目前已知RNA上含有100余种化学修饰，其中m6A, m1A, m5C, pseudouridine, APA是RNA上最主要的几种化学修饰。课题组团队在m6A领域已经做出了系列原创性研究，积累了扎实的学术基础和构建了坚实的实验平台。目前m6A的研究已经成为了一个热点领域，但是大家对于其它类型的RNA修饰关注不是很多，特别是不同的RNA修饰之间如何协调应对外界不同类型的刺激从而协同调控RNA的水平和功能鲜有研究。免疫细胞以及相应的生理病理条件下的免疫反应为研究这一重大前沿问题提供了一个非常好的模型和角度。我们目前的初步研究成果表明各种不同的RNA修饰在T细胞激活的过程中发挥着关键的主动的动态作用，而且这些修饰之间存在着功能上的相互作用和协调。

在接下来的研究中将在以下几个方面开展工作：

（1） m1A RNA 表观遗传修饰在免疫细胞中的功能以及分子机制；

（2） pseudoUridine在免疫细胞中的功能以及其作用的分子机制；

（3） APA在免疫细胞中的功能以及其作用的分子机制；

（4） 开发这些RNA修饰的干预策略应用于肿瘤和炎症的临床前免疫治疗；

（5） 不同RNA修饰类型之间的协同作用及其规律。

There are more than 100 types of different chemical RNA modification, among which m6A, m1A, m5C, pseudoUridine and APA are the major ones. HBL 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.

实验室主页：https://hua-binglilab.com/

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2.    Pirrotta V., and Li HB (2012). A view of nuclear Polycomb bodies. Curr. Opin. Genet. Dev., 22(2):101-9. doi: 10.1016/j.gde.2011.11.004. PMID: 22178420 IF: 5.578

3.    Li HB, Ohno K, Gui H, and Pirrotta V. (2013) Insulators target active genes to transcription factories and Polycomb-repressed genes to PcG bodies. PLoS Genet., 9(4):e1003436. doi: 10.1371/journal.pgen.1003436. PMID: 23637616 (Highlighted by Cell: 153(5), p935) IF: 5.917

4.    Li HB#, Jin C#, Chen Y#, Flavell RA. (2014) Inflammasome activation and metabolic disease progression. Cytokine Growth Factor Rev., 25(6):699-706. doi: 10.1016/j.cytogfr.2014.07.020.  PMID: 25156419 (# equal contribution) IF: 7.638

5.    Zhu S#, Li HB#, Flavell RA. (2014) Resemble and Inhibit: When RLR Meets TGF-β. Mol Cell, 56(6):719-20. doi: 10.1016/j.molcel.2014.12.010. PMID: 25526529 (# equal contribution) IF: 17.97

6.    Cao G#, Li HB#, Yin Z, Flavell RA. (2016) Recent advances in dynamic m6A RNA modification. Open Biology, 6(4): 160003.  doi: 10.1098/rsob.160003. PMID: 27249342  (# equal contribution, rank #8 of the most cited paper since 2011 of the journal) IF: 6.411

7.    Li HB. (2016) Chromosome Conformation Capture in Drosophila. Methods Mol. Biol., 1480:207-12. doi: 10.1007/978-1-4939-6380-5_18. PMID: 27659987 IF:1.167

8.    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. (2016) The DNA Sensing Aim2 Inflammasome Controls Radiation Induced Cell death and Tissue Injury. Science, 354 (6313): 765-768. DOI: 10.1126/science.aaf7532. PMID: 27846608 (# equal contribution) IF: 47.728

9.    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*. (2017) m6A mRNA methylation controls T cell homeostasis by targeting IL-7/STAT5/SOCS pathway. Nature, 2017 Aug 17;548(7667):338-342. doi: 10.1038/nature23450. Epub 2017 Aug 9.. PMID: 28792938 (# equal contribution, * co-corresponding) IF: 49.962

10.    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*. (2018) m6A mRNA methylation sustains Treg suppressive functions. Cell Research, 28(2): 253-256. doi:10.1038/cr.2018.7. PMID: 29303144 (*co-corresponding) IF: 25.617

11.    Yu X, Lao Y, Teng XL, Li S, Zhou Y, Wang F, Guo X, Deng S, Chang Y, Wu X, Liu Z, Chen L, Lu LM, Cheng J, Li B, Su B, Jiang J, Li HB*, Huang C*, Yi J* , Zou Q*. (2018) SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation. Nature Communications, 2018 Aug 8;9(1):3157. doi: 10.1038/s41467-018-05676-6. PMID: 30089837 (* co-corresponding) IF: 14.919

12.    Tong J, Flavell RA*, Li HB*. (2018) RNA m6A modification and its functions in diseases. Frontiers of Medicine, 2018 Aug;12(4):481-489. doi: 10.1007/s11684-018-0654-8. PMID: 30097961 (* co-corresponding, most cited) IF: 4.592

13.    Liu Y, Li HB*, Flavell RA*. (2018) cGAS activation in phased droplets. Cell Research, 2018 Oct;28(10):967-968. doi: 10.1038/s41422-018-0087-6. PMID: 30218060 (* co-corresponding) IF: 25.617

14.    Wang J, Flavell RA*, Li HB*. (2019) Antiviral immunity: a link to bile acids. Cell Research, 2019 Mar;29(3):177-178. doi: 10.1038/s41422-019-0148-5. PMID: 30778178  (* co-corresponding) IF: 25.617

