张从刚

电子邮件：cgzhang@mail.tsinghua.edu.cn

研究方向：

本课题组长期致力于天然免疫及细胞器质量控制的基础与转化研究，重点关注cGAS–STING等固有免疫信号通路的调控机制，以及线粒体、溶酶体等关键细胞器在免疫稳态中的功能。我们综合运用生物化学、化学生物学、分子与细胞生物学、结构生物学及免疫学等多学科手段，系统解析免疫信号调控的分子机制，并探索其在疾病中的干预策略。

当前研究主要聚焦以下方向：

1）天然免疫信号通路的调控机制及靶向药物开发；

2）线粒体与溶酶体质量控制及其在免疫调控中的作用机制；

3）代谢信号（如脂质与能量代谢）与天然免疫的交叉调控；

4）上述机制在感染、肿瘤、炎症、自身免疫疾病、衰老及神经退行性疾病中的功能与转化应用。

代表性科研论文：

1. Han J, Zhang S, Hou Y, Wang Y, Zhang Z, Yang J, Xu Y, Peng Z, Yin H, Chen K, Liu X, Zhang C. A chemical agonist and the Golgi-resident lipid PI4P activate STING by inducing transmembrane helix rearrangement. Immunity. 2026;59(1):34-47.e9.

2. Wang Z, Hou Y, Liu P, Wu R, Yang J, Fan S, Peng Z, Han X, Su B, Zhang C. Membrane integrity changes upon viral infection activate sphingomyelinase SMPDL3B to restrict cGAS-STING signaling via cGAMP degradation. Immunity. 2025;58(11):2670-2684.e10.

3. Hou Y, Wang Z, Liu P, Wei X, Zhang Z, Fan S, Zhang L, Han F, Song Y, Chu L, Zhang C. SMPDL3A is a cGAMP-degrading enzyme induced by LXR-mediated lipid metabolism to restrict cGAS-STING DNA sensing. Immunity. 2023;56(11):2492-2507.e10.

4. Zhang Z, Zhang C. Regulation of cGAS-STING signalling and its diversity of cellular outcomes. Nat Rev Immunol. 2025;25(6):425-444.

5. Wei X, Zhang C. A universe of second messengers for cGLR-STING signaling. Immunity. 2023;56(9):1975-1977.

6.Zhang C ⃰, Shang G ⃰, Gui X, Bai X, Zhang X, Chen J. Z. (2019). Structural Basis of STING Binding with and Phosphorylation by TBK1. Nature. 567: 394-398

7.Shang G⃰, Zhang C ⃰, Chen J. Z, Bai X, Zhang X. (2019). Cryo-EM Structures of STING Reveal Its Mechanism of Activation by Cyclic GMP-AMP. Nature. 567: 389-393.

8. Zhang, C., S. Lee, Y. Peng, E. Bunker, E. Giaime, J. Shen, Z. Zhou, and X. Liu. (2014). PINK1 Triggers Autocatalytic Activation of Parkin to Specify Cell Fate Decisions. Curr Biol. 24:1854-65.