Faculty of Medicine, Dentistry and Health Sciences Department of Microbiology and Immunology

Godfrey Laboratory

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Include: Research Interests | Major Research Projects | Laboratory Staff | Recent Publications

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Professor Dale Godfrey's Home Page

Research Interests

The laboratory is interested in understanding the development and function of NKT cells.

The research program is divided into three major areas.The first is to investigate NKT cell development and homeostasis. The second focus of the laboratory is to understand the role that NK cells play in tumour immunity. The third area of interest is T cell development and the role of glucocorticoid hormones.

Major Research Projects

  1. NKT cell development and selection in mice and humans
  2. NKT cell subsets and functional diversity
  3. NKT cells and tumour immunity
  4. NKT cell function in autoimmunity
  5. The role of glycolipid antigens in NKT cell development and function
  6. Glucocorticoids and T cell development and function
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Laboratory Staff

Laboratory Head: Dale Godfrey

Senior Research Officer: Stuart Berzins

Research Fellows: Sumone Chakravarti, Angela Chan, Adam Uldrich

Research Assistants: Daniel Pellicci, Konstantinos Kyparissoudis, Lila Serwecinska

PhD Students: Jonathan Coquet, Finlay McNab, Jesse Thomas, Douglas Liddicoat, Lauren Pitt, Marie Fletcher, Paul Bolitho

Lab Safety/Training Manager: Nadine Crowe

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Recent Publications

  1. Smyth MJ, Crowe NC, Pellicci D, Kyparissoudis K, Kelly JM, Takeda K, Yagita H, Godfrey DI. Sequential production of interferon-gamma by NK1.1(+) T cells and natural killer cells is essential for the antimetastatic effect of alpha-galactosylceramide. Blood 2002; 99: 1259-1266.

    Highlighted in Curr Opin Immunol – paper alert section.
    Cited by Faculty of 1000 as “Recommended”

  2. Kelly J, Darcy PK, Markby JL, Godfrey DI, Takeda K, Yagita H, Smyth MJ. Potent NK cell-mediated tumor rejection triggered by CD70 promotes subsequent T cell anti-tumor immunity. Nature Immunology 2002; 3: 83-90.

    Highlighted in Curr Opin Immunol – paper alert section
    Cited by Faculty of 1000 as “Must read”

  3. Bouillet P, Purton JF, Godfrey DI, Coultas L, O'Reilly, LA, Puthalakath H, Cory S, Adams JM, Strasser A. Pro-Apoptotic BH3-Only Bcl-2 Family Member Bim Is Required for TCR Ligation-Induced Apoptosis of Autoreactive Thymocytes. Nature 2002; 415: 922-926.

    Highlighted in Science – Perspective article, and Nature Immunology – highlight section.

  4. Pellicci DG, Hammond KJL, Uldrich AP, Baxter AG, Smyth MJ, Godfrey DI. A Natural Killer T (NKT) cell developmental pathway involving a thymus dependent NK1.1-CD4+ CD1d-dependent precursor stage. J Exp Med 2002;195: 835-844.

    Cited by Faculty of 1000 as “Must read”

