李智海

李智海 博士

研究员，国科大杭州高等研究院

浙江省杭州市西湖区象山支路1号 310012

E-mail: zhihaili@ucas.ac.cn

教育背景：

2013.09-2017.12厦门大学 博士 生物化学与分子生物学 导师：夏宁邵 教授，李少伟 教授

2010.09-2013.06 厦门大学 硕士 医学细胞生物学

2006.09-2010.06 西南交通大学 学士 生物信息学

工作经历：

2026.01-至今 国科大杭州高等研究院 研究员

2021.09-2025.12 国科大杭州高等研究院 副研究员

2020.10-2021.08 中国科学院上海药物研究所 副研究员

2018.01-2020.09 中国科学院上海药物研究所 博士后

2016.02-2017.02 美国加州大学洛杉矶分校 访问学者

研究方向：

生物大分子复合物动态调控结构药理研究与新药发现，主要围绕与重大疾病相关的病毒感染与复制过程调控、蛋白质稳态调控等相关功能靶点复合物（体）展开结构与功能研究，并开展基于新机制、新靶点的药物研发。研究成果以第一/通讯作者（含共同）在Cell Research, Nature Structural & Molecular Biology, Nature Communication, Advanced Science, Journal of Medicinal Chemistry和mBio等期刊发表SCI论文，申请或授权发明专利10余项，部分已实现商业转让。

发表论文：

1. Guo S.*, Li J.*, Lin J., Chen Y., Liu C., Liu H., He Z., Zhu Y., Wang L., Yang F., Luo C., Li Z. #, Jin J. #& Ye F. #. Discovery of the First-in-Class Protein Arginine Methyltransferase 1 PROTAC Degrader. Journal of Medicinal Chemistry 2026, https://doi.org/10.1021/acs.jmedchem.5c03030

2. Shen Y.*, Wei J.*, Tang S.*, Wu D., Zong L., Ma S., Xiong Q., Gong R., Xu S., Peng C., Feng Q., Liu S., Liu Q., Ye Y., Zhao Q., Luo C., Huang P., Li Z.#, Kong X.# & Lan X.#. Discovery of a Novel DNMT1 Inhibitor with Improved Efficacy in Treating β-Thalassemia. Advanced Science 2025, e13469

3. Deng Y.*, Yang S.*, Xu H.*, Ding X.*, Xu Y., Ye Z., Chen Y., Zhang Z., Lin J., Xiong H., Zhang Z., Yang K., Hu Y,, Xu K., Luo C., Chen S.#, Lin H.#, Li Z.#. Fluorescence-Coupled Ubiquitination Assay as a High-Throughput Screening Strategy for Novel Cereblon Degraders. Journal of Medicinal Chemistry 2025, 68(10):10111–10127.

4. Wang Z.*, Fan F.*, Li Z.*, Ye F.*, Wang Q., Gao R., Qiu J., Lv Y., Lin M., Xu W., Luo C.# & Yu X.#. Structural insights into the functional mechanism of the ubiquitin ligase E6AP. Nature Communications 2024, 15: 3531. (Featured article)

5. Li Z.*, Pang J.*, Gao R., Wang Q., Zhang M. & Yu X.#. Cryo-electron microscopy structures of capsids and in situ portals of DNA-devoid capsids of human cytomegalovirus. Nature Communications 2023, 14: 2025. (Featured article)

6. Li Z.*, Pang J.*, Dong L.* & Yu X.#. Structural basis for genome packaging, retention, and ejection in human cytomegalovirus. Nature Communications 2021, 12: 4538. (Featured article)

7. Yin W.*, Luan X.*, Li Z.*, Zhou Z.*, Wang Q.*, Gao M., Wang X., Zhou F., Shi J., You E., Liu M., Wang Q., Jiang Y., Jiang H., Xiao G., Zhang L.#, Yu X.#, Zhang S.# & Xu H.E.#. Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin. Nature Structural & Molecular Biology 2021, 28: 319-325.

