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最后学位:医学博士 职称职务:教授、主任 专业方向:病毒学 研究方向:肿瘤病毒感染与致瘤机制 电话号码:027-87688345 电子邮件:klan@whu.edu.cn |
学习经历
1989-1994 重庆医科大学临床医学专业,获医学学士学位
1995-1998 重庆医科大学病理生理学专业,获医学硕士学位
1998-2001 中南大学湘雅医学院病理生理学专业,获医学博士学位
工作经历
1994-1995 四川省屏山县人民医院,住院医师
2002-2006 美国宾夕法尼亚大学医学院,博士后
2006-2016 中国科学院上海巴斯德研究所研究员,博士生导师,肿瘤病毒研究组组长,病原诊断技术研发中心主任
2011-2016 中国科学院上海巴斯德研究所副所长,纪委书记
2017-至今 武汉大学病毒学国家重点实验室主任,生命科学学院教授、博士生导师,医学研究院副院长
获奖与荣誉
2006:美国白血病和淋巴瘤学会Special Fellow Award
2006:中科院“bai人计划”
2008:上海市浦江人才计划
2009:新世纪百千万人才工程国家级人选
2011:国务院政府特殊津贴
2012:药明康德生命化学研究奖
2014:国家杰出青年科学基金获得者
2015:科技部中青年科技创新领军人才
2015:上海市先进工作者
2016:国家万人计划领军人才
2020:武汉大学“珞珈抗疫”十大先锋人物
2020:湖北省抗击新冠肺炎疫情先进个人
2020:武汉大学“我心目中的好导师”
2021:湖北省高等学校优秀共产党员
2021:武汉大学优秀共产党员
2022:湖北省科协系统先进工作者
主要社会兼职
Cell Insight 执行主编
Journal of Virology 编委
Viruses 编委
Journal of Medical Virology 副主编
Virologica Sinica 副主编
Science Bulletin 副主编
中国微生物学会病毒专业委员会副主任委员
湖北省生物工程学会理事长
国家认可委生物安全专业委员会委员
国家病原微生物实验室生物安全专家委员会委员
研究概述
主要从事肿瘤疱疹病毒、重要新发病毒的感染及致病机理研究,在卡波氏肉瘤病毒(KSHV)、新冠病毒(SARS-CoV-2)等方面做出了系统性、原创性的研究工作:在KSHV研究方面,曾揭示KSHV关键开关分子RTA的表达调控机机理,提出RTA-LANA负反馈调控工作模型,得到领域内的广泛认可,对阐明KSHV潜伏感染的形成机制有重要的指导意义;曾利用KSHV作为工作模型,率先发现病毒包装自身及宿主miRNA,不仅揭示了病毒粒子一种新的构成成分,也鉴定了胞外游离型miRNA的一种新的存在形式,具有重要的学术价值;曾阐明KSHV通过操控Notch及BMP等重要信号转导通路参与致瘤的新机制,为发展相关肿瘤有效的治疗手段奠定了重要基础;在新冠病毒研究方面,曾开展病原体鉴定工作并获得成功,成为国内最早鉴定出新型冠状病毒的团队之一,为我国在疫情早期快速锁定病原体做出了重要贡献; 曾首次揭示了新冠病毒气溶胶粒径分布特征,及时向湖北省疫情防控指挥部科技攻关组提交了研究报告,作为决策参考依据等。
代表性论文
1. Han CY#, Zhang D, Gui CW, Huang L, Chang SJ, Dong LH, Bai L, Wu SW, Lan K* .KSHV RTA antagonizes SMC5/6 complex-induced viral chromatin compaction by hijacking the ubiquitin-proteasome system.PLoS Pathog(6.823). 2022 Aug 1;18(8):e1010744. doi: 10.1371/journal.ppat.10 10744
2. Dong LH#, DongJZ#, Xiang M, Lei P, Li ZX, Zhang F, Sun XY, Niu DP, Bai L*, Lan K*. NDRG1 facilitates lytic replication of Kaposi's sarcoma-associated herpesvirus by maintaining the stability of the KSHV helicase. PLoS Pathog. 2021 Jun 2;17(6):e1009645. doi: 10.1371/journal.ppat.1009645. eCollection 2021 Jun
3. Yan H# , Jiao HW# , Liu QY , Zhang Z , Xiong Q, Wang BJ, Wang X, Guo M, Wang LF, Lan K*, Chen Y*, Zhao HB*. ACE2 receptor usage reveals variation insusceptibility to SARS-CoV and SARS-CoV-2 infection among bat species.Nat Ecol Evol. 2021 Mar 1. doi: 10.1038/s41559-021-01407-1
