研究领域

林欣教授的研究工作致力于揭示免疫细胞激活调控的分子机制，以及肿瘤的细胞免疫治疗研究方法；研究团队在免疫细胞激活的机制研究方面发表了一系列高水平的研究论文。团队根据T淋巴细胞激活机制设计了TCR受体为基础的新型CAR-T细胞治疗方法，现在致力于应用这些新型CAR-T细胞疗法治疗肿瘤和自身免疫疾病。

科学贡献

林欣教授的早期研究工作揭示了T细胞受体激活关键信号转导通路，进而激活T淋巴细胞的关键分子机制（Nature Immunology 2002，Immunity 2005，Immunity 2007）；发现了CARD家族分子相关信号通路在激活天然免疫细胞（Nature Immunology 2007，Nature Immunology 2009，Immunity 2013，Nature Medicine 2017）和参与炎症反应中的功能和致病机制（Nature Immunology 2018，Immunity 2018a, Immunity 2018b）。近年来，林欣教授团队根据T淋巴细胞激活机制设计TCR受体为基础的新型CAR-T细胞治疗方法（Science Translational Medicine），相关的CAR-T/TCR-T细胞治疗产品已经进入早期临床试验应用于肿瘤和自身免疫病患者的免疫治疗。

1. Wang, D.; You, Y.; Case, S.M.; Wang, L.; DiStefano, P.S., Nunez, G.; Bertin, J.; Lin, X. (2002) A requirement of CARMA1 in T cell receptor-induced NF-kB activation. Nature Immunology. 3(9): 830-5.

2. Matsumoto, R.; Wang, D.; Blonska, M.; Li, H.; Kobayashi, M.; Pappu, B.; Chen, Y.; Wang, D.; Lin, X. (2005) Phosphorylation of CARMA1 plays a critical role in T cell receptor-induced NF-kB activation. Immunity, 23, 1-11, 2005.

3. Blonska, M.; Pappu, B.; Li, H.; Matsumoto R.; Su, B.; Wang, D.; Lin, X. (2007) The CARMA1-Bcl10 complex selectively regulates JNK2 in the T cell receptor signaling pathway. Immunity, 26(1): 55-66.

4. Hsu, MY, Zhang, Y.; You, Y.; Wang, D.; Li, H.; Duramad, O, Qin, X; Dong, C; Lin, X. (2007) CARD9 is required for innate immune responses against intracellular pathogens. Nature Immunology, 8(2): 198-205.

5. Wu W, Hsu YM, Bi L, Songyang Z, Lin X. (2009) CARD9 facilitates microbe-elicited production of reactive oxygen species by regulating the LyGDI-Rac1 complex. Nature Immunology. Nov; 10(11):1208-14.

6. Zhu LL, Zhao XQ, Jiang CY, You Y, Chen XP, Jiang YY, Jia XM, Lin X (2013) C-type lectin receptors Dectin-3 (CLECSF8) and Dectin-2 form a heterodimeric pattern recognition receptor for host defense against fungal infection. Immunity, 2013 Aug 22; 39(2):324-34.

7. Blonska M, Joo D, Nurieva RI, Zhao X, Chiao P, Sun S-C, Dong C, Lin X (2013) Activation of the Transcription Factor c-Maf in T Cells is Dependent on the CARMA1-IKKb Signaling Cascade. Science Signaling. Dec 17; 6(306): ra110. doi: 10.1126/scisignal.2004273.

8. Jia XM, Tang B, Zhu LL, Liu YH, Zhao XQ, Gorjestani S, Hsu Y-M, Yang L, Guan JH, Xu GT, Lin X (2014) CARD9 mediates Dectin-1-induced ERK activation by linking Ras-GRF1 to H-Ras for anti-fungal immunity. J Exp Med. 2014 Oct 20;211(11):2307-21.

9. Jiang C, Zhou Z, Quan Y, Zhang S, Wang T, Zhao X, Morrison C, Heise MT, He W, Miller MS, and Lin X. (2016) CARMA3 is a host factor regulating the balance of inflammatory and antiviral responses against viral infection. Cell Reports. 2016 Mar 15;14(10):2389-401.

10. Zhao X, Guo Y, Jiang C, Chang Q, Zhang S, Luo T, Zhang B, Jia X, Hung MC, Dong C, Lin X (2017) JNK1 negatively controls antifungal innate immunity by suppressing CD23 expression. Nature Medicine 2017 Mar;23(3):337-346. doi: 10.1038/nm.4260. Epub 2017 Jan 23.

11. Xu X, Xu J, Zheng G, Lu H, Rui W, Guan J, Cheng L, Yang D, Wang M, Duan J, Lv Q, Li J, Zhao X, Chen C, Shi P, Jia X, Lin X. (2018). CARD9^S12N mutation converts alveolar macrophages into IL-5-producing cells and facilitates type 2 immune responses. Nature Immunology, 2018 Jun;19(6):547-560. doi: 10.1038/s41590-018-0112-4. Epub 2018 May 18.

12. Wang M, Zhang S, Zheng G, Huang J, Songyang Z, Zhao X, Lin X. (2018). Gain-of-Function Mutation of Card14 Leads to Spontaneous Psoriasis-like Skin Inflammation through Enhanced Keratinocyte Response to IL-17A. Immunity. 2018 Jun 28. pii: S1074-7613(18)30250-4. doi: 10.1016/j.