8. Li Z.*, Zhang X.*, Dong L., Pang J., Xu M., Zhong Q., Zeng M.S.# & Yu X.#. CryoEM structure of the tegumented capsid of Epstein-Barr virus. Cell Research 2020, 30(10):873-884. (Cover story)

9. Li Z. & Yu X.#. Progress towards revealing the mechanism of herpesvirus capsid maturation and genome packaging. Protein & Cell 2020, 11:316-317.

10. Yin W*, Li Z.*, Jin M.*, Yin Y.L.*, Waal P.W., Pal K., Yin Y., Gao X., He Y., Gao J., Wang X., Zhang Y., Zhou H., Melcher K., Jiang Y., Cong Y.#, Zhou X.E.#, Yu X.# & Xu H.E.#. A complex structure of arrestin-2 bound to a G-protein-coupled receptor. Cell Research 2019, 29(12):971–983.

11. Li Z.*, Song S.*, He M.*, Wang D., Shi J., Liu X., Li Y., Chi X., Wei S., Yang Y., Wang Z., Li J., Qian H., Yu H., Zheng Q., Yan X., Zhao Q., Zhang J., Gu Y.#, Li S.# & Xia N.#. Rational Design of a Triple-Type Human Papillomavirus Vaccine by Compromising Viral-Type Specificity. Nature Communications 2018, 9(1):5360.

12. Wei M.*, Wang D.*, Li Z.*, Song S., Kong X., Mo X., Yang Y., He M., Li Z., Huang B., Lin Z., Pan H., Zheng Q., Yu H., Zhang J., Li S.# & Xia N.#. N-terminal Truncations on L1 Proteins of Human Papillomaviruses Promote their Soluble Expression in Escherichia coli and Self-assembly in Vitro. Emerging Microbes & Infections 2018, 7(1):160.

13. Li Z.*, Wang D.*, Gu Y.*, Song S., He M., Shi J., Liu X., Wei S., Li J., Yu H., Zheng Q., Yan X., Baker T.S., Zhang J., McLellan J.S.#, Li S.# & Xia N.#. Crystal Structures of Two Immune Complexes Identify Determinants for Viral Infectivity and Type-specific Neutralization of Human Papillomavirus. mBio 2017, 8: e00787-17.

14. Pan H.*, Li Z.*, Wang J., Song S., Wang D., Wei M., Gu Y., Zhang J., Li S.# & Xia N.#. Bacterially expressed human papillomavirus type 6 and 11 bivalent vaccine: Characterization, antigenicity and immunogenicity. Vaccine 2017, 35: 3221-3231.  

15. Li Z.*, Yan X.*, Yu H.*, Wang D., Song S., Li Y., He M., Hong Q., Zheng Q., Zhao Q., Gu Y., Zhang J., Janssen M.E.W, Cardone G., Olson N.H., Baker T.S.#, Li S.# & Xia N.#. The C-Terminal Arm of the Human Papillomavirus Major Capsid Protein Is Immunogenic
and Involved in Virus-Host Interaction. Structure 2016, 24: 874-885.

主持项目：

1. 国家自然科学基金面上项目，2025.01-2028.12

2. 杭州市“西湖明珠工程”特殊支持人才，2024.01-2026.12

3. 国科大杭高院自主部署项目青苗计划，2023.12-2026.11

4. 国科大杭高院自主立项交叉项目，2022.11-2024.10

5. 浙江省自然科学基金探索项目，2023.01-2025.12

6. 国家重点研发计划青年科学家项目子任务，2023.01-2025.12

7. 国家自然科学基金青年项目，2020.01-2022.12

8. 中国博士后科学基金面上项目，2019.06-2020.09

9. 上海市青年科技英才扬帆计划，2019.05-2022.04

10. 上海市“超级博士后”激励计划，2018.11-2020.06