付国 FU Guo, Ph.D.                     

E-mail： guofu@xmu.edu.cn

1995年，辽宁大学获学士学位；

1998年，中国医科大学获硕士学位；

2004年，澳大利亚墨尔本大学获博士学位；

2004至2009年，美国Scripps研究所博士后;

2009至2010年，美国Scripps研究所高级研究助理;

2010至2014年, 美国Scripps研究所Staff Scientist;

2014年至今，厦门大学生命科学学院教授

1995, B.Sc., Dept. of Biology, Liaoning University

1998, M.Sc., Dept. of Immunology, China Medical University

2004, Ph.D., Dept. of Microbiology and Immunology, The University of Melbourne, Australia

2004--2009  Research Associate, The Scripps Research Institute, La Jolla, California, USA

2009--2010  Senior Research Associate, The Scripps Research Institute, La Jolla,California, USA

2010--2014  Staff Scientist, The Scripps Research Institute, La Jolla, California, USA

2014--Present, Professor, School of Life Sciences, Xiamen University, Xiamen, China

研究领域（Research Area)

    免疫系统是人体的防御系统，它如同现实生活中的国防系统一样，担负着抵御外敌（如病原细菌，病毒，寄生虫等）和清除内患（如癌变的细胞）的重任。免疫系统可以分为天然免疫系统和获得性免疫系统。顾名思义，天然免疫系统是与生俱来的，它主要担负对外源性病原入侵的识别和早期防御。获得性免疫系统则是在出生后才完成发育并开始发挥功能的，它主要在抗感染免疫反应的后期发挥效应。获得性免疫系统的建立是高等动物特有的宿主防御机制，其中的免疫记忆机制是疫苗接种物质基础。淋巴细胞（如Ｔ和Ｂ细胞）是获得性免疫系统中的重要成员，如同现实生活中的士兵一样，它们承担着具体的战斗任务。因此，它们的发育过程，动员机制，和效应功能理所当然的成为免疫学中重要研究课题（想象一下一名战士如何从军校到部队到最后走上战场）。

    本实验室主要关注的是淋巴细胞的发育和功能研究：1）在发育阶段，淋巴细胞是如何获得对外敌（病原体）和内患（癌细胞）的特异性杀伤，而又不伤及无辜的自身细胞和组织的；2）在效应阶段，淋巴细胞是如何具体发挥杀伤和调节功能的；3）在后免疫应答阶段，淋巴细胞又是如何维持免疫记忆以便应对将来潜在的再次感染。对这些问题的深入细致研究不仅可以满足我们对人类自身的了解，更为重要的是这些问题的解决最终有助于我们更快速更有效的研发药物和疫苗以服务于人类，特别是在当今世界范围内存在着重大传染病蔓延的隐患（如HIV,埃博拉，登革热等）和愈来愈多的自身免疫病（如糖尿病，系统性红斑狼疮等）及过敏性疾病（如哮喘，花粉病等）。

    我们当前的具体课题围绕2个分子在Ｔ细胞中的功能，即Themis 和PKC eta (PKC ). 在先前的工作中 (Nature Immunology, 2009)，我们证明了Themis分子对胸腺Ｔ细胞的发育起着重要作用。在接下的研究中 (Nature, 2013)，我们阐明了Themis发挥作用的分子机制。在后续的研究工作中，1）我们将进一步的深入挖掘Themis发挥作用的分子机理；2）同时展开对Themis在成熟Ｔ细胞中的功能的研究。另一个我们侧重的分子是PKC ， 它是一种丝氨酸和苏氨酸激酶, 之前对于PKC 的研究非常少。在先前的研究中(Science Signaling, 2011)，我们第一次阐明了在小鼠体内PKC 对效应Ｔ细胞的活化和功能有重要的作用。在随后的研究中 (Nature Immunology, 2014)，我们又揭示了PKC 在调节性Ｔ细胞中的重要功能，是该研究领域的一个重要突破。在今后的工作中，我们将围绕PKC在不同的免疫细胞亚群，不同的感染和肿瘤模型中的作用开展工作。

    我们的具体技术手段是建立和运用各种基因敲除或转基因小鼠做为模型或工具来发现和研究对淋巴细胞发育和功能有重要作用的基因及其产物。同时辅助以其他的生物化学和细胞生物学方法。我们将利用学院内外的各种高质量技术平台（如流式细胞仪，荧光显微镜，质谱仪等）。我们的研究范围将先立足于几种病原体感染和常见肿瘤的小鼠模型，然后在适当的时机和条件下拓展到对人体样本的研究。

小常识

    1）现代社会里，正常婴儿出生后挨的第一针通常是免疫接种用的.

    2）有很多学者认为，免疫学家可以被冠以“拯救了最多生命”的职业。想一想，如果没有牛痘接种，天花将会给人类带来灭顶之灾！

    3）疫苗的免疫接种是中国古老的以毒攻毒策略的一个典型应用范例。 

    The immune system is the body's defense system, it is indeed like the military defense system in the real world, bearing the tasks of fighting against foreign enemies (such as pathogenic bacteria, viruses, parasites, etc.) as well as interior traitors (such as cancer cells). The immune system can be divided into innate and acquired immune systems. As the name implies, the innate immune system is installed along with birth, it is mainly responsible for recognizing the invasion of exogenous pathogens and the immediate clearance of these pathogens. Acquired immune system is established after the birth, it mainly participates in later pathogen specific immune response. Acquired immune system is unique to higher animals, moreover the phenomenon of immunological memory is the material basis of vaccination. Lymphocytes (such as T and B cells) are important players of acquired immune system, like soldiers in real life, they bear a specific combat missions. Therefore, their developmental processes, mobilization mechanism, and effector functions become an important research topic in immunology.

