Leslie J Berg PHD
Title Professor
Institution University of Massachusetts Medical School
Department Pathology
Division Academic Pathology
Address University of Massachusetts Medical School
55 Lake Avenue North
Worcester MA 01655
Telephone 508-856-8371
Email
Other Positions
Institution UMMS - Graduate School of Biomedical Sciences
Department Immunology & Virology

Institution UMMS - Graduate School of Biomedical Sciences
Department Interdisciplinary Graduate Program

Institution UMMS - Graduate School of Biomedical Sciences
Department MD/PhD Program

Institution UMMS - Programs, Centers and Institutes
Department Center for AIDS Research
Awards and Honors
2001 American Association of Immunologists Pharmingen Investigator Award for Outstanding Contributions to the field of Immunology
2002 The Medical Foundation Chestnut Hill Award for Excellence in Research
2002 UMMS Outstanding Educator Award
2003 UMMS Educational Achievement Star Award
2004 UMMS Women in Science and Health Achievement Award
2006 American Association of Immunologists Distinguished Service Award
2006 UMMS Outstanding Mentoring Award
2010 UMMS Lamar Souter Award for Excellence in Medical Education
2011 American Association of Immunologists President
Narrative

Dr. Leslie Berg

T lymphocyte development and activation

The research in my laboratory is aimed at understanding the signal transduction pathways important for T lymphocyte development and activation. For these studies, we use a combination of mouse genetics (transgenics and knockouts), biochemistry, and cellular immunology. Our current work focuses on three projects. First, we have identified a tyrosine kinase, Jak3, involved in cytokine receptor signaling, and have generated Jak3-deficient mice. These mice have severe defects in lymphocyte development and function. Second, we have identified a novel tyrosine kinase, Itk, involved in T cell receptor signaling. Using Itk-deficient mice generated in the lab we are currently examining the role of this protein in lymphocyte development and activation.

Publications
1. Malhotra N, Narayan K, Cho OH, Sylvia KE, Yin C, Melichar H, Rashighi M, Lefebvre V, Harris JE, Berg LJ, Kang J. A network of high-mobility group box transcription factors programs innate interleukin-17 production. Immunity. 2013 Apr 18; 38(4):681-93.
  View in: PubMed
 
2. Yin CC, Cho OH, Sylvia KE, Narayan K, Prince AL, Evans JW, Kang J, Berg LJ. The Tec Kinase ITK Regulates Thymic Expansion, Emigration, and Maturation of ?d NKT Cells. J Immunol. 2013 Mar 15; 190(6):2659-69.
  View in: PubMed
 
3. Berg LJ. Signaling pathways that regulate T cell development and differentiation. J Immunol. 2012 Dec 15; 189(12):5487-8.
  View in: PubMed
 
4. Nayar R, Enos M, Prince A, Shin H, Hemmers S, Jiang JK, Klein U, Thomas CJ, Berg LJ. TCR signaling via Tec kinase ITK and interferon regulatory factor 4 (IRF4) regulates CD8+ T-cell differentiation. Proc Natl Acad Sci U S A. 2012 Oct 9; 109(41):E2794-802.
  View in: PubMed
 
5. Narayan K, Sylvia KE, Malhotra N, Yin CC, Martens G, Vallerskog T, Kornfeld H, Xiong N, Cohen NR, Brenner MB, Berg LJ, Kang J. Intrathymic programming of effector fates in three molecularly distinct ?d T cell subtypes. Nat Immunol. 2012 May; 13(5):511-8.
  View in: PubMed
 
6. Chang JT, Ciocca ML, Kinjyo I, Palanivel VR, McClurkin CE, Dejong CS, Mooney EC, Kim JS, Steinel NC, Oliaro J, Yin CC, Florea BI, Overkleeft HS, Berg LJ, Russell SM, Koretzky GA, Jordan MS, Reiner SL. Asymmetric Proteasome Segregation as a Mechanism for Unequal Partitioning of the Transcription Factor T-bet during T Lymphocyte Division. Immunity. 2011 Apr 22; 34(4):492-504.
  View in: PubMed
 
