许琛琦 - 中国科学院上海生物化学与细胞生物研究所 -

个人简介

2004年毕业于中科院生物化学与细胞生物学研究所，获理学博士学位。2004年赴美国哈佛大学医学院Dana-Farber肿瘤研究所从事免疫学研究，先后为博士后(受美国关节炎基金会资助)，instructor。2009年11月回生化与细胞所工作，担任研究员与研究组长，现任所长助理、分子生物学国家重点实验室副主任、中国生物化学与分子生物学会副秘书长。先后入选国家杰出青年基金、科技部中青年科技创新领军人才、上海市科委优秀学术带头人计划；成果入选中国科学十大进展和中国生命科学十大进展；获谈家桢生命科学奖创新奖、中源协和生命医学奖、全国优秀科技工作者、上海青年科技英才等奖项。

研究领域

免疫系统是机体执行免疫应答及免疫功能的重要系统，它能够区分“自身”和“非自身”，并通过清除“非自身物质”来保护机体。免疫系统可以分为固有免疫和适应性免疫。固有免疫系统在低等动物中就开始出现，可以识别病原体所携带的特殊模式以及体内的危险信号，从而迅速地做出免疫反应。适应性免疫系统是高等动物逐渐进化出的特殊功能系统，最大的特点是能够针对不同的抗原做出高度特异性和灵敏性的免疫反应。T淋巴细胞（简称T细胞）是适应性免疫系统的主要功能细胞，在清除病原体和肿瘤细胞过程中发挥着至关重要的作用。T细胞的活性异常与肿瘤、自身免疫病等多种重大疾病直接相关。基于T细胞功能调控的肿瘤免疫治疗已成为治疗肿瘤的主要武器之一，在临床上已取得了巨大的成功。但现有的基于信号转导调控的肿瘤免疫治疗手段只对部分病人有效，因此急需发展新的方法让更多的病人受益。本研究组交叉利用免疫学、生物化学、生物物理学前沿手段，着力于T细胞活性调控的分子机制研究，揭示了T细胞发挥免疫功能的分子基础，并且发展了新的肿瘤免疫治疗方法

