教育经历

2002-2007  美国佐治亚大学，有机化学，博士

1999-2002  沈阳药科大学，药物化学，硕士

1995-1999  山东医科大学，药物化学，学士

工作经历

2015-至今   清华大学药学院，教授

2010-2015  清华大学医学院、药学系，教授

2007-2009  Memorial Sloan-Kettering Cancer Center，博士后

研究简介

长期从事新药发现的化学生物学研究，近年来研究工作主要聚焦‘新型蛋白质靶向降解技术PROTAC的开发和应用’，旨在利用新技术开发难成药靶点新药物，拓展新的治疗格局；利用新型化学敲降技术调控蛋白功能，阐明关键生物学问题。近些年基于PROTAC研究取得了一系列的研究进展：

    （1）提出了 PROTAC 和分子胶协同应用的模式。根据 PROTAC 和分子胶的特点首次设计合成了新型双靶、双机制的降解剂，为靶向降解技术的发展提出了新的思路。

    （2）实现难成药靶点的药物开发，设计合成首例选择性 CDK2 降解剂，解决长期存在的 CDK2靶向选择性挑战，为AML治疗提供一种高效且低毒的分化治疗方案。

    （3）首次报道了新型BTK蛋白高效降解剂开发，克服了临床上B细胞恶性肿瘤由于BTK蛋白突变引起的对临床一线药物依鲁替尼的耐药性。

主要荣誉

中源协和生命医学创新突破奖、树兰医学青年奖、药明康德生命化学研究奖杰出成就奖

获得中国发明专利授权十余项，PCT 国际专利 2 项

代表性成果

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.