7. Marshall HD, Prince AL, Berg LJ, Welsh RM. IFN-alpha beta and self-MHC divert CD8 T cells into a distinct differentiation pathway characterized by rapid acquisition of effector functions. J Immunol. 2010 Aug 1; 185(3):1419-28.
  View in: PubMed
 
8. Andreotti AH, Schwartzberg PL, Joseph RE, Berg LJ. T-cell signaling regulated by the Tec family kinase, Itk. Cold Spring Harb Perspect Biol. 2010 Jul 1; 2(7):a002287.
  View in: PubMed
 
9. Min L, Wu W, Joseph RE, Fulton DB, Berg L, Andreotti AH. Disrupting the intermolecular self-association of Itk enhances T cell signaling. J Immunol. 2010 Apr 15; 184(8):4228-35.
  View in: PubMed
 
10. Berg LJ. Strength of T cell receptor signaling strikes again. Immunity. 2009 Oct 16; 31(4):529-31.
  View in: PubMed
 
11. Shi M, Lin TH, Appell KC, Berg LJ. Cell cycle progression following naive T cell activation is independent of Jak3/common gamma-chain cytokine signals. J Immunol. 2009 Oct 1; 183(7):4493-501.
  View in: PubMed
 
12. Sacristán C, Schattgen SA, Berg LJ, Bunnell SC, Roy AL, Rosenstein Y. Characterization of a novel interaction between transcription factor TFII-I and the inducible tyrosine kinase in T cells. Eur J Immunol. 2009 Sep; 39(9):2584-95.
  View in: PubMed
 
13. Felices M, Yin CC, Kosaka Y, Kang J, Berg LJ. Tec kinase Itk in gammadeltaT cells is pivotal for controlling IgE production in vivo. Proc Natl Acad Sci U S A. 2009 May 19; 106(20):8308-13.
  View in: PubMed
 
14. Prince AL, Yin CC, Enos ME, Felices M, Berg LJ. The Tec kinases Itk and Rlk regulate conventional versus innate T-cell development. Immunol Rev. 2009 Mar; 228(1):115-31.
  View in: PubMed
 
15. Wu W, Berg LJ. c-Abl, an additional tyrosine kinase required for T cell development and function. Cell Cycle. 2008 Dec 15; 7(24):3791.
  View in: PubMed
 
16. Berg LJ. The "bubble boy" paradox: an answer that led to a question. J Immunol. 2008 Nov 1; 181(9):5815-6.
  View in: PubMed
 
17. Shi M, Lin TH, Appell KC, Berg LJ. Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation. Immunity. 2008 Jun; 28(6):763-73.
  View in: PubMed
 
18. Felices M, Berg LJ. The Tec kinases Itk and Rlk regulate NKT cell maturation, cytokine production, and survival. J Immunol. 2008 Mar 1; 180(5):3007-18.
  View in: PubMed
 
19. Lucas JA, Felices M, Evans JW, Berg LJ. Subtle defects in pre-TCR signaling in the absence of the Tec kinase Itk. J Immunol. 2007 Dec 1; 179(11):7561-7.
  View in: PubMed
 
20. Berg LJ. Signalling through TEC kinases regulates conventional versus innate CD8(+) T-cell development. Nat Rev Immunol. 2007 Jun; 7(6):479-85.
  View in: PubMed
 
21. Felices M, Falk M, Kosaka Y, Berg LJ. Tec kinases in T cell and mast cell signaling. Adv Immunol. 2007; 93:145-84.
  View in: PubMed
 
22. Kosaka Y, Felices M, Berg LJ. Itk and Th2 responses: action but no reaction. Trends Immunol. 2006 Oct; 27(10):453-60.
  View in: PubMed
 
23. Atherly LO, Lucas JA, Felices M, Yin CC, Reiner SL, Berg LJ. The Tec family tyrosine kinases Itk and Rlk regulate the development of conventional CD8+ T cells. Immunity. 2006 Jul; 25(1):79-91.
  View in: PubMed
 
24. Mayack SR, Berg LJ. Cutting edge: an alternative pathway of CD4+ T cell differentiation is induced following activation in the absence of gamma-chain-dependent cytokine signals. J Immunol. 2006 Feb 15; 176(4):2059-63.
  View in: PubMed
 