4. Bai L#, Zhao YL#, Dong JZ, Liang SM, Guo M, Liu XJ, Wang X, Huang ZX, Sun XY, Zhang Z, Dong LH, Liu QY, Zheng YC, Niu DP, Xiang M, Song K, Ye JJ, Zheng WC, Tang ZD, Tang ML, Zhou Y, Shen C, Dai M, Zhou L, Chen Y, Yan H, Lan K*, Xu K*. Coinfection with influenza A virus enhances SARS-CoV-2 infectivity. Cell Research. 2021 Apr;31(4):395-403. doi: 10.1038/s41422-021-00473-1
5. Wang DH#, Jiang A#, Feng JP#, Li GN#, Guo D#, Muhammad Sajid, Wu K, Zhang QH, Yann Ponty, Sebastian Will, Liu FY, Yu XH, SP Li, Liu QY, Yang XL, Guo M, Li XQ, Chen MZ, Shi ZL, Lan K*, Chen Y*, Zhou Y*. The SARS-CoV-2 Subgenome Landscape and its Novel Regulatory Features.Mol Cell. Published:March 03, 2021DOI:https://doi.org/10.1016/j.molcel.2021.02.036
6. Wei XQ, Dong JZ, Cheng CC, Ji MJ, Yu L, Luo SQ, Wu SW, Bai L, Lan K*. Host RAB11FIP5 protein inhibits the release of Kaposi’s sarcoma-associated herpesvirus particles by promoting lysosomal degradation of ORF45.PLoS Pathog.2020;16(12):e1009099.doi:10.1371/journal.ppat.1009099. eCollection
7. Liu Y#, Ning Z#*, Chen Y#*, Guo M#, Liu Y, Gali NK, Sun L, Duan Y, Cai J, Westerdahl D, Liu X, Xu K, Ho KF*, Kan H*, Fu Q*, Lan K*. Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. Nature. 2020;582(7813):557-560.
8. Liu W#, Zhang Q#, Chen J#, Xiang R, Song H, Shu S, Chen L, Liang L, Zhou J, You L, Wu P, Zhang B, Lu Y, Xia L, Huang L, Yang Y, Liu F, Semple MG, Cowling BJ, Lan K*, Sun Z*, Yu H*, Liu Y*. Detection of Covid-19 in Children in Early January 2020 in Wuhan,China. N Engl J Med. 2020;382(14):1370-1371.
9. Chen L#, Liu W#, Zhang Q#, Xu K, Ye G, Wu W, Sun Z, Liu F, Wu K, Zhong B, Mei Y, Zhang W, Chen Y, Li Y, Shi M, Lan K*, Liu Y*. RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak. Emerg Microbes Infect. 2020;9(1):313-319.
10. Bai L#, Dong J, Liu Z, Rao Y, Feng P*, Lan K*. Viperin catalyzes methionine oxidation to promote protein expression and function of helicases. Sci Adv ,2019 Aug 28;5(8):eaax1031
11. Zhang F, Liang D, Lin X, Zou Z, Sun R, Wang X, Liang X, Kaye KM, Lan K*. NDRG1 facilitates the replication and persistence of Kaposi's sarcoma-associated herpesvirus by interacting with the DNA polymerase clamp PCNA. PLoS Pathog. 2019;15(2):e1007628
12. Wei X#, Bai L#, Dong L, Liu H, Zhou Z, Xing P, Wu S, Lan K*. NCOA2 promotes lytic reactivation of Kaposi’s sarcoma-associated herpesvirus by enhancing the expression of the master switch protein RTA. PLoS Pathogens, 2019;15(11):e1008160.
