教育背景

1999-2003 四川大学生命科学学院 学士

2004-2010 中国科学院生物物理研究所 博士

工作经历

2010-2013 美国安德森癌症中心 博士后

2014-2024 清华大学医学院 副研究员 

2014-至今 清华大学基础医学院 副研究员

研究领域

阐明免疫细胞激活调控的分子机制，聚焦于C型凝集素受体相关的抗真菌天然免疫信号通路；另一方向是肿瘤的细胞免疫治疗研究方法和转化，包括合成T细胞受体抗原受体（Synthetic T cell receptor and Antigen Receptor，STAR）技术和TCR-T技术平台。

科学贡献

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。并根据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，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患者的免疫治疗。已在《Nature Medicine》、《Nature Immunology》、《Immunity》等国际高水平期刊上发表论文30余篇；申请30余项细胞治疗相关专利；主持国家自然科学基金项目3项和北京市医药新品种研发培育项目1项，作为主要骨干参与科技部重点研发项目、国家自然科学基金重点项目、北京市科技重大专项等10余项。

荣誉奖励

2021年 教育部高等学校科学研究优秀成果自然科学一等奖

代表性论文

1.Zhao X, Mohaupt M, Jiang J, Liu S, Li B, Qin Z. Tumor necrosis factor receptor 2-mediated tumor suppression is nitric oxide dependent and involves angiostasis. Cancer Res. 2007 May 1;67(9):4443-50.

2.Xiao M, Wang C, Zhang J, Li Z, Zhao X, Qin Z. IFNgamma promotes papilloma development by up-regulating Th17-associated inflammation. Cancer Res. 2009 Mar 1; 69(5):2010-7.

3.Zhao X, Rong L, Zhao X, Li X, Liu X, Deng J, Wu H, Xu X, Erben U, Wu P, Syrbe U, Sieper J, Qin Z. TNF signaling drives myeloid-derived suppressor cell accumulation. J Clin Invest. 2012 Nov; 122(11):4094-104.

4.Xia Y, Yang W, Bu W, Ji H, Zhao X, Zheng Y, Lin X, Li Y, Lu Z. Differential regulation of c-Jun protein plays an instrumental role in chemoresistance of cancer cells. J Biol Chem. 2013 Jul 5; 288(27):19321-9.

5.Blonska M, Joo D, Nurieva RI, Zhao X, Chiao P, Sun SC, Dong C, Lin X. Activation of the transcription factor c-Maf in T cells is dependent on the CARMA1-IKKbeta signaling cascade. Sci Signal. 2013 Dec 17; 6(306):ra110.

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

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

8.Zhao XQ, Zhu LL, Chang Q, Jiang C, You Y, Luo T, Jia XM, Lin X. C-type lectin receptor dectin-3 mediates trehalose 6,6'-dimycolate (TDM)-induced Mincle expression through CARD9/Bcl10/MALT1-dependent nuclear factor (NF)-kappaB activation. J Biol Chem. 2014 Oct 24; 289(43):30052-62.

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

10.Wang T, Pan D, Zhou Z, You Y, Jiang C, Zhao X, Lin X. Dectin-3 deficiency promotes colitis development due to impaired antifungal innate immune responses in the gut. PLoS Pathog. 2016 Jun 9; 12(6):e1005662.

11.Zhu LL, Luo TM, Xu X, Guo YH, Zhao XQ, Wang TT, Tang B, Jiang YY, Xu JF, Lin X, Jia XM. E3 ubiquitin ligase Cbl-b negatively regulates C-type lectin receptor-mediated antifungal innate immunity. J Exp Med. 2016 Jul 25; 213(8):1555-70.

12.Joo D, Tang Y, Blonska M, Jin J, Zhao X, Lin X. Regulation of linear Ubiquitin Chain Assembly complex by Caspase-mediated cleavage of RNF31. Mol Cell Biol. 2016 Nov 28; 36(24):3010-3018.

