Faculty Summaries
David L. Wiest, PhD
David L. Wiest, PhD
Member & Professor
  • Deputy Chief Scientific Officer
  • Co-Leader, Blood Cell Development and Function
  • Adjunct Associate Professor, Thomas Jefferson University
Office Phone: 215-728-2966
Lab Phone: 215-728-2968
Fax: 215-728-2412
Office: 383A
Lab: R364


  • Coffey, F., Lee, S.-Y., Buus, T.B., Lauritsen, J.-P.H., Wong, G.W., Zúñiga-Pflücker, J.C., Kappes, D.J., and Wiest, D.L. 2014. The TCR ligand-inducible expression of CD73 marks γδ lineage commitment and a metastable intermediate in effector specification. J. Exp. Med. 211:329-43. PMC3920555


  • Dutta, M., Kraus, Z.J., Gomez-Rodriguez, J., Hwang, S.H., Cannons, J.L., Cheng, J., Lee, S.Y., Wiest, D.L., Wakeland, E.K., Schwartzberg, P.L. 2013. A Role for Ly108 in the Induction of Promyelocytic Zinc Finger Transcription Factor in Developing Thymocytes. J Immunol. 190:2121-2128.
  • O’Leary, M.N., Hughes, K.J., Steffen, K.K., Zhang, Y., Duc, A.-C., Rao, S., Hale, J.S., Shah, S.R., Thompson, W., Morton, J.F., Holstein, C.A., Martin, D.B., Kaeberlein, M., Ladiges, W.C., Fink, P.J., MacKay, V.L., Wiest, D.L., and Kennedy, B.K. 2013. The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1. PLOS Genetics 9:e1003708. PMC3750023
  • Zhang, Y., Duc, A.-C.E., Rao, S., Sun, X.-L., Bilbee, A.N., Rhodes, M., Li, Q., Kappes, D.J., Rhodes, J., and Wiest, D.L., 2013. Control of hematopoietic stem cell emergence by antagonistic functions of ribosomal protein paralogs. Dev. Cell 24:411-425. NIHMS440478


  • Del Blanco B., García-Mariscal A., Wiest D.L., Hernández-Munain C.J. Tcrα Enhancer Activation by Inducible Transcription Factors Downstream of Pre-TCR Signaling. J. Immunol. 2012;188:3278-3293. NIHMS#400500
  • Qiao, Y., Zhu, L., Sofi, H., Lapinski, P.E., Horai, R., Mueller, K., Stritesky, G.L., He, X., Maillard, I., Teh, H.-S., Wiest, D.L, Kappes, D.J., King, P.D., Hogquist, K., Schwartzberg, P.L., Sant’Angelo, D.B., and Chang, C.-H. Development of PLZF expressing innate CD4 T cells require stronger T cell receptor signals than conventional CD4 T cells. PNAS 109:16264-16269. PMC3479572
  • Rao, S., Lee, S.Y., Gutierrez, A., Perrigoue, J., Thapa, R.J., Tu, Z., Jeffers, J.R., Rhodes, M., Anderson, S., Oravecz, T., Hunger, S.P., Timakhov, R.A., Zhang, R., Balachandran, S., Zambetti, G., Testa, J.R., Look, A.T., and Wiest., D.L. 2012. Inactivation of the ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood 120:3764-3773. PMC3488889
  • Roberts, J.L., Buckley, R.H., Liu, B., Pei, J., Lapidus, A., Peri, S., Wei, Q., Shin, J.,. Parrott, R.E., Dunbrack, R., Testa3,, J.R., Zhong, X.-P., and Wiest, D.L. CD45 deficient severe combined immunodeficiency caused by uniparental disomy. PNAS 2012; 109:10456-10461. PMC3387083


