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细胞生物学系

韩代书

课题组简介
本课题组为我国著名细胞生物学家薛社普院士创建,早期从事哺乳类红细胞终末分化与精子发生调控机理的研究。近年来,集中研究生殖系统免疫微环境的调节机制,以及微生物感染与免疫异常引起的男性不育。发现了生殖系统天然防御机制, 开辟了生殖免疫新的研究领域。目前集中在病毒感染对男性生殖的影响,以及生殖系统慢性炎症的病理机制,为相关疾病的预防与诊治提供理论基础。在相关领域的研究中,形成了自己的特色和优势。建立了合理的研究团队,完善的研究平台。

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薛社普
:1917.10.26 – 2017.03.10,1947年毕业于中央大学(现南京大学),1951年在美国圣路易华盛顿大学获理科博士学位。中国科学院院士,历任中国医学科学院基础医学研究所细胞生物室主任;中国解剖学会理事长;解剖学报主编。现任中国解剖学会名誉理事长及国际解剖联合会理事,国际形态科学委员会委员。国家重点细胞生物学科带头人。是我国细胞分化调控研究开拓者之一,首创无核的网织红细胞杂交模型。发现哺乳类红细胞中存在能抑制肿瘤恶性和诱导终末分化的红细胞分化因子,提出该因子是导致哺乳类红细胞自然排核的进化产物。从事实验胚胎诱导分化、神经发生学、肿瘤恶性调控和生殖生物学等方面的科研工作,在国内、外先后发表学术论文200多篇,编著书籍6种。曾获部委级科技进步二等奖三项。







韩代书
(课题组长):1983年毕业于南京大学生物系。1995年毕业于法国巴黎大学,获博士学位,1995年至1998年美国国立卫生研究院(NIH)博士后。1999年回中国医学科学院基础医学研究所,现任北京协和医学院教授,博士研究生导师。目前的主要研究方向:生殖系统免疫调节与相关的不孕不育。








课题组人员

韩代书:男,教授, dshan@ibms.pumc.edu.cn // daishu630@126.com
吴 晗:男,博士后, yzwuhan@hotmail.com
江 倩,女,博士研究生,Qianj881219@163.com
公茂磊,男,博士研究生,maoleigong@126.com
陈 冉,女,博士研究生,chenran19941214@126.com
王 菲,女,硕士研究生,wangfei_wendy@163.com
刘伟华,男,硕士研究生,liuwh_bio@163.com
邢加彰,女,八年制临床医学生,xingjz14@mails.tsinghua.edu.cn


研究方向
生殖系统具有特殊的免疫微环境,既要保护生殖细胞不受免疫系统的攻击,又要抵抗入侵的微生物病原体。免疫异常是不孕不育的重要病因,本实验室研究生殖系统免疫环境的调节机制及免疫相关的不孕不育,主要内容包括:

1.      生殖系统免疫微环境:研究睾丸免疫豁免环境保护精子发生的机制;精子在附睾及雌性生殖道中逃避免疫反应的机制;揭示免疫微环境异常与男性不育的关系。

2.      免疫相关的男性不育:研究微生物感染与自身免疫反应诱导睾丸炎、附睾炎、精囊炎及前列腺炎的机制,关注组织特异细胞中模式识别受体启动的固有免疫应答在诱发组织炎症中的作用。探讨炎症环境破坏精子形成与功能、从而导致男性不育的机制。

3.      免疫相关的女性不育:集中于病毒感染对卵巢功能的影响及其与卵巢早衰的关系,关注颗粒细胞的固有免疫应答在卵巢抗病毒中的作用。探讨病毒感染诱导卵巢炎及其损害女性生育的病理机制。

 

联系方式

中国医学科学院/北京协和医学院

基础医学研究所/基础学院,细胞生物学系,老科研楼630室

北京市东城区东单三条5号,邮编:100005

电话:010-69156457

 

­­­目前承担研究项目

1.    国家自然科学基金面上项目:睾丸免疫环境与睾丸炎的调节机理(31371518)