13. Yuan F#, Gao ZQ, Majerciak V, Bai L, Hu ML, Lin XX, Zheng ZM*, Dong YH*, Lan K*. The crystal structure of KSHV ORF57 reveals dimeric active sites important for protein stability and function. PLoS Pathog. 2018;14(8):e1007232
14. Li G#, Zhu Y, Shao D, Chang H, Zhang X, Zhou D, Gao Y, Lan K*, Deng Q*. Recombinant covalently closed circular DNA of hepatitis B virus induces long-term viral persistence with chronic hepatitis in a mouse model. Hepatology. 2018;67(1):56-70.
15. Wang X#, Zou Z, Deng Z, Liang D, Zhou X, Sun R, Lan K*. Male hormones activate EphA2 to facilitate Kaposi's sarcoma-associated herpesvirus infection: Implications for gender disparity in Kaposi's sarcoma. PLoS Pathog. 2017;13(9):e1006580.
16. Sun R#, Tan X, Wang X, Wang X, Yang L, Robertson ES, Lan K*. Epigenetic Landscape of Kaposi's Sarcoma-Associated Herpesvirus Genome in Classic Kaposi's Sarcoma Tissues. PLoS Pathog. 2017;13(1):e1006167
17. Zou Z#, Meng Z, Ma C, Liang D, Sun R,Lan K*. Guanylate-binding protein 1 inhibits nuclear delivery of Kaposi's sarcoma-associated herpesvirus virions by disrupting formation of actin filament.J Virol.2017 Jul 27;91(16). pii: e00632-17
18. Lin X#, Sun R, Zhang F, Gao Y, Bin L,Lan K*. The Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Inhibits Expression of SUMO/sentrin Specific Peptidase 6 to Facilitate Latency Establishment.J Virol.2017 Aug 10;91(17). pii: e00806-17
19. Li S#, Hu H, He Z, Liang D, Sun R, Lan K*. Fine-Tuning of the Kaposi's Sarcoma-Associated Herpesvirus Life Cycle in Neighboring Cells through the RTA-JAG1-Notch Pathway. PLoS Pathog. 2016;12(10):e1005900
20. Jia B#, Guo M, Li G, Yu D, Zhang X, Lan K*, Deng Q*. Hepatitis B virus core protein sensitizes hepatocytes to tumor necrosis factor-induced apoptosis by suppression of the phosphorylation of mitogen-activated protein kinase kinase 7. J Virol. 2015 ;89(4):2041-51.
21. Hu H#, Dong J, Liang D, Gao Z, Bai L, Sun R, Hu H, Zhang H, Dong Y,Lan K*. Genome-wide mapping of the binding sites and structural analysis of KSHV vIRF2 reveal it is a DNA-binding transcription factor.J Virol.2015 Nov 4;90(3):1158-68
22. Zhao Q#, Liang D, Sun R, Jia B, Xia T, Xiao H, Lan K*. Kaposi's sarcoma-associated herpesvirus-encoded replication and transcription activator impairs innate immunity via ubiquitin-mediated degradation of myeloid differentiation factor 88.J Virol. 2015 Jan;89(1):415-27
23. Liang D# , Hu H, Li S, Dong J, Wang X, Wang Y, He L, He Z, Gao Y, Gao S, Lan K*. Oncogenic Herpesvirus KSHV Hijacks BMP-Smad1-Id Signaling to Promote Tumorigenesis. PLoS Pathog. 2014;10(7):e1004253.
24. Qi Z#, Li G, Hu H, Yang C, Zhang X, Leng Q, Xie Y, Yu D, Zhang X, Gao Y, Lan K*, Deng Q*. Recombinant Covalently Closed Circular Hepatitis B Virus DNA Induces Prolonged Viral Persistence in Immunocompetent Mice. J Virol. 2014;88(14):8045-56
25. Sun R#, Liang D, Gao Y, Lan K*. Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Interacts with Host KAP1 To Facilitate Establishment of Viral Latency. J Virol. 2014;88(13):7331-7344.
26. Wang Z#, Zhu K, Bai W, Jia B, Hu H, Zhou D, Zhang X, Zhang X, Xie Y, Bourgine MM, Michel ML, Lan K*, Deng Q*. Adenoviral delivery of recombinant hepatitis B virus expressing foreign antigenic epitopes for immunotherapy of persistent viral infection. J Virol. 2014;88(5):3004-15.
