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人才隊(duì)伍

孟飛龍
研究員，研究組長(zhǎng)，博士生導(dǎo)師
E-mail: Feilong.Meng@@sibcb.ac.cn
實(shí)驗(yàn)室主頁(yè): https://menglab.sibcb.ac.cn/

個(gè)人簡(jiǎn)介：

　　2003年畢業(yè)于南開(kāi)大學(xué)，獲學(xué)士學(xué)位;2009年畢業(yè)于中國(guó)科學(xué)院上海生科院生化與細(xì)胞所，獲得博士學(xué)位。2009年11月至2015年9月在于美國(guó)哈佛大學(xué)醫(yī)學(xué)院/波士頓兒科醫(yī)院(Harvard Medical School, Boston Children’s Hospital)從事博士后研究，先后獲得Cancer Research Institute Research Fellowship，Lymphoma Research Foundation Postdoctoral Fellowship等基金資助。2015年9月起任中國(guó)科學(xué)院分子細(xì)胞科學(xué)卓越創(chuàng)新中心(上海生物化學(xué)與細(xì)胞生物學(xué)研究所)研究員、博士生導(dǎo)師、研究組長(zhǎng)。

社會(huì)任職：

研究方向：

免疫受體多樣化

研究工作：

　　基因組編碼的遺傳信息是生命活動(dòng)的基礎(chǔ)，而生命活動(dòng)又常伴隨著DNA損傷的被動(dòng)發(fā)生，因此生物進(jìn)化出多套機(jī)制維持其穩(wěn)定性。而“禍福相依”，特定細(xì)胞會(huì)主動(dòng)發(fā)生基因組DNA變異，改變編碼信息，獲得新的功能。適應(yīng)性免疫系統(tǒng)中抗原受體多樣性產(chǎn)生即是哺乳動(dòng)物中少數(shù)的DNA程序性變異過(guò)程之一。在應(yīng)對(duì)復(fù)雜的生存環(huán)境中，免疫B淋巴細(xì)胞經(jīng)歷一系列的基因重排、高頻突變、DNA重組等過(guò)程，產(chǎn)生高效親和力抗體分子。B細(xì)胞特異性DNA脫氨酶AID起始了抗體基因程序性DNA斷裂或突變，最終，單一的DNA序列轉(zhuǎn)化為天文數(shù)字的抗體基因。免疫多樣化的缺陷會(huì)導(dǎo)致各種原發(fā)性免疫缺陷疾病，而程序性DNA損傷的錯(cuò)誤調(diào)控也會(huì)造成其它基因上的DNA損傷，導(dǎo)致免疫系統(tǒng)腫瘤的發(fā)生發(fā)展。
　　研究組致力于探索免疫受體多樣化的機(jī)制，并在體外重構(gòu)抗體多樣化過(guò)程。研究組希望能夠：1)闡明免疫細(xì)胞中程序性DNA損傷發(fā)生和易錯(cuò)解讀機(jī)制;2)解析原發(fā)性免疫缺陷疾病和淋巴瘤的發(fā)生發(fā)展病理機(jī)制;3)探索、建立抗體藥物發(fā)現(xiàn)和生產(chǎn)的迭代技術(shù)。目前我們主要運(yùn)用生物化學(xué)、免疫學(xué)、功能組學(xué)和合成生物學(xué)等方法，結(jié)合動(dòng)物模型，研究蛋白質(zhì)液-液相變、基因?qū)ο蜣D(zhuǎn)錄、DNA力學(xué)性質(zhì)等在AID招募中的作用，以及下游DNA損傷反應(yīng)在免疫系統(tǒng)多樣化中的時(shí)空調(diào)控，并利用堿基編輯工具、合成生物學(xué)手段在體外重構(gòu)免疫反應(yīng)最小功能單元——生發(fā)中心反應(yīng)。