13.Zhang S, Pan D, Jia XM, Lin X, Zhao X^*. The CARMA3-BCL10-MALT1 (CBM) complex contributes to DNA damage-induced NF-κB activation and cell survival. Protein Cell. 2017 Nov; 8(11):856-860.

14.Hou H, Guo Y, Chang Q, Luo T, Wu X, Zhao X^*. C-type lectin receptor: old friend and new player. Med Chem. 2017, 13(6):536~543.

15.Zhao X^*, Guo Y, Jiang C, Chang Q, Zhang S, Luo T, Zhang B, Jia X, Hung MC, Dong C, Lin X. JNK1 negatively controls antifungal innate immunity by suppressing CD23 expression. Nat Med. 2017 Mar; 23(3):337-346. (Co-corresponding)

16.Xu X, Xu JF, Zheng G, Lu HW, Duan JL, Rui W, Guan JH, Cheng LQ, Yang DD, Wang MC, Lv QZ, Li JX, Zhao X, Chen CX, Shi P, Jia XM, Lin X. CARD9S12N facilitates the production of IL-5 by alveolar macrophages for the induction of type 2 immune responses. Nat Immunol. 2018 Jun;19(6):547-560.

17.Tang Y, Tu H, Liu G, Zheng G, Wang M, Li L, Zhao X, Lin X. RNF31 Regulates Skin Homeostasis by Protecting Epidermal Keratinocytes from Cell Death. J Immunol. 2018 Jun 15;200(12):4117-4124.

18.Wang M, Zhang S, Zheng G, Huang J, Songyang Z, Zhao X^*, Lin X. Gain-of-Function Mutation of Card14 Leads to Spontaneous Psoriasis-like Skin Inflammation through Enhanced Keratinocyte Response to IL-17A. Immunity. 2018 Jul 17;49(1):66-79. (Co-corresponding)

19.Wang T, Fan C, Yao A, Xu X, Zheng G, You Y, Jiang C, Zhao X, Hou Y, Hung MC, Lin X. The Adaptor Protein CARD9 Protects against Colon Cancer by Restricting Mycobiota-Mediated Expansion of Myeloid-Derived Suppressor Cells. Immunity. 2018 Sep 18;49(3):504-514.

20.Guo Y, Chang Q, Cheng L, Xiong S, Jia X, Lin X, Zhao X^*. C-type lectin receptor CD23 is required for host defense against Candida albicans and Aspergillus fumigatus infection. J Immunol. 2018 Oct 15;201(8):2427-2440.

21.Tang Y, Joo D, Liu G, Tu H, You J, Jin J, Zhao X, Hung MC, Lin X. Linear ubiquitination of cFLIP induced by LUBAC contributes to TNFa-induced apoptosis. J Biol Chem. 2018 Dec 28;293(52):20062-20072.

22.Zheng G, Jiang C, Li Y, Yang D, Ma Y, Zhang B, Li X, Zhang P, Hu X, Zhao X, Du J, Lin X. TMEM43-S358L mutation enhances NF-κB-TGFβ signal cascade in arrhythmogenic right ventricular dysplasia/cardiomyopathy. Protein Cell. 2019 Feb;10(2):104-119.

23.Cheng L, Deng N, Yang N, Zhao X, Lin X. Malt1 protease is critical in maintaining function of regulatory T cells and may be a therapeutic target for antitumor immunity. J Immunol. 2019 May 15;202(10):3008-3019.

24.Tang Y, Tu H, Zhang J, Zhao X, Wang Y, Qin J, Lin X. K63-linked ubiquitination regulates RIPK1 kinase activity to prevent cell death during embryogenesis and inflammation. Nat Commun. 2019 Sep 13;10(1):4157.

25.Liu G, Rui W, Zheng H, Huang D, Yu F, Zhang Y, Dong J, Zhao X, Lin X. CXCR2-modified CAR-T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma. Eur J Immunol. 2020 May;50(5):712-724.