  • Hu, T., Gimferrer, I., Simmons, A. Wiest, D., and Alberola-Ila, J. The Ras/MAPK Pathway Is Required for Generation of iNKT Cells. PLoS One 2011; 6:e19890. PMC3091886
  • Stadanlick, J.E., Zhiqiang, Z., Lee, S.-Y., Hemann, M., Biery, M., Carleton, M.O., Zambetti, G.P., Anderson, S.J., Oravecz, T., and Wiest, D.L. Developmental arrest of T cells in Rpl22-deficient mice is dependent upon multiple p53 effectors. J. Immunol. 2011; 187:664-6775. PMC3131471


  • Jin Y, Xia M, Saylor C, Narayan K, Kang J, Wiest DL, and Xiong N. Intrinsic programming of thymic T cells for peripheral distribution and development. J Immunol. Forthcoming 2010.
  • Lee SY, Stadanlick J, Kappes DJ, Wiest DL. Towards a molecular understanding of the differential signals regulating αβ/γδ T lineage choice. Sem Immunol. 2010;22:237-246. PMC2906684
  • Park K, He X, Lee HO, Hua X, Li Y, Wiest D, Kappes DJ. TCR-mediated ThPOK induction promotes development of mature (CD24-) γδ thymocytes. EMBO J. 2010;29:2329-2341. PMC2910264
  • Tan Y, You H, Coffey FJ, Wiest DL, Testa JR. Appl1 is Dispensable for Akt Signaling in vivo and Mouse T Cell Development. Genesis. 2010 Sep;48(9):531-539. NIHMS231841
  • Wiest DL. Origins of γδT cells: a forum for opposing perspectives. Editorial. Sem Immunol. 2010;22:191-192.
  • Xia M, Qi Q, Jin Y, Wiest DL, August A, Xiong N. Differential roles for the tyrosine kinase Itk in tissue-specific localization and maintenance of skin intraepithelial T cells. J. Immunol. 2010;184:6807-6814. NIHMS232667


  • Hu, T., Gimferrer, I., Simmons, A. Wiest, D., and Alberola-Ila, J. The Ras/MAPK Pathway Is Required for Generation of iNKT Cells. PLoS One 2011; 6:e19890. PMC3091886
  • Stadanlick, J.E., Zhiqiang, Z., Lee, S.-Y., Hemann, M., Biery, M., Carleton, M.O., Zambetti, G.P., Anderson, S.J., Oravecz, T., and Wiest, D.L. Developmental arrest of T cells in Rpl22-deficient mice is dependent upon multiple p53 effectors. J. Immunol. 2011; 187:664-6775. PMC3131471


  • Lauritsen JP, Wong GW, Lee SY, Lefebvre JM, Ciofani M, Rhodes M, Kappes DJ, Zúñiga-Pflücker JC, Wiest DL. Marked induction of the helix-loop-helix protein Id3 promotes the γδ T cell fate and renders their functional maturation Notch-independent. Immunity. 2009;31(4):565-575.
  • Paul E, Cronan R, Weston PJ et al. Disruption of Supv3L1 damages the skin and causes sarcopenia, loss of fat, and death. Mamm Genome. 2009;20(2):92-108.
  • Timakhov RA, Tan Y, Rao M, Liu Z, Altomare DA, Pei J, Wiest DL, Favorova OO, Knepper JE, Testa JR. Recurrent chromosomal rearrangements implicate oncogenes that contribute to T-cell lymphomagenesis in Akt2 transgenic mice. Genes Chromosomes Cancer. 2009;48(9):786-94.
  • Wiest, D.L. Identification of the last cog in a ligand-independent signaling machine? Pillars Commentary. J. Immunol. 2009;182:5163-4.
  • Xu M, Sharma A, Hossain MZ et al. Sustained expression of pre-TCR induced beta-catenin in post-beta-selection thymocytes blocks T cell development. J Immunol. 2009a;182 (2):759-65.
  • Xu M, Sharma A, Wiest DL et al. Pre-TCR-induced beta-catenin facilitates traversal through beta-selection. J Immunol. 2009b;182(2):751-8.