15.    Zhang X, Flavell RA*, Li HB*. (2019) hnRNPA2B1: a nuclear DNA sensor in antiviral immunity. Cell Research, 2019 Nov;29(11):879-880. doi: 10.1038/s41422-019-0226-8. IF: 25.617

16.    Gao Y*#, Vasic R#, Song Y#, Teng R, Gbyli R, Biancon G, Nelakanti R, Liu C, Kudo E, Lobben K, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Lee V, Dura B, Viero G, Iwasaki A, Fan R, Xiao A, Flavell RA*, Li HB*, Tebaldi T*, Halene S*. (2020) Activation of Double-Stranded RNA Innate Immune Response and Hematopoietic Failure upon Loss of METTL3-Mediated m6A RNA Modification. Immunity, 2020 Jun 16;52(6):1007-1021.e8. doi: 10.1016/j.immuni.2020.05.003. Epub 2020 Jun 3. PMID: 32497523 (* co-corresponding) IF: 31.745

17.    Xu C*, Li HB*, Flavell RA*. (2020) A special collection of reviews on frontiers in immunology. Cell Research, 2020 Aug 28. doi: 10.1038/s41422-020-00403-7. (* co-corresponding, Editorial)

18.    Wang Y#, He K#, Sheng B#, Lei X, Tao WE, Zhu X, Wei Z, Fu R, Wang A, Bai S, Zhang Z, Hong N, Ye C, Tian Y, Wang J, Li M, Zhang K, Li L, Yang H*, Li HB*, Flavell RA*, Zhu S*. (2021) The RNA helicase Dhx15 mediates Wnt-induced anti-microbial protein expression in Paneth cells. Proc. Natl. Acad. Sci. U.S.A., 118 (4) e2017432118  (* co-corresponding) IF: 11.205

19.    Chen H#, Yao J#, Bao R, Dong Y, Zhang T, Du Y, Wang G, Ni D, Xun Z, Niu X, Ye Y*, Li HB*. (2021) Cross-talk of Four Types of RNA Modification Writers Defines Tumor Microenvironment and Pharmacogenomic Landscape in Colorectal Cancer. Molecular Cancer, 20(1):29. doi: 10.1186/s12943-021-01322-w. PMID: 33557837  (* co-corresponding, most cited) IF: 27.401

20.    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*. (2021) Pooled CRISPR Screening Identifies m6A as a Positive Regulator of Macrophage Activation. Science Advances, 2021 Apr 28; 7(18):eabd4742. doi: 10.1126/sciadv.abd4742. PMID: 33910903 (* co-corresponding) IF: 14.136

21.    Chao Y, Li HB*, Zhou J*. Multiple Functions of RNA Methylation in T Cells: A Review. Front Immunol., 2021 Apr 12;12:627455. doi: 10.3389/fimmu.2021.627455. eCollection 2021. PMID: 33912158 (* co-corresponding) IF: 7.561

22.    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*. (2021) m6A Demethylase ALKBH5 Controls CD4+ T cell Pathogenicity and Promotes Autoimmunity. Science Advances, 2021 Jun 16;7(25):eabg0470. doi: 10.1126/sciadv.abg0470. PMID: 34134995 (*co-corresponding) IF: 14.136

23.    Qin Y, Li B, Arumugam S, Lu Q, Mankash SM, Li J, Sun B, Li J, Flavell RA*, Li HB*, Ouyang X*. (2021) m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Rep., 2021 Nov 9;37(6):109968. doi: 10.1016/j.celrep.2021.109968. PMID: 34758326 (* co-corresponding) IF: 9.423

24.    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*. (2022) m6A mRNA modification maintains colonic epithelial cell homeostasis via NF-κb-mediated anti-apoptotic pathway. Science Advances, 2022 Mar 25; 8(12):eabl5723. doi: 10.1126/sciadv.abl5723. PMID: 35333576 (* co-corresponding)

25.    Chen B#, Hu J#, Hu X#, Chen H, Bao R, Zhou Y, Ye Y, Zhan M*, Cai W*, Li H*, Li HB*. (2022) DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion. Nature Communications, 2022 Apr 19; 13(1):2059. doi: 10.1038/s41467-022-29754-y. PMID: 35440133 (* co-corresponding)

26.    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*. (2022) RNA m6A demethylase ALKBH5 regulates the development of γδ T cells. Proc Natl Acad Sci U S A. 2022 Aug 16;119(33):e2203318119. doi: 10.1073/pnas.2203318119. Epub 2022 Aug 8. PMID: 35939687  (* co-corresponding)

27.    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*. (2022) tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis. Nature Immunology, 2022 Sep 22. doi: 10.1038/s41590-022-01301-3. PMID: 36138184  (* co-corresponding)

28.    Yunzhu Chen, Min-Hee Oh, Flavell RA*, Li HB*. (2022) RNA methylation in immune cells. Advances in Immunology, in press.

29.    Ding C#, Yu Z#, Sefik E#, Zhou J, Kaffe E, Li B, Wang L, Hu W*, Flavell RA*, Li HB*. (2022) A Treg specific long non-coding RNA maintains immune-metabolic homeostasis in ageing liver. Nature Aging, under revision