25. Atherly LO, Brehm MA, Welsh RM, Berg LJ. Tec kinases Itk and Rlk are required for CD8+ T cell responses to virus infection independent of their role in CD4+ T cell help. J Immunol. 2006 Feb 1; 176(3):1571-81.
  View in: PubMed
 
26. Li CR, Berg LJ. Itk is not essential for CD28 signaling in naive T cells. J Immunol. 2005 Apr 15; 174(8):4475-9.
  View in: PubMed
 
27. Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL. Tec family kinases in T lymphocyte development and function. Annu Rev Immunol. 2005; 23:549-600.
  View in: PubMed
 
28. Miller AT, Wilcox HM, Lai Z, Berg LJ. Signaling through Itk promotes T helper 2 differentiation via negative regulation of T-bet. Immunity. 2004 Jul; 21(1):67-80.
  View in: PubMed
 
29. Berg LJ, Nussenzweig M. Signals that regulate lymphocyte development and differentiation. Curr Opin Immunol. 2004 Apr; 16(2):163-6.
  View in: PubMed
 
30. Wilcox HM, Berg LJ. Itk phosphorylation sites are required for functional activity in primary T cells. J Biol Chem. 2003 Sep 26; 278(39):37112-21.
  View in: PubMed
 
31. Lucas JA, Miller AT, Atherly LO, Berg LJ. The role of Tec family kinases in T cell development and function. Immunol Rev. 2003 Feb; 191:119-38.
  View in: PubMed
 
32. Vergara-Silva A, Schaefer KL, Berg LJ. Compartmentalized Eph receptor and ephrin expression in the thymus. Gene Expr Patterns. 2002 Dec; 2(3-4):261-5.
  View in: PubMed
 
33. Vergara-Silva A, Schaefer KL, Berg LJ. Compartmentalized Eph receptor and ephrin expression in the thymus. Mech Dev. 2002 Dec; 119 Suppl 1:S225-9.
  View in: PubMed
 
34. Lucas JA, Atherly LO, Berg LJ. The absence of Itk inhibits positive selection without changing lineage commitment. J Immunol. 2002 Jun 15; 168(12):6142-51.
  View in: PubMed
 
35. Miller AT, Berg LJ. New insights into the regulation and functions of Tec family tyrosine kinases in the immune system. Curr Opin Immunol. 2002 Jun; 14(3):331-40.
  View in: PubMed
 
36. Miller AT, Berg LJ. Defective Fas ligand expression and activation-induced cell death in the absence of IL-2-inducible T cell kinase. J Immunol. 2002 Mar 1; 168(5):2163-72.
  View in: PubMed
 
37. Soldevila G, Castellanos C, Malissen M, Berg LJ. Analysis of the individual role of the TCRzeta chain in transgenic mice after conditional activation with chemical inducers of dimerization. Cell Immunol. 2001 Dec 15; 214(2):123-38.
  View in: PubMed
 
38. Cui Y, Hackenmiller R, Berg L, Jean F, Nakayama T, Thomas G, Christian JL. The activity and signaling range of mature BMP-4 is regulated by sequential cleavage at two sites within the prodomain of the precursor. Genes Dev. 2001 Nov 1; 15(21):2797-802.
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39. Berg LJ, Kang J. Molecular determinants of TCR expression and selection. Curr Opin Immunol. 2001 Apr; 13(2):232-41.
  View in: PubMed
 
40. Gozalo-Sanmillan S, McNally JM, Lin MY, Chambers CA, Berg LJ. Cutting edge: two distinct mechanisms lead to impaired T cell homeostasis in Janus kinase 3- and CTLA-4-deficient mice. J Immunol. 2001 Jan 15; 166(2):727-30.
  View in: PubMed
 
41. Yang WC, Ching KA, Tsoukas CD, Berg LJ. Tec kinase signaling in T cells is regulated by phosphatidylinositol 3-kinase and the Tec pleckstrin homology domain. J Immunol. 2001 Jan 1; 166(1):387-95.
  View in: PubMed
 