  • Lauritsen JP, Kurella S, Lee SY et al. Egr2 is required for Bcl-2 induction during positive selection. J Immunol. 2008;181(11):7778-85.
  • Tan Y, Timakhov RA, Rao M et al. A novel recurrent chromosomal inversion implicates the homeobox gene Dlx5 in T-cell lymphomas from Lck-Akt2 transgenic mice. Cancer Res. 2008;68(5):1296-302.


  • Anderson SJ, Lauritsen JP, Hartman MG et al. Ablation of ribosomal protein L22 selectively impairs alphabeta T cell development by activation of a p53-dependent checkpoint. Immunity 2007;26(6):759-72.
  • Carter JH, Lefebvre JM, Wiest DL et al. Redundant role for early growth response transcriptional regulators in thymocyte differentiation and survival. J Immunol 2007;178(11):6796-805.
  • Koltsova EK, Ciofani M, Benezra R et al. Early growth response 1 and NF-ATc1 act in concert to promote thymocyte development beyond the beta-selection checkpoint. J Immunol. 2007a;179(7):4694-703.
  • Koltsova EK, Wiest DL, Vavilova TP. Transcription factors NFAT2 and Egr1 cooperatively regulate the maturation of T-lymphoma in vitro. Biochemistry (Mosc). 2007b;72(9):954-61.
  • Mao C, Tili EG, Dose M et al. Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. J Immunol. 2007; 178(9):5443-53.
  • Michie AM, Chan AC, Ciofani M et al. Constitutive Notch signalling promotes CD4 CD8 thymocyte differentiation in the absence of the pre-TCR complex, by mimicking pre-TCR signals. Int Immunol. 2007;19(12):1421-30.
  • Roberts JL, Lauritsen JP, Cooney M et al. T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex. Blood. 2007;109(8):3198-206.
  • Schrum AG, Gil D, Dopfer EP et al. High-sensitivity detection and quantitative analysis of native protein-protein interactions and multiprotein complexes by flow cytometry. Sci STKE. 2007;2007(389):pl2.
  • Zayed H, Xia L, Yerich A et al. Correction of DNA protein kinase deficiency by spliceosome-mediated RNA trans-splicing and sleeping beauty transposon delivery. Mol Ther. 2007;15(7):1273-9.


  • Ciofani M, Knowles GC, Wiest DL et al. Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation. Immunity 2006; 25 (1):105-16.
  • Ke J, Gururajan M, Kumar A et al. The role of MAPKs in B cell receptor-induced down-regulation of Egr-1 in immature B lymphoma cells. J Biol Chem 2006; 281 (52):39806-18.
  • Lauritsen JP, Haks MC, Lefebvre JM et al. Recent insights into the signals that control alphabeta/gammadelta-lineage fate. Immunol Rev 2006; 209:176-90.
  • Yamasaki S, Ishikawa E, Sakuma M et al. Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development. Nat Immunol 2006; 7 (1):67-75.
  • Zayed H, McIvor RS, Wiest DL et al. In vitro functional correction of the mutation responsible for murine severe combined immune deficiency by small fragment homologous replacement. Hum Gene Ther 2006; 17 (2):158-66.


  • Dionne CJ, Tse KY, Weiss AH et al. Subversion of T lineage commitment by PU.1 in a clonal cell line system. Dev Biol. 2005;280(2):448-66.
  • Haks MC, Lefebvre JM, Lauritsen JP et al. Attenuation of gammadeltaTCR signaling efficiently diverts thymocytes to the alphabeta lineage. Immunity. 2005;22(5):595-606.
  • Lefebvre JM, Haks MC, Carleton MO et al. Enforced expression of Spi-B reverses T lineage commitment and blocks beta-selection. J Immunol. 2005;174(10):6184-94.


  • La Gruta NL, Liu H, Dilioglou S et al. Architectural changes in the TCR:CD3 complex induced by MHC:peptide ligation. J Immunol. 2004;172(6):3662-9.


    • Haks MC, Belkowski SM, Ciofani M et al. Low activation threshold as a mechanism for ligand-independent signaling in pre-T cells. J Immunol. 2003;170(6):2853-61.


