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王金勇 研究员

血液/免疫再生与转化研究组

欢迎您的加入血液/免疫再生与转化研究组!
- 工作人员:王金勇、王童洁、朱艳平、刘丽娟
- 博士后:黄德浩、张琪、翁启童 刘艳红
- 研究生:吴冰燕、彭欢、熊佳品、李剑焕、王瑶、郑秀娟、林云轻、王智乾、肖子芸、张帆、吴嘉欣

 

 

  多能干细胞来源的再生型血液/免疫细胞,因兼具基因精准预编辑、无限来源、现货式、广谱等特点,是自体或异体细胞无法替代、 面向未来的新型细胞药物。

  研究组主要从事血液/免疫细胞再生核心技术的研发及转化应用。利用人多能干细胞,通过小分子、细胞因子、环境滋养细胞等构建诱导微环境、结合类器官培养技术,体外再生血液/免疫细胞种子、性能特化或增强的末端成熟细胞。利用特定动物模型,尝试异种人源化免疫细胞体内再生。进一步利用商业化肿瘤细胞系及PDX动物模型探索再生型血液/免疫细胞治疗疾病的能力。最终,开发建立血液/免疫细胞(包括NK,T,B,单核/粒,造血多谱系等细胞)再生技术体系,为细胞疗法临床转化和应用提供技术支撑。



图1. 转录因子Hoxb5体内将B细胞重编程为T细胞,实现体内抗肿瘤



图2. 多能干细胞定向再生T细胞,实现体内抗肿瘤



图3. 间充质干细胞修复骨髓微环境,遏制白血病

 

 

研究内容和目标:
我组主要从事多能干细胞诱导分化获得可移植的血液以及免疫细胞种子、体外模拟发育微环境获得成熟血液及免疫细胞、细胞疗法与抗肿瘤新技术开发等研究。

 

代表性发表论文:

