Epigenetics & Immunity

There are more than 100 types of different chemical RNA modifications, among which m6A, m1A, m5C, pseudouridine and APA are the major ones. Our lab has made a series of pioneering discoveries in the m6A studies, won international reputations in the field, and laid solid experimental foundation. m6A research has been the frontier of the epigenetics field, but it is under-explored for other types of RNA modifications, especially the cross-talks among those RNA modifications in response to environmental stimulation are unknown. Immune cells, especially T cells and macrophages in various inflammatory disease and tumor, provide an ideal perspective to explore this frontier. Combine mouse reverse genetics and state-of-art omics techniques, our research focuses on the following areas:

(1) Function of m1A modification in T cells and macrophages;

(2) Function of pseudouridine modification in T cells and macrophages;

(3) Function of APA modification in T cells and macrophages;

(4) Develop inhibitors to those RNA modification and apply to tumor immunotherapy;

(5) Cross-talks of those RNA modifications.

    1. A Treg specific long non-coding RNA maintains immune-metabolic homeostasis in ageing liver. (2023). Ding C#, Yu Z#, Sefik E#, Zhou J#, Kaffe E, Wang G, Li B, Flavell RA, Hu W, Ye Y & Li HB*. Nature Aging. READ

    2. tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis. Nature Immunology (2022). Liu Y#, Zhou J#, Li X#, Zhang X#, Shi J#, Wang X, Li H, Miao S, Chen H, He X, Dong L, Lee GR, Zhen J, Liu RJ, Su B, Ye Y, Flavell RA*, Yi C*, Wu Y*, Li HB*. READ

    3. RNA m6A demethylase ALKBH5 regulates the development of γδ T cells. Proc Natl Acad Sci U S A. (2022). Ding C#, Xu H#, Yu Z#, Roulis M, Qu R, Zhou J, Oh J, Craford J, Gao Y, Jackson R, Sefik E, Li S, Wei Z, Skadow M, Yin Z, Ouyang X, Wang L, Zou Q, Su B, Hu W*, Flavell RA*, Li HB*. READ

    4. DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion. Nature Communications (2022). Chen B#, Hu J#, Chen H, Bao R, Zhou Y, Zhan M*, Ye Y*, Li H*, Li HB*. READ

    5. m6A mRNA modification maintains colonic epithelial cell homeostasis via NF-κb-mediated anti-apoptotic pathway. Science Advances (2022). Zhang T#, Ding C#*, Chen H# Zhao J, Chen J, Chen B, Mao K, Hao Y, Roulis M, Xu H, Kluger Y, Zou Q, Ye Y, Zhan M*, Flavell RA*, Li HB*. READ

    6. m6A Demethylase ALKBH5 Controls CD4+ T cell Pathogenicity and Promotes Autoimmunity. Science Advances (2021), Zhou J#, Zhang X#, Hu J, Qu R, Yu Z, Xu H, Chen H, Yan L, Ding C, Zou Q, Ye Y, Wang Z, Flavell RA*, Li HB*. READ

    7. Pooled CRISPR screening identifies m6A as a positive regulator of macrophage activation. Science Advances (2021). Tong J#, Wang X#, Liu Y#, Ren X, Wang A, Chen Z, Yao J, Mao K, Liu T, Meng FL, Pan W, Zou Q, Zhou Y, Xia Q*, Flavell RA*, Zhu S*, Li HB*. READ

    8. Cross-talk of Four Types of RNA Modification Writers Defines Tumor Microenvironment and Pharmacogenomic Landscape in Colorectal Cancer. Molecular Cancer (2021). Chen H#, Yao J#, Bao R, Dong Y, Zhang T, Du Y, Wang G, Ni D, Xun Z, Niu X, Ye Y*, Li HB*. READ

    9. m6A mRNA methylation sustains Treg suppressive functions. Cell Research (2018). Tong J#, Cao G#, Zhang T#, Sefik E, Vesely M, Broughton J, Zhu S, Li H, Li B, Chen L, Chang HY, Su B, Flavell RA*, Li HB*. READ

    10. m6A mRNA methylation controls T cell homeostasis by targeting IL-7/STAT5/SOCS pathway. Nature (2017). Li HB#*, Tong J#, Zhu S#, Batista PJ, Duffy EE, Zhao J, Bailis W, Cao G, Kroehling L, Chen Y, Wang G, Broughton JP, Chen YG, Kluger Y, Simon MD, Chang HY, Yin Z*, Flavell RA*. READ

    11. The DNA Sensing Aim2 Inflammasome Controls Radiation Induced Cell death and Tissue Injury. Science (2016). Hu B#, Jin C#, Li HB#, Tong J, Ouyang X, Cetinbas NM, Zhu S, Strowig T, Lam FC, Zhao C, Henao-Mejia J, Yilmaz O, Fitzgerald KA, Eisenbarth SC, Elinav E, Flavell RA. READ

      ( *: co-corresponding authors; #: co-first authors)

    1. N6 - Methyladenosine defines a new checkpoint in γδ T cell development. Bioessays (2023). Zhao J, Ding C*, Li HB*. READ

    2. RNA methylation in immune cells. Advances in Immunology (2022). Chen Y, Oh MH, Flavell RA*, Li HB*. READ

    3. Multiple Functions of RNA Methylation in T Cells: A Review. Front Immunol.(2021). Chao Y, Li HB*, Zhou J *. READ

    4. A special collection of reviews on frontiers in immunology. Cell Research (2020). Xu C*, Li HB*, Flavell RA*. READ

    5. hnRNPA2B1: a nuclear DNA sensor in antiviral immunity. Cell Research (2019). Zhang X, Flavell RA*, Li HB*. READ

    6. Antiviral immunity: a link to bile acids. Cell Research (2019). Wang J, Flavell RA*, Li HB*. READ

    7. RNA m6A modification and its functions in diseases. Frontiers of Medicine (2018). Tong J, Flavell RA*, Li HB*. READ

    8. cGAS activation in phased droplets. Cell Research (2018) . Liu Y, Li HB*, Flavell RA*. READ

      ( *: co-corresponding authors; #: co-first authors)

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