Research Areas

Being engaged in chemical biology research and drug discovery for a long time, I have discovered multiple small molecule, peptide, protein and antibody preclinical candidates (PCC) in metabolic diseases, cancer, regenerative medicine and inflammatory bowel disease (IBD), and gained rich first-hand experience in various stages of drug discovery, that includes target discovery, hit identification, lead optimization, PCC and IND etc.

Highlights

Dr. Weijun Shen has gained significant experience and made outstanding achievements in the chemical biology research and drug discovery. Dr. Shen has supervised more than 30 doctoral and master level scientists and more than 50 drug discovery projects. He has more than 10 issued patents in small molecule drug discovery, peptide and protein engineering, and antibody engineering。He has published more than 40 papers in peer-reviewed journals with high impact factors, including Nature、Nature Chemistry, J. Am. Chem. Soc., Science Advances, Nature Communications, Nature Chemical Biology, Angew Chem Int Ed Engl, ACS Central Sciences, ACS Chem Biol, J Med Chem et al. Dr. Shen has discovered seven preclinical candidates which are undergoing or about to undergo IND enabling and clinical research. 

His main research area and achievements include: 

(1) long-acting peptide engineering and drug discovery： Dr. Shen has established a PEG-Fatty acid stapling technology for α-helical peptide to improve their in vitro potency and in vivo stability, half-life and efficacy. Dr. Shen has submitted more than 6 PCT applications and has applied this technology to more than 10 GPCR targets and achieved five long-acting GPCR agonists as preclinical candidates (PCC). 

(2） β Cell regeneration medicine and type I diabetes: Dr. Shen has made outstanding contributions in drug discovery of small molecule regenerative medicine for type I diabetes (T1D). Based on the deep understanding of β-cell biology and T1D disease, Dr. Shen has utilized β-cell lines, primary islets from rodents and human cadaver donors, and successfully carried out a series of high-throughput phenotypic screening and discovered a series of small molecule hit compounds that can be used for β-cell proliferation and protection. Through the target discovery and mechanism of action studies, Dr. Shen and his team has discovered novel signaling pathways and mechanisms for β-cell regeneration, and have won long-term support from the Juvenile Diabetes Research Foundation (JDRF) and published more than a dozen high impact papers and filed multiple patent applications. 

(3) Small molecule drug discovery and chemical biology research: Through biochemical and cell-based phenotypic assays and high-throughput screening, Dr. Shen and his team have generated novel small molecule hit compounds, optimized them into lead candidates and preclinical candidates with medicinal chemistry, identified and validated their novel mechanism of action and novel signaling pathways. Significant contributions have been made in the small molecule drug discovery, discovery of novel targets and disease biology, which have resulted in a series of small molecule preclinical candidates and multiple PCT applications.

Honors

• 2017   美中生物医药协会（SABPA）个人成就奖-Achievement Award

• 2016   美中生物医药协会（SABPA）团队奖（太平洋合作部）-Team Award

• 2014   美中生物医药协会（SABPA）个人成就奖

• 2013   美中生物医药协会（SABPA）团队奖（中国联络部）

• 2007   内布拉斯加大学Norman H Cromwell优秀研究生奖               

• 2005   内布拉斯加大学Henry and Jean Holtzclaw奖学金

• 2005   内布拉斯加大学Milton E. Mohr奖学金

Reviewer of Journals

• 科学转化医学 Science Translational Medicine

• 细胞干细胞 Cell Stem Cell

• 科学报告 Scientific Reports

• 德国应用化学 Angew. Chem. Int. Ed.

• 细胞化学生物学 Cell Chem Biol

• 美国化学会化学生物学 ACS Chem Biol

• 药物化学 /JMedChem, Advanced Therapeutics

• 生物有机化学 Bioorganic Chem

• 生物化学杂志 Biochem Journal

• 分子药理学 Molecular Pharmacology 

Selected Publications

1. Sophia Z. Shalhout*, Peng-Yu Yang*, Edyta Grzelak, Kayla Nutsch, Sida Shao, Claudio Zambaldo, Jonathan Edyta, Lara Ibrahim, Caroline Stanton, Stormi Chadwick, Emily Chen, Michael DeRan, Sijia Li, Mitchell Hull, Xu Wu, Arnab Chatterjee, Weijun Shen*, Fernando Camargo*, Peter G. Schultz* & Michael J. Bollong*，YAP-dependent Proliferation by a Small Molecule Targeting Annexin A2，Nature Chemical Biology，2021

2. Sam Lear*, Elsa Pflimlin*, Zhihong Zhou*, David Huang, Van T.B. Nguyen-Tran, Sean B. Joseph, Shane Roller, Scott Peterson, Jing Li, Matthew Tremblay, Peter G. Schultz and Weijun Shen*, Engineering of a Potent, Long-Acting NPY2R Agonist for Combination with a GLP-1R Agonist as a Multi-Hormonal Treatment for Obesity, J. Med. Chem.,2020.

