研究工作：

研究方向：细胞中双链RNA感受器（dsRNA sensors）可以识别病毒RNA并启动抗病毒天然免疫反应。这些感受器必须精确区分细胞自我RNA和病毒RNA，而当这一功能失常，可能导致异常免疫激活和自身免疫性疾病。我们实验室主要聚焦以下研究方向：

1）探索dsRNA sensors区分“自我”与“非我”RNA的分子机制，以及它们如何利用这些机制形成免疫原性和非免疫原性阈值；

2）探索细胞内的免疫原性RNA来源及其产生的条件；

3）开发针对dsRNA sensors的新治疗策略，应用于自身免疫和肿瘤等疾病。

研究理论：实验室早期研究发现，dsRNA sensor MDA5是一个分子马达，能够通过ATP水解驱动进行易位运动（translocation）。这种持续的易位运动有效防止了MDA5在自身RNA上静止和异常聚集，从而避免了其自发组装成纤丝并被错误激活。导致自身免疫疾病的MDA5突变体则完全丧失了ATP水解和易位能力，犹如“熄火的马达”在自身RNA上“搁浅聚集”，自发形成纤丝并持续激活干扰素信号，最终引发自身免疫病。目前，MDA5如何利用易位运动产生免疫原性和非免疫原性阈值，以及内源免疫原性RNA如何逃避该识别机制，仍然是领域内尚未解决的科学难题。

1. Han,C.*,Li,C.*,Xu,Y.F.*,Rao,M.,Chen,L.L.# and Liu,J.# Stepwise Ligand Capture Primes PKR for Activation and RNA Discrimination. Under review(2026)
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4. Wang,Y., Zhang,S., Yang,X.,Hwang,J., Zhan,C., Lian,C., Wang,C., Gui,T., Wang,B.,Xie,X.,Dai,P.,Zhang,L.,Tian,Y.,Zhang,H.,Han,C.,Cai,Y.,Hao,Q.,Ye,X.,Liu,X.,Liu,J., Cao,Z.,Huang,S., Song,J., Pan-Hammarstrom,Q.,Zhao,Y.,Frederick W.Alt, Zheng,X., Da,L.T., Yeap,L.S.,and Meng,F.L.# Mesoscale DNA feature in antibody-coding sequence facilitates somatic hypermutation. Cell 186, 2193–2207(2023)
5. Yang, X.W.*, Han, X.P.*, Han, C., London, J., Fishel R.# and Liu, J.# MutS functions as a clamp loader by positioning MutL on the DNA during mismatch repair, Nat Commun 13, 5808 (2022).
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7. Wu, M.*, Xu, G.*, Han, C.*, Luan, PF., Xing,YH. , Nan, F., Yang, LZ., Huang,YK., Yang,ZH., Shan, L., Yang, L., Liu, J.⁺and Chen, L.⁺lncRNA SLERT controls phase separation of FC/DFCs to facilitate Pol I transcription, Science 373(6554):547-555 (2021).  (*Equal contribution)
8. Yang, X.W. and Liu, J. Observing Protein One-Dimensional Sliding: Methodology and Biological Signifificance, Biomolecules 11(11):1618 (2021).
9. Liu, J.*, Lee, R.*, Britton, M. B.* et al. MutL Sliding Clamps Coordinate Exonuclease-Independent Escherichia coli Mismatch Repair. Nat Commun 10, 5294 (2019).  (*Equal contribution)
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12. Liu, J.*, Hanne, J.* et al. Cascading MutS and MutL Sliding Clamps Control DNA Diffusion to Activate Mismatch Repair. Nature 539 (7630), 583-587 (2016). (*Equal contribution)
13. Senavirathne, G.*; Liu, J.*, Lopez, M. A. et al. Widespread Nuclease Contamination in Commonly Used Oxygen-Scavenging Systems. Nat Methods 12, 901-2 (2015). (*Equal contribution)
14. Liu, J.*, Xiao, S.*, Hao, Y.H. & Tan, Z. Strand-Biased Formation of G-Quadruplexes in DNA Duplexes Transcribed with T7 RNA Polymerase. Angew Chem Int Ed Engl 54, 8992-6 (2015). (*Equal contribution)
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