2.    国家重点基础研究发展计划(973计划)项目:长非编码RNA在精子发生中的功能及机制(2015CB943001)

3.    “十三五”国家重点研发专项:干细胞移植的分子免疫调控机理(2016YFA0101001)

4.    中国医学科学院医学创新工程项目:组织干细胞衰老关键分子机理及干预研究(2017-I2M-3-007);

5.    中国医学科学院医学“一带一路”科技先导专项:感染与免疫相关的不孕不育机制研究。

 

近五年发表论文:

1.     Jiang Q, Wang F, Shi L, Zhao X, Gong M, Liu W, Song C, Li Q, Chen Y, Wu H, and Han D. C-X-C Motif Chemokine Ligand 10 Produced by Mouse Sertoli Cells in Response to Mumps Virus Infection Induces Male Germ Cell Apoptosis. Cell Death Dis 2017; 8: e3146.

2.     Su L, Cheng YC, Lee WM, Zhang M, Yang F, Zhao B, Han D, Liu Y, and Hu D. Abcb1a and Abcb1b Genes Function Differentially in Blood-Testis Barrier Dynamics in the Rat. Cell Death Dis 2017; 8: e3038.

3.     Yan K, Feng D, Liang J, Wang Q, Deng L, Zhang X, Ling B, and Han D. Cytosolic DNA Sensor-Initiated Innate Immune Responses in Mouse Ovarian Granulosa Cells. Reproduction 2017; 153: 821-34.

4.     王菲,韩代书。感染及免疫相关的男性不育。中国科学:生命科学,2017; 47:180-189

5.     Wu H, Zhao X, Wang F, Jiang Q, Shi L, Gong M, Liu W, Gao B, Song C, Li Q, Chen Y, and Han D. Mouse Testicular Cell Type-Specific Antiviral Response against Mumps Virus Replication. Front Immunol 2017; 8: 117.

6.     江倩, 赵祥, 薛社普, 韩代书. 睾丸免疫调节与睾丸炎: Tyro3/Axl/Mer 受体酪氨酸激酶与模式识别受体的功能. 科学通报, 2017; 62: 1153–1162

7.     Ma W, Li S, Ma S, Jia L, Zhang F, Zhang Y, Zhang J, Wong G, Zhang S, Lu X, Liu M, Yan J, Li W, Qin C, Han D, Qin C, Wang N, Li X, and Gao GF. Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice. Cell 2016; 167: 1511-24.e10.

8.     Wang Q, Wu H, Cheng L, Yan K, Shi L, Zhao X, Jiang Q, Wang F, Chen Y, Li Q, Han D. Mumps virus induces innate immune responses in mouse ovarian granulosa cells through the activation of Toll-like receptor 2 and retinoic acid-inducible gene I. Mol Cell Endocrinol. 2016; 436:183-94.

9.     Cheng L, Chen Q, Zhu W, Wu H, Wang Q, Shi L, Zhao X, Han D. Toll-like Receptors 4 and 5 Cooperatively Initiate the Innate Immune Responses to Uropathogenic Escherichia coli Infection in Mouse Epididymal Epithelial Cells. Biol Reprod. 2016; 94:58.

10. Li N, Mruk DD, Mok KW, Li MW, Wong CK, Lee WM, Han D, Silvestrini B, Cheng CY. Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption. FASEB J. 2016; 30:1436-52.

11. Chen Q, Deng T, Han D. Testicular immunoregulation and spermatogenesis. Semin Cell Dev Biol. 2016. pii: S1084-9521(16)30019-2.

12. Wu H, Shi L, Wang Q, Cheng L, Zhao X, Chen Q, Jiang Q, Feng M, Li Q, Han D. Mumps virus-induced innate immune responses in mouse Sertoli and Leydig cells. Sci Rep. 2016; 6:19507

13. Deng T, Chen Q, Han D. The roles of TAM receptor tyrosine kinases in the mammalian testis and immunoprivileged sites. Front Biosci (Landmark Ed). 2016; 21:316-27.

14. Li N, Mruk DD, Mok KW, Li MW, Wong CK, Lee WM, Han D, Silvestrini B, Cheng CY. Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption. FASEB J. 2016; 30:1436-52.

