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表观遗传调控与干预重点实验室

范祖森博士研究员博士生导师

国家“杰出青年基金”、基金委创新群体首席科学家、国家“新世纪百千万人才工程”获得者
中科院生物物理所，中科院感染与免疫重点实验室，研究组长

研究方向：（1）天然免疫新亚群发现与抗感染机制；（2）非编码RNA与免疫调控；（3）肿瘤干细胞与肿瘤免疫调控。

电子邮件：fanz@ibp.ac.cn

电话：010-64888457

通讯地址：北京市朝阳区大屯路15号（100101）

英文版个人网页：http://english.ibp.cas.cn/sourcedb/rck/EN_xsszmA_G/202005/t20200519_341417.html

简历：

　　范祖森，二级研究员，创新课题组组长，国科大微免教研室副主任，金沙集团1862cc特聘核心骨干研究员,国科大岗位教授（A类）。范祖森1998年获上海交通大学医学院免疫学博士学位，随后到哈佛大学医学院从事博士后研究，于2003年晋升为哈佛大学讲师。2004年作为研究员回到生物物理所工作，2005年获"杰出青年"基金资助，2006年入选"新世纪百千万人才工程"国家级人才。2010年享受"国务院特殊津贴"专家。2014年获得谈家桢生命科学创新奖，2016、2018年评为中科院优秀研究生导师等，2018年获得北京市科技进步一等奖，2019年基金委创新群体首席科学家，2020年国家重点研发专项首席科学家，2021年获得北京自然科学二等奖。课题组长期从事天然免疫抗感染/抗肿瘤应答调控、肿瘤干细胞调控和肿瘤免疫治疗等研究，在天然免疫细胞新亚群发现、天然免疫抗感染识别机制、肿瘤干细胞自我更新机制等方面，取得了一系列有重要国际影响力的原创性成果。在Cell（2篇）、Nat Immunol（6篇）、Immunity（4篇）、Cell Stem Cell（2篇）、Nat Cell Biol、Neuron、Cell Res（3篇）、JEM（5篇）、JCI（2篇）、NSMB、Nat Commun（11篇）、 EMBO J（4篇）、Blood等国际权威学术期刊发表SCI高水平研究论文100余篇，研究处于国际领先水平。课题组经过多年的研究积累业已形成一流的免疫生物学研究平台和优秀的科研文化氛围，在天然免疫抗感染应答与肿瘤免疫领域培养出一支优秀的科研团队。已培养了40余位博士毕业生和10余位博士后，10余人获得中科院院长特别奖、优秀奖及优秀博士论文，10余人晋升为名校及中科院教授岗位（包括中科院2名、北大3名、清华、复旦等教授），10余人获得中组部“青年千人”、基金委“优青”等。

获奖及荣誉：

社会任职：

研究方向：

　　本课题组从事天然免疫抗感染应答调控、肿瘤干细胞调控和肿瘤免疫治疗研究。主要研究内容分为天然免疫细胞新亚群发现与抗感染机制、非编码RNA与免疫调控、以及肿瘤干细胞调控与肿瘤免疫等三个方向。

