王晨辉

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王晨辉,教授,博士生导师,国家海外高层次人才青年项目获得者。实验室近年来主要从事癌症和感染性疾病的分子检验和治疗靶标研究。通过研究,发现了BTNL2TAGAPEPHB2DOCK2ACE2RNF186等一系列用于疾病诊断和治疗的分子靶标,并阐释了这些分子在疾病中发挥的作用和机制。另外,不断推动基础研究成果向临床应用转化推进,针对ACE2BTNL2的基因工程抗体有望进入临床试验。近五年来以通讯作者或共同通讯作者在Nature Communications4篇),PNAS1篇),Cellular and Molecular Immunology1篇),Autophagy1篇),J Immunol2篇)著名学术期刊发表学术论文9篇。所有论文一共引用1500余次,单篇最高引用242次(Google引用)。美国免疫学家协会会员(AAI member)。2016年入选中组部高层次人才青年项目。近五年来,获得了自然科学基金委原创探索计划项目、面上项目、中组部青年人才项目、科技部重点研发计划项目子课题等多个国家以及省部级科研项目资助。国家自然科学基金二审评委。国家重点研发计划评审专家。


主要研究成果

1)感染性疾病分子靶标研究:发现分子TAGAP在抗真菌免疫以及T细胞分化中的作用机制(Nature Communications, 2020年);发现分子EPHB2是人巨噬细胞表面一个识别真菌成分的受体(Journal of Immunology, Cutting Edge, 2021年);发现分子MYO1F参与抗真菌免疫的机制,并为抗真菌感染提供了小分子抑制剂前药PNAS,2021);联合中科院微生物所、国家疾病预防控制中心、国家食品药品检定研究院、上海君实生物制作出针对新冠病毒受体ACE2的人源化广谱基因工程抗体抑制剂,并进入临床前测试(nature communications, 2021);发现DOCK2分子参与真菌感染性疾病的作用机制(Cellular and Molecular Immunology, 2022)。

2)自身免疫疾病分子靶标研究:发现分子Act1的一个突变导致银屑病的分子机制,并为银屑病的治疗提供了靶点(Nature Immunology, 2013年);发现T细胞中炎症小体的激活机制,并为多发性硬化症提供了新的治疗靶点Nature Immunology, 2016年);发现NOTCH激活在IL-17信号通路以及多发性硬化症中的作用机制,并为多发性硬化症提供了多肽类前药(Nature Communications, 2017年);发现分子Act1T细胞中的负调控作用,并为狼疮肾炎提供了治疗靶点Nature Communications, 2018年);发现分子RNF186导致溃疡性结肠炎的分子机制,并为溃疡性结肠炎的治疗提供了靶点和前药(Autophagy, 2020年);发现长链非编码RNA-TRAF3IP2-AS1导致银屑病易感性的作用机制Journal of Immunology, 2021年)

3) 抗肿瘤分子靶标研究:发现BTNL2是肺腺癌一个新的诊断和治疗靶标Nature Communications, 2022年)


学习和工作经历(按时间倒叙):

2015.9-至今   华中科技大学生命科学与技术学院     教授

2010.11-2015.9     克利夫兰医学中心免疫系              博士后        导师:李晓霞

2007.9-2010.7       军事医学科学院     细胞生物学     博士学位    导师:张学敏

2004.9-2007.7       军事医学科学院     细胞生物学     硕士学位    导师:张学敏

 

实验室研究方向:

1)感染性疾病的分子靶标研究(真菌、病毒感染性疾病);

2)自身免疫疾病分子靶标研究(主要研究多发性硬化症、炎症性肠病等自身免疫疾病);

3)肿瘤免疫新分子靶标研究。


论文发表(回国后)

2022

(1)  Yanyun Du#, Qianwen Peng#, Du Cheng, Ting Pan, Wanwei Sun, Heping Wang, Xiaojian Ma, Ruirui He, Huazhi Zhang, Zhihui Cui, Xiong Feng, Zhiqiang Liu, Tianxin Zhao, Wenjun Hu, Lei Shen, Wenyang Jiang, Na Gao, Bradley N. Martin, Cun-Jin Zhang, Zhanguo Zhang, Chenhui Wang*. Cancer cell-expressed BTNL2 facilitates tumour immune escape via engagement with IL-17A-producing γδ T cells. Nature Communications, 2022 Jan 11;13(1):231.