26.Yang D, Zhao X, Lin X. Bcl10 is required for the development and suppressive function of Foxp3+ regulatory T cells. Cell Mol Immunol. 2021 Jan;18(1):206-218.

27.Ren Z, Yue Y, Zhang Y, Dong J, Liu Y, Yang X, Lin X, Zhao X, Wei Z, Zheng Y, Wang T. Changes in the peripheral blood Treg cell proportion in hepatocellular carcinoma patients after transarterial chemoembolization with microparticles. Front Immunol. 2021 Feb 24;12:624789.

28.Zhang S, Wang M, Wang C, Wang G, Sun K, Xiong S, Cheng L, Yang D, Lin X, Zhao X. Intrinsic Abnormalities of Keratinocytes Initiate Skin Inflammation through the IL-23/T17 Axis in a MALT1-dependent Manner. J Immunol. 2021 Feb 15;206(4):839-848.

29.Liu Y, Liu G, Wang J, Zheng Z, Jia L, Rui W, Huang D, Zhou Z, Zhou L, Wu X, Lin S, Zhao X, Lin X. Chimeric STAR Receptors Utilizing TCR Machinery Mediate Robust Response to Solid Tumors. Sci Transl Med. 2021 Mar 24;13(586). (Co-corresponding)

30.Liu G, Rui W, Zhao X, Lin X. Enhancing CAR-T cell efficacy in solid tumors by targeting the tumor microenvironment. Cell Mol Immunol. 2021 May;18(5):1085-1095.

31.Wu X, Tang Y, Zhang S, Zhao X, Lin X. MyD88-dependent signaling is required for HOIP deficiency-induced autoinflammation. J Immunol. 2021 Jul 15;207(2):542-554.

32.Tu H, Tang Y, Zhang J, Cheng L, Joo D, Zhao X, Xin Lin. Linear Ubiquitination of RIPK1 on Lys612 Regulates Systemic Inflammation via Preventing Cell Death. J Immunol. 2021 Jul 15;207(2):602-612.

33.Wang J, Zhang X, Zhou Z, Liu Y, Yu L, Jia L, Yang J, Li J, Yu H, Li W, Liu G, Rui W, Zheng H, Zhao X, Lin X, Lu P. A novel adoptive synthetic TCR and antigen receptor (STAR) T-Cell therapy for B-Cell acute lymphoblastic leukemia. Am J Hematol. 2022 Aug;97(8):992-1004.

34.Cheng L, Wei Z, Yang Z, Lu R, Yang M, Yu M, Yang N, Li S, Gao M, Zhao X, Lin X. Carma3 Protects from Liver Injury by Preserving Mitochondrial Integrity in Liver Sinusoidal Endothelial Cells. J Immunol. 2022 Aug 1;209(3):456-464.

35.Yang D, Pei G, Dong S, Zhang W, Deng H, Zhao X, Li P, Lin X. Bcl10 phosphorylation-dependent droplet-like condensation positively regulates DNA virus-induced innate immune signaling. Sci China Life Sci. 2022 Sep 15. doi: 10.1007/s11427-022-2169-x. Online ahead of print.

36.Liu G, Rui W, Zhao X, Lin X. 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.

37.Tu H, Xiong W, Zhang J, Zhao X, Lin X. Tyrosine phosphorylation regulates RIPK1 activity to limit cell death and inflammation. Nat Commun. 2022 Nov 3;13(1):6603.

38.Gong L, Sun H, Liu L, Sun X, Fang T, Yu Z, Sui W, Xu J, Wang T, Feng F, Lei L, Rui W, Liu Y, Zhao X, An G, Lin X, Qiu L, Hao M. LILRB4 represents a promising target for immunotherapy by dual targeting tumor cells and myeloid-derived suppressive cells in multiple myeloma. Haematologica. 2024 May 30. Online ahead of print.