研究组长

1994 - 1998    北京大学生命科学学院生物技术系，学士

1998 - 2003    中国医学科学院基础医学研究所，博士

2004 - 2008    芝加哥大学病理系，博士后

2009          芝加哥大学病理系，研究助理教授

2009.10 至今   中国科学院生物物理研究所，研究员

2015.10 至今   中国科学院大学生命科学学院，岗位教授

淋巴组织微环境与T淋巴细胞的发育和功能

1. 淋巴器官的发育和功能

淋巴器官是免疫系统中最基本的组织结构之一。在淋巴器官中，各种基质细胞（上皮细胞、内皮细胞、成纤维细胞等）形成丰富多样、复杂有序的免疫微环境，对于各种免疫细胞的发育和功能至关重要。我们利用多种基因工程小鼠，围绕胸腺、淋巴结、肠道相关淋巴组织等典型淋巴器官，研究它们的发育、稳态和重塑的细胞和分子机制，研究淋巴器官中重要基质细胞的发育分化和稳态平衡的细胞和分子机制，研究淋巴器官各种微环境对免疫细胞（特别是T细胞）发育、分化、稳态、活化、迁移等各种行为的影响和作用机制，揭示淋巴器官微环境在自身免疫、感染免疫和肿瘤免疫等方面的生理和病理意义。

2. T细胞的发育和功能

T细胞是机体适应性免疫应答的重要组成部分。T细胞的发育分化、稳态平衡、应答响应、免疫记忆等行为，受到免疫微环境（外因）与T细胞自身（内因）多方面因素的调控。除了从免疫微环境的角度研究T细胞发育和功能的外在调控机制，我们还从表观遗传的角度，研究T细胞发育和功能的内在调控机制，研究淋巴器官微环境外部信号与T细胞内在表观遗传调控的关系，揭示其生理和病理意义。

3. 疫苗免疫学

疫苗是人为操纵机体免疫系统功能的重要方式之一，既是推动免疫学理论发展的有力工具，也是免疫学理论研究的转化应用载体。我们一方面以肿瘤和重大传染性疾病为对象，致力于新型治疗性疫苗的研发；另一方面以疫苗为模型，探索淋巴器官微环境和表观遗传因素对T细胞免疫应答和免疫记忆的影响和调控机制，为疫苗研发提供新思路。

1. Zhu, M.* Immunological perspectives on spatial and temporal vaccine delivery. Adv Drug Deliv Rev. 178, 113966. (2021)

2. Duan, H., Jing, L., Jiang, X., Ma, Y., Wang, D., Xiang, J., Chen, X., Wu, Z., Yan, H., Jia, J., Liu, Z., Feng, J., Zhu, M.*, and Yan, X.* CD146 bound to LCK promotes TCR signaling and anti-tumor immune response in mice. J Clin Invest. 131(21):e148568. (2021)

3. Xia, H., Zhong, S., Zhao, Y., Ren, B., Wang, Z., Shi, Y., Chai, Q., Wang, X.*, and Zhu, M.* Thymic Egress Is Regulated by T Cell-Derived LTβR Signal and via Distinct Thymic Portal Endothelial Cells. Front Immunol. 12, 707404. (2021)

4. Wang, W., Huang, B., Zhu, Y., Tan, W.*, and Zhu, M.* Ferritin nanoparticle-based SARS-CoV-2 RBD vaccine induces a persistent antibody response and long-term memory in mice. Cell Mol Immunol. 18, 749-751. (2021)

5. Wang, W., Zhou, X., Bian, Y., Wang, S., Chai, Q., Guo, Z., Wang, Z., Zhu, P., Peng, H., Yan, X., Li, W., Fu, Y-X., Zhu, M.* Dual-targeting nanoparticle vaccine elicits a therapeutic antibody response against chronic hepatitis B. Nature Nanotechnology 15:406-416. (2020)