15. Yan K, Cheng L, Liu P, Liu Z, Zhao S, Zhu W, Wang Q, Wu H, Han D. Polyinosinic-Polycytidylic Acid Perturbs Ovarian Functions Through Toll-Like Receptor 3-Mediated Tumor Necrosis Factor A Production in Female Mice. Biol Reprod. 2015; 93:11.

16. Li N, Mruk DD, Wong CK, Lee WM, Han D, Cheng CY. Actin-bundling protein plastin 3 is a regulator of ectoplasmic specialization dynamics during spermatogenesis in the rat testis. FASEB J. 2015; 29:3788-805.

17. Li N, Mruk DD, Wong CK, Han D, Lee WM, Cheng CY. Formin 1 Regulates Ectoplasmic Specialization in the Rat Testis Through Its Actin Nucleation and Bundling Activity. Endocrinology. 2015; 156:2969-83.

18. Zhu W, Zhao S, Liu Z, Cheng L, Wang Q, Yan K, Chen Q, Wu H, Han D. Pattern recognition receptor-initiated innate antiviral responses in mouse epididymal epithelial cells. J Immunol. 2015; 194:4825-35.

19. Liu Z, Zhao S, Chen Q, Yan K, Liu P, Li N, Cheng CY, Lee WM, Han D. Roles of Toll-like receptors 2 and 4 in mediating experimental autoimmune orchitis induction in mice. Biol Reprod. 2015; 92:63.

20. Yu L, Liu P, Liu Z, Zhu W, Yan K, Chen Q, Han D. p204-mediated innate antiviral responses in mouse adipose cells and their effects on cell functions. Immunol Cell Biol. 2015; 93:147-57.

21. Li N, Liu Z, Zhang Y, Chen Q, Liu P, Cheng CY, Lee WM, Chen Y, Han D. Mice lacking Axl and Mer tyrosine kinase receptors are susceptible to experimental autoimmune orchitis induction. Immunol Cell Biol. 2015; 93:311-20.

22. Zhao S, Zhu W, Xue S, Han D. Testicular defense systems: immune privilege and innate immunity. Cell Mol Immunol. 2014; 11:428–437.

23. Zhu W, Liu P, Yu L, Chen Q, Liu Z, Yan K, Lee WM, Cheng CY, Han D. p204-initiated innate antiviral response in mouse Leydig cells. Biol Reprod. 2014; 91:8.

24. Qian X, Mruk DD, Cheng YH, Tang EI, Han D, Lee WM, Wong EW, Cheng CY. Actin binding proteins, spermatid transport and spermiation. Semin Cell Dev Biol. 2014; 30:75-85. Review.

25. Xiao X, Mruk DD, Wong EW, Lee WM, Han D, Wong CK, Cheng CY. Differential effects of c-Src and c-Yes on the endocytic vesicle-mediated trafficking events at the Sertoli cell blood-testis barrier: an in vitro study. Am J Physiol Endocrinol Metab. 2014; 307:E553-62.

26. Chen Q, Zhu W, Liu Z, Yan K, Zhao S, Han D. Toll-like receptor 11-initiated innate immune response in male mouse germ cells. Biol Reprod. 2014; 90:38.

27. Yan K, Liu P, Liu Z, Zhao S, Cheng L, Han D. Polyinosinic-Polycytidylic acid initiates ovarian innate antiviral response and inhibits steroidogenesis in female mice. Biol Reprod. 2014; 90:11.

28. Yu L, Yan K, Liu P, Li N, Liu Z, Zhu W, Chen Y, Han D. Pattern recognition receptor-initiated innate antiviral response in mouse adipose cells. Immunol Cell Biol.  2014; 92:105-15. 

29. 朱伟伟,赵树涛,薛社普,韩代书。睾丸免疫豁免与天然免疫。科学通报。2014; 59:2652-2662.

