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Yong-Jun Liu, MD, PhD

 

 

  

EDUCATION

 

MD, Norman Bethune University, Chang Chun, Jilin, China

PhD, University of Birmingham, School of Medicine, Birmingham, United Kingdom

 

 

MAJOR CONTRIBUTIONS TO SCIENCE

 

1. Identified BCR and CD40 signaling as one of the major molecular mechanisms for selecting high-affinity antigen-specific B cells in the germinal center, a important mechanism for affinity maturation in antibody responses.

 

  • Liu Y-J, Joshua DE, Williams GT, Smith CA, Gordon J and MacLennan ICM. Mechanisms of antigen-driven selection in germinal centre. Nature 1989;342:929-31.
  • Arpin C, Déchanet J, Van Kooten K, Merville P., Grouard G. Briére F, Banchereau J and Liu Y-J. Generation of memory B cells and plasma cells in vitro. Science 1995;268:720-22.

 

 

2. Development of the first technology for detecting antigen-specific B cells in situ, which allowed the identification of extrafollicular and germinal center reaction during antigen-specific immune responses in the secondary lymphoid tissues.

 

  • Liu Y-J, Oldfield S and MacLennan ICM. Memory B cells in T cell-dependent antibody responses colonize the splenic marginal zone. Eur J Immunol 1988;8:335.
  • Liu Y-J, Zhang J, Lane PJL, Chan EYT and MacLennan ICM. Sites of specific B cell activation in primary and secondary responses to T cell dependent and T cell-independent antigens. Eur J Immunol 1991;21:2951-62.

 

 

3. Isolation and molecular characterization of human B cell subsets.

 

  • Pascual V, Liu Y-J, Magalski A, de Bouteiller O, Banchereau J and Capra JD. Analysis of somatic mutation in B-cell subsets of human tonsil correlates with phenotypic differentiation from the naive to the memory B-cell compartment. J Exp Med 1994;180:329.
  • Liu Y-J, Barthelemy C, de Bouteiller O, Arpin C, Durand I and Banchereau J. Memory B cells from human tonsils colonize mucosal epithelium and directly present antigen to T cells by rapid up-regulation of B7.1 and B7.2. Immunity 1995;2:239-48.
  • Liu Y-J, Malisan F, de Bouteiller O, Christiane G, Lebecque S, Banchereau J, Frederick CM, Max EE and Martinez-Valdez H. Within germinal centers isotype switching of Immunoglobulin genes occurs after the onset of somatic mutation. Immunity 1996;4:241-50.
  • Liu Y-J, de Bouteille O, Arpin C, Briére F, Galibert L, Ho S, Martinez-Valdez H, Banchereau J and Lebecque S. Normal human IgD-IgM+ germinal center B cells can express up to 80 mutations in the variable region of their IgD transcripts. Immunity 1996;4:603-13, 2.
  • Lebecque S. de Bouteiller O, Arpin C, Banchereau J. and Liu Y-J. Germinal centers founder cells display propensity for apoptosis before onset of somatic mutation. J Exp Med 1997;185:563-71.
  • Arpin C, de Bouteiller O, Razanajaona D, Fugier-Vivier I, Brière F, Banchereau J, Lebecque S and Liu Y-J. The normal counterpart of IgD myeloma cells in germinal center displays extensively mutated IgVH gene, cm-cd switch, andl light chain expression. J Exp Med 1998;187:1169-78.

 

 

4. Discovery of plasmacytoid dendritic cells.

 

  • Grouard G, Rissoan MC, Filgueira L, Durand I, Banchereau J and Liu Y-J. The enigmatic plasmacytoid T cells develop into dendritic cells with IL-3 and CD40-ligand. J Exp Med 1997;185:1101-11.
  • Rissoan MC, Soumelis V, Kadowaki N, Grouard G, Briére F, de Waal Malefyt R and Liu Y-J. Reciprocal control of T helper cell and dendritic cell differentiation. Science 1999;283:1183-6.
  • Siegal FP, Kadowaki N, Shodell M, Shodell M, Fitzerald-Bocarsly PA, K Shah, Ho S, Antonenko S and Liu Y-J. The nature of the principal type 1 interferon-producing cells in human blood. Science 1999;284:1835-7.
  • Kadowaki K, Ho S, Antonenko S, de Waal Malefyt R, Kastelein RA, Bazan F and Liu Y-J. Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J Exp Med 2001;194:863-9.

 

 

5. Discovery of the role of TSLP in DC-mediated T cell development, allergic inflammation and established the concept of inflammatory Th2.

 

  • Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, Gilliet M, Ho S, Antonenko S, Lauerma A, Smith K, Gorman D, Zurawski S, Abrams J, Menon S, McClanahan T, de Waal-Malefyt R, Bazan F, and Kastelein RA, and Liu Y-J. Human epithelial cells trigger dendritic cell-mediated allergic inflammation by producing TSLP. Nature Immunol 2002;3:673-80.
  • Watanabe N, Hanabuchi S, Soumelis V, Wei Y, Ho S, de Waal-Malefyt R and Liu Y-J. Human thymic stromal lymphopoietin promotes dendritic-cell–mediated CD4+ T-cell homeostatic expansion. Nature Immunol 2004;5:426-34.
  • Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, Liu Y-J. Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 2005;436(7054):1181-5.
  • Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, Watanabe N, Qin FX, Yao Z, Cao W, Liu Y-J. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med 2005;202(9):1213-23.