42. Baird AM, Lucas JA, Berg LJ. A profound deficiency in thymic progenitor cells in mice lacking Jak3. J Immunol. 2000 Oct 1; 165(7):3680-8.
  View in: PubMed
 
43. Bunnell SC, Diehn M, Yaffe MB, Findell PR, Cantley LC, Berg LJ. Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade. J Biol Chem. 2000 Jan 21; 275(3):2219-30.
  View in: PubMed
 
44. Berg L, Rönnelid J, Sanjeevi CB, Lampa J, Klareskog L. Interferon-gamma production in response to in vitro stimulation with collagen type II in rheumatoid arthritis is associated with HLA-DRB1(*)0401 and HLA-DQ8. Arthritis Res. 2000; 2(1):75-84.
  View in: PubMed
 
45. Thomis DC, Aramburu J, Berg LJ. The Jak family tyrosine kinase Jak3 is required for IL-2 synthesis by naive/resting CD4+ T cells. J Immunol. 1999 Nov 15; 163(10):5411-7.
  View in: PubMed
 
46. Fernandes DM, Baird AM, Berg LJ, Rock KL. A monoclonal antibody reactive with a 40-kDa molecule on fetal thymocytes and tumor cells blocks proliferation and stimulates aggregation and apoptosis. J Immunol. 1999 Aug 1; 163(3):1306-14.
  View in: PubMed
 
47. Grossman WJ, Verbsky JW, Yang L, Berg LJ, Fields LE, Chaplin DD, Ratner L. Dysregulated myelopoiesis in mice lacking Jak3. Blood. 1999 Aug 1; 94(3):932-9.
  View in: PubMed
 
48. Baird AM, Gerstein RM, Berg LJ. The role of cytokine receptor signaling in lymphocyte development. Curr Opin Immunol. 1999 Apr; 11(2):157-66.
  View in: PubMed
 
49. Yelon D, Schaefer KL, Berg LJ. Alterations in CD4-binding regions of the MHC class II molecule I-Ek do not impede CD4+ T cell development. J Immunol. 1999 Feb 1; 162(3):1348-58.
  View in: PubMed
 
50. Durum SK, Candèias S, Nakajima H, Leonard WJ, Baird AM, Berg LJ, Muegge K. Interleukin 7 receptor control of T cell receptor gamma gene rearrangement: role of receptor-associated chains and locus accessibility. J Exp Med. 1998 Dec 21; 188(12):2233-41.
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51. Baird AM, Thomis DC, Berg LJ. T cell development and activation in Jak3-deficient mice. J Leukoc Biol. 1998 Jun; 63(6):669-77.
  View in: PubMed
 
52. Liu KQ, Bunnell SC, Gurniak CB, Berg LJ. T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells. J Exp Med. 1998 May 18; 187(10):1721-7.
  View in: PubMed
 
53. Bunnell SC, Berg LJ. The signal transduction of motion and antigen recognition: factors affecting T cell function and differentiation. Genet Eng (N Y). 1998; 20:63-110.
  View in: PubMed
 
54. Thomis DC, Lee W, Berg LJ. T cells from Jak3-deficient mice have intact TCR signaling, but increased apoptosis. J Immunol. 1997 Nov 15; 159(10):4708-19.
  View in: PubMed
 
55. Heyeck SD, Wilcox HM, Bunnell SC, Berg LJ. Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity. J Biol Chem. 1997 Oct 3; 272(40):25401-8.
  View in: PubMed
 
56. Ohta K, Pang XP, Berg L, Hershman JM. Growth inhibition of new human thyroid carcinoma cell lines by activation of adenylate cyclase through the beta-adrenergic receptor. J Clin Endocrinol Metab. 1997 Aug; 82(8):2633-8.
  View in: PubMed
 
57. Thomis DC, Berg LJ. The role of Jak3 in lymphoid development, activation, and signaling. Curr Opin Immunol. 1997 Aug; 9(4):541-7.
  View in: PubMed
 
58. Yelon D, Berg LJ. Structurally similar TCRs differ in their efficiency of positive selection. J Immunol. 1997 Jun 1; 158(11):5219-28.
  View in: PubMed
 
