李思睿--中国科学院分子细胞科学卓越创新中心

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李思睿
研究员，研究组长，博士生导师
E-mail: sirui.li@sibcb.ac.cn
实验室主页:

个人简介：

2011年本科毕业于延边大学，2018年博士毕业于中国科学院大学生物物理研究所，2018年起以博士后身份先后在德克萨斯大学安德森癌症中心（MD Anderson Cancer Center）和北卡罗莱纳大学教堂山分校（UNC Lineberger Comprehensive Cancer Center）从事肿瘤免疫治疗方向的研究。2024年加入中科院分子细胞科学卓越创新中心(生物化学与细胞生物学研究所)。聚焦核酸识别信号重塑肿瘤免疫微环境的机理研究，解析了内源STING信号诱导调节性B淋巴细胞亚群负调控NK细胞功能的免疫逃逸新机制，并据此开发了多款肿瘤免疫疗法。

社会任职：

研究方向：

核酸感知信号和肿瘤免疫治疗

研究工作：

肿瘤免疫治疗领域蓬勃发展，而天然免疫靶点药物的转化应用相对滞后，深入解析天然免疫靶点蛋白的细胞生物学属性、超越传统的设计范式，实现有序控制免疫应答是开发新兴肿瘤疗法的重大挑战之一。在癌症发生、发展和转移各阶段或者暴露于放化疗、免疫治疗时，肿瘤微环境的分子模式和细胞组成发生实质性转变。核酸识别受体广泛表达于各类免疫细胞，精细感知肿瘤微环境的转变，进而影响免疫细胞的激活、浸润、增殖、分化及发挥功能等，最终表现为幅度不一的肿瘤免疫应答或肿瘤免疫逃逸。基于肿瘤微环境中免疫细胞感知的多样性，课题组将致力于解析肿瘤负向调控因素的多层次作用模式并开发新型肿瘤免疫疗法。利用小鼠肿瘤模型及临床样本，结合多组学高通量数据分析、蛋白设计和mRNA-LNP递送等手段，研究天然免疫核酸识别信号介导的负调控作用，挖掘关键调控因子，开发新型免疫疗法，建立快速、特异的抗肿瘤免疫应答和持久的免疫监视。

