• Room G31, 19 Innovation Walk

    Clayton

    Australia

Accepting PhD Students

20062019
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Personal profile

Biography

Stephen Daley is an immunologist with a particular interest in T cells. His research focusses on T cell development in the thymus, where T cells 'learn' to recognise healthy cells at the molecular level. This helps the immune system avoid excessive damage to healthy cells during immune responses against pathogens and tumours.

Stephen Daley is a Biomedicine Discovery Fellow in the Infection and Immunity Program, Monash Biomedicine Discovery Institute, at Monash University, Melbourne. Dr Daley's research combines flow cytometry, mouse genetics, transplantation, and T-cell repertoire profiling to define how self-reactive T cells behave in the thymus and how these behaviours changes as a consequence of inherited mutations that trigger autoimmune diseases.

Stephen Daley trained in Veterinary Medicine and Surgery at the University of Queensland, graduating in 2000. After a brief period in practice, in 2002 he was awarded a Rhodes Scholarship to undertake a DPhil at Oxford University with Professor Herman Waldmann FRS, receiving his DPhil in 2007. Dr Daley then joined Professor Chris Goodnow's laboratory as a postdoctoral fellow. In 2013 he shared in the publication of a paper, in Journal of Experimental Medicine, which showed that self-reactive T cells are eliminated at two separate stages of development in the normal thymus.

Research interests

To be able to stave off infections and cancers throughout life, our immune systems first need to recognise and tolerate the ~200 different cell types in healthy human bodies ('self'). Reflecting its oppositeness from well-known responses in which immune cells are (positively) selected, this response is called 'negative selection'.

For T cells, negative selection occurs during development in the thymus. Researchers have analysed negative selection of certain T cells, but the field has been frustrated by the lack of a molecular marker that identifies all cells undergoing negative selection. Our 2013 Journal of Experimental Medicine paper described just such a marker, Helios. This innovation allows any researcher to enumerate and analyse T cells undergoing negative selection in mice or humans.

In both species, we have found evidence for 2 "waves" of T cell negative selection in the thymus. The first "wave" occurs early in development, when the T cells are probably located in the cortex of the thymus. We think this "wave" eliminates T cells with receptors that bind strongly to one or more self-antigens.

The second "wave" occurs later in development when the T cells are located in the medulla of the thymus. This "wave" also involves T cells with receptors that bind strongly to self-antigen. Why, then, did these cells fail to get eliminated in the first wave? We think the answer is because different set of self-antigens are presented to T cells in the cortex versus the medulla of the thymus. Some T cells in the second wave survive, and up-regulate expression of a transcription factor called Foxp3, which cripples their inflammatory potential. These Foxp3-expressing T cells dampen self-destructive immune responses. Autoimmune diseases may originate from defects in Foxp3-expressing T cells.

Our research aims to understand the separate but complementary functions of the 2 "waves" of T cell negative selection in the thymus, and how autoimmune diseases may originate with failure of one or both "waves".

Available PhD and Honours projects involve analysis of T-cell selection in normal mice and mice susceptible to autoimmune diseases. Further details will be provided upon request.

Education/Academic qualification

Immunology, DPhil, University of Oxford

2 Oct 20025 Apr 2006

Research area keywords

  • T cells
  • thymus
  • T-regulatory cells
  • autoimmune diseases

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Projects 2016 2019

De novo mutations and the pathogenesis of childhood-onset autoimmune disease

Daley, S., Roscioli, T., Deenick, E. K., Gray, P. E. A., Craig, M., Wong, M., Teo, J., Gunton, J., Andrews, T. D. & Goodnow, C.

1/01/1631/12/19

Project: Other

Research Output 2006 2019

αβ T-cell receptors with a central CDR3 cysteine are enriched in CD8αα intraepithelial lymphocytes and their thymic precursors

Wirasinha, R. C., Singh, M., Archer, S. K., Chan, A., Harrison, P. F., Goodnow, C. C. & Daley, S. R., Jul 2018, In : Immunology and Cell Biology. 96, 6, p. 553-561 9 p.

Research output: Contribution to journalArticleResearchpeer-review

IL-2 prevents deletion of developing T-regulatory cells in the thymus

Hu, D. Y., Wirasinha, R. C., Goodnow, C. C. & Daley, S. R., Jun 2017, In : Cell Death and Differentiation. 24, 6, p. 1007-1016 10 p.

Research output: Contribution to journalArticleResearchpeer-review

A timeline demarcating two waves of clonal deletion and Foxp3 up-regulation during thymocyte development

Hu, D., Yap, J. Y., Wirasinha, R., Howard, D. R., Goodnow, C. C. & Daley, S. R., 2016, In : Immunology and Cell Biology. 94, 4, p. 357 - 366 10 p.

Research output: Contribution to journalArticleResearchpeer-review

Helios marks strongly autoreactive CD4+ T cells in two major waves of thymic deletion distinguished by induction of PD-1 or NF-kappaB

Daley, S. R., Hu, D. Y. & Goodnow, C. C., 2013, In : Journal of Experimental Medicine. 210, 2, p. 269 - 285 17 p.

Research output: Contribution to journalArticleResearchpeer-review

Cysteine and hydrophobic residues in CDR3 serve as distinct T-cell self-reactivity indices

Daley, S. R., Koay, H. F., Dobbs, K., Bosticardo, M., Wirasinha, R. C., Pala, F., Castagnoli, R., Rowe, J. H., Ott de Bruin, L. M., Keles, S., Lee, Y. N., Somech, R., Holland, S. M., Delmonte, O. M., Draper, D., Maxwell, S., Niemela, J., Stoddard, J., Rosenzweig, S. D., Poliani, P. L. & 4 others, Capo, V., Villa, A., Godfrey, D. I. & Notarangelo, L. D., Jul 2019, In : Journal of Allergy and Clinical Immunology. 144, 1, p. 333-336 4 p.

Research output: Contribution to journalLetterResearchpeer-review

Prizes

2014 Gordon Ada Award

Stephen Daley (Recipient), 2012

Prize: Prize (including medals and awards)

Activities 2011 2011

  • 1 Editorial responsibility

Immunology and Cell Biology (Journal)

Stephen Daley (Associate editor)
1 Jan 201131 Dec 2012

Activity: Publication peer-review and editorial work typesEditorial responsibility