edf壹定发

全体研究组长

时玉舫(客座)
博士 研究员 博士生导师

中科院肿瘤与微环境重点实验室,免疫与组织干细胞课题组组长

研究方向:干细胞、肿瘤、免疫、自身免疫性疾病

电子邮件(E-mail):shiyufang2@gmail.com

电话(Tel):54923350

邮政编码:200031

简历 & 研究方向
2017-至     今  edf壹定发 研究员
2008-2016年  edf壹定发上海生命科学研究院/上海交通大学医学院健康科学研究所 研究员
2008-2014年 edf壹定发上海生命科学研究院/上海交通大学医学院健康科学研究所 所长
2003-2008年  美国新泽西医科和牙科大学-罗伯特伍德约翰逊医学院分子遗传学、微生物学和免疫学系 终身教授
2001-2008年  美国新泽西癌症研究所 研究员
2001-2003年  美国新泽西医科和牙科大学-罗伯特伍德约翰逊医学院分子遗传学、微生物学和免疫学系 终身副教授
1999-2001年  美国红十字协会Holland医学生物研究所免疫学部 终身副教授
1996-1999年  美国乔治华盛顿大学微生物学和免疫学系 助理教授、博士生导师
1995-1999年  美国红十字协会Holland医学生物研究所免疫学部Scientist I 助理教授
1992-1995年  加拿大多伦多大学免疫学系 博士后
1986-1989年  加拿大阿尔伯塔大学动物学系 助教
1982-1985年  山东农学院畜牧兽医系 助教

研究方向(1000字以内)
1. 间充质干细胞的免疫调节:间充质干细胞在组织修复中具有重要作用,而损伤组织与炎症反应密切相关。因此,了解间充质干细胞与免疫细胞之间的作用关系是必要的。大家已经发现,炎症因子赋予间充质干细胞免疫调节能力,并且这种免疫调节能力具有“可塑性”。大家的研究将系统阐明间充质干细胞与免疫之间的相互作用及机制,相关研究成果对于理解多种免疫性疾病的病理机制和探寻相关疾病的治疗新策略具有重要意义。
2. 肿瘤免疫调控:免疫监视是控制肿瘤发生发展的关键。随着研究的不断进展,免疫疗法成为继手术治疗、放化疗之外的肿瘤治疗的另一重要研究方向。虽然已有许多免疫疗法在肿瘤治疗过程中显示出一定的疗效,但却无一被证实能够治愈肿瘤。大家的研究重点将集中在肿瘤基质(即癌细胞生存的土壤)上,以其了解肿瘤微环境中免疫反应调控的具体机制。
3. 免疫细胞代谢调控:促炎和抑炎的免疫细胞具有不同的代谢偏好,研究表明胞内的代谢活动不仅为免疫细胞提供了能量,也决定了免疫细胞的功能。大家的研究旨在一方面解析代谢对免疫细胞的功能的调控机制,另一方面开发靶向免疫细胞代谢的新策略来治疗免疫失调性疾病。
4. 不同T细胞亚群的活化诱导细胞凋亡(AICD)过程及机制:T细胞受抗原刺激后会迅速增殖,并伴随细胞死亡。因此,了解不同T细胞群体的死亡机制对控制传染病、癌症和自身性免疫疾病具有重要意义。

代表性论文(* 通讯编辑)

