Peptide ligands stabilized by small molecules, Angewandte Chemie International Edition, 2014, 53, 1602-1606.

4 Chen, I. Rentero Rebollo, S. A. Buth, J. Morales-Sanfrutos, J. Touati, P. G. Leiman, C. Heinis, Bi-cyclic peptide ligands pulled out of cysteine-rich peptide libraries, Journal of the American Chemical Society, 2013, 135, 6562-6569.

5 S. Chen, D. Gfeller, S. A. Buth, O. Michielin, P. G. Leiman, C. Heinis, Improving binding affinity and stability of peptide ligands by substituting glycines with D-amino acids, ChemBioChem, 2013, 14, 1316-1322.

6 S. Chen, J. Yim and M. Bogyo. Synthetic and biological approaches to map the substrate specificities of proteases, Biological Chemistry, 2019, 401(1), 165-182.

7 V. Baeriswyl, S. Calzavarini, S. Chen, A. Zorzi, L. Bologna, A. Angelillo-Scherrer, C. Heinis, A Synthetic Factor XIIa Inhibitor Blocks Selectively Intrinsic Coagulation Initiation, ACS ChemBiol. 2015, 10, 1861-1870.

8 S. Bellotto, S. Chen, I. Rentero-Rebollo, H. Wegner, C. Heinis, Phage selection of photoswitchable peptide ligands, J. Am. Chem. Soc. 2014, 136, 5880–5883.

9 S. Chen, J. Touati, C. Heinis, Tracking chemical reactions on the surface of filamentous phage using mass spectrometry, Chem. Commun. (Camb) 2014, 50, 5267-5269.

10 B. Lee, S. Chen, C. Heinis, R. Scopelliti, K. Severin, Pattern-based sensing of peptides and aminoglycosides with a single molecular probe, Org. Lett. 2013, 15, 3456-3459.

11 S. Chen, J. Morales-Sanfrutos, A. Angelini, B. Cutting, C. Heinis, Structurally diverse cyclisation linkers impose different backbone conformations in bi-cyclic peptides, ChemBioChem 2012, 13, 1032-1038.

12 V. Baeriswyl, H. Rapley, L. Pollaro, C. Stace, D. Teufel, E. Walker, S. Chen, G. Winter, J. Tite, C. Heinis, Bi-cyclic peptides with optimized ring size inhibit human plasma kallikrein and its orthologues while sparing paralogous proteases, ChemMedChem 2012, 7, 1173-1176.

13 A. Angelini, J. Morales-Sanfrutos, P. Diderich, S. Chen, C. Heinis, Bicyclization and tethering to albumin yields long-acting peptide antagonists, J. Med. Chem. 2012, 55, 10187-10197.

14 A. Angelini, L. Cendron, S. Chen, J. Touati, G. Winter, G. Zanotti, C. Heinis, Bi-cyclic peptide inhibitor reveals large contact interface with a protease target, ACS Chem. Biol. 2012, 7, 817-821.

15 S. Chen, H. Huang, X. Liu, J. Shen, H. Jiang, H. Liu, Microwave-assisted efficient copper-promoted N-arylation of amines with arylboronic acids, J. Comb. Chem. 2008, 10, 358-360.

16 S. Chen, C. Heinis, in Biotherapeutics: Recent Developments using Chemical and Molecular Biology, CHAPTER 9 Phage Selection of Mono- and Bi-cyclic Peptide Ligands, The Royal Society of Chemistry, 2013, pp. 241-262.

17 S. Chen, C. Heinis, Phage Selection of Bi-cyclic Peptides Based on Two Disulfide Bridges. Methods in Molecular Biology，2015, 1248, pp. 119-137.

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