　　一、天然免疫细胞新亚群发现与抗感染/抗肿瘤机制

　　我们发现鉴定了数个天然免疫识别受体，揭示了其抗感染免疫识别应答作用（Nat Immunol，2015、2016、2018; Cell Stem Cell，2013）；揭示了免疫细胞颗粒酶抗感染/抗肿瘤的作用及结构基础（Cell，2003; Nat Immunol，2003; Mol Cell Biol，2002；Blood，2006；Cell Death Differ，2006、2007、2009、2012a、2012b、2013；J Immunol，2006、2009a、2009b、2009c、2010、2012a、2012b、2013、2015）。发现鉴定了NKB、ILCreg、Tuft-2等数个天然免疫细胞的新亚群，发现新亚群NKB细胞通过分泌IL-18活化NK和ILC1细胞，参与抗感染免疫应答（Immunity 2016、2017）。发现一群新的ILC调节细胞亚群（ILCreg），通过分泌IL-10参与调控肠道炎症转归和肠癌的发生（Cell，2017、2018; Cell Res，2020）,发现Tuft-2细胞维持肠道稳态维持的机制（Immunity 2022）。我们将利用单细胞测序等新技术，继续发现鉴定天然免疫细胞新亚群及其功能。我们将深入探索新亚群ILCreg的谱系建立机制，探究调控ILC细胞亚型转变的调节机制。探究生理及病理诱导ILC细胞亚型转变的调控作用和分子机制，探明ILC亚型相互转变对肠道疾病发生的调控作用。揭示天然免疫抗感染/抗肿瘤应答调控及可塑性机制，以期为感染性疾病及肿瘤的防治提供理论依据。

　　二、非编码RNA与免疫调控

　　非编码RNA（ncRNA）的发现和功能机制是生物医学领域的研究前沿。我们近期发现，环形RNA cia-cGAS在免疫前体HSC细胞核内结合DNA识别受体cGAS抑制其活化，维持HSC的稳态（Immunity，2018）。发现环形RNA circPan3和IL-13R mRNA结合调节ILC2介导的IL-13R信号，维持肠道稳态（Nat Immunol，2019）。发现LncGATA6在肠道干细胞的自我更新维持和肠癌发生中发挥重要作用（Nat Cell Biol，2018）。还发现lncKdm2b通过招募NURF复合物活化转录因子Zfp292的表达，维持ILC3细胞的扩增和免疫应答效应（Nat Immunol，2017; EMBO J，2018）。发现环形RNA circZbtb20和circTmem241调控ILC3细胞分化和功能的新机制（Nature Commun，2022、CMI，2022）。我们将利用RNA-seq、高通量筛选等技术，鉴定新型ncRNA，探究ncRNA对ILC细胞的谱系建立、激活应答、免疫效应等调控作用，揭示其发挥功能的分子机制，阐释ncRNA与免疫疾病的致病关系，为疾病诊断和干预提供新靶点和新策略。

　　三、肿瘤干细胞与肿瘤免疫调控

　　肿瘤干细胞具有超强的致瘤能力和自我更新潜能，靶向肿瘤干细胞是肿瘤治愈的新希望。我们鉴定了肝癌组织中共表达CD13和CD133的少量肿瘤干细胞（Cell Stem Cell，2015），揭示了数个重要基因参与调控肝癌干细胞的自我更新机制（JCI，2015；Nature Commun，2015）。率先鉴定发现了多个新lncRNA对肝癌干细胞自我更新维持的调控作用（Cell Stem Cell，2015；NSMB，2016；Nature Commun，2016；J Heptol，2018、2019; Cancer Res，2017）。还鉴定发现多个新circRNA对肝癌干细胞自我更新维持的调控作用（Mol Cancer，2021；JCI，2021）。还率先鉴定发现tRNA m1A修饰在肝癌干细胞中异常增高并阐释了m1A修饰调控肿瘤干细胞干性维持的新机制（Nature Commun，2021）。发现肠道菌群代谢物调控肠道干细胞和肠癌干细胞的新机制（Neuron，2022、Cell Res，2022）。课题组还鉴定了识别膀胱癌干细胞的新靶标抗体（Clin Cancer Res，2014），揭示了新靶标抗体干预膀胱癌生长的机制（Cancer Res，2016）。基于新靶标抗体，研发了膀胱癌的靶向抗体药物和早期诊断试剂盒。我们将聚焦消化道肿瘤，继续鉴定发现新的肿瘤干细胞标志物，研究肿瘤微环境调控肿瘤干细胞重编程和自我更新机制，研发靶向肿瘤干细胞的抗肿瘤药物，以期发现有效的肿瘤免疫治疗策略，普惠肿瘤患者。

