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Renren Wen, PhD

Renren Wen, PhD

Associate Investigator

Education and training

Postdoctoral Training
St. Jude Children’s Research Hospital
Memphis, Tennessee

Doctoral Training
PhD, University of Tennessee Medical School, 1996

Contact Us

Renren Wen, PhD

Associate Investigator
Email (414) 937-3852 Fax: (414) 937-6284

  • Research Interests

    Immunobiology

    The long-term interest of my lab is to understand how T-cell development and activations are regulated. My current study is focused on studying the role of two proteins involved in regulating T-cell development and functions: phospholipase C-γ (PLCγ) and B cell lymphoma 10 (Bcl10). PLCγ activation is one of the key events following TCR stimulation.

    There are two PLCγ isoforms, PLCγ1 and PLCγ2. We have shown that PLCγ1 deficiency at late T-cell developmental stage impaired T-cell positive and negative selection, affected mature T-cell development and function, and resulted in T-cell lymphopenia and autoimmune diseases. Recently, we have also shown that PLCγ1 and PLCγ2 play an additive role in TCR signal transduction. Currently, we are studying the role of PLCγ1 and PLCγ2 in early T-cell lymphopoiesis and performing structural functional study of PLCγ1 and PLCγ2 in T-cell system.

    Bcl10 gene is an adaptor protein cloned from the recurrent 1p22 breakpoint of chromosomal translocation t(1;14)(p22;q32) involved in mucosa associated lymphoid tissue (MALT) lymphoma. This translocation resulted in high-level expression of Bcl10 in MALT lymphoma with the t(1;14)(p22;q32). Therefore, high expression of Bcl10 is a potential mechanism for MALT lymphoma development. Bcl10 functions in TCR signaling downstream of PLCγ1, and is essential for TCR-mediated nuclear factor kappa B (NF-κB) activation, aberrant activation of which is associated with tumor development. Bcl10 deficiency impaired T-cell development, proliferation and interleukine-2 production. We have demonstrated that TCR-induced phosphorylation of Bcl10 is a mechanism of downregulating Bcl10 protein level and thus terminating TCR-mediated NF-κB activation. Currently, we are further studying the mechanism on how phosphorylation of Bcl10 affects its function in TCR signal transduction.