承擔(dān)科研項(xiàng)目情況：

代表論著：

1. Dai, P.#, Tan, Y.#, Luo, Y.#, Liu, T., Huang, Y., Shang, Y., Huang, M.E., Liu, X., Zhang, S., Wang, Y., Li, Q.-X., Li, N., Li, L., Qin, Y., Liu, J., Liu, L.D., Xie, X., Cai, Y., Chen, F.X., Zheng, X., Yeap, L.-S., Wang, J.*, Hu, J.*, Meng, F.-L.*, (2025). Transcription-coupled AID deamination damage depends on ELOF1-associated RNA polymerase II. Mol Cell, 85, 1280-1295.e9.
2. Qin, Y., Meng, F.-L.*, (2024). Taming AID mutator activity in somatic hypermutation. Trends Biochem Sci 49, 622–632.
3. Liu, X., Meng, F.-L.*, (2024). Defining two subpopulations of marginal zone B cells. Cell Mol Immunol 21, 412–413.
4. Min Emma Huang^#; Yining Qin^#; Yafang Shang^#; Qian Hao; Chuanzong Zhan; Chaoyang Lian; Simin Luo; Liu Daisy Liu; Senxin Zhang; Yu Zhang; Yang Wo; Niu Li; Shuheng Wu; Tuantuan Gui; Binbin Wang; Yifeng Luo; Yanni Cai; Xiaojing Liu; Ziye Xu; Pengfei Dai; Simiao Li; Liang Zhang; Junchao Dong; Jian Wang; Xiaoqi Zheng; Yingjie Xu; Yihua Sun; Wei Wu; Leng-Siew Yeap*; Fei-Long Meng* ; C- to-G editing generates double-strand breaks causing deletion, transversion and translocation, Nature Cell Biology, 2024, 26: 294-304
5. Wang Y, Meng F L*, and Yeap L S.*, (2024). DNA flexibility can shape the preferential hypermutation of antibody genes. Trends Immunol., 2024,45(3): 2.
6. Wang, Y.^#, Zhang, S., Yang, X., Hwang, J.K., 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-Hammarstro?m, Q., Zhao, Y., Alt, F.W., Zheng, X., Da, L.T., Yeap, L.S.*, and Meng, F.L.* (2023). Mesoscale DNA Feature in Antibody-Coding Sequence Facilitates Somatic Hypermutation. Cell. 2023 May 11;186(10):2193-2207.e19.
7. Wang, Y., Zhang, S., Zheng, X., Yeap, L.S.*, and Meng, F.L.* (2023). A high-throughput protocol for deamination of long single-stranded DNA and oligo pools containing complex sequences STAR Protocols. 4(4):102602
8. Lin K#, Zhou Y#, Ai J#, Wang Y#, Zhang S#, Qiu C#, Lian C, Gao B, Liu T, Wang H, Zhang H, Zhang Y, Fu Z, Li D, Jiang N, Guo J, Wu J, Wang YO, Song S, Li Q, Yin Y, Xia J, Xu Y, Yeap LS, Zheng X, Gu Y, Liu H*, Zhang W*, and Meng FL* (2022) B cell Receptor Signatures Associating with Strong and Poor SARS-CoV-2 Vaccine Response. Emerging Microbes & Infections 11(1):452-464
9. Xie X#, Gan T#, Rao B#, Zhang W, Panchakshari RA, Yang D, Ji X, Cao Y, Alt FW, Meng FL*, Hu J*. (2022) C-terminal deletion-induced condensation sequesters AID from IgH targets in immunodeficiency. EMBO J. e109324
10. Meng F.L., ?Guest Editor (2022). Install, repair and outcomes: a special issue on physiological and programmed DNA lesions. Acta Biochim Biophys Sin. doi: 10.3724/abbs.2022058.
11. Liu DL, Lian C, Yeap LS* and Meng FL* (2021) The development of neutralizing antibodies against SARS-CoV-2 and their common features. J Mol Cell Biol 10;12(12):980-986
12. Yuan C, Chen H, Tu S, Huang HY, Pan Y, Gui X, Kuang M, Shen X, Zheng Q, Zhang Y, Cheng C, Hong H, Tao X, Peng Y, Yao X, Meng F*, Ji H*, Shao Z*, Sun Y*. (2021) A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks. Genome Biol. 22(1):156