27. Qi Z#, Li G, Hu H, Yang C, Zhang X, Leng Q, Xie Y, Yu D, Zhang X, Gao Y, Lan K*, Deng Q*. Recombinant Covalently Closed Circular Hepatitis B Virus DNA Induces Prolonged Viral Persistence in Immunocompetent Mice. J Virol. 2014;88(14):8045-56.
28. Hu H#, Zhang H, Gao Z, Wang D, Liu G, Xu J,Lan K*, Dong Y*. Structure of the type VI secretion phospholipase effector Tle1 provides insight into its hydrolysis and membrane targeting.Acta Crystallogr D Biol Crystallogr. 2014 Aug;70(Pt 8):2175-85
29. Han J, Wang L, Liu J, Jin M, Hao F, Zhang P, Zhang Z, Wen D, Wu X, Liu G, Ji L, Xu D, Zhou D, Leng Q,Lan K*, Zhang C*. Co-circulation of three HA and two NA subtypes of avian influenza viruses in Huzhou, China, April 2013: implication for the origin of the novel H7N9 virus.J Virol. 2014 Jun;88(11):6506-11
30. Wang X, He Z, Xia T, Li X, Liang D, Lin X, Wen H,Lan K*. Latency-Associated Nuclear Antigen of Kaposi Sarcoma-Associated Herpesvirus Promotes Angiogenesis through Targeting Notch Signaling Effector Hey1.Cancer Res. 2014 Apr 1;74(7):2026-37.
31. Han J, Jin M, Zhang P, Liu J, Wang L, Wen D, Wu X, Liu G, Zou Y, Lv X, Dong X, Shao B, Gu S, Zhou D, Leng Q, Zhang C,Lan K*. Epidemiological link between exposure to poultry and all influenza A(H7N9) confirmed cases in Huzhou city, China, March to May 2013.Euro Surveill. 2013 May 16;18(20). pii: 20481.
32. Han J, Niu F, Jin M, Wang L, Liu J, Zhang P, Xie B, Wu X, Wen D, Ji L, Liu G, Yang Z, Zhang C, Zhou D, Leng Q,Lan K*. Clinical presentation and sequence analyses of HA and NA antigens of the novel H7N9 viruses.Emerg Microbes Infect.2013 May;2(5):e23.
33. Xia T, L évy L, Levillayer F, Jia B, Li G, Neuveut C, Buendia MA,Lan K*, Wei Y*.The Four and a Half LIM-only Protein 2 (FHL2) Activates Transforming Growth Factorβ(TGF-β) Signaling by Regulating Ubiquitination of the E3 Ligase Arkadia.J Biol Chem. 2013 Jan 18;288(3):1785-94.
34. Yang Y, Xia T, Li N, Zhang J, Yang Y, Cong W, Deng Q,Lan K*, Zhou W*. Combined effects of p53 and MDM2 polymorphisms on susceptibility and surgical prognosis in hepatitis B virus-related hepatocellular carcinoma.Protein Cell. 2013 Jan;4(1):71-81.
35. Lin X#, Li X, Liang D, Lan K*. MicroRNAs and unusual small RNAs discovered in Kaposi's sarcoma-associated herpesvirusvirions. J Virol. 2012;86(23): 12717-30.
36. Jin Y#, He Z, Liang D, Zhang Q, Zhang H, Deng Q, Robertson ES, Lan K*. Carboxyl-Terminal Amino Acids 1052 to 1082 of the Latency-Associated Nuclear Antigen (LANA) Interact with RBP-Jκ and Are Responsible for LANA-Mediated RTA Repression. J Virol. 2012;86(9):4956-69
37. Liu Y#, Sun R, Lin X, Liang D, Deng Q, Lan K*. Kaposi's sarcoma-associated herpesvirus-encoded microRNA miR-K12-11 attenuates transforming growth factor beta signaling through suppression of SMAD5. J Virol. 2012; 86(3):1372-81.
38. Li X#, Liang D, Lin X, Robertson ES, Lan K*. Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen reduces interleukin-8 expression in endothelial cells and impairs neutrophil chemotaxis by degrading nuclear p65. J Virol. 2011;85(17):8606-15.