　　【课题组常年招收有志青年才俊从事博士后研究】

承担项目情况：

代表论著：

2022

1. Z. Xiong, X. Zhu, J. Geng, Y. Xu, R. Wu, C. Li, D. Fan, X. Qin, Y. Du, Y. Tian*, Fan Z*. Intestinal Tuft-2 cells exert antimicrobial immunity via sensing bacterial metabolite N-undecanoylglycine. Immunity. 2022 Apr 12;55(4):686-700

2. P. Zhu, T. Lu, Z. Chen, B. Liu, D. Fan, C. Li, J Wu, L He, X Zhu, Y. Du, Y. Tian, Fan Z*. 5-hydroxytryptamine produced by enteric serotonergic neurons initiates colorectal cancer stem cell self-renewal. Neuron. 2022 7;S0896-6273.

3. P. Zhu, T. Lu, J. Wu, D. Fan, B. Liu, X. Zhu, H. Guo, Y. Du, F. Liu, Y. Tian, Fan Z*. Gut microbiota drives macrophage-dependent self-renewal of intestinal stem cells via niche enteric serotonergic neurons. Cell Res. 32(6),555-569 (2022)

4. N. Liu, J. He, D. Fan, Y. Gu, J. Wang, H. Li, X. Zhu, Y. Du, Y. Tian, B. Liu, Fan Z*. Circular RNA circTmem241 drives group III innate lymphoid cell differentiation via initiation of Elk3 transcription. Nat Commun. 2022 Aug 11;13(1):4711.

5. B. Ye, L. Yang, B. Liu, N. Liu, D. Fan, H. Li, L. Sun, Y. Du, S. Wang, Y. Tian, Fan Z*. Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity. Cell Mol Immunol. 2022 May;19(5):619-633.

6. Hui Guo, Jiahang Zhang, Zhimin Jiang, Xiaoxiao Zhu, Jing Yang, Rui Mu，Ying Du, Yong Tian* Pingping Zhu* & Zusen Fan*. CircBtnl1 suppresses self-renewal of intestinal stem cells via disruption of Atf4 mRNA stability. EMBO J. 2022 Accepted

2021

7. Gu Y, Wang Y, He L, Zhang J, Zhu X, Liu N, Wang J, Lu T, He L, Tian Y*, Fan Z*. Circular RNA circIPO11 drives self-renewal of liver cancer initiating cells via Hedgehog signalling. Mol Cancer. 2021 Oct 14;20(1):132.

8. Wang Y, Wang J, Li X, Xiong X, Wang J, Zhou Z, Zhu X, Dominissini D, Gu Y, He L, Tian Y*, Yi C*, Fan Z*. N 1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism. Nat Commun. 2021;12(1):6314.

9. Chen Z, Lu T, Huang L, Wang Z, Yan Z, Guan Y, Hu W, Fan Z*, Zhu P*. circular RNA cia-MAF drives self-renewal and metastasis of liver tumor-initiating cells via transcription factor MAFF. J Clin Invest. 2021;148020.

10. Liu B, Liu N, Zhu X, Yang L, Ye B, Li H, Zhu P, Lu T, Tian Y*, Fan Z*. Circular RNA circZbtb20 maintains ILC3 homeostasis and function via Alkbh5-dependent m6A demethylation of Nr4a1 mRNA. Cell Mol Immunol. 2021;18(6):1412-1424.

11. Chen Z, Wu J, Liu B, Zhang G, Wang Z, Zhang L, Wang K, Fan Z*, Zhu P*. Identification of cis-HOX-HOXC10 axis as a therapeutic target for colorectal tumor-initiating cells without APC mutations. Cell Rep. 2021;36(4):109431.

2020

12. Wang S, Qu Y, Xia P, Chen Y, Zhu X, Zhang J, Wang G, Tian Y, Ying J, Fan Z*. Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer. Cell Res. 2020 Jul;30(7):610-622.