 

 

6. Discovery of the pDC receptor and its function.

 

  • Cao W, Bover L, Cho M, Wen X, Hanabuchi S, Bao M, Rosen DB, Wang YH, Shaw JL, Du Q, Li C, Arai N, Yao Z, Lanier LL, Liu Y-J. Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J Exp Med 2009;206:1603-14.

 

 

7. Discovery of novel DNA/RNA sensors.

 

  • Kim T, Pazhoor S, Bao M, Zhang Z, Hanabuchi S, Facchinetti V, Bover L, Plumas J, Chaperot L, Qin J, Liu Y-J. Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells. Proc Natl Acad Sci USA 2010;107(34):15181-6.
  • Zhang Z, Kim T, Bao M, Facchinetti V, Jung SY, Ghaffari AA, Qin J, Cheng G, Liu Y-J. DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Immunity 2011;34(6):866-78.
  • Zhang Z, Yuan B, Bao M, Lu N, Kim T, Liu Y-J. The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nat Immunol 2011;12(10):959-65.

 

 

CURRENT GRANTS

 

Characterizing DExD/H Box Helicases as Viral Sensors in Human Dendritic Cells

National Institute of Allergy & Infectious Diseases (R37AI091947)

05/01/11 – 04/30/16

 

Targeting Plasmacytoid Dendritic Cells to Treat Human Myeloma

National Cancer Institute (R01 CA163881)

02/01/2012 - 01/31/2017

 

Understanding the Early and Late Endosomal TLR9-Mediated Responses to Viral DNA

NIH/NIAID (R01 AIO97348)

09/01/2011 - 08/31/2016

 

 

PUBLICATIONS (total 230 from 1988-2012)

 

Key Publications during the past 5 years (2007-2012)

 

1.  Ito T, Yang M, Wang YH, Lande R, Gregorio J, Perng OA, Qin XF, Liu Y-J, and Gilliet M. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J Exp Med 2007;204:105-15.

 

2.  Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, Hippe A, Corrigan CJ, Dong C, Homey B, Yao Z, Ying S, Huston DP, and Liu Y-J. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC activated Th2 memory cells. J Exp Med 2007;204(8):1837-47.

 

3.  Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Wang YH, Su B, Nestle FO, Zal T, Mellman I, Schröder JM, Liu Y-J, and Gilliet M. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 2007;449(7162):564-9.

 

4.  Cao W, Zhang L, Rosen DB, Bover L, Watanabe G, Bao M, Lanier LL, and Liu Y-J. BDCA2/Fc epsilon RI gamma complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells. PLoS Biol 2007;5(10):e248.

 

5.  Esashi E, Wang YH, Perng O, Qin XF, Liu Y-J, and Watowich SS. The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8. Immunity 2008;28(4):509-20. (Co-corresponding author).

 

6.  Ito T, Hanabuchi S, Wang, Park WR, Arima K, Bover L, Qin XF, Gilliet M, and Liu Y-J Two functional subsets of Foxp3+ regulatory T cells in human thymus and periphery. Immunity 2008;28:870-80.

 

7.  Gilliet M, Cao W, and Liu Y-J. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol 2008;8(8):594-606.

 

8.  Voo KS, Wang YH, Santori FR, Boggiano C, Wang YH, Arima K, Bover L, Hanabuchi S, Khalili J, Marinova E, Zheng B, Littman DR, and Liu Y-J. Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci USA 2009;106(12):4793-8.

 

9.  Cao W, Bover L, Cho M, Wen X, Hanabuchi S, Bao M, Rosen DB, Wang YH, Shaw JL, Du Q, Li C, Arai N, Yao Z, Lanier LL, and Liu Y-J. Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J Exp Med 2009;206(7):1603-14.

 

10.  Lu N, Wang YH, Wang YH, Arima K, Hanabuchi S, and Liu Y-J. TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell homeostasis. J Exp Med 2009;206(10):2111-9.

 

11.  Arima K, Watanabe N, Hanabuchi S, Chang M, Sun SC, Liu Y-J. Distinct signal codes generate dendritic cell functional plasticity. Sci Signal 2010 Jan 19;3(105):ra4.

 

12.  Kim T, Pazhoor S, Bao M, Zhang Z, Hanabuchi S, Facchinetti V, Bover L, Plumas J, Chaperot L, Qin J, Liu Y-J. Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells. Proc Natl Acad Sci USA 2010;107(34):15181-6.

 

13.  Wang YH, Voo KS, Liu B, Chen CY, Uygungil B, Spoede W, Bernstein JA, Huston DP, Liu Y-J. A novel subset of CD4(+) T(H)2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma. J Exp Med 2010;207(11):2479-91.

 

14.  Lande R, Ganguly D, Facchinetti V, Frasca L, Conrad C, Gregorio J, Meller S, Chamilos G, Sebasigari R, Riccieri V, Bassett R, Amuro H, Fukuhara S, Ito T, Liu Y-J, Gilliet M. Neutrophils Activate Plasmacytoid Dendritic Cells by Releasing Self-DNA-Peptide Complexes in Systemic Lupus Erythematosus. Sci Transl Med 2011;3(73):73ra19.

 

15.  Zhang Z, Kim T, Bao M, Facchinetti V, Jung SY, Ghaffari AA, Qin J, Cheng G, Liu YJ. DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Immunity 2011;34(6):866-78.

 

16.  Zhang Z, Yuan B, Bao M, Lu N, Kim T, Liu YJ. The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nat Immunol 2011;12(10):959-65.

 

 

 



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