Guo FU, Ph.D.
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.
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.
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.