Education

2000, B.Sc., Beijing Normal University;

2006, Ph.D., Peking University.

Professional Experience

2006-2009, Postdoctoral Fellow, The Scripps Research Institute, La Jolla, California, USA;

2009-2010, Postdoctoral Fellow, Cleveland Clinic, Cleveland, Ohio, USA;

2010-2014, Postdoctoral Fellow, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA;

2014-present, Professor, School of Life Sciences, Xiamen University, Xiamen, China.

Research Area

The immune system is the defense system that protects host from invading pathogens and clears tumors cells. The vertebrate immune system is comprised of innate and adaptive immune system. As the name implies, the innate immune system is installed along with birth, and is evolutionarily conserved and primitive.  

The innate immune system provides the first line of defense against invading pathogens. It is always immediately available to combat a wide range of pathogens but does not lead to lasting immunity and is not specific for any individual pathogen. Adaptive immune system is unique to vertebrates, is established after birth, and does not come into play until there is antigenic challenge to the organism.

Based on the cell types involved, adaptive immunity can be classified into T cell-mediated cellular immunity and B cell-mediated humoral immunity. The germinal center reaction is the most important physiological process in humoral immunity. Only through germinal center selection, antigen-activated B cells can differentiate into long-lived memory B cells and plasma cells secreting high affinity antibodies. This process is controlled by Follicular helper T cells (TFH). Therefore, elucidating the cellular and molecular mechanisms underlying T cell help to B cell is of critical importance for the design of better vaccines.

Bcl-6 is an essential transcription factor that instructs the program of TFH differentiation. Inducible Costimulator (ICOS)also plays a critical role in this process, by inducing the expression of Bcl-6 through PI3K-Akt signaling pathway. Our study demonstrated that transcription factor Foxo1 inhibits TFH differentiation, by suppressing Bcl-6 expression. ICOS-PI3K-Akt signaling leads to the phosphorylation of Foxo1, which is subsequently targeted for ubiquitination and degradation by E3 ubiquitin ligase Itch. Itch-deficient CD4+ T cells fail to degrade Foxo1 upon ICOS-PI3K-Akt signaling, and therefore, exhibit impaired Bcl-6 induction and TFH differentiation. Hence, our study revealed the important roles of Itch and Foxo1 in TFH differentiation. In the future, we will focus on the molecular mechanisms underlying Bcl-6 induction and regulation by upstream signaling pathways, including cell-cell contact and cell metabolism. We will investigate functions of candidate genesin the immune system, especially in TFH differentiation, by utilizing genetically modified mice and immune disease models (such as bacterial and viral infections). For genes with important functions, we will elucidate their cellular and molecular mechanisms of action by employing multiple experimental approaches.

Selected Publications

1. Chen R, Bélanger S, Frederick MA, Li B, Johnston RJ,Xiao N, Liu YC, Sharma S, Peters B, Rao A, Crotty S#, Pipkin ME#. In vivo RNA interference screens identify regulators of antiviral CD4(+) and CD8(+) T cell differentiation.Immunity. 2014 Aug 21;41(2): 325-38.

2. Sabouri AH, Marcondes MC, Flynn C, Berger M,Xiao N, Fox HS, Sarvetnick NE#. TLR signaling controls lethal encephalitis in WNV-infected brain. Brain Res. 2014 Jul 29;1574: 84-95.

3.Xiao N, Eto D, Elly C, Peng G, Crotty S#,Liu YC#. The E3 ubiquitin ligase Itch is required for the differentiation of T follicular helper cells.Nat Immunol. 2014 Jul;15(7): 657-66.

4. Yu M, Zhou H, Zhao J,Xiao N, Roychowdhury S, Schmitt D, Hu B, Harding CV, Hise AG, Hazen SL, Defranco AL, Fox PL, Morton RE, Dicorleto PE, Febbraio M, Nagy LE, Smith JD, Wang JA, Li X^#. MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases.J Exp Med. 2014 May 5; 211(5): 887-907.

5. Burkart C, Arimoto KI, Tang T, Cong X,Xiao N, Liu YC, Kotenko SV, Ellies LG, Zhang DE#. Usp18 deficient mammary epithelial cells create an antitumour environment driven by hypersensitivity to IFN-λ and elevated secretion of Cxcl10.EMBO Mol Med. 2013 Jul;5(7): 967-82.

6. Arnold CN, Barnes MJ, Berger M, Blasius AL, Brandl K, Croker B, Crozat K, Du X, Eidenschenk C, Georgel P, Hoebe K, Huang H, Jiang Z, Krebs P, La Vine D, Li X, Lyon S, Moresco EM, Murray AR, Popkin DL, Rutschmann S, Siggs OM, Smart NG, Sun L, Tabeta K, Tomisato W, Webster V, Won S, Xia Y,Xiao N, Beutler B^#. ENU-induced phenovariance in mice: inferences from 587 mutations.BMC Res Notes. 2012 Oct 24;5(1): 577.

7. Cui W,Xiao N, Xiao H, Zhou H, Yu M, Gu J, Li X^#. β-TrCP-Mediated IRAK1 Degradation Releases TAK1-TRAF6 from the Membrane to the Cytosol for TAK1-Dependent NF-κB Activation.Mol Cell Biol. 2012 Oct;32(19): 3990-4000.

8. Siggs OM*,Xiao N*, Wang Y, Shi H, Tomisato W, Li X, Xia Y, Beutler B#. iRhom2 is required for the secretion of mouse TNFα. Blood. 2012 Jun 14;119(24): 5769-71.

9.Xiao N, Eidenschenk C, Krebs P, Brandl K, Blasius AL, Xia Y, Khovananth K, Smart NG, Beutler B#. The Tpl2 mutation sluggish impairs type I IFN production and increases susceptibility to group B streptococcal disease.J Immunol. 2009 Dec 15;183(12): 7975-83.

10. Jimenez-Dalmaroni MJ,Xiao N, Corper AL, Verdino P, Ainge GD, Larsen DS, Painter GF, Rudd PM, Dwek RA, Hoebe K^#, Beutler B^#, Wilson IA^#. Soluble CD36 ectodomain binds negatively charged diacylglycerol ligands and acts as a co-receptor for TLR2.PLoS One. 2009 Oct 22;4(10): e7411.

11. Brandl K, Rutschmann S, Li X, Du X,Xiao N, Schnabl B, Brenner DA, Beutler B#.Enhanced sensitivity to DSS colitis caused by a hypomorphic Mbtps1 mutation disrupting the ATF6-driven unfolded protein response.ProcNatlAcadSci USA. 2009 Mar 3;106(9): 3300-5.

12.  Xu L*,Xiao N*, Liu F, Ren H, Gu J#. Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria.ProcNatlAcadSci USA. 2009 Feb 3;106(5): 1530-5.