    • Carleton M, Haks MC, Smeele SA et al. Early growth response transcription factors are required for development of CD4(-)CD8(-) thymocytes to the CD4(+)CD8(+) stage. J Immunol 2002;168(4):1649-58.


    • Berger MA, Carleton M, Rhodes M et al. Identification of a novel pre-TCR isoform in which the accessibility of the TCR beta subunit is determined by occupancy of the 'missing' V domain of pre-T alpha. Int Immunol. 2000;12(11):1579-91.
    • Kruisbeek AM, Haks MC, Carleton M et al. Branching out to gain control: how the pre-TCR is linked to multiple functions. Immunol Today. 2000;21(12):637-44.
    • Liu H, Rhodes M, Wiest DL et al. On the dynamics of TCR:CD3 complex cell surface expression and downmodulation. Immunity. 2000;13(5):665-75.
    • Trop S, Rhodes M, Wiest DL et al. Competitive displacement of pT alpha by TCR-alpha during TCR assembly prevents surface coexpression of pre-TCR and alpha beta TCR. J Immunol. 2000;165(10):5566-72.


    • Ashe JM, Wiest DL, Abe R et al. ZAP-70 protein promotes tyrosine phosphorylation of T cell receptor signaling motifs (ITAMs) in immature CD4(+)8(+) thymocytes with limiting p56(lck). J Exp Med. 1999; 189(7):1163-8.
    • Carleton M, Ruetsch NR, Berger MA et al. Signals transduced by CD3epsilon, but not by surface pre-TCR complexes, are able to induce maturation of an early thymic lymphoma in vitro. J Immunol. 1999;163(5):2576-85.
    • Dave VP, Allman D, Wiest DL et al. Limiting TCR expression leads to quantitative but not qualitative changes in thymic selection. J Immunol. 1999;162(10):5764-74.
    • Gui M, Wiest DL, Li J et al. Peripheral CD4+ T cell maturation recognized by increased expression of Thy-1/CD90 bearing the 6C10 carbohydrate epitope. J Immunol. 1999;163(9):4796-804.
    • Keefe R, Dave V, Allman D et al. Regulation of lineage commitment distinct from positive selection. Science. 1999;286(5442):1149-53.
    • Michie AM, Trop S, Wiest DL et al. Extracellular signal-regulated kinase (ERK) activation by the pre-T cell receptor in developing thymocytes in vivo. J Exp Med. 1999;190(11):1647-56.
    • Trop S, Steff AM, Denis F et al. The connecting peptide domain of pT alpha dictates weak association of the pre-T cell receptor with the TCR zeta subunit. Eur J Immunol. 1999;29(7):2187-96.
    • Wiest DL, Berger MA, Carleton M. Control of early thymocyte development by the pre-T cell receptor complex: A receptor without a ligand? Semin Immunol. 1999;11(4):251-62.


    • Dave VP, Keefe R, Berger MA et al. Altered functional responsiveness of thymocyte subsets from CD3delta-deficient mice to TCR-CD3 engagement. Int Immunol. 1998;10(10):1481-90.
    • Fuller-Espie S, Hoffman Towler P, Wiest DL et al. Transmembrane polar residues of TCR beta chain are required for signal transduction. Int Immunol. 1998;10(7):923-33.
    • Wasserman R, Li YS, Shinton SA et al. A novel mechanism for B cell repertoire maturation based on response by B cell precursors to pre-B receptor assembly. J Exp Med. 1998;187(2):259-64.


    • Berger MA, Dave V, Rhodes MR et al. Subunit composition of pre-T cell receptor complexes expressed by primary thymocytes: CD3 delta is physically associated but not functionally required. J Exp Med. 1997;186(9):1461-7.
    • Wiest DL, Ashe JM, Howcroft TK et al. A spontaneously arising mutation in the DLAARN motif of murine ZAP-70 abrogates kinase activity and arrests thymocyte development. Immunity. 1997a;6(6):663-71.
    • Wiest DL, Bhandoola A, Punt J et al. Incomplete endoplasmic reticulum (ER) retention in immature thymocytes as revealed by surface expression of "ER-resident" molecular chaperones. Proc Natl Acad Sci U S A. 1997b;94(5):1884-9.


