范祖森

国科大微免教研室副主任，中科院研究员

范祖森，中科院研究员，中科院“百人计划”获得者，男，二级研究员，博士生导师，创新课题组组长，国科大微免教研室副主任，中国科学院特聘核心骨干研究员，国科大岗位教授（A类）；基金委创新群体首席科学家，国家重点研发专项首席科学家，获得“杰出青年”基金资助，入选“新世纪百千万人才工程”国家级人才，享受“国务院特殊津贴”专家，中科院优秀研究生导师。

人物经历

1998年在上海第二医科大学获得免疫学博士学位后，到中国科学院上海生物化学研究所分子生物学国家重点实验室从事博士后研究，被晋升为副研究员。随后到美国哈佛大学医学院血液研究中心继续从事博士后研究，作为主要骨干全过程参加了细胞毒性T淋巴细胞（CTL）杀伤肿瘤机理的研究，阐明了颗粒酶A介导靶细胞凋亡的新机制。论文以第一作者的身份发表在Cell, Nature Immunology 和Mol. Cell. Biol. 等杂志上。Cell 和Nature Immunology上的论文均附有同行专家评论，在Science上作为免疫学的重要发现做过介绍，受到同行的高度重视。受Current Opinion Immunology 邀请撰写了该研究领域的综述评论。多年来一直从事分子生物学和免疫学研究工作，发表论文30余篇。去年7月被晋升为哈佛大学医学院讲师和血液研究所副研究员。上海第二医科大学客座教授和上海市外国专家局外聘专家。美国分子生物学学会会员和美国免疫家学会会员。作为中国科学院2004年度“百人计划”引进回国工作。研究方向：细胞周期调控与细胞癌变机制；组蛋白修饰与基因转录调控；细胞毒性 T淋巴细胞(CTL) 诱导的肿瘤杀伤机理；肿瘤及病毒感染性疾病的免疫靶向治疗。

2013年1月30号范祖森课题组从事肿瘤干细胞、免疫细胞发育分化及肿瘤靶标发现与肿瘤个体化治疗等领域的研究，主要研究方向为免疫细胞谱系建立的信号转导、抗肿瘤免疫机制、肿瘤干细胞鉴定及干预机制、肿瘤新靶标的鉴定与抗体靶向药物研发等领域的研究，课题组经过多年的研究积累业已形成优秀的研究平台和科研文化氛围。现因工作需要特招聘1-2名博士后/副研究员。

受聘者应在细胞生物学、分子生物学、免疫学、干细胞生物学、生物医药等相关领域获得博士学位，在实验室接受过博士或博士后训练，并具有良好的研究论文发表和英语写作交流能力，要求具有良好的组织协调能力。

应聘者将根据自己的研究兴趣结合实验室的研究领域开展前瞻性研究，并经过2-3年科学训练使其达到国际先进水平，达成自己的科学梦想。

研究方向

1. 免疫细胞清除肿瘤和病毒的免疫效应机制

2. 免疫细胞的活化和谱系建立的时相遗传调控机制

3. 肿瘤干细胞、肿瘤标志物、肿瘤的个体化药物研发

科研成果

代表论文

1. Shuo Wang*, Pengyan Xia*, Buqing Ye, Guanling Huang, Jing Liu, Zusen Fan*. Transient activation of autophagy via Sox2-mediated suppression of mTOR is an important early step in reprogramming to pluripotency. Cell Stem Cell

2. Pengyan Xia1*, Shuo Wang1*, Ying Du1, Zhenao Zhao2, Lei Shi1, Lei Sun3, Guanling Huang1, Buqing Ye1, Chong Li1, Zhonghua Dai1, Ning Hou4, Xuan Cheng4, Qingyuan Sun2, Lei Li2, Xiao Yang4+, Zusen Fan*. WASH inhibits autophagy through suppression of Beclin 1 ubiquitination

3. Buqing Ye1*, Zhonghua Dai1*, Benyu Liu1, Rui Wang1, Chong Li1, Guanling Huang1, Shuo Wang1, Pengyan Xia1, Xuan Yang1, Kazuhiko Kuwahara2, Nobuo Sakaguchi2, Zusen Fan*

4. 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

5. Wang L, Li Q, Wu L, Liu S, Zhang Y, Yang X, Zhu P, Zhang H, Zhang K, Lou J, Liu P, Tong L, Sun F, Fan Z*. Identification of SERPINB1 As a Physiological Inhibitor of Human Granzyme H, J