承担科研项目情况：

代表论著：

1. S Li*, B Mirlekar*, BM Johnson, WJ Brickey, JA Wrobel, N Yang, D Song, S Entwistle, X Tan, M Deng, Y Cui, W Li, BG Vincent, MG Jr., Y Pylayeva-Gupta^#, JPY Ting^#. STING-induced regulatory B cells compromise NK function in cancer immunity. Nature, 2022, 610(7931): 373-380. DOI: 10.1038/s41586-022-05254-3. PMID: 36198789. PMCID: PMC9875944.
  Highlighted by: Cancer Discovery (2022, DOI: 10.1158/2159-8290.CD-RW2022-183); Cell. Mol. Immunol. (2022, DOI: 10.1111/imcb.12601); Immunol. Cell Biol. (2022, DOI:10.1038/s41423-022-00952-4); Trends Pharmacol. Sci. (2023, DOI: 10.1016/j.tips.2022.11.002); Med. Rev. (2023, DOI: doi.org/10.1515/mr-2022-0037).
2. Y Wang*, S Li*, M Hu, Y Yang, E McCabe, L Zhang, AM Withrow, JPY Ting^#, R Liu^#. Universal STING mimic boosts antitumor immunity via preferential activation of tumour control signalling pathways. Nature Nanotechnology, 2024: 1-11. DOI: 10.1038/s41565-024-01624-2. PMID: 38480836.
  Highlighted by: Nature Nanotechnology (2024, DOI: 10.1038/s41565-024-01637-x)
3. KC Barnett*^#, S Li*, K Liang*, JPY Ting^#. A 360° view of the inflammasome: mechanisms of activation, cell death, and disease. Cell, 2023, 186(11): 2288-2312. DOI: 10.1016/j.cell.2023.04.025. PMID: 37236155. PMCID: PMC10228754.
4. X Lu, X Li, L Li, C Han^#, S Li^#. Advances in the prerequisite and consequence of STING downstream signalosomes. Medical Review, 2024. DOI: 10.1515/mr-2024-0016.
5. Z Zhou, S Huang, F Fan, Y Xu, C Moore, S Li^#, C Han^#. The multiple faces of cGAS-STING in antitumor immunity: prospects and challenges. Medical Review, 2024. DOI: 10.1515/mr-2023-0061.
6. X Lu*, X Kong*, H Wu*, J Hao, S Li, Z Gu, X Zeng, Y Shen, S Wang, J Chen, X Fei, Y Sun, X Li, L Jiang, F Yang^#, J Wang^#, Z Cai^#. UBE2M-mediated neddylation of TRIM21 regulates obesity-induced inflammation and metabolic disorders. Cell Metabolism, 2023. PMID: 37343564.
7. WJ Brickey, DL Caudell, AN Macintyre, JD Olson, Y Dai, S Li, GO Dugan, JD Bourland, LM O'Donnell, JA Tooze, G Huang, S Yang, H Guo, MN French, AN Schorzman, WC Zamboni, GD Sempowski, Z Li, K Owzar, NJ Chao, JM Cline, JPY Ting##. The TLR2/TLR6 ligand FSL-1 mitigates radiation-induced hematopoietic injury in mice and nonhuman primates. PNAS, 2023. DOI: 10.1073/pnas.2122178120. PMID: 38051771.
8. B Mirlekar, Y Wang, S Li, M Zhou, S Entwistle, TD Buysscher, A Morrison, G Herrera, C Harris, B Vincent, JPY Ting, N Rashid, W Kim, J Yeh, and Y Pylayeva-Gupta. Balance between immunoregulatory B cells and plasma cells drives pancreatic tumor immunity.Cell Reports Medicine, 2022, 3(9). DOI: 10.1016/j.xcrm.2022.100744. PMID: 36099917. PMCID: PMC9512696.
9. K Yang*, W Han*, X Jiang*, A Piffko, J Bugno, C Han, S Li, H Liang, Z Xu, W Zheng, L Wang, J Wang, X Huang, JPY Ting, Y Fu, W Lin^#, RR Weichselbaum^#. Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration. Nature Nanotechnology, 2022, 17(12): 1322-1331. DOI: 10.1038/s41565-022-01225-x. PMID: 36302963.
10. Y Wang, K Tiruthani, S Li, M Hu, G Zhong, Y Tang, S Roy, L Zhang, J Tan, C Liao, R Liu. mRNA Delivery of a Bispecific Single-Domain Antibody to Polarize Tumor-Associated Macrophages and Synergize Immunotherapy against Liver Malignancies. Advanced Materials, 2021, 33(23): 2007603. DOI: 10.1002/adma.202007603. PMID: 33945178. PMCID: PMC8240965.
11. L Li, Y Shi, S Li, J Liu, S Zu, X Xu, M Gao, N Sun, C Pan, L Peng, H Yang, G Cheng. ADP-Ribosyltransferase PARP11 Suppresses Zika Virus in Synergy with PARP12. Cell & Bioscience, 2021, 11(1): 1-13. DOI: 10.1186/s13578-021-00628-y. PMID: 34187568. PMCID: PMC8240438.
12. M Deng, J Tam, L Wang, K Liang, S Li, L Zhang, H Guo, X Luo, Y Zhang, A Petrucelli, B Davis, B Conti, WJ Brickey, C Ko, Y Lei, S Sun, and JPY Ting, TRAF3IP3 negatively regulates cytosolic RNA induced anti-viral innate immune signaling through promoting TBK1 K48 ubiquitination. Nature communications, 2020, 11(1): 2193. DOI: 10.1038/s41467-020-16014-0. PMID: 32366851. PMCID: PMC7198545.
13. Y Hong*, S Li*, J Wang and Y Li^#, In vitro inhibition of hepatic stellate cell activation by the autophagy-related lipid droplet protein ATG2A. Scientific Reports, 2018, 8(1): 9232. DOI: 10.1038/s41598-018-27686-6. PMID: 29915313. PMCID: PMC6006255.
14. M Xu, M Liu, X Du, S Li, H Li, X Li, Y Li, Y Wang, Z Qin, Y Fu, and S Wang, Intratumoral delivery of IL-21 overcomes anti-Her2/Neu resistance through shifting tumor-associated macrophages from M2 to M1 phenotype. The Journal of Immunology, 2015, 194(10): 4997-5006. DOI: 10.4049/jimmunol.1402603. PMID: 25876763.
15. M Xu, X Du, M Liu, S Li, X Li, Y Fu, S Wang. The tumor immunosuppressive microenvironment impairs the therapy of anti-HER2/neu antibody. Protein & cell, 2012, 3: 441-449. DOI: 10.1007/s13238-012-2044-3. PMID: 22717982. PMCID: PMC4875483.
(* designates co-first author) (# designates co-senior authors).

个人简介：

社会任职：

研究方向：

研究工作：

承担科研项目情况：

代表论著：

获奖及荣誉：

研究组成员：