59. Thomis DC, Berg LJ. Peripheral expression of Jak3 is required to maintain T lymphocyte function. J Exp Med. 1997 Jan 20; 185(2):197-206.
  View in: PubMed
 
60. Andreotti AH, Bunnell SC, Feng S, Berg LJ, Schreiber SL. Regulatory intramolecular association in a tyrosine kinase of the Tec family. Nature. 1997 Jan 2; 385(6611):93-7.
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61. Gurniak CB, Thomis DC, Berg LJ. Genomic structure and promoter region of the murine Janus-family tyrosine kinase, Jak3. DNA Cell Biol. 1997 Jan; 16(1):85-94.
  View in: PubMed
 
62. Bunnell SC, Henry PA, Kolluri R, Kirchhausen T, Rickles RJ, Berg LJ. Identification of Itk/Tsk Src homology 3 domain ligands. J Biol Chem. 1996 Oct 11; 271(41):25646-56.
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63. Kammer W, Lischke A, Moriggl R, Groner B, Ziemiecki A, Gurniak CB, Berg LJ, Friedrich K. Homodimerization of interleukin-4 receptor alpha chain can induce intracellular signaling. J Biol Chem. 1996 Sep 27; 271(39):23634-7.
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64. Fayolle C, Abdel-Motal UM, Berg L, Deriaud E, Jondal M, Leclerc C. Induction of cytotoxic T-cell response by optimal-length peptides does not require CD4+ T-cell help. Immunology. 1996 Sep; 89(1):41-5.
  View in: PubMed
 
65. Gurniak CB, Berg LJ. A new member of the Eph family of receptors that lacks protein tyrosine kinase activity. Oncogene. 1996 Aug 15; 13(4):777-86.
  View in: PubMed
 
66. Yelon D, Spain LM, Lim K, Berg LJ. Alterations in CD4 dependence accompany T cell development and differentiation. Int Immunol. 1996 Jul; 8(7):1077-90.
  View in: PubMed
 
67. Lyons DS, Lieberman SA, Hampl J, Boniface JJ, Chien Y, Berg LJ, Davis MM. A TCR binds to antagonist ligands with lower affinities and faster dissociation rates than to agonists. Immunity. 1996 Jul; 5(1):53-61.
  View in: PubMed
 
68. Gurniak CB, Berg LJ. Murine JAK3 is preferentially expressed in hematopoietic tissues and lymphocyte precursor cells. Blood. 1996 Apr 15; 87(8):3151-60.
  View in: PubMed
 
69. Abdel-Motal UM, Berg L, Rosén A, Bengtsson M, Thorpe CJ, Kihlberg J, Dahmén J, Magnusson G, Karlsson KA, Jondal M. Immunization with glycosylated Kb-binding peptides generates carbohydrate-specific, unrestricted cytotoxic T cells. Eur J Immunol. 1996 Mar; 26(3):544-51.
  View in: PubMed
 
70. Abdel-Motal UM, Berg L, Bengtsson M, Dahmén J, Kihlberg J, Magnusson G, Nilsson U, Jondal M. Major histocompatibility complex class I binding glycopeptides for the estimation of 'empty' class I molecules. J Immunol Methods. 1995 Dec 15; 188(1):21-31.
  View in: PubMed
 
71. Thomis DC, Gurniak CB, Tivol E, Sharpe AH, Berg LJ. Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking Jak3. Science. 1995 Nov 3; 270(5237):794-7.
  View in: PubMed
 
72. Liao JC, Berg LJ, Jay DG. Chromophore-assisted laser inactivation of subunits of the T-cell receptor in living cells is spatially restricted. Photochem Photobiol. 1995 Nov; 62(5):923-9.
  View in: PubMed
 
73. Raab M, Cai YC, Bunnell SC, Heyeck SD, Berg LJ, Rudd CE. p56Lck and p59Fyn regulate CD28 binding to phosphatidylinositol 3-kinase, growth factor receptor-bound protein GRB-2, and T cell-specific protein-tyrosine kinase ITK: implications for T-cell costimulation. Proc Natl Acad Sci U S A. 1995 Sep 12; 92(19):8891-5.
  View in: PubMed
 