(2) Xiaojian Ma#, Xi Tan#, Bingbing Yu#, Wanwei Sun#, Heping Wang, Huijun Hu, Yanyun Du, Ruirui He, Ru Gao, Qianwen Peng, Zhihui Cui, Ting Pan, Xiong Feng, Junhan Wang, Chengqi Xu, Bin Zhu*, Wei Liu*, Chenhui Wang*. DOCK2 regulates antifungal immunity through regulating RAC GTPase activity. Cell Mol Immunol. 2022 Jan 25:1-17.

(3) Chen L, Zhou C, Chen Q, Shang J, Liu Z, Guo Y, Li C, Wang H, Ye Q, Li X, Zu S, Li F, Xia Q, Zhou T, Li A, Wang C, Chen Y, Wu A, Qin C, Man J. Oncolytic Zika virus promotes intratumoral T cell infiltration and improves immunotherapy efficacy in glioblastoma. Mol Ther Oncolytics. 2022 Feb 1;24:522-534.

(4) Cao R, Li Z, Wu C, Ji S, Li Y, Cao X, Dong X, Jiang M, Pang T, Wang C, Li J, Xu Y, Zhang CJ*Identification of a Small Molecule with Strong Anti-Inflammatory Activity in Experimental Autoimmune Encephalomyelitis and Sepsis through Blocking Gasdermin D Activation. J Immunol. 2022 Aug 15;209(4):820-828. 

(5) Huazhi Zhang#Zhihui Cui#, Ting Pan#, Huijun Hu#, Ruirui He, Ming Yi, Wanwei Sun, Ru Gao, Heping Wang, Xiaojian Ma, Qianwen Peng, Xiong Feng, Shuyan Liang, Yanyun Du*, Chenhui Wang*RNF186/EPHB2 Axis Is Essential in Regulating TNF Signaling for Colorectal Tumorigenesis in Colorectal Epithelial Cells. J Immunol. 2022. In press


2021年:

(1)    Wanwei Sun#*, Xiaojian Ma#, Heping Wang, Yanyun Du, Jianwen Chen, Huijun Hu, Ru Gao, Ruirui He, Qianwen Peng, Zhihui Cui, Huazhi Zhang, Junhan Wang, Xinming Jia, Bradley N. Martin, Cun-Jin Zhang*, Xiaoxia Li, Chenhui Wang*MYO1F regulates anti-fungal immunity by regulating acetylation of microtubules. PNAS. 2021 Jul 27;118(30):e2100230118;

(2)    Du Y#, Shi R#, Zhang Y#, Duan X, Li L, Zhang J, Wang F, Zhang R, Shen H, Wang Y, Wu Z, Peng Q, Pan T, Sun W, Huang W, Feng Y, Feng H, Xiao J, Tan W*, Wang Y*Wang C*, Yan J*. A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants. Nat Commun. 2021 Aug 17;12(1):5000 (co-corresponding author).

(3)    Wanwei Sun#; Heping Wang#; Huijun Hu; Xiaojian Ma; Huazhi Zhang; Jianwen Chen; Yanyun Du; Ruirui He; Zhihui Cui; Qianwen Peng; Chenhui Wang*; Cutting Edge: EPHB2 is a co-receptor for fungal recognition and phosphorylation of Sykin the dectin-1 signaling pathway, J Immunol. 2021 Apr 1;206(7):1419-1423. 

(4)    Ruirui He#, Songfang Wu#, Ru Gao#, Jianwen Chen, Qianwen Peng, Huijun Hu, Liwen Zhu, Yanyun Du, Wanwei Sun, Xiaojian Ma, Huazhi Zhang, Zhihui Cui, Heping Wang, Bradley N. Martin, Yueying Wang*, Cun-jin Zhang*Chenhui Wang*; Identification of a LncRNA TRAF3IP2-AS1 as key regulator of IL-17 signaling through the SRSF10-IRF1-Act1 axis in autoimmune diseases. J Immunol. 2021, 206 (10) 2353-2365.


