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Yong-Jun Liu, MD, PhD

 

 

         Yong-Jun Liu, MD, PhD

Investigator

Director, Baylor Institute for Immunology Research

Chief Scientific Officer, Baylor Research Institute

Vice-President, Baylor Research Institute

W. W. Caruth, Jr., Chair in Organ Transplantation Immunology

3434 Live Oak Street

Dallas, TX 75204

(214) 820-7450

Yong-Jun.Liu@BaylorHealth.edu

 

 

   
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 342:929-931, 1989.
  • 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 268:720-722, 1995.

 

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 8:335, 1988.
  • 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. 21:2951-2962, 1991.

 

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. 180:329, 1994.
  • 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 2:239-248, 1995.
  • 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 4:241-250,1996.
  • 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 4:603-613, 1996.12.
  • 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 185:563-571, 1997.
  • 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 187:1169-1178, 1998.

 

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 185:1101-1111, 1997.
  • 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 283:1183-1186, 1999.
  • 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 284:1835-1837, 1999.
  • 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 194:863-869, 2001.

 

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 3:673-680, 2002.
  • 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 5:426-434, 2004.
  • 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. 436(7054):1181-1185, 2005.
  • 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. 202(9):1213-23, 2005.

 

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. 206:1603-1614, 2009.

 

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 U S A. 107(34):15181-6, 2010.
  • 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. 34(6):866-78, 2011.
  • 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 Sep 4. doi: 10.1038/ni.2091. [Epub ahead of print].

 

 

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 Dendritic Cells to Block Immunosuppression in Breast Cancer Center

Cancer Prevention and Research Institute of Texas (RP110319)

12/01/10 – 11/30/13

 

Translational Development of Novel Vaccine Therapies

Leukemia & Lymphoma Society (7262-08)

10/01/07 – 9/30/12                             

(Project 1 Principal Investigator & Core Leader)                  

 

Molecular Mechanisms of pDC Interactions

National Cancer Institute (P01 CA128913-03)

09/10/2008 – 08/31/2013

(Project 1 Principal Investigator)

 

Harnessing Human DC Subsets for Improved Mucosal Vaccines

National Institute of Allergy & Infectious Diseases (U19AI057234)

04/01/2009 - 03/31/2014

 

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

 

Targeting Toll-Like Receptors and OX40 in Human Melanoma

Department of Defense (W81XWH-11-1-0418 Mod P000001)

08/01/2011 - 08/31/2016

 

 

PUBLICATIONS (total 230 from 1988 to 2012)

Key Publications during the past 5 years (2007 to 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. 204, 105-115, 2007.

 

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. 204(8):1837-47, 2007.

 

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. 449(7162):564-9, 2007.

 

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. 5(10):e248, 2007.

 

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. 28(4):509-20, 2008. (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. 28:870-880. 2008.

 

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

 

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 U S A. 106(12):4793-8, 2009.

 

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. 206(7):1603-14, 2009.

 

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. 206(10):2111-9, 2009.

 

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 U S A. 107(34):15181-6, 2010.

 

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. 207(11):2479-91, 2010.

 

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. 3(73):73ra19, 2011.

 

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. 34(6):866-78, 2011.

 

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 Sep 4. doi: 10.1038/ni.2091. [Epub ahead of print].

 

 



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