  5. Crowe NY, Smyth MJ*, Godfrey DI*. * Equal chief investigators. A critical role for natural killer T (NKT) cells in immunosurveillance against methylcholanthrene induced fibrosarcomas. J Exp Med 2002;196: 119-127.
  6. Purton JF, Zahn Y, Hardy CL, Liddicoat D, Lew A, Cole TJ*, Godfrey DI*. * Equal chief investigators. Normal T cell development, repertoire diversity, and peripheral maintenance in the absence of glucocorticoid receptor signalling. Eur J Immunol 2002; 32: 3546-3555.
  7. Zhan Y, Purton JF, Godfrey DI, Cole TJ, Heath WR, Lew AM. (2003) Without peripheral interference, thymic deletion is mediated in a cohort of double positive cells without classical activation. PNAS 2003; 100: 1197-2002.
  8. Cornish AL, Davey GM, Metcalf D, Purton JF, Corbin JE, Greenhalgh CJ, Darwiche R, Wu L, Nicola NA, Godfrey DI, Heath WR, Hilton DJ, Alexander WS, and Starr R. SOCS-1 has IFNg-independent actions in T-cell homeostasis. J Immunol 2003;170: 878-886.
  9. Chong MMW, Darwiche R, Cornish AL, Stanley EG, Purton JF, Godfrey DI, Hilton DJ, Starr R, Alexander WS, Kay TWH. Thymocyte-Specific Deletion of Suppressor of Cytokine Signaling-1 Demonstrates its Role in Regulating Interleukin-7-Dependent CD8+ T cell Differentiation. Immunity 2003;18: 475-487.
  10. Pellicci DG, Uldrich AP, Kyparissoudis K, Crowe NY, Brooks AG, Sidobre S, Kronenberg M, Smyth MJ, Godfrey DI. Intrathymic NKT cell development is blocked by the presence of a-galactosylceramide. Eur J Immunol 2003; 33: 1816-1823.
  11. Cretney E, Uldrich AP, Berzins SP, Strasser A, Godfrey DI, Smyth MJ. 2003. Normal thymocyte negative selection in TRAIL-deficient mice. J Exp Med 2003; 198: 491-496.
  12. Crowe NY, Uldrich AP, Kyparissoudis K, Hammond KJL, Hayakawa Y, Sidobre S, Keating R, Kronenberg M, Smyth MJ, Godfrey DI. Glycolipid Antigen Drives Rapid Expansion and Sustained Cytokine Production by NKT Cells. J Immunol 2003;171: 4020-4027.
  13. Esteban LE, Tsoutsman T, Jordan MA, Roach D, Poulton LD, Brooks A, Naidenko OV, Sidobre S, Godfrey DI, Baxter AG. Genetic Control of NKT Cell Numbers Maps to Major Diabetes and Lupus Loci. J Immunol 2003;171: 2873-2878

    Cited in Faculty of 1000 as “Recommended”.