74. Lieberman SA, Spain LM, Wang L, Berg LJ. Enhanced T cell maturation and altered lineage commitment in T cell receptor/CD4-transgenic mice. Cell Immunol. 1995 Apr 15; 162(1):56-67.
  View in: PubMed
 
75. Spain LM, Yelon D, Berg LJ. Do the CD4 and CD8 lineages represent parallel pathways? Semin Immunol. 1994 Aug; 6(4):213-20.
  View in: PubMed
 
76. Spain LM, Jorgensen JL, Davis MM, Berg LJ. A peptide antigen antagonist prevents the differentiation of T cell receptor transgenic thymocytes. J Immunol. 1994 Feb 15; 152(4):1709-17.
  View in: PubMed
 
77. Sakaguchi S, Ermak TH, Toda M, Berg LJ, Ho W, Fazekas de St Groth B, Peterson PA, Sakaguchi N, Davis MM. Induction of autoimmune disease in mice by germline alteration of the T cell receptor gene expression. J Immunol. 1994 Feb 1; 152(3):1471-84.
  View in: PubMed
 
78. Berg LJ. Insights into the role of the immune system in prion diseases. Proc Natl Acad Sci U S A. 1994 Jan 18; 91(2):429-32.
  View in: PubMed
 
79. Spain LM, Berg LJ. Quantitative analysis of the efficiency of clonal deletion in the thymus. Dev Immunol. 1994; 4(1):43-53.
  View in: PubMed
 
80. Heyeck SD, Berg LJ. Developmental regulation of a murine T-cell-specific tyrosine kinase gene, Tsk. Proc Natl Acad Sci U S A. 1993 Jan 15; 90(2):669-73.
  View in: PubMed
 
81. Spain LM, Berg LJ. Developmental regulation of thymocyte susceptibility to deletion by "self"-peptide. J Exp Med. 1992 Jul 1; 176(1):213-23.
  View in: PubMed
 
82. Berg LJ, Frank GD, Davis MM. The effects of MHC gene dosage and allelic variation on T cell receptor selection. Cell. 1990 Mar 23; 60(6):1043-53.
  View in: PubMed
 
83. Berg LJ, Davis MM. T-cell development in T cell receptor alphabeta transgenic mice. Semin Immunol. 1989 Nov; 1(2):105-16.
  View in: PubMed
 
84. Berg LJ. Generation of the T cell repertoire. Curr Opin Immunol. 1989 Oct; 2(1):87-92.
  View in: PubMed
 
85. Berg LJ, Pullen AM, Fazekas de St Groth B, Mathis D, Benoist C, Davis MM. Antigen/MHC-specific T cells are preferentially exported from the thymus in the presence of their MHC ligand. Cell. 1989 Sep 22; 58(6):1035-46.
  View in: PubMed
 
86. Berg LJ, Fazekas de St Groth B, Pullen AM, Davis MM. Phenotypic differences between alpha beta versus beta T-cell receptor transgenic mice undergoing negative selection. Nature. 1989 Aug 17; 340(6234):559-62.
  View in: PubMed
 
87. Davis MM, Berg LJ, Lin AY, Fazekas de St Groth B, Devaux B, Sagerstrom CG, Bjorkman PJ, Elliott JF. TCR recognition and selection in vivo. Cold Spring Harb Symp Quant Biol. 1989; 54 Pt 1:119-28.
  View in: PubMed
 
88. Berg LJ, Fazekas de St Groth B, Ivars F, Goodnow CC, Gilfillan S, Garchon HJ, Davis MM. Expression of T-cell receptor alpha-chain genes in transgenic mice. Mol Cell Biol. 1988 Dec; 8(12):5459-69.
  View in: PubMed
 
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Co-Authors  
Brehm, Michael
Gerstein, Rachel
Kang, Joonsoo
Rock, Kenneth
Welsh, Raymond
See all (9) people
Physical Neighbors  
Nieburgs, Herbert
Rock, Kenneth
Selin, Liisa
Welsh, Raymond
Strutt, Tara

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