13. Xiong Z, Xia P, Zhu X, Geng J, Wang S, Ye B, Qin X, Qu Y, He L, Fan D, Du Y, Tian Y, Fan Z*. Glutamylation of deubiquitinase BAP1 controls self-renewal of hematopoietic stem cells and hematopoiesis. J Exp Med. 2020 Feb 3;217(2):e20190974

14. Liu B, Ye B, Zhu X, Yang L, Li H, Liu N, Zhu P, Lu T, He L, Tian Y, Fan Z*. An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution. Nat Commun. 2020 Aug 14;11(1):4076.

15. Ye B, Yang L, Qian G, Liu B, Zhu X, Zhu P, Ma J, Xie W, Li H, Lu T, Wang Y, Wang S, Du Y, Wang Z, Jiang J, Li J, Fan D, Meng S, Wu J, Tian Y, Fan Z*. The chromatin remodeler SRCAP promotes self-renewal of intestinal stem cells. EMBO J. 2020 Jul 1;39(13):e103786. Epub 2020 May 25.

2019

16. Zhu P, Zhu X, Wu J, He L, Lu T, Wang Y, Liu B, Ye B, Sun L, Fan D, Wang J, Yang L, Qin X, Du Y, Li C, He L, Ren W, Wu X, Tian Y*, Fan Z*. IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3. Nat Immunol. 2019;20(2):183-194.

17. Wu J, Zhu P, Lu T, Du Y, Wang Y, He L, Ye B, Liu B, Yang L, Wang J, Gu Y, Lan J, Hao Y, He L, Fan Z*. The long noncoding RNA LncHDAC2 drives the self-renewal of liver cancer stem cells via activation of Hedgehog Signaling. J Hepatol. 2019;70(5):918-929.

18. Liu B, Yang L, Zhu X, Li H, Zhu P, Wu J, Lu T, He L, Liu N, Meng S, Zhou L, Ye B*, Tian Y*, Fan Z*. Yeats4 drives ILC lineage commitment via activation of Lmo4 transcription. J Exp Med. 2019; pii: jem.20182363.

19. Zhen Xiong^1,2,4, Pengyan Xia^1,4, Xiaoxiao Zhu^3,4, Jingjing Geng^1,2, Shuo Wang¹, Buqing Ye¹, Xiwen Qin^1,2, Yuan Qu^1,2, Luyun He^1,2, Dongdong Fan³, Ying Du¹, Yong Tian^2,3*, Zusen Fan^1,2*. Glutamylation of deubiquitinase BAP1 controls self-renewal of hematopoietic stem cells and hematopoiesis. J Exp Med. 2019 (in press).

20. Wang Y, Zhu P, Luo J, Wang J, Liu Z, Wu W, Du Y, Ye B, Wang D, He L, Ren W, Wang J, Sun X, Chen R, Tian Y*, Fan Z*. LncRNA HAND2-AS1 promotes liver cancer stem cell self-renewal via BMP signaling. EMBO J. 2019 Sep 2;38(17):e101110.

2018

21. Xia P, Wang S, Xiong Z, Zhu X, Ye B, Du Y, Meng S, Qu Y, Liu J, Gao G, Tian Y*, Fan Z*. The ER membrane adaptor ERAdP senses the bacterial second messenger c-di-AMP and initiates anti-bacterial immunity. Nat Immunol. 2018;19(2):141-150.

22. Xia P, Wang S, Ye B, Du Y, Li C, Xiong Z, Qu Y, Fan Z*. A Circular RNA Protects Dormant Hematopoietic Stem Cells from DNA Sensor cGAS-Mediated Exhaustion. Immunity 2018; 48(4):688-701.