  14. Berzins SB, Kyparissoudis K, Pellicci DG, Smyth MJ, Baxter AG, Hammond KJ, Sidobre S, Kronenberg M, Godfrey DI. Systemic NKT cell deficiency in NOD mice is not detected in peripheral blood: Implications for human studies. Immunol Cell Biol 2004; 82: 247-52.
  15. Street SEA, Hayakawa Y, Tanner J, Zhan Y, Lew AM, MacGregor D, Raulet D, Diefenbach A. Yagita H, Godfrey DI, Smyth MJ. Innate immune surveillance of spontaneous B cell lymphomas by NK cells and gd+T cells. J Exp Med 2004; 199: 879-884.
  16. Sedelies K, Sayers TJ, Edwards KM, Chen W, Pellicci DG, Godfrey DI. Trapani JT. Discordant regulation of granzyme H and granzyme B expression in human lymphocytes. J Biol Chem 2004; 279: 26581-26587.
  17. Villunger A, Marsden VS, Zhan Y, Erlacher M, Lew AM, Bouillet P, Berzins SP, Godfrey DI, Heath WR, Strasser A. Negative selection of semi-mature CD4+8-HSA+ thymocytes requires the BH3-only protein Bim but is independent of death receptor signaling. PNAS 2004; 101: 7052-7057.
  18. Zhan Y, Funda D, Every AL, Funda P, Purton JF, Cole TJ, Godfrey DI, Brady JL, Mannering SI, Harrison LC, Lew AM. GITR upregulation by glucocorticoid-receptor-dependent and -independent pathways is associated with different T-cell fates. Int Immunol 2004; 16: 1315-1321.
  19. Purton JF, Monk JA, Liddicoat DR, Kyparissoudis K, Sakkal S, Richardson SJ, Godfrey DI,* & Cole TJ*. * equal chief investigators. Expression of the glucocorticoid receptor from the 1A promoter correlates with T lymphocyte sensitivity to glucocorticoid-induced cell death. J Immunol 2004; 173: 3816-3824.
  20. Berzins SP, Pellicci DG, Smyth MJ, Cochrane A. Godfrey DI. Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples. Eur J Immunol 2005; 35: 1399-1407.
  21. Smyth MJ, Wallace ME, Swann J, Godfrey DI, Hayakawa Y. Sequential activation of NKT cells and NK cells provides effective innate immunotherapy of cancer. J Exp Med 2005; 201: 1973-1985.
  22. Pao LI, Sumaria N, Kelly JM, Cretney E, Wallace ME, Uldrich AP, Godfrey DI, Papadimitriou JM, Mullbacher A, Rajewsky K, Degli-Esposti MA, Smyth MJ. The NK cell protease granzyme M is not critical for NK cell-mediated death, but is involved in host innate response to cytomegalovirus infection. J Immunol 2005; 175: 3235-3243.
  23. Uldrich AP*, Crowe NY*, Kyparissoudis K, Pellicci DG, Zhan Y, Lew A, Bouillet P, Strasser A, Smyth MJ, Godfrey DI. NKT cell stimulation with glycolipid antigen in vivo: Costimulation-dependent expansion, BIM-dependent contraction and hyporesponsiveness to further antigenic challenge. J Immunol 2005; 175: 3092-3101.
  24. Pellicci DG, Hammond KJL, Coquet JM, Kyparissoudis K, Brooks AG, Kedzierska K, Keating R, Turner SJ, Berzins SP, Smyth MJ, Godfrey DI. DX5/CD49b positive T cells are not synonymous with CD1d-dependent NKT cells. J Immunol 2005;175: 4416-4425.
  25. McNab F*, Berzins SP*, Pellicci DG, Kyparissoudis K, Field K, Smyth MJ, Godfrey DI. The influence of CD1d in post-selection NKT cell maturation and homeostasis. J Immunol 2005; 175: 3762-3768.
    *equal first authors
  26. Morris ES, Kelli PA, MacDonald, Rowe V, Banovic T, Kuns RD, Don ALJ, Olver SD, Kienzle N, Porcelli SA, Pellicci DG, Godfrey DI, Smyth MJ and Hill GR. NKT cell-dependent leukaemia eradication following stem cell mobilization with potent G-CSF analogues. J Clin. Invest 2005; 115: 3093-3103.
  27. Brodnicki TC, Fletcher AL, Pellicci DG, Berzins SP, McClive P, Quirk F, Webster KE, Scott HE, Boyd RL, Godfrey DI, Morahan G. Localization of Idd11 Is Not Associated with Thymus and NKT Cell Abnormalities in NOD Mice. Diabetes 2005; 54: 3453-3457.
  28. Crowe NY, Coquet JM, Berzins SP, Kyparissoudis K, Keating R, Pellicci DG, Godfrey DI Smyth MJ. **Equal chief investigators (DIG is corresponding author). Differential ability of NKT cell subsets to mediate tumor rejection. J Exp Med 2005; 202: 1279-1288.
  29. Terabe M, Swann J, Ambrosino E, Sinha P, Takaku S, Hayakawa Y, Godfrey DI, Ostrand-Rosenberg S, Smyth MJ, Berzofsky, J. A non-classical non-Va14Ja18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J Exp Med 2005; 202: 1627-1633.
  30. Smyth MJ, Swann J, Teng MWL, Kyparissoudis K, Godfrey DI, Hayakawa Y. CD4+CD25+ T regulatory cells suppress NK cell-mediated immunotherapy of cancer. J Immunol 2006; 176: 1582-1587.
  31. Cornish AL, Keating R, Kyparissoudis K, Stock AT, Allan RS, Jones CM, Smyth MJ, Carbone FR, Godfrey DI. NKT cells are not critical for HSV-1 disease resolution. Immunol Cell Biol 2006; 84: 13-19.
  32. Kjer-Nielsen L, Borg NA, Pellicci DG, Beddoe T, Kostenko L, Clements CS, Williamson NA, Smyth MJ, Besra GS, Reid HH, Bharadwaj M, Godfrey DI, Rossjohn J, McCluskey J. A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition. J Exp Med 2006; 203: 661-673.
  33. Berzins SP, McNab F, Smyth MJ, Godfrey DI. Long-term retention of NK1.1+ NKT cells in the thymus. J Immunol 2006; 176: 4059-4065.
  34. Uldrich AP, Berzins SP, Malin MA, Bouillet P, Strasser A, Smyth MJ, Boyd RL*, Godfrey DI*. *Equal chief investigators. Antigen challenge inhibits thymic emigration. J Immunol 2006; 176: 4553-4561.
  35. Coquet JM, Kyparissoudis K, Pellicci DG, Besra G, Berzins SP, Smyth MJ, Godfrey DI. IL-21 is produced by NKT cells and modulates NKT cell activation and cytokine production. J Immunol 2007; 178: 2827-34.
  36. Borg NA, Wun KS, Kjer-Nielsen L, Wilce MC, Pellicci DG, Koh R, Besra GS, Bharadwaj M, Godfrey DI, McCluskey J, Rossjohn J. CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 2007; 448: 44-9.

 

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