30. Yu W, Zheng H, Lin W, Tajima A, Zhang Y, Zhang X, Zhang H, Wu J, Han D, Rahman NA, Korach KS, Gao GF, Inoue I, Li X. Estrogen promotes Leydig cell engulfment by macrophages in male infertility. J Clin Invest. 2014; 124:2709-21

31. Zhu W, Chen Q, Yan K, Liu Z, Li N, Zhang X, Yu L, Chen Y, Han D. RIG-I-like receptors mediate innate antiviral response in mouse testis. Mol Endocrinol. 2013; 27:1455-67.

32. Qi N, Liu P, Zhang Y, Wu H, Chen Y, Han D. Development of a spontaneous liver disease resembling autoimmune hepatitis in mice lacking tyro3, axl and mer receptor tyrosine kinases. PLoS One. 2013; 8:e66604.

33. Chen B, Xue Z, Yang G, Shi B, Yang B, Yan Y, Wang X, Han D, Huang Y, Dong W. Akt-signal integration is involved in the differentiation of embryonal carcinoma cells. PLoS One. 2013; 8:e64877.

34. Zhang Y, Li N, Chen Q, Yan K, Liu Z, Zhang X, Liu P, Chen Y, Han D. Breakdown of immune homeostasis in the testis of mice lacking Tyro3, Axl and Mer receptor tyrosine kinases. Immunol Cell Biol. 2013; 91:416-26.

35. Yan K, Zhu W, Yu L, Li N, Zhang X, Liu P, Chen Q, Chen Y, Han D. Toll-like receptor 3 and RIG-I-like receptor activation induces innate antiviral responses in mouse ovarian granulosa cells. Mol Cell Endocrinol. 2013; 372:73-85.

36. Zhang X, Wang T, Deng T, Xiong W, Lui P, Li N, Chen Y, Han D. Damaged spermatogenic cells induce inflammatory gene expression in mouse Sertoli cells through the activation of Toll-like receptors 2 and 4. Mol Cell Endocrinol. 2013; 365:162-73.

37. Deng T, Feng X, Liu P, Yan K, Chen Y, Han D. Toll-like receptor 3 activation differentially regulates phagocytosis of bacteria and apoptotic neutrophils by mouse peritoneal macrophages. Immunol Cell Biol. 2013; 91:52-9.

38. Li N, Wang T, Han D. Structural, cellular and molecular aspects of immune privilege in the testis. Front Immunol. 2012; 3:152.

39. Wang T, Zhang X, Chen Q, Deng T, Zhang Y, Li N, Shang T, Chen Y, Han D. Toll-like receptor 3-initiated antiviral responses in mouse male germ cells in vitro. Biol Reprod. 2012; 86:106.

40. Deng T, Zhang Y, Chen Q, Yan K, Han D. Toll-like receptor-mediated inhibition of Gas6 and ProS expression facilitates inflammatory cytokine production in mouse macrophages. Immunology. 2012; 135:40-50.

 

著作章节

1.     Gong M, Han D. Immune Environment in the Testis. In: C. Yan Cheng (Editor), Molecular Mechanisms in Spermatogenesis (Second Edition), Springer publishers.

2.     Wang F, Jiang Q, Han D. Testicular immunoregulation: The role of Tyro3, Axl, and Mer receptor tyrosine kinases and pattern recognition receptors. In: C. Yan Cheng (Editor), Spermatogenesis: Biology and Clinical Implications. In press. Springer publishers.

3.     Jiang Q, Han D. Infectious and immunological aspects of male infertility. In: Manuela Simoni and Ilpo Huhtaniemi (Editor), Endocrinology of the Testis and Male Reproduction. In press. Springer publishers.

4.     Han D, Liu Z, Yan K. Immunology of the Testis and Privileged Sites. 2016, In: Ratcliffe M.J.H (Editor in Chief), Encyclopedia of Immunobiology, Vol. 5, pp. 46-53. Oxford: Academic Press.

5.     Deng T, Han D. Testicular Immune Environment for Spermatogenesis. 2016, In: Gladys Robinson (Editor), Spermatogenesis: Molecular Mechanisms, Regulation and Biological Perspectives, pp. 71-100. Nova publishers.