2020年:

(1)    Chen, Jianwen#; He, Ruirui#; Sun, Wanwei*; Gao, Ru; Peng, Qianwen; Zhu, Liwen; Du, Yanyun; Ma, Xiaojian; Guo, Xiaoli; Zhang, Huazhi; Tan, Chengcheng; Wang, Junhan; Zhang, Wei; Weng, Xiufang; Man, Jianghong; Bauer, Hermann; Wang,Qing K.; Martin, Bradley N.; Zhang, Cun-Jin*; Li, Xiaoxia; Wang, Chenhui*; TAGAP instructs Th17 differentiation by bridging Dectin activation to EPHB2 signaling in innate antifungal response, Nature Communications, 2020 Apr 20;11(1):1913.

(2)    Zhang, Huazhi#; Cui, Zhihui#; Cheng, Du; Du, Yanyun; Guo, Xiaoli; Gao, Ru; Chen, Jianwen; Sun, Wanwei; He, Ruirui; Ma, Xiaojian; Peng, Qianwen;Martin, Bradley N; Yan, Wei; Rong, Yueguang*Wang, Chenhui*; RNF186 regulates EFNB1 (ephrin B1)-EPHB2-induced autophagy in the colonic epithelial cells forthe maintenance of intestinal homeostasis., Autophagy, 2020, Dec(17): 1-18.

(3) Liu, Zhuo; Zhu, Liwen; Lu, Zhengjuan; Chen, Huiping; Fan, Lizhen; Xue,Qun; Shi, Jianquan; Li, Meiying; Li, Hui; Gong, Jie; Shi, Jingping; Wang, Tao;Jiang, Mei-Ling; Cao, Runjing; Meng, Hailan; Wang, Chenhui; Xu, Yun; Zhang, Cun-Jin*; IL-37 Represses the Autoimmunity in Myasthenia Gravis via Directly Targeting Follicular Th and B Cells, The Journal of Immunology, 2020, 204(7):1736-1745.


2018年:

(1)   Zhang Cun-Jin#Wang, Chenhui#; Jiang Meiling#; Gu Chunfang; Xiao Jianxin; Chen Xing; Martin Bradley N; Tang Fangqiang; Yamamoto Erin; Xian Yibo;Wang Han; Li Fengling; Sartor R Balfour; Smith Howard; Husni M Elaine; Shi Fu-Dong; Gao Ji; Carman Julie; Dongre Ashok; McKarns Susan C; Coppieters Ken; Jorgensen Trine N; Leonard Warren J; Li Xiaoxia*; Act1 is a negative regulator in T and B cells via direct inhibition of STAT3, Nature Communications, 2018,9(1): 0-2745 (co-first author).

(2)  Cun Jin Zhang#; Meiling Jiang#; Hao Zhou; Weiwei Liu; Chenhui Wang; Zizhen Kang; Bing Han; Quanri Zhang; Xing Chen; Jianxin Xiao; Amanda Fisher;William J Kaiser; Masanori A Murayama; Yoichiro Iwakura; Ji Gao; Julie Carman; Ashok Dongre; George Dubyak; Derek W Abbott; Fu Dong Shi; Richard M Ransohoff*; Xiaoxia Li*; TLR-stimulated IRAKM activates caspase-8 inflammasome in microglia and promotes neuroinflammation, Journal of Clinical Investigation, 2018, 128(12): 5399-5412.


2017年:

(1)   Wang, Chenhui#*; Zhang, Cun-Jin#; Martin, N Bradley#; Bulek, Katarzyna; Kang, Zizhen; Zhao, Junjie; Bian, Guanglin; Carman, Julie A; Gao, Ji; Dongre,Ashok; Xue, Haibo; Miller, Stephen D; Qian, Youcun; Hambardzumyan, Dolores; Hamilton, Tom; Ransohoff, M Richard*; Li, Xiaoxia*; IL-17 induced NOTCH1 activation in oligodendrocyte progenitor cells enhances proliferation and inflammatory gene expression., Nat Commun, 2017, 8: 15508-15508 (co-correspondence author).