23. Zhu P, Wu J, Wang Y, Zhu X, Lu T, Liu B, He L, Ye B, Wang S, Meng S, Fan D, Wang J, Yang L, Qin X, Du Y, Li C, He L, Ren W, Wu X, Tian Y*, Fan Z*. LncGata6 maintains stemness of intestinal stem cells and promotes intestinal tumorigenesis.Nat Cell Biol. 2018; 20(10):1134-1144.

24. Wang Y, Zhu P, Wang J, Zhu X, Luo J, Meng S, Wu J, Ye B, He L, Du Y, He L, Chen R*, TTian Y*, Fan Z*. Long noncoding RNA lncHand2 promotes liver repopulation via c-Met signaling.J Hepatol 2018; 69(4):861-872.

25. Ye B, Liu B, Hao L, Zhu X, Yang L, Wang S, Xia P, Du Y, Meng S, Huang G, Qin X, Wang Y, Yan X, Li C, Hao J, Zhu P, He L, Tian Y*, Fan Z*. Klf4 glutamylation is required for cell reprogramming and early embryonic development in mice.Nat Commun. 2018; 9(1):1261.

26. Ye B, Liu B, Yang L, Zhu X, Zhang D, Wu W, Zhu P, Wang Y, Wang S, Xia P, Du Y, Meng S, Huang G, Wu J, Chen R*, Tian Y*, Fan Z*. LncKdm2b controlsself-renewal of embryonic stem cells viaactivation of transcription factor Zbtb3. EMBO J. 2018; 37(8).

2017

27. Wang S*, Xia P, Chen Y, Qu Y, Xiong Z, Ye B, Du Y, Tian Y, Yin Z, Xu Z, Fan Z*. Regulatory Innate Lymphoid Cells Control Innate Intestinal Inflammation. Cell. 2017;171(1):201-216.

28. Liu B, Ye B, Yang L, Zhu X, Huang G, Zhu P, Du Y, Wu J, Qin X, Chen R*, Tian Y*, Fan Z*. Long non-coding RNA lncKdm2b is required for the maintenance of group 3 innate lymphoid cells by initiating Zfp292 expression. Nat Immunol. 2017;18(5):499-508.

29. Wang S*, Xia P, Fan Z*. Natural-Killer-like B Cells Function as a Separate Subset of Innate B Cells. Immunity. 2017; 47(2):201-202.

30. Xia P, Liu J, Wang S, Ye B, Du Y, Xiong Z, Han ZG, Tong L, Fan Z*. WASH maintains NKp46+ ILC3 cells by promoting AHR expression. Nat Commun. 2017;8:15685.

31. Liu B, Ye B, Zhu X, Huang G, Yang L, Zhu P, Du Y, Wu J, Meng S, Tian Y*, Fan Z*. IL-7Rα glutamylation and activation of transcription factor Sall3 promote group 3 ILC development. Nat Commun. 2017;8(1):231.

32. Ye B, Liu B, Yang L, Huang G, Hao L, Xia P, Wang S, Du Y, Qin X, Zhu P, Wu J, Sakaguchi N, Zhang J, Fan Z*. Suppression of SRCAP chromatin remodelling complex and restriction of lymphoid lineage commitment by Pcid2. Nat Commun. 2017; 8(1): 1518.

33. Yang Z^#, Li C^#, Fan Z^#, Liu H, Zhang X, Cai Z, Xu L, Luo J, Huang Y, He L, Liu C, Wu S. Single-cell Sequencing Reveals Variants in ARID1A, GPRC5A and MLL2 Driving Self-renewal of Human Bladder Cancer Stem Cells. Eur Urol. 2017;71(1):8-12.

34. Yan X, Zhang D, Wu W, Wu S, Qian J, Hao Y, Yan F, Zhu P, Wu J, Huang G, Huang Y, Luo J, Liu X, Liu B, Chen X, Du Y, Chen R*, Fan Z*. Mesenchymal stem cells promote hepatocarcinogenesis via lncRNA-MUF interaction with ANXA2 and miR-34a. Cancer Res. 2017; 77(23):6704-6716.