近期论文

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Xu X#, Li H#, Xu, C*. Structural understanding of T cell receptor triggering. Cellular & Molecular Immunology, DOI: https://doi.org/10.1038/s41423-020-0367-1,2020. Huang B, Song B, Xu C*. Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities. Nature Metabolism, DOI: https://doi.org/10.1038/s42255-020-0174-0,2020. Li H*, Yan C, Guo J, Xu C*. Ionic protein–lipid interactions at the plasma membrane regulate the structure and function of immunoreceptors. Advances in Immunology, 144 pp 65-85, 2019. Wu P, Zhang T, Liu B, Fei P, Cui L, Qin R, Zhu H, Yao D, Martinez R, Hu W, An C, Zhang Y, Liu J, Shi J, Fan J, Yin W, Sun J, Zhou C, Zeng X, Xu C, Wang J, Evavold B, Zhu C, Chen W*, Lou J*. Mechano-regulation of Peptide-MHC Class I Conformations Determines TCR Antigen Recognition. Molecular Cell. 73(5):1015-1027, 2019. Meng X#, Liu X#, Guo X, Jiang S, Chen T, Hu Z, Liu H, Bai Y, Xue M, Hu R, Sun SC, Liu X, Zhou P, Huang X, Wei L, Yang W, Xu C*. FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells. Nature. 564 (7734): 130-135, 2018. Guo J#, Zhang Y#, Li H#, Chu H#, Wang Q, Jiang S, Li Y, Shen H, Li G*, Chen J*, Xu C*. Intramembrane ionic protein-lipid interaction regulates integrin structure and function. PLoS Biology, 16(11):e2006525, 2018. Chen X#, Sun X#, Yang W#, Yang B#, Zhao X, Chen S, He L, Chen H, Yang C, Xiao L, Chang Z, Guo J, He J, Zhang F, Zheng F, Hu Z, Yang Z, Lou J, Zheng W, Qi H, Xu C, Zhang H, Shan H, Zhou XJ, Wang Q, Shi Y, Lai L, Li Z*, Liu W*. An autoimmune disease variant of IgG1 modulates B cell activation and differentiation. Science. 362 (6415): 700-705, 2018. Wang J, Yan C, Xu C, Chua B, Li P*, Chen F*. Polybasic RKKR motif in the linker region of lipid droplet (LD)-associated protein CIDEC inhibits LD fusion activity by interacting with acidic phospholipids. Journal of Biological Chemistry. 293(50):19330-19343, 2018. Xu C, Xie H, Guo X, Gong H, Liu L, Qi H, Xu C, Liu W*. A PIP2-derived amplification loop fuels the sustained initiation of B cell activation. Science Immunology, 2(17), 2017 Bietz A#, Zhu H#, Xue M, Xu C*. Cholesterol Metabolism in T Cells. Frontiers in Immunology, 8:1664, 2017 Yang W#, Pan W#, Chen S#, Trendel N#, Jiang S#, Xiao F, Xue M, Wu W, Peng Z, Li X, Ji H, Liu X, Jiang H, Wang H, Shen H, Dushek O*, Li H*, Xu C*. Dynamic regulation of CD28 conformation and signaling by charged lipids and ions. Nature Structural & Molecular Biology, 24(12), pp 1081-1092, 2017. Wang H, Wang S, Li C, Li H, Mao Y, Liu W, Xu C*, Long D*. Probing Transient Release of Membrane-Sequestered Tyrosine-Based Signaling Motif by Solution NMR Spectroscopy. The Journal of Physical Chemistry Letters, 8(16), pp 3765-3769, 2017. Li L#, Guo X#, Shi X#, Li C#, Wu W, Yan C, Wang H, Li H, Xu C*. Ionic CD3-Lck interaction regulates the initiation of T-cell receptor signaling. Proceedings of the National Academy of Sciences of the United States of America (Plus), 114(29), pp E5891-E5899, 2017. Guo X#, Yan C#, Li H#, Huang W#, Shi X, Huang M, Wang Y, Pan W, Cai M, Li L, Wu W, Bai Y, Zhang C, Liu Z, Wang X, Zhang F X, Tang C, Wang H, Liu W, Ouyang B, Catherine C Wong, Cao Y*, Xu C*. Lipid-dependent conformational dynamics underlie the functional versatility of T-cell receptor. Cell Research, 27(4), pp 505-525, 2017. Xu L#, Xia M#, Guo J#, Sun X#, Li H, Xu C, Gu X, Zhang H, Yi J, Fang Y, Xie H, Wang J, Shen Z, Xue B, Sun Y, Meckel T, Chen Y, Hu Z, Li Z*, Xu C*, Gong H*, Liu W*. Impairment on the lateral mobility induced by structural changes underlies the functional deficiency of the lupus-associated polymorphism FcγRIIB-T232. The Journal of Experimental Medicine, 213(12), pp 2707-2727, 2016. Wu W, Shi X, Xu C*. Regulation of T cell signalling by membrane lipids. Nature Reviews Immunology, 16(11), pp 690-701, 2016. Liu W*, Wang H, Xu C*. Antigen Receptor Nanoclusters:Small Units with Big Functions. Trends in Immunology, 37(10), pp 680-689, 2016. Yang W#, Bai Y#, Xiong Y, Zhang J, Chen S, Zheng X, Meng X, Li L, Wang J, Xu C, Yan C, Wang L, Chang C, Chang T, Zhang T, Zhou P Song B, Liu W, Sun S, Liu X, Li B*, Xu C*. Potentiating the anti tumour response of CD8+ T cells by modulating cholesterol metabolism. Nature, 531(7596), pp 651-655, 2016. Cui Y#, Chen X#, Zhang J, Sun X, Liu H, Bai L, Xu C, Liu X*. Uhrf1 Controls iNKT Cell Survival and Differentiation through the Akt-mTOR Axis. Cell Reports, 15(2), pp 256-263, 2016. Chen X#, Pan W#, Sui Y, Li H, Shi X, Guo X, Qi H, Xu C*, Liu W*. Acidic phospholipids govern the enhanced activation of IgG-B cell receptor. Nature Communications, 6(8552), 2015.