6. Long, H., Zhang, L., Lv, M., Wen, Z., Zhang, W., Chen, X., Zhang, P., Li, T., Chang, L., Jin, C., Wu, G., Wang, X., Yang, F., Pei, J., Chen, P., Margueron, R., Deng, H., Zhu, M.*, and Li, G.* H2A.Z facilitates licensing and activation of early replication origins. Nature 577, 576-581. (2020)

7. Pian, Y., Chai, Q., Ren, B., Wang, Y., Lv, M., Qiu, J., Zhu, M.* Type 3 Innate Lymphoid Cells Direct Goblet Cell Differentiation via the LT-LTβR Pathway during Listeria Infection. J Immunol 205:853-863. (2020)

8. Wang, Z., Wang, W., Chai, Q., and Zhu, M.* Langerhans cells control lymphatic vessel function during inflammation via LIGHT-LTβR signaling. J Immunol 202, 2999-3007. (2019)

9. Wang, W., Liu, Z., Zhou, X., Guo, Z., Zhang, J., Zhu, P., Yao, S., and Zhu, M.* Ferritin nanoparticle-based SpyTag/SpyCatcher-enabled click vaccine for tumor immunotherapy. Nanomedicine 16, 69-78. (2019)

10. Wang, Z., Chai, Q.*, and Zhu, M.* Differential roles of LTbetaR in endothelial cell subsets for lymph node organogenesis and maturation. J Immunol 201, 69-76. (2018)

11. Liu, X., Liu, L., Ren, Z., Yang, K., Xu, H., Luan, Y., Fu, K., Guo, J., Peng, H., Zhu, M.*, and Fu, Y. X.* Dual targeting of innate and adaptive checkpoints on tumor cells limits immune evasion. Cell Rep 24, 2101-2111. (2018)

12. Jin, C., and Zhu, M.* RelB intrinsically regulates the development and function of medullary thymic epithelial cells. Science China Life Sciences 61(9):1039-1048. (2018)

13. Jin, L., Guo, X., Shen, C., Hao, X., Sun, P., Li, P., Xu, T., Hu, C., Rose, O., Zhou, H., Yang, M., Qin, C.-F., Guo, J., Peng, H., Zhu, M., Cheng, G., Qi, X., and Lai, R. Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-β receptor. Nature Immunology 19, 342-353. (2018)

14. Liu, Z., Zhou, C., Qin, Y., Wang, Z., Wang, L., Wei, X., Zhou, Y., Li, Q., Zhou, H., Wang, W., Fu, Y.-X.*, Zhu, M.*, and Liang, W.* Coordinating antigen cytosolic delivery and danger signaling to program potent cross-priming by micelle-based nanovaccine. Cell Discovery 3, 17007. (2017)

15. Wu, W., Shi, Y., Xia, H., Chai, Q., Jin, C., Ren, B., and Zhu, M.* Epithelial LTbetaR signaling controls the population size of the progenitors of medullary thymic epithelial cells in neonatal mice. Scientific reports 7, 44481. (2017)

16. Tang, H., Zhu, M., Qiao, J., Fu, YX. Lymphotoxin signaling in tertiary lymphoid structures and immunotherapy. Cell Mol Immunol 14(10):809-818. (2017)

17. Shi, Y., Wu, W., Chai, Q., Li, Q., Hou, Y., Xia, H., Ren, B., Xu, H., Guo, X., Jin, C., Lv, M., Wang, Z., Fu, Y., and Zhu, M.* LTbetaR controls thymic portal endothelial cells for hematopoietic progenitor cell homing and T cell regeneration. Nature Communications 7, 12369. (2016)

18. Liu, Z., Zhou, H., Wang, W., Fu, Y.-X., and Zhu, M.* A novel dendritic cell targeting HPV16 E7 synthetic vaccine in combination with PD-L1 blockade elicits therapeutic antitumor immunity in mice. OncoImmunology 5, e1147641. (2016)