13. Wang T, Fan C, Yao A, Xu X, Zheng G, You Y, Jiang C, Zhao X, Hung MC, Lin X. (2018). The adaptor protein CARD9 protects against colitis-associated colon cancer by restricting mycobiota-mediated expansion of myeloid-derived suppressor cells. Immunity, 2018 Sep 18;49(3):504-514

14. Tang Y, Tu H, Zhang J, Zhao X, Lin X (2019). K63-linked ubiquitination regulates RIPK1 kinase activity to prevent cell death during embryogenesis and inflammation. Nat Commun. 2019 Sep 13;10(1):4157. doi: 10.1038/s41467-019-12033-8.

15. Liu G, Rui W, Zheng H, Huang D, Yu F, Zhang Y, Dong J, Zhao X, and Lin X (2020) CXCR2-modified CAR-T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma. Euro J Immunol. 2020 May;50(5):712-724. doi: 10.1002/eji.201948457. Epub 2020 Feb 10.PMID: 31981231

16. Liu G, Rui W, Zhao X, Lin X (2021) Enhancing CAR-T cell efficacy in solid tumor by targeting tumor microenvironment. Cell Mol Immunol, 2021 May;18(5):1085-1095. doi: 10.1038/s41423-021-00655-2. Epub 2021 Mar 30.

17. Liu Y, Liu G, Wang J, Zheng Z, Jia L, Rui W, Huang D, Zhou Z, Zhou L, Wu X, Song Lin S, Zhao X, Lin X (2021) Chimeric STAR receptors using TCR machinery mediate robust responses against solid tumors. Sci. Transl. Med. 2021 Mar 24;13(586): eabb5191. doi: 10.1126/scitranslmed.abb5191.

18. Wang J, Zhang X, Zhou Z, Liu Y, Jia L, Yang J, Liu G, Li J, Yu L, Li W, Rui W, Zheng H, Zhao X, Lin X, Lu P (2022) A Feasibility and Safety Study of a Novel CD19-Directed Synthetic T Cell Receptor and Antigen Receptor (STAR) T-cell Therapy for Refractory and Relapsed (R/R) B Cell Acute Lymphoblastic Leukemia (B-ALL). Am J Hematol. 2022 Aug;97(8):992-1004.

19. Liu G, Chen H, Cao X, Jia L, Rui W, Zheng H, Huang D, Liu F, Liu Y, Zhao X, Lu P, Lin X (2022) Efficacy of pp65-specific TCR-T cell therapy in treating cytomegalovirus infection after hematopoietic stem cell transplantation. Am J Hematol. 2022 Nov;97(11):1453-1463. doi: 10.1002/ajh.26708. Epub 2022 Sep 22.

20. Tu H, Xiong W, Zhang J, Zhao X, and Lin X (2022) Tyrosine phosphorylation regulates RIPK1 activity to limit cell death and inflammation. Nat. Commun. 2022 Nov 3;13(1):6603. doi: 10.1038/s41467-022-34080-4.

21. Zhang J, Tu H, Zheng Z, Zhao X, Lin X. (2023）RNF31 promotes tumorigenesis via inhibiting RIPK1 kinase-dependent apoptosis Oncogene. 2023 Mar 30. doi: 10.1038/s41388-023-02669-8. Online ahead of print.

22. Zheng Y, Jiang H, Yang N, Shen S, Huang D, Jia L, Ling J, Xu L, Li M, Yu K, Ren X, Cui Y, Lan X, Lin S, Lin X. (2023) Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment. Cell Mol Immunol 2023 Dec 4. doi: 10.1038/s41423-023-01110-0. Online ahead of print.

23. Xin Y, Xiong S, Zhou L, Lin X (2024) Activation of BLT1 is a prerequisite for fungal phagocytosis of neutrophils mediated by complement receptor 3. Cell Mol Immunol 2024 Mar;21(3):245-259. doi: 10.1038/s41423-024-01130-4.Epub 2024 Jan 31.

24. Huang D, Li Y, Rui W, Zhou Z, Xiong W, Sun K, Yu L, Wang J, Liu V, Zhou J, Chen C, Chen J, Lan X, Fu Y, Zhao X, Lin X (2024) TCR-mimic STAR Receptor Conveys Superior Sensitivity over CAR and TCR in Targeting tumors with low-neoantigen-density. Cell Reports 2024 Nov 26;43(11):114949.

25. Yu L, Zhou Z, Yu H, Liu Y, Huang D, Wang J. Lin X, (2025) Converting TCR-based chimeric antigen receptor STAR into dual-specific targeting receptor for cancer immunotherapy. Mol Ther. 2025 Apr 2;33(4):1552-1565.

1. 2003, Young Investigator Award, Exceptional Scholar Program, SUNY at Buffalo

2. 2004-2008, Investigator Award, Cancer Research Institute

3. 2004-2009, Scholar Award, The Leukemia and Lymphoma Society

4. 2008-2011, Faculty Scholar Award, University of Texas MD Anderson Cancer Center

5. 2009-2010, President, Texas Chapter, Society of Chinese Biologist Association (SCBA)

6. 2010 安德森癌症中心冠名讲席教授 （United Resources Endowed Professorship）

7. 2013 长江学者讲座教授

8. 2014 国家高层次人才国家特聘专家

9. 2019 清华大学拜耳讲席教授