    Our laboratory's main research interest is the development and function of lymphocytes: a) in the developmental stage, how lymphocyte gain the property to fight foreign pathogens without attacking body’s own tissues; 2) in the effector phase, how lymphocytes exert killing and regulatory function; 3) in the immune response contraction phase, how immunological memory is maintained. Investigations on these issues can not only extend our understanding of human beings, but also help us more rapidly and effectively develop drugs and vaccines, especially in today's world when infectious diseases pose a major threat (such as HIV, Ebola, dengue, etc.) and an increasingly occurrence of autoimmune diseases (such as diabetes, systemic lupus erythematosus, etc.) and allergy (such as asthma, hay fever etc.).

    We currently focus on two molecules involved in T cell biology, namely Themis and PKC eta (PKC η). Our previous work showed that Themis is required for normal T-cell development. In the follow-up studies, we found that Themis can only exert its negative regulatory function upon low-to-intermediate strength T cell receptor (TCR) stimulation, but not at high affinity TCR stimulation. Our future plan is that, 1) we will further characterize the molecular mechanism of how Themis controls T cell development in-depth; 2) investigating the function of Themis in mature T cells. The other molecule is PKC η. PKC η is a serine and threonine kinase, it is highly expressed in T cells. In a previous study, we demonstrated that PKC η plays an important role in T cell activation and function. In subsequent studies, we revealed that PKC η is also required for regulatory T cell function, which is an important breakthrough in the regulatory T cell signaling field. In the future, we will study the role of PKC η in other immune cell subsets under the condition of infections and tumor.

    Our specific technical routes are developing and utilizing a variety of gene knockout or transgenic mice as a model or tool to discover and study genes important for lymphocyte development and function. These approaches will be supplemented with other biochemical and cell biological methods. We will take the advantage of a variety of high-quality technology platforms inside and outside of School of Life Science (e.g. flow cytometry, fluorescence microscopy, mass spectrometry, etc.). We will be focusing on several common pathogens and tumor models, and then under the appropriate timing and conditions extend to the study of human samples.

代表性论文 (Selected Publications,*first author, ^#corresponding author) 

1. Bertin S, Aoki-Nonaka Y, de Jong PR, Nohara LL, Xu H, Stanwood SR, Srikanth S, Lee J, To K, Abramson L, Yu T, Han T, Touma R, Li X, González-Navajas JM, Herdman S, Corr M, Fu G, Dong H, Gwack Y, Franco A, Jefferies WA, Raz E. The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4+ T cells. Nature Immunology. 2014 Oct 5.

2. Fu G, Rybakin V, Brzostek J, Paster W, Acuto O, Gascoigne NR. Fine- tuning T cell receptor signaling to control T cell development. Trends in Immunology. 2014 Jul; 35(7): 311-318. Review.

3. Kong KF*, Fu G*, Zhang Y, Yokosuka T, Casas J, Canonigo-Balancio A, Becart S, Kim G, Yates JR 3rd, Kronenberg M, Saito T, Gascoigne NR, Altman A. Protein Kinase C-η Controls CTLA-4-Mediated Regulatory T Cell Function. *Equal contribution. Nature Immunology. 2014 May; 15(5): 465-72.

4. Nabekura T, Kanaya M, Shibuya A, Fu G, Gascoigne NR, Lanier L. Costimulatory Molecule DNAM-1 Is Essential for Optimal Differentiation of Memory Natural Killer Cells during Mouse Cytomegalovirus Infection. Immunity. 2014 Feb 20; 40(2): 225-34.

5. Fu G, Casas J, Rigaud S, Rybakin V, Lambolez F, Brzostek J, Hoerter JAH, Paster W, Acuto O, Cheroutre H, Sauer K, Gascoigne NR. Themis sets the signal threshold for positive and negative selection in T cell development. Nature. 2013 Dec 19;504(7480):441-5.

6. Gascoigne NR, Fu G. Tespa1: another gatekeeper for positive selection. Nature Immunology, 2012 May 18;13(6):530-2.

 7.Fu G#, Gascoigne NR#. Protein kinase C, an emerging player in T cell biology. Cell Cycle. 2012, Mar 1;11(5). #corresponding author.

8.FuG#, HuJ, Niederberger-MagnenatN, RybakinV, Casas J, YachiPP, FeldsteinS, MaB, HoerterJAH, AmpudiaJ, RigaudS, LambolezF, GavinAL, SauerK, CheroutreH, GascoigneNRJ#. Protein Kinase C η Is Required for T Cell Activation and Homeostatic Proliferation. Science Signaling. 2011 Dec 6; 4(202): ra84. #corresponding author.

9.Fu G#,Gascoigne NR#. Multiplexed labeling of samples with cell tracking dyes facilitates rapid and accurate internally controlled calcium flux measurement by flow cytometry. Journal of Immunological Methods. 2009 Oct 31; 350(1-2): 194-9. #corresponding author.

10.Fu G*, Vallée S*, Rybakin V, McGuire MV, Ampudia J, Brockmeyer C, Salek M, Fallen PR, Hoerter JA, Munshi A, Huang YH, Hu J, Fox HS, Sauer K, Acuto O, Gascoigne NR. Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling. Nature Immunology. 2009 Aug; 10(8): 848-56. *Equal contribution.

11.Fu G, Wijburg OL, Cameron PU, Price JD, Strugnell RA. Salmonella enterica Serovar Typhimurium infection of dendritic cells leads to functionally increased expression of the macrophage-derived chemokine. Infection and Immunity. 2005 Mar; 73(3): 1714-22.