2016

35. Xia P, Ye B, Wang S, Zhu X, Du Y, Xiong Z, Tian Y*, Fan Z*. Glutamylation of the DNA sensor cGAS regulates its binding and synthase activity in antiviral immunity. Nat Immunol. 2016;17(4):369-78.

36. Wang S, Xia P, Chen Y, Huang G, Xiong Z, Liu J, Li C, Ye B, Du Y, Fan Z*. Natural Killer-like B Cells Prime Innate Lymphocytes against Microbial Infection. Immunity. 2016;45(1):131-44.

37. Zhu P, Wang Y, Huang G, Ye B, Liu B, Wu J, Du Y, He L, Fan Z*. lnc-β-Catm elicits EZH2-dependent β-catenin stabilization and sustains liver CSC self-renewal. Nat Struct Mol Biol. 2016;23(7):631-9.

38. Wang S, Xia P, Huang G, Zhu P, Liu J, Ye B, Du Y, Fan Z*. FoxO1-mediated autophagy is required for NK cell development and innate immunity. Nat Commun. 2016; 7:11023.

39. Zhu P, Wang Y, Wu J, Huang G, Liu B, Ye B, Du Y, Gao G, Tian Y, He L, Fan Z*. LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells. Nat Commun. 2016;7:13608.

40. Li C, Du Y, Yang Z, He L, Wang Y, Hao L, Ding M, Yan R, Wang J*, Fan Z*. GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells. Cancer Res. 2016;76(5):1273-83.

2015

41. Xia P, Wang S, Ye B, Du Y, Huang G, Zhu P, Fan Z*. Sox2 functions as a sequence-specific DNA sensor in neutrophils to initiate innate immunity against microbial infection. Nat Immunol. 2015; 16(4):366-375.

42. Wang Y, He L, Du Y, Zhu P, Huang G, Luo J, Yan X, Ye B, Li C, Xia P, Zhang G, Tian Y, Chen R*, Fan Z*. The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling. Cell Stem Cell. 2015; 16(4):413-25.

43. Zhu P, Wang Y, He L, Huang G, Du Y, Zhang G, Yan X, Xia P, Ye B, Wang S, Hao L, Wu J, Fan Z*. ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells. J Clin Invest. 2015;125(10):3795-808.

44. Xia P, Wang S, Du Y, Huang G, Satoh T, Akira S, Fan Z*. Insulin-InsR signaling drives multipotent progenitor differentiation toward lymphoid lineages. J Exp Med. 2015; 212(13):2305-21.

45. Xia P, Wang S, Xiong Z, Ye B, Huang L, Han Z*, Fan Z*. IRTKS negatively regulates antiviral immunity through PCBP2 sumoylation-mediated MAVS degradation. Nat Commun. 2015;6:8132.

46. Zhu P, Wang Y, Du Y, He L, Huang G, Zhang G, Yan X, Fan Z*. C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signaling. Nat Commun. 2015; 6:7122.

2014

47. Xia P, Wang S, Huang G, Zhu P, Li M, Ye B, Du Y, Fan Z*. WASH is required for the differentiation commitment of hematopoietic stem cells in a c-Myc-dependent manner. J Exp Med. 2014;211(10): 2119-2134.

48. Ye B, Li C, Yang Z, Wang Y, Hao J, Wang L, Li Y, Du Y, Hao L, Liu B, Wang S, Xia P, Huang G, Sun L, Tian Y*, Fan Z*. Cytosolic carboxypeptidase CCP6 is required for megakaryopoiesis by modulating Mad2 polyglutamylation. J Exp Med. 2014;211(12):2439-2454.

49. Xia P, Wang S, Huang G, Du Y, Zhu P, Li M, Fan Z*. RNF2 is recruited by WASH to ubiquitinate AMBRA1 leading to downregulation of autophagy. Cell Res., 2014; 24:943–958.

