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严君,北京脑重大疾病研究院教授、博士生导师,北京市青年人才,北京药学会应用药理专委会委员。北京协和医科大学&中国医学科学院药物研究所药理学博士,美国MD安德森癌症中心(MD Anderson Cancer Center)博士后、研究科学家。参加多项美国NIH项目。2019年底入职首医北京脑重大疾病研究院组建脑肿瘤免疫实验室,承担国家级科研项目。主要从事肿瘤免疫的基础和转化研究,集中在肿瘤免疫机理的探索及免疫治疗的开发:脑肿瘤免疫细胞亚群和基质成分影响肿瘤发生发展的机制;代谢重编排对肿瘤与免疫的调控作用;低氧对肿瘤免疫的影响;鉴定肿瘤治疗新靶点及开发相应的肿瘤治疗新方法/药物。近年来在NatureCommunications、Journal of Hepatology、Journal of the National Cancer Institute、CancerLetters、Immunity等高影响力期刊发表多篇研究论文,申请发明专利国内2项、国际2项,已获授权1项。参与的研究项目 “TLRs介导的免疫-自噬调节纤维化和肿瘤发生发展的机制及药靶发现”获得“中华医学科技奖”三等奖和“北京市科学技术奖”三等奖。
实验室利用临床标本和动物模型,采集和分析多组学数据,通过细胞和分子生物学等实验手段,发现和验证肿瘤免疫相关新靶点、新机制,开发抗肿瘤新疗法、新药物。主要包括以下三个方向:
1、O2对肿瘤免疫的影响及机制研究;
2、代谢重编排对肿瘤与免疫的调控作用;
3、脑肿瘤免疫细胞新亚群和基质成分影响肿瘤发生发展的作用及机制。
国家自然科学基金(面上项目):肿瘤细胞内源性FGL2在巨噬细胞调控脑肿瘤发生发展中的作用和机制 2021.1-2024.12 主持
北京市自然科学基金(市教委科技重点项目):低氧诱导的EPAS1-NT5E炎症通路促进胶质瘤发生发展的作用和机制 2022.3-2024.12 主持
Selected Publications
A. Peer-Reviewed Original Research Articles
1. Yan J#,Zhao Q, Wang J, Tian X, Wang J, Xia X, Ott M, Rao G, Heimberger AB, Li S#.FGL2-wired macrophages secrete CXCL7 to regulate the stem-like functionality ofglioma cells. Cancer Letters. 2021; 506:83-94.
2. Liu SS, Liu C, Lv XX, Cui B, Yan J, Li YX, Li K, Hua F, Zhang XW, Yu JJ, YuJM, Wang F, Shang S, Li PP, Zhou ZG, Xiao Y, Hu ZW The chemokine CCL1 triggersan AMFR-SPRY1 pathway that promotes differentiation of lung fibroblasts intomyofibroblasts and drives pulmonary fibrosis. Immunity. 2021; 54:1–15.
3. Yan J, Zhao Q, Gabrusiewicz K, Kong LY, Xia X, Wang J, Ott M, Xu J, Davis RE, HuoL, Rao G, Sun SC, Watowich SS, Heimberger AB, Li S. FGL2 promotes tumor progression inthe CNS by suppressing CD103+ dendritic cell differentiation. NatureCommunications. 2019; 10(1):448.
4. Latha K*, Yan J*, Yang Y, Gressot LV, Kong LY, Manyam G, Ezhilarasan R, WangQ, Sulman EP, Eric Davis R, Huang S, Fuller GN, Rao A, Heimberger AB, Li S, RaoG. The Role of Fibrinogen-Like Protein 2 on Immunosuppression andMalignant Progression in Glioma. JNCI J Natl Cancer Inst. 2019;111(3):292-300.
5. Noh H, Zhao Q, Yan J, Kong LY, Gabrusiewicz K, Hong S, Xia X, Heimberger AB,Li S. Cell surface vimentin-targeted monoclonal antibody 86C increasessensitivity to temozolomide in glioma stem cells. Cancer Lett. 2018; 433:176-185.
6. Mitra A, Yan J, Xia X, Zhou S, Chen J, Mishra L, Li S. IL6-mediatedinflammatory loop reprograms normal to epithelial-mesenchymal transition+metastatic cancer stem cells in preneoplastic liver of transforming growthfactor beta–deficient β2-spectrin+/− mice. Hepatology. 2017; 65(4): 1222-1236.
7. Yan J, Mitra A, Hu J, Cutrera JJ, Xia X, Doetschman T, Gagea M, Mishra L, Li S.Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokineprofile in NKT cells. Journal of Hepatology. 2016; 64(5):1128-36.
8. Yan J, Kong LY, Hu J, Gabrusiewicz K, Dibra D, Xia X, Heimberger AB, Li S. FGL2 as aMultimodality Regulator of Tumor-Mediated Immune Suppression and TherapeuticTarget in Gliomas. JNCI J Natl Cancer Inst. 2015;107 (8): djv137.
9. Mitra A, Satelli A, Jun Yan, et al. IL-30 (IL27p28) attenuates liver fibrosisthrough inducing NKG2D-rae1 interaction between NKT and activated hepaticstellate cells in mice. Hepatology. 2014; 60(6):2027-39.
10. H Lin, J Yan, ZY Wang, et al. Loss of immunity-supported senescenceenhances susceptibility to hepatocellular carcinogenesis and progression inToll‐like receptor 2-deficientmice. Hepatology. 2013; 57(1):171-82.
11. ZY Wang, J Yan, H Lin, et al. Toll-like receptor 4 activity protectsagainst hepatocellular tumorigenesis and progression by regulating expressionof DNA repair protein Ku70 in mice. Hepatology. 2013; 57(5):1869-81.
12. Yan J, Wang ZY, Yang HZ, Liu HZ, Mi S, Lv XX, Fu XM, Yan HM,Zhang XW, Zhan QM, Hu ZW.Timing is Critical for an Effective Anti-MetastaticImmunotherapy: The Decisive Role of IFNγ/STAT1-Mediated Activation ofAutophagy. PLOS ONE. 2011; 6(9): e24705.
B. Review Articles
1. Hu J*, Yan J*, Rao G*, Latha K, Overwijk WW, Heimberger AB, Li S. TheDuality of Fgl2-Secreted Immune Checkpoint Regulator Versus Membrane-AssociatedProcoagulant: Therapeutic Potential and Implications. International Reviewsof Immunology. 2016 ;35(4):325-339.
2. Yan J, Li S, Li S. The Role of the Liver in Sepsis. International Reviews ofImmunology. 2014; 33(6):498-510.
C. Patents
1. Li SL, Yan J,Xia XQ, Hu JM, Zhao QN. Fgl2monoclonal antibodies and their use in treating malignant tumors. U.S. Patent Application No. 62/501,870, (WO2018204928A1).
2. Hu ZW, Yan J, andCui B. TraditionalChinese medicine composite for preventing or treating fibrosis diseases as wellas preparation method and application of same. Chinese National InventionPatent (CN 201210183664). 2012. Patent Cooperation Treaty (WO2013181978 A1).2013.
3. Hu ZW, Yan J, He LS, Cui B, et al. The application of combination of TLR4and TLR9 agonists for inhibiting tumor metastasis. Chinese NationalInvention Patent (200610112299.5). 2006.
4. Du GH,Zhu HB, Zhang L, Yan J and Zang YQ. High throughput screening method ofacyl coenzyme A-cholesterol acyltransferase inhibitors by detection the levelof sulfydryl. Chinese National Invention Patent (200610092035.8). 2006.
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