  • Lab

    Guoping Fu
    Sr. Research Associate 

  • Publications
    • Chen Y, Yu M, Dai X, Zogg M, Wen R, Weiler H, Wang D.Critical role for Gimap5 in the survival of mouse hematopoietic stem and progenitor cells. J Exp Med. 2011, 208:923-935. PMCID: PMC3092340
    • Wuerzberger-Davis S, Chen Y, Yang DT, Bates P, Ladell NC, Yu M, Podd A, Zeng H, Wen R, Wang D and Miyamoto S. In vivo roles of IkBα-mediated NF-κB/Rel nucleo-cytoplasmic shuttling. Immunity. 2011, 34:188-200. PMCID: PMC3111750
    • Fu G, Chen Y, Yu M, Podd A, Di L, He Y, Williams CB, North PE, Wang D, and Wen R. Phospholipase Cγ1 is essential for T-cell development, activation and tolerance. J Exp Med. 2010, 207:309-318. PMCID: PMC2822604
    • Jana S, Jailwala P, Haribhai D, Waukau J, Glisic S, Grossman W, Mishra M, Wen R, Wang D, Williams CB, Ghosh S. The role of NF-κB and Smad3 in TGF-beta-mediated Foxp3 expression. Eur J Immunol. 2009, 39:2571-83. PMID: 19701891
    • Schuman J, Chen Y, Podd A, Liu H, Wen R, Chen ZJ and Wang D. A critical role of TAK1 in B cell development and activation. Blood. 2009, 113:4566-4574. PMCID: PMC2680363.
    • Chen Y, Wang X, Di L, Fu G, Chen Y, Bai L, Liu J, Feng X, McDonald JM, Michalek S, He Y, Yu M, Fu YX, Wen R, Wu H and Wang D. Phospholipase Cγ2 mediates RANKL-stimulated lymph-node organogenesis and osteoclastogenesis. J Biol Chem. 2008, 283:29593-29601. PMCID: PMC2570883.
    • Zeng H, Chen Y, Yu M, Xue L, Gao X, Morris SW, Wang D, and Wen R. T cell ceceptor-mediated activation of CD4+CD44hi T cells bypasses Bcl10: an implication of differential NF-kB dependence of na├»ve and memory T cells during T cell receptor-mediated responses. J Biol Chem. 2008, 5:24392-24399. PMCID: PMC2528987
    • Chen Y, Yu M, Podd A, Wen R, Chrzanowska-Wodnicka M, White GC, and Wang D. A critical role of Rap1b in B cell trafficking and marginal zone B cell development. Blood. 2008; 111:4627-4636. PMCID: PMC2343596
    • Malarkannan S, Regunathan J, Chu H, Chen Y, Zeng H, Kutlesa S, Wen R and Wang D. Activation of Bcl10 is essential for the signaling divergence of NKG2D-mediated cytotoxicity and cytokine generation in NK cells. J. Immunol. 2007, 15: 3752-3762. PMID: 17785812
    • Bai L, Chen Y, He Y, Dai X, Lin X, Wen R, and Wang D, Phospholipase Cγ2 contributes to light chain gene activation and receptor editing. Mol Cell Biol. 2007 27: 5957-5967. PMCID: PMC1952164.
    • Dai X, Chen Y, Di L, Podd A, Li G, Bunting KD, Hennighausen L, Wen R and Wang D. Stat5 is essential for early B cell development but not for B cell maturation and function. J Immunol. 2007; 179:1068-1079
    • Zeng H, Di L, Fu G, Cheng Y, Gao X, Xu L, Lin X, and Wen R. Phosphorylation of Bcl10 negatively regulates T cell receptor-mediated NF-κB activation. Mol Cell Biol. 2007, 27: 5235-5245. PMID: 17502353
    • Misra RS, Russell JQ, Koenig A, Hinshaw-Makepeace JA, Wen R, Wang D, Huo H, Littman DR, Ferch U, Ruland J, Thome M and Budd RC. Caspase-8 and c-FLIPL associate in lipid rafts with NF-kB adaptors during T cell activation. J Biol Chem. 2007, 282: 19365-19374. PMID: 17462996
    • Chen Y, Pappu B, Zeng H, Xue L, Morris SW, Lin X, Wen R *and Wang D*. Bcl10 is essential for FcεR-mediated degranulation and IL-6 production in mast cells. J Immunol. 2007, 178: 49-57. *equal senior authorship. PMID: 17182539
    • Wang D, You Y, Lin P, Xue L, Morris SW, Zeng H, Wen R, Lin X. Bcl10 plays a critical role in NF-κB activation induced by G protein-coupled receptors. Proc Natl Acad Sci U S A. 2007, 104:145-150. PMCID: PMC1765424
    • Wen R*, Chen Y, Fu G, Schuman J, Yang C, Cleveland JL and Wang D*. An essential role of phospholipase Cγ2 in early B cell development and Myc-mediated lymphomagenesis. Mol Cell Biol. 2006, 26:9364-9376. *equal senior authorship, PMCID: PMC1698523
