天然免疫是人体免疫防御的第一道屏障,通过采用“模式识别受体”模式来识别病原体和自身异常的特异性分子,包括病原相关分子模式(PAMP)和损伤相关分子模式(DAMP)。中枢神经系统异常导致的应激和细胞的损伤,通过释放内源性损伤相关分子,介导一些列中枢神经系统疾病的发生和发展。近年来,胞质的DNA感知通路(cGAS-cGAMP-STING)的突破引起了广泛的关注,除了参与抗病毒反应,我们的前期研究首次鉴定DNA感知通路cGAS蛋白是参与体内无菌性炎症的重要分子(Nature, 2019; PNAS,2017),这一发现将众多重大疾病与天然免疫调控联系在一起,开启了研究多种人类疾病发病机制的全新视角,为疾病治疗提供新的线索,特别是神经系统疾病,包括神经退行性疾病、脑卒中、肿瘤等。同时,我们发现代谢物可以作为“信号分子“的非经典代谢功能(Cancer Cell,2011;Cell Research,2014),调控免疫细胞的分化(Nature Metabolism,2022),开启了代谢与免疫互作调控研究的新方向。我们关注免疫,代谢和中枢神经细胞的互作,整合复旦大学附属华山医院神经系统疾病的临床资源,将通过单细胞测序和CRISPR技术,结合经典的分子生物学和实验动物模型,以神经退行性疾病、肿瘤等重大脑疾病为载体,主要研究以下几个问题:
1. 天然免疫识别、活化和炎症发生的分子与细胞机制,
2. 无菌性炎症的神经-免疫-代谢的互作和调控机制,
3. 神经系统疾病的异质性解析,
4. 无菌炎症性脑疾病的药物发现和转化研究,
5. 基于免疫和代谢干预的脑肿瘤转化研究。
Xiaoyue Gao, Qiyuan Zhuang, Yun Li, Guochao Li, Zheng Huang, Shenzhi Chen, Shaoxing Sun, Hui Yang#, Lan Jiang#, Ying Mao#. Single‐Cell Chromatin Accessibility Analysis Reveals Subgroup‐Specific TF‐NTR Regulatory Circuits in Medulloblastoma . Advanced Science, 2024:e2309554
Qiyuan Zhuang, Ying Liu, Hanze Wang, Ziyang Lin, Li Sun, Yue Liu, Yingying Lyu, Liang Chen, Hui Yang#, Ying Mao#, LILRB3 suppresses immunity in glioma and is associatedwith poor prognosis. Clinical and Translational Medicine, 2023 Oct;13(10):e1396
Qi Fan, Hanze Wang, Tianyi Gu, Huihui Liu, Peng Deng, Bo Li, Hui Yang#, Ying Mao#, Zhicheng Shao#.Modeling the precise interaction of glioblastoma with human brain region-specific organoids. iScience, 2024 Feb 5;27(3):109111
Qi Liu, Fangming Zhu, Xinnan Liu,., Hui Yang#, Bin Li# and Xuemei Tong#, Non-oxidative pentose phosphate pathway controls regulatory T cell function by integrating metabolism and epigenetics. Nature Metabolism, 2022, 4:559–574. (#corresponding author).
News & Views: TKT deficiency puts Tregs to rest (Nature Metabolism)
Xiang Gui*, Hui Yang*, Tuo Li, Xiaojun Tan, Peiqing Shi, Minghao Li, Fenghe Du & Zhijian J. Chen. Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature, 2019, 567: 262–266. (*Contribute equally) , ESI高被引论文(1%), Highlighted by: Nature, Nature Reviews Molecular Cell Biology. Selected by: Faculty of 1000.
Hui Yang, Hanze Wang, Junyao Ren, Qi Chen, and Zhijian J. Chen. cGAS is Essential for Cellular Senescence. PNAS, 2017, 114(23):E4612-E4620. ESI高被引论文(1%),Highlighted by: Nature, Immunity, Nature Cell Biology.
Wei Xu*, Hui Yang*, Ying Liu*, Ying Yang, Ping Wang, Se-Hee Kim, Shinsuke Ito, Chen Yang, Pu Wang, Meng-Tao Xiao, Li-xia Liu, Wen-qing Jiang, Jing Liu, Jin-ye Zhang, Bin Wang, Stephen Frye, Yi Zhang, Yan-hui Xu, Qun-ying Lei, Kun-Liang Guan, Shi-min Zhao, and Yue Xiong. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011,19:17 (* Contribute equally, Cover story) , ESI高被引论文(1%), Selected by: Faculty of 1000
Hao Lin, Chaxian Liu, Ankang Hu, Duanwu Zhang, # Hui Yang#, Ying Mao#. Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives. Journal of Hematology & Oncology, 2024 May 8;17(1):31
Qiyuan Zhuang, Hui Yang#, Ying Mao#.The oncogenesis of glial cells in diffuse gliomas and clinical opportunities. Neuroscience Bulletin, 2023 Mar;39(3):393-408
Yingying Lyu, Hui Yang#, Liang Chen#,. Metabolic regulation on the immune environment of glioma through gut microbiota. Seminars in Cancer Biology, 2021 May 7; S1044-579. (#corresponding author)
Yang, Hui. Beutler, Beutler. & Zhang, Duanwu. Emerging roles of spliceosome in cancer and immunity. Protein Cell .2021. https://doi.org/10.1007/s13238-021-00856-5
Ankang Hu, Li Sun, Hao Lin, Yuheng Liao, Hui Yang#, Ying Mao#. Harnessing innate immune pathways for therapeutic advancement in cancer. Signal Transduction and Targeted Therapy, 2024 Mar 25;9(1):68
Hui Yang*, Lisha Zhou*, Yuzheng Zhao, Yi Yang, Yue Xiong, Dan Ye, and Kun-Liang Guan. SIRT3-dependent GOT2 acetylation status affects the malate–aspartate NADH shuttle activity and pancreatic tumor growth. EMBO Journal, 2015, 34: 1110. (*Contribute equally)
Hui Yang, Huaipeng Lin, Haiyan Xu, Lei Zhang, Lu Cheng, Bo Wen, Jianyong Shou, Kun-Liang Guan, Yue Xiong, and Dan Ye. TET-catalyzed 5-methylcytosine hydroxylation is dynamically regulated by metabolites. Cell Research. 2014,24:1017
Hui Yang#, Yingying Lyu, Fajian Hou#. SARS-CoV-2 infection and the antiviral innate immune response. Journal of Molecular Cell Biology, DOI:10.1093/jmcb/mjaa071. (#corresponding author).
地址: 上海市徐汇区医学院路138号科研2号楼二楼
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电话/传真: 021-54237056
邮箱: hui_yang@fudan.edu.cn