Innate immunity is the first barrier of the body's immune defense system.It recognizesforeignpathogensoroneself’sabnormal molecules by using aseries ofpattern recognition receptors. And those corresponding pathogenic molecules are calledpathogen-associated molecular patterns (PAMP) and damage-associated molecule patterns (DAMP). Stress and cellular damageinduced by CNS abnormalitiesare often associated withthe onset and progression of several CNS diseases, which are caused bythe release of endogenous damage-associated molecules. In recent years, thediscovery andbreakthrough of the cytoplasmic DNA sensing pathway (cGAS-cGAMP-STING)haveattracted widespread attention. In addition to itsrolesin antiviral responses, our previous studiesfirstidentified theDNA-sensorcGAS asanimportantproteininvolved in chronic inflammation in vivo (Nature, 2019; PNAS,2017). Thisfindingreveals thatnumeroushumandiseasesare regulated by innateimmunity, opening a new perspective to study the pathogenesis of many human diseases and providing new clues for disease treatment, especiallyforneurological diseases, including neurodegenerative diseases, stroke, andbraintumors. At the same time, we discoveredthe non-classical functions of themetabolites(Cancer Cell, 2011; Cell Research, 2014), whichcanalsofunction as "signaling molecules" to regulate the differentiation of immune cells (Nature Metabolism, 2022). This findingopensup a new directionfor the study ofmetabolism-immune interplay. We focus on the interactions between immunityandmetabolisminimmunesystem and neuron system. Byintegratingclinical resources of neurological diseases in Huashan Hospital of Fudan University,single-cellsequencing and CRISPR technology,alongwithusingexperimental animal models,neurodegenerative diseasemodels or tumor models, we hope to address thefollowing questions:
1.The molecular and cellular mechanisms ofinnateimmune recognition, activation and inflammationresponses.
2.Theinteractions amongneuro-immune-metabolismandtheregulatory mechanisms of chronic inflammation.
3.Heterogeneousanalysisof neurological disorders.
4.Drug discovery and translational research inchronic inflammatory brain diseases.
5.Translational studies of brain tumors based on immune and metabolic interventions.
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.
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).