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  • 李思睿
  • 研究員，研究組長，博士生導(dǎo)師
  • E-mail: sirui.li@sibcb.ac.cn
  • 實驗室主頁: 
    個人簡介：

  • 2011年本科畢業(yè)于延邊大學(xué)，2018年博士畢業(yè)于中國科學(xué)院大學(xué)生物物理研究所，2018年起以博士后身份先后在德克薩斯大學(xué)安德森癌癥中心（MD Anderson Cancer Center）和北卡羅萊納大學(xué)教堂山分校（UNC Lineberger Comprehensive Cancer Center）從事腫瘤免疫治療方向的研究。2024年加入中科院分子細胞科學(xué)卓越創(chuàng)新中心(生物化學(xué)與細胞生物學(xué)研究所)。聚焦核酸識別信號重塑腫瘤免疫微環(huán)境的機理研究，解析了內(nèi)源STING信號誘導(dǎo)調(diào)節(jié)性B淋巴細胞亞群負調(diào)控NK細胞功能的免疫逃逸新機制，并據(jù)此開發(fā)了多款腫瘤免疫療法。

    社會任職：
    研究方向：
  • 核酸感知信號和腫瘤免疫治療
    研究工作：

  • 腫瘤免疫治療領(lǐng)域蓬勃發(fā)展，而天然免疫靶點藥物的轉(zhuǎn)化應(yīng)用相對滯后，深入解析天然免疫靶點蛋白的細胞生物學(xué)屬性、超越傳統(tǒng)的設(shè)計范式，實現(xiàn)有序控制免疫應(yīng)答是開發(fā)新興腫瘤療法的重大挑戰(zhàn)之一。在癌癥發(fā)生、發(fā)展和轉(zhuǎn)移各階段或者暴露于放化療、免疫治療時，腫瘤微環(huán)境的分子模式和細胞組成發(fā)生實質(zhì)性轉(zhuǎn)變。核酸識別受體廣泛表達于各類免疫細胞，精細感知腫瘤微環(huán)境的轉(zhuǎn)變，進而影響免疫細胞的激活、浸潤、增殖、分化及發(fā)揮功能等，最終表現(xiàn)為幅度不一的腫瘤免疫應(yīng)答或腫瘤免疫逃逸。 基于腫瘤微環(huán)境中免疫細胞感知的多樣性，課題組將致力于解析腫瘤負向調(diào)控因素的多層次作用模式并開發(fā)新型腫瘤免疫療法。利用小鼠腫瘤模型及臨床樣本，結(jié)合多組學(xué)高通量數(shù)據(jù)分析、蛋白設(shè)計和mRNA-LNP遞送等手段，研究天然免疫核酸識別信號介導(dǎo)的負調(diào)控作用，挖掘關(guān)鍵調(diào)控因子，開發(fā)新型免疫療法，建立快速、特異的抗腫瘤免疫應(yīng)答和持久的免疫監(jiān)視。

    承擔(dān)科研項目情況：
    代表論著：
    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).

    獲獎及榮譽：
    研究組成員：
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