郑文婷 副研究员 肿瘤免疫细胞治疗及生物活性材料

原佳沛 副研究员 计算生物学与3D基因组学

王可飞 2021级博士研究生（南方医科大学临床医学学士）

黄文萱 2021级博士研究生（直博）（南京医科大学临床医学学士）

刘微 2021级硕士研究生（中山大学医学院临床医学学士）

陈连婷 2021级硕士研究生（南京医科大学临床医学学士）

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      癌症是威胁人类健康的重大疾病，免疫治疗是癌症治疗的一个前沿方向。然而，肿瘤具有的高度抑制性的免疫微环境限制了免疫治疗的效果，导致疗效差和患者生存率低等临床现状和科学问题。我们先前的研究工作以增强肿瘤免疫治疗效果为目标，以T细胞命运重编程和肿瘤区域免疫重构为切入点，对肿瘤微环境中T细胞功能状态的调控机制进行了深入研究，获得了具有原创特色的研究成果，鉴定出调控肿瘤微环境中抑制性Treg细胞及效应性CD8 T细胞功能状态的关键因子和信号通路，揭示了重构肿瘤免疫微环境及增强过继性T细胞治疗的新靶点，并且建立了基于CRISPR-Cas9基因编辑技术的小鼠体内高通量文库筛选方法，相关研究成果有望应用到临床肿瘤治疗中。      

      课题组将结合前期的研究基础、中国医学科学院血液病医院（中国医学科学院血液学研究所）优势的血液病学研究平台资源和临床资源以及国家需求，系统性的研究血液肿瘤（包括白血病，淋巴瘤及骨髓瘤等）微环境中免疫细胞命运与功能变化的调控机制，以及免疫细胞与肿瘤细胞及微环境基质细胞间的相互作用，最终为该类疾病研发拥有自主知识产权的新型免疫疗法和治疗靶点。

代表性论著：

1.     Lim SA#, Wei J#, Nguyen TM, Shi H, Su W, Palacios G, Dhungana Y, Chapman NM, Long L, Saravia J, Vogel P, Chi H. (2021) Lipid signalling enforces functional specialization of Treg cells in tumours. Nature, 591(7849):306-311. (#equal contribution) (Selected by News and Views, Nature, 591(7849):204-206, 2021; F1000 recommended article)

2.     Wei J, Zheng W, Chapman NW, Geiger TL, Chi H. (2021) T cell metabolism in homeostasis and cancer immunity. Current Opinion in Biotechnology, 68:240-250. (Invited review) 

3.     Wei J#, Long L#, Zheng W, Dhungana Y, Lim S, Guy C, Wang Y, Wang Y-D, Qian C, Xu B, KC A, Saravia J, Huang H, Yu J, Doench JG, Geiger TL, Chi H. (2019) Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy. Nature, 576(7787):471-476.  (#equal contribution) (Selected by News and Views, Nature, 576(7787):392-393, 2019; Selected by Research Highlights, Nature Reviews Drug Discovery, 19:91, 2020; Selected by Research Highlight, Nature Immunology, 21:103, 2020; F1000 recommended article)

4.     Wei J, Raynor J, Nguyen TL, Chi H. (2017) Nutrient and metabolic sensing in T cell responses. Frontiers in Immunology, 8:247. (Invited review) 

5.     Wei J, Long L, Yang K, Guy C, Shrestha S, Chen Z, Wu C, Vogel P, Neale G, Green DR, Chi H. (2016) Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis. Nature Immunology, 17(3):277-85. (Cover Story; Selected by Research Highlights, Nature Reviews Immunology, 16(4):203, 2016) 

6.     Wei J#, Yang K#, Chi H. (2014) Cutting edge: Discrete functions of mTOR signaling in invariant NKT cell development and NKT17 fate decision. The Journal of Immunology, 193(9):4297-4301. (#equal contribution) 

7.     Xia S#, Wei J#, Wang J, Sun H, Zheng W, Li Y, Sun Y, Zhao H, Zhang S, Wen T, Zhou X, Gao JX, Wang P, Wu Z, Zhao L, Yin Z. (2014) A requirement of dendritic cell-derived interleukin-27 for the tumor infiltration of regulatory T cells. Journal of Leukocyte Biology, 95(5):733-742. (#equal contribution) 

8.     Wei J#, Xia S#, Sun H, Zhang S, Wang J, Zhao H, Wu X, Chen X, Hao J, Zhou X, Zhu Z, Gao X, Gao JX, Wang P, Wu Z, Zhao L, Yin Z. (2013) Critical role of dendritic cell-derived IL-27 in antitumor immunity through regulating the recruitment and activation of NK and NKT cells. The Journal of Immunology, 191(1):500-8. (#equal contribution) 

9.     Wei J#, Wang H#, Zhu M, Ding D, Li D, Yin Z, Wang L, Yang Z. (2013) Janus nanogels of PEGylated Taxol and PLGA-PEG-PLGA copolymer for cancer therapy. Nanoscale, 5(20):9902-7. (#equal contribution) 

10.  Wang H#, Wei J#, Yang C, Zhao H, Li D, Yin Z, Yang Z. (2012) The inhibition of tumor growth and metastasis by self-assembled nanofibers of taxol. Biomaterials, 33(24):5848-53. (#equal contribution) 

11.  Zheng W, Wei J, Zebley C, Jones LL, Dhungana Y, Wang YD, Mavuluri J, Long L, Fan Y, Youngblood B, Chi H, Geiger TL. (2021) Regnase-1 suppresses TCF-1+ precursor exhausted T cell formation to limit CAR T cell responses against ALL. Blood, doi:10.1182/blood.2020009309

12.  Huang H#, Zhou P#, Wei J, Long L, Shi H, Dhungana Y, Chapman NM, Fu G, Saravia J, Raynor JL, Liu S, Palacios G, Wang YD, Qian C, Yu J, Chi H. (2021) In vivo CRISPR screening reveals nutrient signaling processes underpinning CD8 + T cell fate decisions. Cell, 184(5):1245-1261. (#equal contribution) 

13.  Su W, Chapman NW, Wei J, Zeng H, Dhungana Y, Shi H, Saravia J, Zhou P, Long L, Rankin S, Kc A, Vogel P, Chi H. (2020) Protein Prenylation Drives Discrete Signaling Programs for the Differentiation and Maintenance of Effector T reg Cells. Cell Metabolism, 32(6):996-1011.

14.  Wang Y, Du X, Wei J, Long L, Tan H, Guy C, Dhungana Y, Qian C, Neale G, Fu YX, Yu J, Peng J, Chi H. (2019) LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity. Cell Research, 29(5):391-405.

15.  Shrestha S, Yang K, Wei J, Karmaus PW, Neale G, Chi H. (2014) Tsc1 promotes the differentiation of memory CD8+ T cells via orchestrating the transcriptional and metabolic programs. Proc Natl Acad Sci U S A.,111(41):14858-63. 

16.  Zhang S, Liang R, Luo W, Liu C, Wu X, Gao Y, Hao J, Cao G, Chen X, Wei J, Xia S, Li Z, Wen T, Wu Y, Zhou X, Wang P, Zhao L, Wu Z, Xiong S, Gao X, Gao X, Chen Y, Ge Q, Tian Z, Yin Z. (2013) High susceptibility to liver injury in IL-27 p28 conditional knockout mice involves intrinsic interferon-γ dysregulation of CD4+ T cells. Hepatology, 57(4):1620-31.