陈小芬 教授 国家优秀青年科学基金获得者 福建省高校新世纪优秀人才 厦门大学南强青年拔尖A类人才 学科(方向):神经科学 所在系部:神经科学研究所 办公电话:0592-2880567 邮 箱:chenxf@xmu.edu.cn | |
研究领域:
阿尔茨海默病(Alzheimer's Disease, AD)是一种以渐进性认知功能丧失为主要特征的神经退行性疾病,是最为常见的老年痴呆类型。目前AD的发病机制尚未完全阐明,亦缺乏治愈AD的有效药物。随着近年来研究的深入,小胶质细胞在神经系统疾病中的功能和地位日益凸显。目前,小胶质细胞已是公认的、脑稳态与脑功能障碍的积极参与者,也是治疗包括AD等众多中枢神经系统疾病极具潜力的新靶标。载脂蛋白E(Apolipoprotein E,ApoE)和髓细胞触发受体2(Triggering receptor expressed on myeloid cells 2 ,TREM2)是目前发现的、与散发型AD发生风险最为相关的两个基因。在AD病理环境中,小胶质细胞高表达ApoE和TREM2,但二者在AD发病机制与靶向治疗中发挥的作用有待于进一步的解析。课题组拟结合生化、分子、遗传、细胞生物学、电生理、动物行为学以及AD临床样本等,揭示ApoE和TREM2参与AD发生和发展的分子和细胞机制,并指导开发潜在的AD治疗策略。
学习经历:
2000–2004:厦门大学生命科学学院,生物科学学士
2004–2009:中科院上海生化与细胞研究所,生化与分子生物学博士
工作经历:
2009 - 2012:美国加州大学洛杉矶分校(UCLA),博士后
2014 - 2015:美国梅奥医学中心(Mayo Clinic),访问学者
2012.11 – 2018.10:yl23411永利官网登录,副教授
2018.11-至今:yl23411永利官网登录,教授
代表性成果:
Zhong L, Sheng X, Wang W, Li Y, Zhuo R, Wang K, Zhang L, Hu DD, Hong Y, Chen L, Rao H, Li T, Chen M, Lin Z, Zhang YW, Wang X, Yan XX, Chen X, Bu G, Chen XF (2023). TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration. Immunity. 56(8):1794-1808.
Wang W, Li Y, Ma F, Sheng X, Chen K, Zhuo R, Wang C, Zheng H, Zhang YW, Bu G, Chen XF§, Zhong L§ (2023). Microglial repopulation reverses cognitive and synaptic deficits in an Alzheimer's disease model by restoring BDNF signaling. Brain Behav Immun. 113:275-288.
Liang R, Rao H, Pang Q, Xu R, Jiao Z, Lin L, Li L, Zhong L, Zhang Y, Guo Y, Xiao N, Liu S, Chen XF§, Su XZ§, Li J§ (2023). Human ApoE2 protects mice against Plasmodium berghei ANKA experimental cerebral malaria. mBio. 24: e0234623.
Sheng X, Yao Y, Huang R, Xu Y, Zhu Y, Chen L, Zhang L, Wang W, Zhuo R, Can D, Chang CC, Zhang YW, Xu H, Bu G, Zhong L, Chen XF (2021). Identification of the minimal active soluble TREM2 sequence for modulating microglial phenotypes and amyloid pathology. J Neuroinflammation. 18(1):286.
Zhong L, Xu Y, Zhuo R, Wang T, Wang K, Huang R, Wang D, Gao Y, Zhu Y, Sheng X, Chen K, Wang N, Zhu L, Can D, Martens YA, Shinohara M, Liu CC, Du D, Sun H, Wen L, Xu H, Bu G, Chen XF (2019). Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer’s disease model. Nat Commun. 10(1):2923.
Sun F, Chronis C, Kronenberg M, Chen XF, Su T, Lay FD, Plath K, Kurdistani SK, Carey MF (2019). Promoter-Enhancer Communication Occurs Primarily within Insulated Neighborhoods. Mol Cell. 73(2):250-263.e5.
Zhong L, Wang Z, Wang D, Wang Z, Martens YA, Wu L, Xu Y, Wang K, Li J, Huang R, Can D, Xu H, Bu G, Chen XF (2018). Amyloid-beta modulates microglial responses by binding to the triggering receptor expressed on myeloid cells 2 (TREM2). Molecular Neurodegeneration. 13(1):15.