13. Li T#, Cai H#, Zhao Y#, Li Y#, Lai Y#, Yao H#, Liu LD#, Sun Z#, van Vlissingen MF, Kuiken T, GeurtsvanKessel CH, Zhang N, Zhou B, Lu L, Gong Y, Qin W, Mondal M, Duan B, Xu S, Richard AS, Raoul H, Chen J, Xu C, Wu L, Zhou H, Huang Z, Zhang X, Li J, Wang Y, Bi Y, Rockx B, Chen J, Meng FL*, Lavillette D*, Li D*. (2021) Uncovering a conserved vulnerability site in SARS-CoV-2 by a human antibody. EMBO Mol Med. 13(12):e14544
14. Liu X#, Liu T#, Shang Y#, Dai P#, Zhang W, Lee BJ, Huang M, Yang D, Wu Q, Liu LD, Zheng X, Zhou BO, Dong J, Yeap LS, Hu J, Xiao T, Zha S, Casellas R, Liu XS, and Meng FL*. (2020). ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells. Cell Research. 30(9):732-744.
15. Yang D, Sun Y, Chen J, Zhang Y, Fan S, Huang M, Xie X, Cai Y, Shang Y, Gui T, Sun L, Hu J, Dong J, Yeap LS, Wang X, Xiao W and Meng FL*, (2020). REV7 is required for processing AID initiated DNA lesions in activated B cells. Nat Commun. 11(1):2812.
16. Li J, Shang Y, Wang L, Zhao B, Sun C, Li J, Liu S, Li C, Tang M, Meng FL*, Zheng P*.Genome integrity and neurogenesis of postnatal hippocampal neural stem/progenitor cells require a unique regulator Filia. (2020) Sci Adv. 6(44):eaba0682.
17. Yeap LS* and Meng FL* (2019). Cis- and trans- factors affecting AID targeting and mutagenic outcomes in antibody diversification. Adv Immunol. 141, 51-103.
18. Liu LD, Huang M, Dai P, Liu T, Fan S, Cheng X, Zhao Y, Yeap LS and Meng FL* (2018). Intrinsic Nucleotide Preference of Diversifying Base Editors Guides Antibody Ex Vivo Affinity Maturation. Cell Rep 25, 884-892 e883
19. Liu X and Meng FL*, (2018). Generation of Genomic Alteration from Cytidine Deamination. Adv Exp Med Biol 1044, 49-64.
20. 劉婷婷，孟飛龍* (2016). 抗體多樣化及相關(guān)免疫系統(tǒng)疾病研究進(jìn)展. 中國(guó)細(xì)胞生物學(xué)學(xué)報(bào) 38(5).（博士后訓(xùn)練階段）
21. Meng FL, Alt FW, Tian M, “The Mechanism of Class Switch Recombination” in Molecular Biology of B Cells, 2nd Edition, Honjo T, Alt FW, Reth M, Radbruch A; Elsevier, 2014
22. Ba Z#, Meng FL#, Gostissa M#, Huang PY, Ke Q, Wang Z, Dao MN, Fujiwara Y, Rajewsky K*, Zhang B* and Alt FW*. (2015). A Rapid Embryonic Stem Cell-Based Mouse Model for B-cell Lymphomas Driven by Epstein-Barr Virus Protein LMP1. Cancer Immunol Res 3, 641-649.
23. Meng FL#, Du Z#, Federation A#, Hu J, Wang Q, Kieffer-Kwon KR, Meyers RM, Amor C, Wasserman CR, Neuberg D, Casellas R, Nussenzweig M, Bradner JE*, Liu XS, Alt FW* (2014) Convergent Transcription at Intragenic Super-Enhancers Targets AID-initiated Genomic Instability. Cell. 159, 1538-1548.
24. Alt FW*, Zhang Y, Meng FL, Guo C, Schwer B (2013) Mechanisms of programmed DNA lesions and genomic instability in the immune system. Cell. 152(3):417-29
25. Basu U#, Meng FL#, Keim C#, Grinstein V, Pefanis E, Eccleston J, Zhang T, Myers D, Wasserman CR, Wesemann DR, Januszyk K, Gregory RI, Deng H, Lima CD, Alt FW*. (2011) The RNA Exosome Targets Activation Induced Cytidine Deaminase to Both Strands of Transcribed Duplex DNA Substrates. Cell 144(3):353-63.?

獲獎(jiǎng)及榮譽(yù)：

研究組成員：

實(shí)驗(yàn)室2024年合影