19. Lv, M., Wu, W., Zhang, Y., and Zhu, M.* Herpes virus entry mediator licenses Listeria infection induced immunopathology through control of type I interferon. Scientific reports 5, 12954. (2015)

20. Liu, Z., Zhou, H., Wang, W., Tan, W., Fu, Y. X., and Zhu, M.* A novel method for synthetic vaccine construction based on protein assembly. Scientific reports 4, 7266. (2014)

21. Shi, Y., and Zhu, M.* Medullary thymic epithelial cells, the indispensable player in central tolerance. Sci China Life Sci 56, 392-398. (2013)

22. Zhu, M.*, and Fu, Y. Proinflammatory IL-17 induces iBALT development. Cell Mol Immunol 9, 101-102. (2012)

23. Zhu, M.*, Yang, Y., Wang, Y., Wang, Z., and Fu, Y.-X. LIGHT regulates inflamed draining lymph node hypertrophy. J Immunol 186, 7156-7163. (2011)

24. Zhu, M., and Fu, Y.-X. The role of core TNF/LIGHT family members in lymph node homeostasis and remodeling. Immunol Rev 244, 75-84. (2011)

25. Zhu, M.*, and Fu, Y.-X.* Deflating the Lymph Node. Immunity 34, 8-10. (2011)

26. Zhu, M.*, and Fu, Y. The complicated role of NF-kappaB in T-cell selection. Cell Mol Immunol 7, 89-93. (2010)

27. Zhu, M.*, Brown, N. K., and Fu, Y.-X.* Direct and indirect roles of the LT[beta]R pathway in central tolerance induction. Trends in Immunology 31, 325-331. (2010)

28. Wang, Y., Zhu, M., Yu, P., and Fu, Y. X. Promoting immune responses by LIGHT in the face of abundant regulatory T cell inhibition. J Immunol 184, 1589-1595. (2010)

29. Zhou, P., Fang, X., McNally, B. A., Yu, P., Zhu, M., Fu, Y. X., Wang, L., Liu, Y., and Zheng, P. Targeting lymphotoxin-mediated negative selection to prevent prostate cancer in mice with genetic predisposition. Proc Natl Acad Sci U S A 106, 17134-17139. (2009)

30. Wang, Y., Zhu, M., Miller, M., and Fu, Y. X. Immunoregulation by tumor necrosis factor superfamily member LIGHT. Immunol Rev 229, 232-243. (2009)

31. Zhu, M.*, and Fu, Y. X.* Coordinating development of medullary thymic epithelial cells. Immunity 29, 386-388. (2008)

32. Zhu, M., Chin, R. K., Tumanov, A. V., Liu, X., and Fu, Y. X. Lymphotoxin beta receptor is required for the migration and selection of autoreactive T cells in thymic medulla. J Immunol 179, 8069-8075. (2007)

33. Li, J., Li, Y., Yao, J. Y., Jin, R., Zhu, M. Z., Qian, X. P., Zhang, J., Fu, Y. X., Wu, L., Zhang, Y., and Chen, W. F. Developmental pathway of CD4+CD8- medullary thymocytes during mouse ontogeny and its defect in Aire-/- mice. Proc Natl Acad Sci U S A 104, 18175-18180. (2007)

34. Zhu, M., Chin, R. K., Christiansen, P. A., Lo, J. C., Liu, X., Ware, C., Siebenlist, U., and Fu, Y. X. NF-kappaB2 is required for the establishment of central tolerance through an Aire-dependent pathway. J Clin Invest 116, 2964-2971. (2006)

35. Chin, R. K.^#, Zhu, M.^#, Christiansen, P. A., Liu, W., Ware, C., Peltonen, L., Zhang, X., Guo, L., Han, S., Zheng, B., and Fu, Y. X. Lymphotoxin pathway-directed, autoimmune regulator-independent central tolerance to arthritogenic collagen. J Immunol 177, 290-297. (2006)

（资料来源：朱明昭研究员，2021-12-24）