Zhong L*, Chen XF*,§, Wang TT, Wang Z, Liao CY, Wang ZQ, Huang RZ, Wang DX, Li XX, Wu LB, Zheng HH, Painter M, Atagi Y, Liu CC, Zhang YW, Fryer, Xu H, Bu G§ (2017). Soluble TREM2 promotes microglial survival and induces inflammatory responses via distinct signaling pathways. J Exp Med. 214(3):597-607.
Zhong L, Zhang ZL, Li XX, Liao CY, Mou PF, Wang TT, Wang ZQ, Wang Z, Wei M, Xu H, Bu G, Chen XF (2017). TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway. Front. Aging Neurosci. 9:204.
Yang L*, Liu CC*, Zheng H, Kanekiyo T, Atagi Y, Jia L, Wang D, N'songo A, Can D, Xu H, Chen XF§, Bu G§ (2016). LRP1 modulates the microglial immune response via regulation of JNK and NF-κB signaling pathways. J Neuroinflammation. 13(1):304.
Kang RR, Li P, Wang TT, Li XX, Wei ZC, Zhang ZL, Zhong L, Cao LL, Heckman MG, Zhang YW, Xu H, Huang CM, Bu G, Chen XF (2016). Apolipoprotein E epsilon 2 allele and low serum cholesterol as risk factors for gastric cancer in a Chinese Han population. Scientific Reports 6:19930.
Zhong L, Xie YZ, Cao TT, Wang Z, Wang T, Li X, Shen RC, Xu H, Bu G, Chen XF (2016). A rapid and cost-effective method for genotyping apolipoprotein E gene polymorphism. Molecular Neurodegeneration. 11(1):2.
Zhong L*, Chen XF*,§, Zhang ZL, Wang Z, Shi XZ, Xu K, Zhang YW, Xu H, Bu G§ (2015). DAP12 stabilizes the C-terminal fragment of the triggering receptor expressed on myeloid cells-2 (TREM2) and protects against LPS-induced pro-inflammatory response. J Biol Chem. 290(25):15866-77.
Chen XF§, Zhang YW, Xu H, Bu G§. (2013). Transcriptional regulation and its misregulation in Alzheimer's disease. Molecular Brain. 6(1):44-53.
Chen XF, Lehmann L., Lin J., Vashisht A., Schmidt, Ferrari R., Huang CY., McKee R., Mosley A., Plath K., Kurdistani S., Wohlschlegel J., Carey M.§ (2012). Mediator and SAGA Have Distinct Roles in Pol II Preinitiation Complex Assembly and Function. Cell Reports 2:1061-1067.
Chen XF, Kuryan B., Kitada T., Tran N., Li B., Carey M. (2012). The Rpd3 Core Complex is a Chromatin Stabilization Module. Current Biology 22(1):1-8.
Chen XF, Meng FL, Zhou JQ (2009). Telomere Recombination Accelerates Cellular Aging in Saccharomyces cerevisiae. PLoS Genetics 5(6): e1000535.
主持的科研项目:
国家自然科学基金面上项目,32170952,2022/01-2025/12。
美国BrightFocus基金会(BrightFocus Foundation),A2021023S,2021/07-2024/06。
国家自然科学基金优秀青年科学基金项目,81922021,2020/01-2022/12。
阿尔茨海默氏症协会国际研究基金(Alzheimer's Association International Research Grant),2018/02-2021/02。
深圳市科技计划基础研究项目,JCYJ20210324122004012, 2021/10-2024/10。
深圳市知识创新计划基础研究项目,JCYJ20170818140904167,2018/01-2019/12。
广东省自然科学杰出青年基金项目,2016A030306005,2016/06-2020/06。
中央高校基本科研业务费-厦门大学校长基金(培育基金),20720180055,2018/01-2020/12。
福建省省高校新世纪优秀人才支持计划,2015/01-2015/12。
中央高校基本科研业务费-厦门大学校长基金(成长基金),2072015005,2015/01-2017/12。
国家自然科学基金青年基金项目,31400914,2015/01-2017/12。
国家自然科学基金面上项目,81370459,2014/01-2017/12。
所有论文列表:
https://www.ncbi.nlm.nih.gov/myncbi/xiaofen.chen.1/bibliography/public/