  1. WE Fibbe*, Y Shi*. FOXO3, a Molecular Search for the Fountain of Youth. Cell Stem Cell. 2019 Mar 7;24(3):351-352.
  2. X Li#, B Shang#, Y Li, Y Shi*, C Shao*. IFNγ and TNFα synergistically induce apoptosis of mesenchymal stem/stromal cells via the induction of nitric oxide. Stem cell research & therapy. 2019 Jan 11;10(1):18.
  3. L Du#, L Lin#, Q Li, K Liu, Y Huang, X Wang, K Cao, X Chen, W Cao, F Li, C Shao, Y Wang, Y Shi*. IGF-2 Preprograms Maturing Macrophages to Acquire Oxidative Phosphorylation-Dependent Anti-inflammatory Properties. Cell metabolism. 2019 Feb 4. pii: S1550-4131(19)30006-3.
  4. X Li, C Shao, Y Shi*, W Han*. Lessons learned from the blockade of immune checkpoints in cancer immunotherapy. Journal of hematology & oncology. 2018 Feb 27;11(1):31.
  5. Y Shi*, Y Wang, Q Li, K Liu, J Hou, C Shao, Y Wang*. Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nature Reviews Nephrology. 2018 Aug;14(8):493-507.
  6. Wang G, Cao K, Liu K, Xue Y, Roberts AI, Li F, Han Y, Rabson AB, Wang Y, Shi Y*. Kynurenic acid, an IDO metabolite, controls TSG-6-mediated immunosuppression of human mesenchymal stem cells. Cell Death Differ. 2018 Jul;25(7):1209-1223.
  7. Shi Y*, Du L, Lin L, Wang Y. Tumour-associated mesenchymal stem/stromal cells: emerging therapeutic targets. Nat Rev Drug Discov. 2017, 16(1):35-52.
  8. Yu P, Huang Y, Xu C, Lin L, Han Y, Sun W, Hu G, Rabson A, Wang Y*, Shi Y*. Downregulation of CXCL12 in mesenchymal stromal cells by TGFβ promotes breast cancer metastasis. Oncogene. 2017, 36(6):840-849.
  9. Yu P, Huang Y, Han Y, LY Lin, Rabson A, Wang Y*, Shi Y*. TNFα-activated mesenchymal stromal cells promote breast cancer metastasis through recruiting CXCR2+ neutrophils. Oncogene. 2017, 36(4):482-490.
  10. Yang Q, Zheng C, Cao J, Cao G, Shou P, Lin L, Velletri T, Jiang M, Chen Q, HanY, Li F, Wang Y, Cao W, Shi Y*. Spermidine alleviates experimental autoimmuneencephalomyelitis through inducing inhibitory macrophages. Cell Death Differ. 2016, 23(11):1850-1861.
  11. Lin L#, Du L#, Cao K, Huang Y, Yu P, Zhang L, Li F, Wang Y*, Shi Y*. Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour promotion capabilities. Oncogene. 2016, 35(46):6038-6042.
  12. Zheng C, Yang Q, Cao J, Xie N, Liu K, Shou P, Qian F, Wang Y, Shi Y*. Local proliferation initiates macrophage accumulation in adipose tissue during obesity. Cell Death Dis. 2016, 7:e2167.
  13. Zheng C, Yang Q, Xu C, Shou P, Cao J, Jiang M, Chen Q, Cao G, Han Y, Li F, Cao W, Zhang L, Zhang L, Shi Y*, Wang Y*. CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages. Proc Natl Acad Sci U S A. 2015, 112(52):E7239-48.
  14. Cao K, Wang G, Li W, Zhang L, Wang R, Huang Y, Du L, Jiang J, Wu C, He X, Roberts AI, Li F, Rabson AB, Wang Y, Shi Y*. Histone deacetylase inhibitors prevent activation-induced cell death and promote anti-tumor immunity. Oncogene. 2015, 34(49):5960-70.
  15. Wang Y, Chen X, Cao W, Shi Y*. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014, 15(11):1009-16.
  16. Han X, Yang Q, Lin L, Xu C, Zheng C, Chen X, Han Y, Li M, Cao W, Cao K, Chen Q, Xu G, Zhang Y, Zhang J, Schneider RJ, Qian Y, Wang Y, Brewer G, Shi Y*. Interleukin-17 enhances immunosuppression by mesenchymal stem cells. Cell Death Differ. 2014, 21(11):1758-68.
  17. Chen X, Gan Y, Li W, Su J, Zhang Y, Huang Y, Roberts AI, Han Y, Li J, Wang Y, Shi Y*. The interaction between mesenchymal stem cells and steroids during inflammation. Cell Death Dis. 2014, 5:e1009.
  18. Ling W, Zhang J, Yuan Z, Ren G, Zhang L, Chen X, Rabson AB, Roberts AI, Wang Y, Shi Y*. Mesenchymal Stem Cells Employ IDO to Regulate Immunity in Tumor Microenvironment. Cancer Res. 2014, 74(5):1576-87.
  19. Chen Q, Shou P, Zhang L, Xu C, Zheng C, Han Y, Li W, Huang Y, Zhang X, Shao C, Roberts AI, Rabson AB, Ren G, Zhang Y, Wang Y, Denhardt DT, Shi Y*. An Osteopontin-Integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells. Stem Cells. 2014, 32(2):327-37.