6. 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

7. 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 alpha1/beta dimer of infected host cells

8. Tang H, Li C, Wang L, Zhang H, Fan Z*,Granzyme H of cytotoxic lymphocytes is required for clearance of the hepatitis B virus through cleavage of the hepatitis B virus X protein, J Immunol

9. Wang L, Zhang K, Wu L, Liu S, Zhang H, Zhou Q, Tong L, Sun F, Fan Z*, Structural insights into the substrate specificity of human granzyme H: the functional roles of a novel RKR motif

10. Guo Y, Chen J, Shi L, Fan Z*. VCP cleavage by granzyme K disrupts endoplasmic reticulum associated protein degradation to force tumor target cell death

11. Hu D, Liu S, Shi L, Li C, Wu L, Fan Z. Cleavage of survivin by Granzyme M triggers degradation of the survivin-X-linked inhibitor of apoptosis protein (XIAP) complex to free caspase activity leading to cytolysis of target tumor cells

12. Hua G, Wang S, Zhong C， Xue P, Fan Z*. Ignition of p53 bomb by granzyme K sensitizes tumor cells to NK cell-mediated cytolysis

13. Zhang H, Zhong C, Shi L, Guo Y, Fan Z*. Granulysin induces cathepsin B release of lysosomes of target tumor cells to target mitochondria through processing of Bid

14. Wu L, Wang L, Hua G, Liu K, Yang X, Zhai Y, Bartlam M, Sun F, Fan Z*. Structural Basis for Proteolytic Specificity of the Human Apoptosis-Inducing Granzyme M

15. 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

16. Hou Q, Zhao T, Zhang H, Lu H, Zhang Q, Sun L, Fan Z*. Granzyme H induces apoptosis of target tumor cells characterized by DNA fragmentation and Bid-dependent mitochondrial damage

17. Guo Y, Chen J, Zhao T, Fan Z*. Granzyme K degrades the redox/DNA repair enzyme Ape1 to trigger oxidative stress of target cells leading to cytotoxicity

18. Hua G, Zhang Q, Fan Z*. Heat shock protein 75 (TRAP1) antagonizes reactive oxygen species generation and protects cells from granzyme M-mediated apoptosis. J Biol Chem

19. Zhao T, Zhang H, Guo Y, Fan Z*. Granzyme K directly processes Bid to release cytochrome c and endonuclease G leading to mitochondria- dependent cell death

20. Zhao T, Zhang H, Guo Y, Zhang Q, Lu H, Hou Q, Hua G, Fan Z*. Granzyme K Induces rapid caspase-independent cell death with apoptotic nuclear morphology and single-stranded DNA nicks

21. Fan Z*, Yu P, Wang Y, Lee Y, Wang Y, Fu M, Liu W, Sun Y, Fu YX. NK activation by LIGHT primes tumor specific CD8+ T cell immunity to reject established tumors

22. Lu H, Hou Q, Zhao T, Zhang H, Zhang Q, Fan Z*. Granzyme M directly cleaves ICAD to unleash caspase-activated DNase leading to DNA fragmentation

23. Fan Z*, Zhang H, Zhang Q. Tumor suppressor pp32 represses cell growth by inhibiting transcription by blocking acetylation and phosphorylation of hostone H3 and initiating its proapoptotic activity

24. Fan Z*, Zhang Q. Molecular mechanisms of lymphocyte-mediated cytotoxicity. Cell Mol Immunol

25. *Fan Z. CTL-mediated killing mechanism against cancers. J

26. Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J*. The tumor metastasis suppressor NM23-H1 is a granzyme A-activated DNase that nicks DNA during CTL-mediated apoptosis and the nucleosome assembly protein SET is its inhibitor

27. 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

28. Lieberman J*, Fan Z*. Nuclear war: the Granzyme A-bomb. Curr Opin Immunology

29. 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

30. Beresford PJ, Zhang D, Oh DY, Fan Z, Greer EL, Russo ML, Jaju M, Lieberman J. Granzyme A activates an endoplasmic reticulum-associated cas Caspase-independent nuclease to induce single-stranded DNA

科研项目

（1）免疫应答效应相关蛋白质的生物学功能及其作用机制研究，主持，部委级，2010-01--2014-12

（2） SET蛋白复合体的结构与功能研究，主持，国家级，2009-01--2012-12

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