Education

2002-2007, Ph.D. Organic Chemistry, Department of Chemistry, University of Georgia, Athens, Georgia, USA, mentor: Prof. Geert-Jan Boons.

1999-2002, M.S. Medicinal chemistry, Shenyang Pharmaceutical University, Shenyang, China, mentor: Prof. Ji-Xiang Chen.

1995-1999, B.S. Medicinal Chemistry, Shandong Medical University, Jinan, China.

Academic Experience

2015-present   Professor, School of Pharmaceutical Sciences, Tsinghua University.

2010-2015       Professor, School of Medicine, Department of Pharmacy, Tsinghua University.

2007-2009       Postdoc, Memorial Sloan-Kettering Cancer Center. 

Overview of Academic Research

Dr. Rao has been engaged in the chemical biology area of new drug discovery for a long period of time. In recent years, Dr. Rao’s research interest mainly focuses on the development and application of PROTAC based targeted protein degradation technology, aiming to develop drugs for undruggable targets and expand new therapeutic pattern; Use new chemical knockdown technology to regulate protein function and clarify key biological issues. In recent years, a series of research progress has been made in the research field of PROTAC:

(1) A collaborative application model of PROTAC and molecular glue was proposed. According to the characteristics of PROTAC and molecular glue, a new type of dual-target and dual-mechanism degradation agent was designed and synthesized for the first time, which provided a new idea for the development of targeted degradation technology.

(2) The team achieved the drug development for undruggable targets, designed and synthesized the first selective CDK2 degradation agent, solved the long existing challenge of CDK2 targeted selectivity, and provided an efficient and low-toxicity differentiation treatment scheme for AML treatment.

(3) Rao group reported the development of a new type of highly effective degradation agent for BTK protein for the first time, which overcomed the drug resistance of B-cell malignant tumors to the first-line clinical drug-ibrutinib caused by BTK protein mutation.

Major Honor and Awards

1. Wuxi apptec Life Science and Chemistry Awards

2. The VCANBIO Award for Innovations and Breakthroughs in Life Sciences and Medicine

3. Shulan Medical Award for Young Scholar

4. Obtained more than 10 Chinese invention patents and 2 PCT international patents

Representative Research Achievements 

1. C. Cao, M. He, L. Wang, Y. He, Y. Rao*, 'Chemistries of bifunctional PROTAC degraders', Chemical Society Reviews, 2022, 51, 7066 - 7114. DOI: 10.1039/d2cs00220e.

2.  Z. Yang, Y. Sun, Z. Ni, C. Yang, Y. Tong, Y. Liu, H. Li and Y. Rao*, 'Merging PROTAC and molecular glue for degrading BTK and GSPT1 proteins concurrently', Cell Research, 2021, 25, 1-4. DOI: 10.1038/s41422-021-00533-6.

3.  L. Wang, X. Shao, T. Zhong, Y. Wu, A. Xu, X. Sun, H. Gao, Y. Liu, T. Lan, Y. Tong, X. Tao, W. Du, W. Wang, Y. Chen, T. Li, X. Meng, H. Deng, B. Yang, Q. He, M. Ying*, Y. Rao*, 'Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy', Nature Chemical Biology, 2021, 16, 567-575. DOI: 10.1038/s41589-021-00742-5.

4.  Y. Sun, N. Ding, Y. Song, Z. Yang, W. Liu *, J. Zhu*, Y. Rao*, ‘Degradation of Bruton's tyrosine kinase mutants by PROTACs for potential treatment of ibrutinib-resistant Non-Hodgkin lymphomas’, Leukemia, 2019, 33, 2105–2110. DOI: 10.1038/s41375-019-0440-x.

5.  X. Sun, J. Wang, X. Yao, W. Zheng, Y. Mao, T. Lan, L. Wang, Y. Sun, X. Zhang, Q. Zhao, J. Zhao, R-P. Xiao, X. Zhang*, G. Ji*, Y. Rao*, ‘A Chemical Approach for Global Protein Knockdown from Mice to Non-human Primates’, Cell Discovery, 2019, 5, 1–13. DOI: 10.1038/s41421-018-0079-1.

6.  Y. Sun, X. Zhao, N. Ding, H. Gao, Y. Wu, Y. Yang, M. Zhao, J. Hwang, Y. Song, W. Liu *, Y. Rao*, ‘PROTAC-Induced BTK Degradation as a Novel Therapy for Mutated BTK C481S Induced Ibrutinib-Resistant B-Cell Malignancies’, Cell Research, 2018, 22, 779–781.

7. Y. Yang, H. Gao, X. Sun, Y. Sun, Y. Qiu, Q. Weng*, Y. Rao*, ‘A Global PROTAC Toolbox for Degrading BCR-ABL Overcomes Drug-Resistant Mutants and Adverse Effects’, Journal of Medicinal Chemistry, 2020, 63, 8567-8583. DOI: 10.1021/acs.jmedchem.0c00967.

8. H. Gao, C. Zheng, J. Du, Y. Wu, Y. Sun, C. Han*, K. Kee*, Y. Rao*, ‘FAK-targeting PROTAC as a chemical tool for the investigation of non-enzymatic FAK function in mice’, Protein & Cell, 2020, 11, 534 -539. DOI: 10.1007/s13238-020-00732-8.

9. M. Li, Y. Yang, Q. Zhao, Y. Wu, L. Song, H. Yang, M. He, H. Gao, B. Song, J. Luo*, Y. Rao*, ‘Degradation Versus Inhibition: Development of Proteolysis-Targeting Chimeras for Overcoming Statin-Induced Compensatory Upregulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase’. Journal of Medicinal Chemistry, 2020, 63, 4908-4928. DOI: 10.1021/acs.jmedchem.0c00339.

10. H. Yang, W. Lv, M. He, H. Deng, H. Li, W. Wu*, Y. Rao*, ‘Plasticity in designing PROTACs for selective and potent degradation of HDAC6’, Chemical Communications, 2019, 55, 14848-14851, DOI: 10.1039/C9CC08509B.