  20. Su J, Chen X, Huang Y, Li W, Li J, Cao K, Cao G, Zhang L, Li F, Roberts AI, Kang H, Yu P, Ren G, Ji W, Wang Y, Shi Y*. Phylogenetic distinction of iNOS and IDO function in mesenchymal stem cell-mediated immunosuppression in mammalian species. Cell Death Differ. 2014, 21(3):388-96.
  21. Yu B, He Z, You P, Han Q, Xiang D, Chen F, Wang M, Liu C, Lin X, Borjigin U, Zi X, Li J, Zhu H, Li W, Han C, Wangensteen KJ, Shi Y, Hui L, Wang X, Hu Y. Reprogramming fibroblasts into bipotential hepatic stem cells by defined factors. Cell Stem Cell. 2013, 13:328-340.
  22. Liu B, Chen X, Wang Y, Shi Y. Curative effect of hepatic portal venous administration of autologous bone marrow in AIDS patients with decompensatedliver cirrhosis. Cell Death Disease. 2013, 4:e739.
  23. Li W, Ren G, Huang Y, Su J, Han Y, Li J, Chen X, Cao K, Chen Q, Shou P, Zhang L, Yuan ZR, Roberts AI, Shi S, Le AD, Shi Y*. Mesenchymal stem cells: a double-edged sword in regulating immune responses. Cell Death Differ. 2012, 19(9):1505-13.
  24. Shi Y*, Su J, Roberts AI, Shou P, Rabson AB, Ren G. How mesenchymal stem cells interact with tissue immune responses. Trends Immunol. 2012, 33(3):136-43.
  25. Shi Y*, Wei L, Wang Y, Ren G. Stem Cells Deployed for Bone Repair Hijacked by T Cells. Cell Stem Cell. 2012, 10(1):6-8.
  26. Swaims AY, Khani F, Zhang Y, Roberts AI, Devadas S, Shi Y*, Rabson AB*. Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T-cells. Blood. 2010 Oct 21;116(16):2994-3003. (*equal contribution)
  27. Shi YF, Hu GZ, Su JJ, Li WZ, Chen Q, Shou PS, Xu CL, Chen XD, Huang Y, Zhu ZX, Huang X, Han XY, Xie NX, Ren GW. Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair. Cell Res. 2010, 20:519-528.
  28. Ren G, Su J, Zhang L, Zhao X, Ling W, L'huillie A, Zhang J, Lu Y, Roberts AI, Ji W, Rabson AB, Shi YF. Species Variation in the Mechanisms of Mesenchymal Stem Cell-Mediated Immunosuppression. Stem Cells. 2009, 27:1954-1962.
  29. Ren GW, Zhang LY, Zhao X, Xu GW, Zhang YY, Roberts AI, Zhao RC, Shi YF. Mesenchymal Stem Cell-Mediated Immunosuppression Occurs via Concerted Action of Chemokines and Nitric Oxide. Cell Stem Cell (by Cell Press). 2008, 2:141-150.
  30. Ren G, Su J, Zhang L, Zhao X, Ling W, L'huillie A, Zhang J, Lu Y, Roberts AI, Ji W, Rabson AB, Shi YF. Species Variation in the Mechanisms of Mesenchymal Stem Cell-Mediated Immunosuppression. Stem Cells. 2009, 27:1954-1962.
  31. Zhang YY, Xu GW, Zhang LY, Roberts AI, Shi YF. Th17 Cells Undergo Fas-mediated Activation-induced Cell Independent of IFN-γ. J Immunol. 2008, 181:190-196.
  32. Das J, Eynott P, Van Kaer L, Das G* and Shi Y*. NKT cells and CD8+ T-cells are dispensable for T-cell dependent allergic airway inflammation. Nature Medicine. 2006, 12:1345-1346.
  33. Das G, Mittal J, Zhang YY, Bothwell A, Van Kare Luc, Shi YF. Pivotal Roles of Major Histocompatibility Complex Class Ib Restricted CD8+ T Cells in Autoimmune Diseases. J Exp Med. 2006, 203:2603-11.
  34. Devadas S, Das J, Liu C, Zhang L, Roberts AI, Pan Z, Moore PA, Das G, Shi Y. Granzyme B is critical for T cell receptor-induced cell death of Type 2 helper T cells. Immunity. 2006, 25:237-247.
  35. Yin D, Tuthill D, Mufson RA and Shi YF. Chronic restraint stress promotes lymphocyte apoptosis by modulating CD95 expression. J Exp Med. 2000, 191:1423-1428.
  36. Yin D, Mufson RA, Wang R and Shi YF. Fas-mediated cell death promoted by opioids. Nature. 1999, 397:218.
  37. Shi YF, Glynn JM, Guilbert LJ, Cotter TG, Bissonnette RP and Green DR. Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas. Science. 1992, 257:212-214. (with cover illustration)
  38. Shi YF, Sahai BM and Green DR. Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes. Nature. 1989, 339:625-626.
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