    • Wiest DL, Ashe JM, Abe R et al. TCR activation of ZAP70 is impaired in CD4+CD8+ thymocytes as a consequence of intrathymic interactions that diminish available p56lck. Immunity. 1996;4(5):495-504.


    • Kearse KP, Roberts JP, Wiest DL et al. Developmental regulation of alpha beta T cell antigen receptor assembly in immature CD4+CD8+ thymocytes. Bioessays. 1995;17(12):1049-54.
    • Wiest DL, Burgess WH, McKean D et al. The molecular chaperone calnexin is expressed on the surface of immature thymocytes in association with clonotype-independent CD3 complexes. Embo J. 1995;14(14):3425-33.


    • Benveniste P, Takahama Y, Wiest DL et al. Engagement of the external domains of CD45 tyrosine phosphatase can regulate the differentiation of immature CD4+CD8+ thymocytes into mature T cells. Proc Natl Acad Sci U S A. 1994;91(15):6933-7.
    • Kearse KP, Roberts JL, Munitz TI et al. Developmental regulation of alpha beta T cell antigen receptor expression results from differential stability of nascent TCR alpha proteins within the endoplasmic reticulum of immature and mature T cells. Embo J. 1994;13(19):4504-14.
    • Wiest DL, Kearse KP, Shores EW et al. Developmentally regulated expression of CD3 components independent of clonotypic T cell antigen receptor complexes on immature thymocytes. J Exp Med. 1994;180(4):1375-82.


    • Kearse KP, Wiest DL, Singer A. Subcellular localization of T-cell receptor complexes containing tyrosine-phosphorylated zeta proteins in immature CD4+CD8+ thymocytes. Proc Natl Acad Sci U S A. 1993;90(6):2438-42.
    • Nakayama T, Wiest DL, Abraham KM et al. Decreased signaling competence as a result of receptor overexpression: overexpression of CD4 reduces its ability to activate p56lck tyrosine kinase and to regulate T-cell antigen receptor expression in immature CD4+CD8+ thymocytes. Proc Natl Acad Sci U S A. 1993;90(22):10534-8.
    • Shores EW, Nakayama T, Wiest DL et al. Structurally distinct T cell receptor complexes on developmentally distinct T cell populations in severe combined immunodeficiency mice expressing a TCR beta transgene. J Immunol. 1993;150(4):1263-75.
    • Wiest DL, Yuan L, Jefferson J et al. Regulation of T cell receptor expression in immature CD4+CD8+ thymocytes by p56lck tyrosine kinase: basis for differential signaling by CD4 and CD8 in immature thymocytes expressing both coreceptor molecules. J Exp Med. 1993;178(5):1701-12.


    • Cenciarelli C, Hou D, Hsu KC et al. Activation-induced ubiquitination of the T cell antigen receptor. Science 1992;257(5071):795-7.


    • Cenciarelli C, Hou D, Hsu KC et al. Activation-induced ubiquitination of the T cell antigen receptor. Science. 1992;257(5071):795-7.
    • Wiest DL, Burkhardt JK, Hester S et al. Membrane biogenesis during B cell differentiation: most endoplasmic reticulum proteins are expressed coordinately. J Cell Biol. 1990;110(5):1501-11.


    • Wiest DL, Burkhardt JK, Stockdale AM et al. Expression of intracisternal A-type particles is increased when a B-cell lymphoma differentiates into an immunoglobulin-secreting cell. J Virol. 1989;63(2):659-68.


    • Stockdale AM, Dul JL, Wiest DL et al. The expression of membrane and secreted immunoglobulin during the in vitro differentiation of the murine B cell lymphoma CH12. J Immunol. 1987;139(10):3527-35.


    • Gaffney EV, Dell'Aquila ML, Lingenfelter SE et al. Characterization of a colony-stimulating factor produced by the human monocytic leukemia cell line, THP-1. J Leukoc Biol. 1986;39(4):409-21.