  1. Huang, D., Zhao, Q., Zhang, M., Weng, Q., Zhang, Q., Wang, K., Dong, F., Cheng, H., Hu, F., Wang, J., Hoxb5 reprogrammes murine multipotent blood progenitors into haematopoietic stem cell-like cells. Cell Proliferation, 2022.
  2. Zhang, Q., Wu, B., Weng, Q., Hu, F., Lin, Y., Xia, C., Peng, H., Wang, Y., Liu, X., Liu, L.Xiong, J., Geng, Y., Zhao, Y., Zhang, M., Du, J., Wang, J., Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors. Cell Mol Immunol, 2022. 19(4): p. 492-503.
  3. Wang, T., Xia, C., Weng, Q., Wang, K., Dong, Y., Hao, S., Dong, F., Liu, X., Liu, L., Geng, Y., Guan, Y., Du, J., Cheng, T., Cheng, H., Wang, J. Loss of Nupr1 promotes engraftment by tuning the quiescence threshold of hematopoietic stem cell repository via regulating p53-checkpoint pathway. Haematologica, 2022 Jan 1;107(1):154-166.
  4. Wang, T., Lv, C., Hu, F., Liu, L., Wang, J. (2020) Two-step protocol for regeneration of immunocompetent T cells from mouse pluripotent stem cells. Blood Science 2, 79-88.
  5. Guo, R., Wu, H., Du, J., Wang, J. (2020) T cell regeneration: an update on progress and challenges. Blood Science 2, 22-26.
  6. Hu, F., Huang, D., Luo, Y., Zhou, P., LV, C., Wang, K., Weng, Q., Liu, X., Guan Y., Geng, Y., Du, J., Chen J., Wang, J., and Wu, H. (2020) Haematopoietic lineage-converted T cells carrying tumour associated antigen-recognizing TCRs effectively kill tumour cells. Journal for ImmunoTherapy of Cancer, DOI: 10.1136/jitc-2019-000498.
  7. LV, C., Chen, S., Hu, F., Huang, D., Wang, T., Du, J., Wang, J., and Wu, H. (2020) Pluripotent stem cell-derived CD19-CAR iT cells effectively eradicate B-cell lymphoma in vivo. Cellular & Molecular Immunology, DOI: 10.1038/s41423-020-0429-4.
  8. Xia, C., Wang, T., Cheng, H., Dong, Y., Weng, Q., Sun, G., Zhou, P., Wang, K., Liu, X., Geng, Y., Ma, S., Hao, S., Xu, L., Guan, Y., Du, J., Du, X., Li, Y., Zhu, X., Shi, Y., Xu, S., Wang, D., Cheng, T., and Wang, J. (2020) Mesenchymal stem cells suppress leukemia via macrophage-mediated functional restoration of bone marrow microenvironment. Leukemia, 34(9):2375-2383.
  9. Guo, R., Hu, F., Weng, Q., Lv, C., Wu, H., Liu, L., Li, Z., Zeng, Y., Bai, Z., Zhang, M., Liu, Y., Liu, X., Xia, C., Wang, T., Zhou, P., Wang, K., Dong, Y., Luo, Y., Zhang, X., Guan, Y., Geng, Y., Du, J., Li, Y., Lan, Y., Chen, J., Liu, B., and Wang, J. (2020) Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors. Cell Research 30, 21-33.
  10. Weng, Q., Hu, F., Zhang, M., Dong, Y., Lv, C., Wang, Y., Liu, X., Wang, J. (2018) A protocol for generating induced T cells by reprogramming B cells in vivo. Cell Regeneration 7, 7-15.
  11. Zhang, M., Dong, Y., Hu, F., Yang, D., Zhao, Q., Lv, C., Wang, Y., Xia, C., Weng, Q., Liu, X., Li, C., Zhou, P., Wang, T., Guan, Y., Guo, R., Liu, L., Geng, Y., Wu, H., Du, J., Hu, Z., Xu, S., Chen, J., He, A., Liu, B., Wang, D., Yang, Y. G., and Wang, J. (2018) Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes. Nat Immunology 19, 279-290.
  12. Li, X., Xia, C., Wang, T., Liu, L., Zhao, Q., Yang, D., Hu, F., Zhang, M., Huang, K., Geng, Y., Zheng, Y., Guan, Y., Wu, H., Chen, X., Pan, G., Chen, J., Du, J., and Wang, J. (2017) Pyrimidoindole derivative UM171 enhances derivation of hematopoietic progenitor cells from human pluripotent stem cells. Stem Cell Research 21, 32-39.
  13. Chen, X., Zhao, Q., Li, C., Geng, Y., Huang, K., Zhang, J., Wang, X., Yang, J., Wang, T., Xia, C., Liu, X., Meng, M., Yang, D., Zheng, Y., Du, J., Zhang, X., Chen, J., Pan, G., and Wang, J. (2015) OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo. Stem Cell Research 15, 395-402.
  14. Yang, D., Zhang, X., Dong, Y., Liu, X., Wang, T., Wang, X., Geng, Y., Fang, S., Zheng, Y., Chen, X., Chen, J., Pan, G., and Wang, J. (2015) Enforced expression of Hoxa5 in haematopoietic stem cells leads to aberrant erythropoiesis in vivo. Cell Cycle 14, 612-620.
  15. Wang, T., Li, C., Xia, C., Dong, Y., Yang, D., Geng, Y., Cai, J., Zhang, J., Zhang, X., and Wang, J. (2015) Oncogenic NRAS hyper-activates multiple pathways in human cord blood stem/progenitor cells and promotes myelomonocytic proliferation in vivo. Am J Transl Res 7, 1963-1973.
  16. Wang, J., Kong, G., Liu, Y., Du, J., Chang, Y. I., Tey, S. R., Zhang, X., Ranheim, E. A., Saba-El-Leil, M. K., Meloche, S., Damnernsawad, A., Zhang, J., and Zhang, J. (2013) Nras(G12D/+) promotes leukemogenesis by aberrantly regulating hematopoietic stem cell functions. Blood 121, 5203-5207.
  17. Wang, J., Liu, Y., Li, Z., Wang, Z., Tan, L. X., Ryu, M. J., Meline, B., Du, J., Young, K. H., Ranheim, E., Chang, Q., and Zhang, J. (2011) Endogenous oncogenic Nras mutation initiates hematopoietic malignancies in a dose- and cell type-dependent manner. Blood 118, 368-379.
  18. Wang, J., Liu, Y., Li, Z., Du, J., Ryu, M. J., Taylor, P. R., Fleming, M. D., Young, K. H., Pitot, H., and Zhang, J. (2010) Endogenous oncogenic Nras mutation promotes aberrant GM-CSF signaling in granulocytic/monocytic precursors in a murine model of chronic myelomonocytic leukemia. Blood 116, 5991-6002.