Research Area
Our laboratory focuses on fundamental and translational research in innate immunity and organelle quality control. We are particularly interested in the regulatory mechanisms of innate immune signaling pathways, including cGAS–STING, as well as the roles of key organelles such as mitochondria and lysosomes in maintaining immune homeostasis.
By integrating multidisciplinary approaches, including biochemistry, chemical biology, molecular and cellular biology, structural biology, and immunology, we aim to dissect the molecular basis of immune regulation and explore therapeutic strategies targeting these pathways.
Our current research directions include:
1. Mechanisms and pharmacological modulation of innate immune signaling pathways;
2. Quality control of mitochondria and lysosomes and their roles in immune regulation;
3. Crosstalk between metabolic signaling (e.g., lipid and energy metabolism) and innate immunity;
4. Functional and translational implications of these mechanisms in infection, cancer, inflammation, autoimmune diseases, aging, and neurodegenerative disorders.
Selected Publications
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 G ⃰, 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.