50. Li C, Yang Z, Du Y, Tang H, Chen J, Hu D, Fan Z. BCMab1, A Monoclonal Antibody against Aberrantly Glycosylated Integrin α3β1, Has Potent Antitumor Activity of Bladder Cancer In Vivo. Clin Cancer Res. 2014;20(15):4001-13.

51. Ye B, Dai Z, Liu B, Wang R, Li C, Huang G, Wang S, Xia P, Yang X, Kuwahara K, Sakaguchi N, Fan Z. Pcid2 inactivates developmental genes in human and mouse embryonic stem cells to sustain their pluripotency by modulation of Eid1 stability. Stem Cells. 2014;32(3): 623-635.

2013

52. Wang S, Xia P, Ye B, Huang G, Liu J, Fan Z*. Transient activation of autophagy via Sox2-Mediated suppression of mTOR is an important early step in reprogramming to pluripotency. Cell Stem Cell. 2013;13(5):617–625.

53. Xia P, Wang S, Du Y, Zhao Z, Shi L, Sun L, Huang G, Ye B, Li C, Dai Z, Hou N, Cheng X, Sun Q, Li L, Yang X, Fan Z*. WASH inhibits autophagy through suppression of Beclin 1 ubiquitination. EMBO J. 2013;32(20): 2685-2696.

54. Liu S, Zhang H, Li M, Hu D, Li C, Ge B, Jin B, Fan Z*. Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells. Cell Death Differ. 2013;20(3):456-464.

2012

55. Wang S, Xia P, Shi L, Fan Z*. FADD cleavage by NK cell granzyme M enhances its self-association to facilitate procaspase-8 recruitment for auto-processing leading to caspase cascade. Cell Death Differ. 2012;19(4):605-615. (IF:8.8)

56. Zhong C, Li C, Wang X, Toyoda T, Gao G, Fan Z*. Granzyme K inhibits replication of influenza virus through cleaving the nuclear transport complex importin α1/β dimer of infected host cells. Cell Death Differ. 2012;19(5):882-890.

2011年以前文章

57. Shi L, Wu L, Wang S, Fan Z*. Granzyme F induces a novel death pathway characterized by Bid-independent cytochrome c release without caspase activation. Cell Death Differ. 2009, 16(12): 1694-1706.

58. Zhao T, Zhang H, Guo Y, Zhang Q, Hua G, Lu H, Hou Q, Liu H, Fan Z*. Granzyme K cleaves the nucleosome assembly protein SET to induce single-stranded DNA nicks of target cells. Cell Death Differ. 2007,14(3): 489-499.

59. Fan Z*, Yu P, Wang Y, Wang Y, Fu ML, Liu W, Sun Y, Fu YX*. NK-cell activation by LIGHT triggers tumor-specific CD8+ T-cell immunity to reject established tumors. Blood. 2006, 107(4): 1342-1351.

60. Fan Z*, Zhang H, Zhang Q. Tumor suppressor pp32 represses cell growth through inhibition of transcription by blocking acetylation and phosphorylation of histone H3 and initiating its proapoptotic activity. Cell Death Differ. 2006, 13(9): 1485-1494.

61. Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J*. Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell 2003, 112(5): 659-672.

62. Fan Z, Beresford PJ, Zhang D, Xu Z, Novina CD, Yoshida A, Pommier Y, Lieberman J*. Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. Nat Immunol. 2003, 4(2): 145-153.

63. Lieberman J*, Fan Z*. Nuclear war: the granzyme A-bomb. Curr Opin Immunol. 2003, 15(5): 553-559.

64. Fan Z, Beresford PJ, Zhang D, Lieberman J*. HMG2 interacts with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzyme A. Mol Cell Biol. 2002, 22(8): 2810-2820.

（资料来源：范祖森研究员，2023-01-11）