3. Peng Sang, Zhihong Zhou, Yan Shi, Candy Lee, Zaid Amso, David Huang, Timothy Odom, Vân T.B. Nguyen-Tran, Weijun Shen*, Jianfeng Cai* The Activity of Sulfono-γ-AApeptide Helical Foldamers That Mimic GLP-1, Science Advances 2020

4. Amin Ardestani*, Sijia Li*, Karthika Annamalai, Blaz Lupse, Shirin Geravandi, Aleksandra Dobrowolski, Shan Yu, Siying Zhu, Tyler D. Baguley, Murali Surakattula, Janina Oetjen, Lena Hauberg-Lotte, Raquel Herranz, Sushil Awal, Delsi Altenhofen, Nguyen-Tran, Sean Joseph, Peter G Schultz, Arnab K. Chatterjee, Nikki Rogers, Matthew S. Tremblay*, Weijun Shen* and Kathrin Maedler* Neratinib Protects Pancreatic Beta Cells in Diabetes，Nature Communications，2019.

5. Hiroshi Deguchi, Zihan Guo, Mohammed Hayat, Elsa Pflimlin, Sam Lear, Weijun Shen*and John H.Griffin*,Molecular interaction site on procoagulant myosin for factor Xa-dependent prothrombin activation, J. Biol. Chem. 2019,294(41):15176-15181.

6. Xuekai Zhang, Gang Lu, Meng Sun, Madhu Mahankali, Yanfei Ma, Mingming Zhang, Wangde Hua, Yuting Hu, Qingbing Wang, Jinghuo Chen, Gang He*, Xiangbing Qi*, Weijun Shen*, Peng Liu* and Gong Chen* A General Strategy for Synthesis of Cyclophane-Braced Peptide Macrocycles via Palladium-Catalyzed Intramolecular sp3 C−H Arylation, Nature Chemistry 2018,10.1038/s41557-018-0006-y

7. Seung H. Choi, Madhupriya Mahankali, Sang Jun Lee, Mitch Hull, H. Michael Petrassi, Arnab K. Chatterjee, Peter G Schultz*, Katherine A. Jones* and Weijun Shen* Targeted disruption of Myc-Max oncoprotein complex by a small molecule, ACS Chem.Biol., 2017,Nov 17,12(11):2715-2719.

8. Sang Jun Lee*, Madhupriya Mahankali, Abdallah Bitar, Huafei Zou, Elizabeth Chao, Hung Nguyen, Jose Gonzalez, Dawna Caballero, Mitch Hull, Danling Wang, Peter G Schultz, & Weijun Shen*, A Novel Role for RARα Agonists as Apolipoprotein CIII Inhibitors Identified from High Throughput Screening, Scientific Reports, 2017

9. Chris J. Novotny*, Sirkku Pollari, Jin H. Park, Mark A. Lemmon, Weijun Shen* & Kevan M. Shokat*, Overcoming Resistance to HER2 Inhibitors Through State-Specific Kinase Binding, Nature Chem. Biol., 2016.

10. Peng-Yu Yang*, Huafei Zou, Elizabeth Chao, Lance Sherwood, Vanessa Nunez, Michael Keeney, Esi Ghartey-Tagoe, Zhongli Ding, Herlinda Quirino, Xiaozhou Luo, Gus Welzel, Guohua Chen, Parminder Singh, Ashley K. Woods*, Peter G. Schultz* and Weijun Shen* Engineering a long-acting, potent GLP-1 analog for microstructure-based transdermal delivery，Proc Natl Acad Sci USA，2016。

11. Weijun Shen*, Brandon Taylor, Qihui Jin, Van Nguyen-Tran, Shelly Meeusen, You-Qing Zhang,Anwesh Kamireddy, Austin Swafford, Andrew F. Powers, John Walker , John Lamb, Badry Bursalaya,Michael DiDonato, George Harb, Minhua Qiu , Christophe M. Filippi, Lisa Deaton, Carolina N. Turk,Wilma L. Suarez-Pinzon, Yahu Liu, Xueshi Hao, Tingting Mo, Shanshan Yan, Jing Li, Ann E. Herman,w ,Bernhard J. Hering, Tom Wu, H. Martin Seidel, Peter McNamara, Richard Glynne* & Bryan Laffitte*, Inhibition of DYRK1A and GSK3B induces human β-cell proliferation, Nature Communications, 2015, 6:8372

12. Weijun Shen*, Matthew S Tremblay*, Vishal A Deshmukh, Weidong Wang, Christophe M Filippi, George Harb, You-qing Zhang, Anwesh Kamireddy, Janine E Baaten, Qihui Jin, Tom Wu, Jonathan G Swoboda, Charles Y Cho, Jing Li, Bryan A Laffitte, Peter McNamara, Richard Glynne, Xu Wu, Ann E Herman, and Peter G Schultz*, Small- molecule inducers of β cell proliferation identified by high-throughput screening, J. Am. Chem. Soc. 2013.