(2)   Liu, Caini#; Zhu, Liang#; Fukuda, Koichi; Ouyang, Suidong; Chen, Xing; Wang, Chenhui; Zhang, Cun-Jin; Martin, Bradley; Gu, Chunfang; Qin, Luke; Rachakonda, Suguna; Aronica, Mark; Qin, Jun*; Li, Xiaoxia*; The flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit to alleviate inflammation in vivo., Sci Signal, 2017, 10(467).

(3)   Wang, Jingjing; Fa, Jingjing; Wang, Pengyun; Jia, Xinzhen; Peng,Huixin; Chen, Jing; Wang, Yifan; Wang, Chenhui; Chen, Qiuyun; Tu, Xin; Wang, K Qing*; Xu, Chengqi*; NINJ2- A novel regulator of endothelial inflammation and activation., Cell Signal, 2017, 35: 231-241.


论文发表(回国前):

(1) Martin, N Bradley#; Wang, Chenhui#; Zhang, Cun-jin; Kang, Zizhen; Gulen, Muhammet Fatih; Zepp, Jarod A; Zhao, Junjie; Bian, Guanglin; Do, Jeong-su; Min,Booki; Pavicic, Paul G Jr; El-Sanadi, Caroline; Fox, Paul L; Akitsu, Aoi; Iwakura, Yoichiro; Sarkar, Anasuya; Wewers, Mark D; Kaiser, William J; Mocarski, Edward S; Rothenberg, Marc E; Hise, Amy G; Dubyak, George R; Ransohoff, M Richard*; Li, Xiaoxia*; T cell-intrinsic ASC critically promotes T(H)17-mediated experimental autoimmune encephalomyelitis., Nat Immunol, 2016, 17(5): 583-592 (co-first author).

(2)    Martin, N Bradley#; Wang, Chenhui#; Willette-Brown, Jami; Herjan, Tomasz; Gulen, F Muhammet; Zhou, Hao; Bulek, Katarzyna; Franchi, Luigi; Sato,Takashi; Alnemri, Emad S; Narla, Goutham; Zhong, Xiao-Ping; Thomas, James; Klinman, Dennis; Fitzgerald, Katherine A; Karin, Michael; Nunez, Gabriel; Dubyak, George; Hu, Yinling*; Li, Xiaoxia*; IKKalpha negatively regulates ASC-dependent inflammasome activation., Nat Commun, 2014, 5: 4977-4977 (co-first author).

(3)    Wu, Ling#; Wang, Chenhui#; Boisson, Bertrand; Misra, Saurav; Rayman, Patricia; Finke, James H; Puel, Anne; Casanova, Jean-Laurent*; Li, Xiaoxia*; The differential regulation of human ACT1 isoforms by Hsp90 in IL-17 signaling., J Immunol, 2014, 193(4): 1590-1599 (co-first author).

(4)    Gong, Lin#; Wang, Chenhui#; Huang, Yi Jiao; Liu, Feng; Li, Teng; Dai, Jiang; Li, Ai Ling; Zhou, Tao; Xia, Qing*; Chen, Liang*; CUEDC2 interacts with heat shock protein 70 and negatively regulates its chaperone activity., Biochem Biophys Res Commun, 2014, 447(1): 64-69 (co-first author).

(5)    Wang, Chenhui#; Wu, Ling#; Bulek, Katarzyna; Martin, Bradley N; Zepp, Jarod A; Kang, Zizhen; Liu, Caini; Herjan, Tomasz; Misra, Saurav; Carman, JulieA; Gao, Ji; Dongre, Ashok; Han, Shujie; Bunting, Kevin D; Ko, Jennifer S; Xiao,Hui; Kuchroo, Vijay K; Ouyang, Wenjun; Li, Xiaoxia*; The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone hsp90., Nat Immunol, 2013, 14(1): 72-81.

