Ph.D - Wuhan University
Post-doctoral training - Harvard Medical School
The innate immune system uses pattern recognition receptors in different cellular compartments to sense microbial components that mark invading pathogens. Cytosolic nucleic acid, such as viral RNA and DNA, and even host DNA leaked from the nucleus and the mitochondria, are recognized by different pattern recognition receptors, such as cGAS and RIG-I. Once engaged with the ligands, these pattern recognition receptors activate NF-kB, IRF and other transcriptional factors to induce a cohort of cytokines and chemokines. These innate immune responses are critical for blocking viral infection and limiting tumorigenesis. However, aberrant innate immune responses may cause autoimmune diseases and inflammatory diseases. The long-term goal of our research is to study the role of innate immunity in host defense, autoimmune disease, and tumorigenesis. Currently, my laboratory works in three directions:
- Regulatory mechanisms of innate immune signaling pathways. We are elucidating the regulatory mechanisms of nucleic acid-sensing pathways, including RIG-I/MAVS and cGAS/STING signaling pathways, and how these pathways are deregulated in autoimmune diseases and tumorigenesis.
- Role of innate immunity in infectious diseases. We are working on host innate defense to viruses, including influenza A virus and coronavirus. We have established comparative virus-host protein interaction networks. We will continue to investigate the novel host factors limiting viral infection.
- Role of innate immunity in vaccine and tumorigenesis. We are working on the role of cGAMP as an adjuvant in influenza vaccine and an immunomodulator for cancer therapy.
Selected Publications (* corresponding author)
1. Song K, Wu Y, Fu B, Wang L, Hao W, Hua F, Sun Y, Dorf M, Li S* (2021). Leaked mitochondrial C1QBP inhibits activation of the DNA sensor cGAS. Journal of Immunology, (chosen for Top Reads), doi.org/10.4049/jimmunol.2100392
2. Wang L, Song K, Hao W, Wu Y, Patil G, Hua F, Sun Y, Huang C, Ritchey J, Jones C, Liu L, Guan J, Li S* (2021). FIP200 restricts RNA virus infection by facilitating RIG-I activation. Communications Biology2
3. Zeng J, Dong S, Luo Z, Xie X, Fu B, Li P, Liu C, Yang X, Chen Y, Wang X, Liu Z, Wu J, Yan Y, Wang F, Chen J, Zhang J, Long G, Goldman S, Li S*, Zhao Z, Liang Q (2020) Zika virus capsid disrupts corticogenesis by suppressing Dicer activity and miRNA biogenesis. Cell Stem Cell, 27, doi.org/10.1016/j.stem.2020.07.012, (Featured Article).
4. Zhao M, Song K, Hao W, Wang L, Patil G, Li Q, Xu L, Hua F, Fu B, Schwamborn J, Dorf M, Li S* (2020) Non-proteolytic ubiquitination of OTULIN regulates NF-κB signaling pathway. Journal of Molecular Cell Biology, 10.1093/jmcb/mjz081
5. Patil G, Zhao M, Song K, Hao W, Bouchereau D, Wang L, Li S* (2018) TRIM41-mediated ubiquitination of nucleoprotein limits influenza A virus infection. Journal of Virology, 92(16), doi: 10.1128/JVI.00905-18.
6. Fu B, Wang L, Li S*, Dorf ME (2017). ZMPSTE24 defends against influenza and other pathogenic viruses. Journal of Experimental Medicine, 214(4):919-929. doi: 10.1084/ jem.20161270
7. Wang L, Fu B, Li W, Patil G, Liu L, Dorf ME, Li S* (2017). Comparative influenza protein interactomes identify the role of plakophilin 2 in virus restriction. Nature Communications (8) 13876 doi: 10.1038/ncomms13876
8. Fu B, Wang L, Ding H, Jens C. Schwamborn, Li S*, Dorf ME (2015) TRIM32 senses and restricts influenza A virus by ubiquitination of PB1 polymerase. PLoS Pathogens, 11(6): e1004960. doi: 10.1371/journal.ppat.1004960.