39. Liang D#, Gao Y, Lin X, He Z, Zhao Q, Deng Q, Lan K*. A human herpesvirus miRNA attenuates interferon signaling and contributes to maintenance of viral latency by targeting IKKε. Cell Res. 2011;21(5):793-806.
40. Liang D, Lin X,Lan K*. Looking at Kaposi's Sarcoma-Associated Herpesvirus-Host Interactions from a microRNA Viewpoint.Front Microbiol. 2011;2:271.
41. Qin Y, Li Y, Liu W, Tian R, Guo Q, Li S, Li H, Zhang D, Zheng Y, Wu L,Lan K*,Wang J*. Penicilliummarneffei-stimulated dendritic cells enhance HIV-1 trans-infection and promote viral infection by activating primary CD4+ T cells.PLoS One. 2011;6(11):e27609
42. Lin X, Liang D, He Z, Deng Q, Robertson ES,Lan K*. miR-K12-7-5p encoded by Kaposi's sarcoma-associated herpesvirus stabilizes the latent state by targeting viral ORF50/RTA.PLoS One. 2011 Jan 20;6(1):e16224.
43. He Z#, Liu Y, Liang D, Wang Z, Robertson ES, Lan K*. Cellular corepressor TLE2 inhibits replication-and-transcription- activator-mediated transactivation and lytic reactivation of Kaposi's sarcoma-associated herpesvirus. J Virol. 2010;84(4):2047-62.
44. Lan K , Murakami M, Bajaj B, Kaul R, He Z, Gan R, Feldman M, Robertson ES*. Inhibition of KSHV-infected primary effusion lymphomas in NOD/SCID mice by gamma-secretase inhibitor.Cancer Biol Ther. 2009 Nov;8(22):2136-43.
45. Liu Y, Cao Y, Liang D, Gao Y, Xia T, Robertson ES,Lan K*. Kaposi's sarcoma-associated herpesvirus RTA activates the processivity factor ORF59 through interaction with RBP-Jkappa and a cis-acting RTA responsive element.Virology. 2008 Oct 25;380(2):264-75.
46. Lan K , Verma SC, Murakami M, Bajaj B, Kaul R, Robertson ES. Kaposi's sarcoma herpesvirus-encoded latency-associated nuclear antigen stabilizes intracellular activated Notch by targeting the Sel10 protein.Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16287-92.
47. Lan K, Murakami M, Choudhuri T, Tsai DE, Schuster SJ, Wasik MA, and Robertson E. Detection of Epstein-Barr Virus in T-Cell Prolymphocytic Leukemia cells in vitro.J Clin Virol.2008;43:260-5.
48. Verma S,Lan K, Choudhuri T, Cotter MA, and Robertson E. An autonomous replicating element within the KSHV genome.Cell Host Microbe.2007 Aug 16;2(2):106-18.
49. Lan K, Choudhuri T, Murakami M, Kuppers DA, and Robertson E. Intracellular Activated Notch1 Is Critical for Proliferation of KSHV Associated B Lymphoma Cell Lines in vitro.J Virol. 2006, 80(13):6411-6419
50. Lan K, Murakami M, Choudhuri T, Kuppers D, and Robertson E. Intracellular Activated Notch1 Can Reactivate KSHV from Latency.Virology.2006, 351:393-403.
51. Lan K, Kuppers D, Verma S, Sharma N, Murakami M, and Robertson E. Induction of KSHV Latency Associated Nuclear Antigen by the Lytic Transactivator RTA: A Novel Mechanism for Establishment of Latency.J Virol. 2005;79(12):7453-65
52. Lan K, Kuppers D, and Robertson E. KSHV Reactivation is Regulated by Interaction of LANA with RBP-Jk, the Major Downstream Effector of the Notch Signaling Pathway.J Virol.2005;79(6):3468-78
53. Lan K, Kuppers DA, Verma SC, and Robertson E. Kaposi ’s Sarcoma-Associated Herpesvirus-Encoded Latency-Associated Nuclear Antigen Inhibits Lytic Replication by Targeting Rta: a Potential Mechanism for Virus-Mediated Control of Latency.J Virol. 2004;78: 6585-6594