(6)    Boisson, Bertrand*; Wang, Chenhui; Pedergnana, Vincent; Wu, Ling; Cypowyj, Sophie; Rybojad, Michel; Belkadi, Aziz; Picard, Capucine; Abel,Laurent; Fieschi, Claire; Puel, Anne; Li, Xiaoxia; Casanova, Jean-Laurent*; AnACT1 mutation selectively abolishes interleukin-17 responses in humans with chronic mucocutaneous candidiasis., Immunity, 2013, 39(4): 676-686.

(7)    Kang, Zizhen; Wang, Chenhui; Zepp, Jarod; Wu, Ling; Sun, Kevin; Zhao,Junjie; Chandrasekharan, Unni; DiCorleto, Paul E; Trapp, Bruce D; Ransohoff, M Richard*; Li, Xiaoxia*; Act1 mediates IL-17-induced EAE pathogenesis selectively in NG2+ glial cells., Nat Neurosci, 2013, 16(10): 1401-1408.

(8)    Kang, Zizhen; Swaidani, Shadi; Yin, Weiguo; Wang, Chenhui; Barlow,Jillian L; Gulen, Muhammet Fatih; Bulek, Katarzyna; Do, Jeong-su; Aronica, Mark; McKenzie, Andrew N J; Min, Booki; Li, Xiaoxia*; Epithelial cell-specificAct1 adaptor mediates interleukin-25-dependent helminth expulsion through expansion of Lin(-)c-Kit(+) innate cell population., Immunity, 2012, 36(5):821-833.

(9)    Kang, Zizhen#; Liu, Liping#; Spangler, Roo; Spear, Charles; Wang, Chenhui; Gulen, Muhammet Fatih; Veenstra, Mike; Ouyang, Wenjun; Ransohoff, M Richard*; Li, Xiaoxia*; IL-17-induced Act1-mediated signaling is critical for cuprizone-induced demyelination., J Neurosci, 2012, 32(24): 8284-8292.

(10)   Liu, Caini#; Swaidani, Shadi#; Qian, Wen; Kang, Zizhen; Sun, Paige; Han, Yue; Wang, Chenhui; Gulen, Muhammet Fatih; Yin, Weiguo; Zhang, Chunjiang;Fox, Paul L; Aronica, Mark; Hamilton, Thomas A; Misra, Saurav; Deng, Junpeng; Li, Xiaoxia*; A CC' loop decoy peptide blocks the interaction between Act1 and IL-17RA to attenuate IL-17- and IL-25-induced inflammation., Sci Signal, 2011, 4(197): ra72-ra72.


论文发表(博士期间):

(1)    Zhang, H-Y#; Man, J-H#; Liang, B; Zhou, T; Li, T; Li, H-Y; Wang, C-H; Li, W-H; Jin, B-F; Zhang, P-J; Zhao, J; Pan, X; He, K; Gong, W-L; Zhang, X-M*; Li, A-L*; Tumor-targeted delivery of biologically active TRAIL protein. Cancer Gene Ther, 2010, 17(5): 334-343.

(2)    Li, Hui-Yan#; Liu, Hui#; Wang, Chen-Hui; Zhang, Ji-Yan; Man, Jiang-Hong; Gao, Yan-Fei; Zhang, Pei-Jing; Li, Wei-Hua; Zhao, Jie; Pan, Xin; Zhou, Tao; Gong, Wei-Li; Li, Ai-Ling*; Zhang, Xue-Min*; Deactivation of the kinase IKK by CUEDC2 through recruitment of the phosphatase PP1., Nat Immunol, 2008, 9(5): 533-541.

(3)    Zhou, Tao#; Liang, Bing#; Su, Gui-Ying; Gong, Wei-Li; Li, Hui-Yan; Tian, Li-Feng; He, Kun; Zhao, Jie; Man, Jiang-Hong; Li, Tao; Li, Wei-Hua; Zhang, Zhi-Yi; Wang, Chen-Hui; Li, Ai-Ling; Liu, Hui; Pan, Xin; Zhang, Pei-Jing; Jin, Bao-Feng; Zhang, Xue-Min*; Identification of ubiquitin targetproteins using cell-based arrays., J Proteome Res, 2007, 6(11): 4397-4406.