    • Regunathan J, Chen Y, Kutlesa S, Dai X, Bai L, Wen R, Wang D, and Malarkannan S. Differential and non-redundant roles of PLCγ2 and PLCγ1 in the terminal maturation of NK cells. J Immunol. 2006, 177:5365-5376. PMID: 17015722
    • Chen Y, Dai X, Haas AL, Wen R, Wang D. Proteasome-dependent down-regulation of activated Stat5A in the nucleus. Blood. 2006; 108: 566 – 574. PMCID: PMC1895487
    • Dai X, Chen Y, Schuman J, Hua Z, Adamson JW, Wen R, Wang D. Distinct roles of PI3K and PLCγ2 in B cell receptor-mediated signal transduction. Mol Cell Biol. 2006;26:88-99. PMCID: PMC1317611
    • Zhu M, Granillo O, Wen R, Yang K, Dai X, Wang D, and Zhang W. Negative Regulation of Lymphocyte Activation by the Adaptor Protein LAX. J Immunol. 2005;174:5612 – 5619. PMID: 15843560
    • Wen R, Chen Y , Schuman J, Fu G, Yang S, Newman D, Wang D. An important role of phospholipase C gamma 1 in pre-B cell development and allelic exclusion. EMBO J. 2004;23:4007-4017. PMCID: PMC524341
    • Zhu Y, Chen L, Huang Z, Alkan S, Bunting KD, Wen R, Wang D, and Hua Huang. IL-5 primes Th2 cytokine-producing capacity in eosinophils through a STAT5-dependent mechanism. J Immunol. 2004;173:2918-2922. PMID: 15322148
    • Xue L, Morris SW, Orihuela C, Tuomanen E, Cui X, Wen R, Wang D. Defective development and function of Bcl10-deficient follicular, marginal zone and B1 B cells. Nat Immunol. 2003;4:857-865. PMID: 12910267
    • Wen R, Chen Y, Xue L, Schuman J, Yang S, Morris SW, Wang D. Phospholipase Cγ2 provides survival signals via Bcl2 and A1 in different subpopulations of B cells. J Biol Chem. 2003;278:43654-43662. PMID: 12928432
    • Chen Y, Wen R, Yang S, Schuman J, Yi T, Feng GS, Wang D. Identification of Shp-2 as a Specific Stat5A Phosphatase. J Biol Chem. 2003;278:16520-16527. PMID: 12615921
    • Wen R, Jou S, Hoffmeyer A, Wang D. Phospholipase Cγ2 is essential for specific functions of FcεR and FcγR. J Immunol. 2002;169:6743-6752. PMID: 12471105
    • Wang D, Boylin EC, Minegishi Y, Wen R, Smith CIE, Ihle JN, Conley ME. Variations in the human phospholipase Cγ2 gene in patients with B-cell defects of unknown etiology. Immunogenetics 2001;53:550-556. PMID: 11685467
    • Wen R, Wang D, McKay C, Bunting K, Zambetti GP, Korsmeyer S, Ihle JN, Cleveland JL. Jak-3 selectively regulates Bax and Bcl-2 expression to promote T cell development. J Biol Chem. 2001;21:678-689. PMID: 11134353
    • Wang D, Feng J, Wen R, Marine JC, Sangster MS, Parganas E, Cleveland JL, Jackson CW, Murry PJ, Ihle JN. Phospholipase Cγ2 is essential in the functions of B cell and several Fc receptors. Immunity. 2000;13:25–35. PMID: 10933392
    • Inoue K, Wen R, Rehg JE, Adachi M, Cleveland JL, Roussel MF, Sherr CJ. Disruption of the ARF transcriptional activator DMP1 Facilitates cell immortalization, Ras transformation and tumorigenesis. Genes & Dev. 2000;14:1797-809. PMID: 10898794
    • Wen R, Surman S, Blackman MA, Woodland DL. Carboxy-terminal residues of MHC class II-associated peptides control TSST-1 binding and presentation.Eur J Immunol1997;27:772-781.
    • Wen R, Surman S, Blackman MA, Woodland DL. The conventional CD4+ T cell response to staphylococcal enterotoxin B is modified by its superantigenic activity. Cell Immunol. 1997;176:166-172. PMID: 9073390
    • Wen R, Cole GA, Surman S, Blackman MA, Woodland DL. MHC class II-associated peptides control the presentation of bacterial superantigen to T-cells. J Exp Med. 1996;183:1083-1092. PMID: 8642250
    • Wen R, Blackman MA, Woodland DL. Variable influence of T cell receptor/MHC interactions on the recognition of bacterial superantigens by T cells. J. Immunol. 1995;155:1884-1892. PMID: 7636239
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