Immunology and Diabetes - Senior Research Staff - Prof Thomas Kay

Prof Thomas Kay

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Director
Unit Head, Immunology and Diabetes

 



Education and Professional Experience

1978            B Med Sci, University of Melbourne
1980            MBBS, University of Melbourne
1987            Fellowship, Royal Australasian College of Physicians
1989            PhD, Walter and Eliza Hall Institute, University of Melbourne
1993            Fellowship, Royal College of Pathologists of Australasia

Achievements

1989-94       Neil Hamilton Fairley Fellowship, NH&MRC
1991            Endocrine Society (USA) New Investigator Award
1992            Golden Jubilee Fellowship, RACP
1995            Viertel Foundation Clinical Investigator Award
1997            Career Development Award, Juvenile Diabetes Foundation
2003            Diabetes Australia Millennium Grant Award
2004            Juvenile Diabetes Research Foundation International Mary Jane Kugel Award

Research Interests

My research group works on the immunopathogenesis of type 1 diabetes. We use pancreatic beta cells and T cells purified from genetically-modified mice to investigate the role of perforin, death receptors and inflammatory cytokines in beta cell death and diabetes. I also lead a Melbourne-wide clinical islet transplant program that will begin treating diabetic patients by infusion of isolated islet cells in 2006. It is hoped that a detailed knowledge of how beta cells are destroyed in our research studies will indicate the most effective forms of immunoprotection and could eventually allow beta cell replacement as a treatment for type 1 diabetic patients without systemic immunosuppression.

Selected Publications

  1. Krishnamurthy B, Dudek NL, McKenzie MD, Purcell AW, Brooks AG, Gellert S, Colman PG, Harrison LC, Lew AM, Thomas HE, Kay TWH (2006) Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP. J Clin Invest 116:3258-65.
  2. Chong MMW, Cornish AL, Darwiche R, Stanley EG, Purton JF, Godfrey DI, Hilton DJ, Starr R Alexander WS, Kay TWH (2003) Suppressor of Cytokine Signaling-1 is a Critical Regulator of Interleukin-7-Dependent CD8+ T cell Differentiation. Immunity 18:475-8.
  3. Chong MM, Chen Y, Darwiche R, Dudek NL, Irawaty W, Santamaria P, Allison J, Kay TWH, Thomas HE (2004) Suppressor of cytokine signaling-1 overexpression protects pancreatic β cells from CD8+ T cell-mediated autoimmune destruction. J Immunol 172:5714-21.
  4. Mannering SI, Harrison LC, Williamson NA, Morris JS, Thearle DJ, Jensen KP, Kay TWH, Rossjohn J, Falk BA, Nepom GT, Purcell AW (2005) The insulin A-chain epitope recognized by human T-cells is post-translationally modified. J Exp Med 202:1191-7.
  5. Thomas HE, Darwiche R, Corbett JA, Kay TWH (2002) Interleukin-1 and interferon-γ-induced pancreatic beta cell dysfunction is mediated by beta cell nitric oxide production. Diabetes 51:311-16
  6. Krishnamurthy B, Mariana L, Gellert SA, Colman P, Harrison LC, Lew AM, Santamaria P, Thomas HE, Kay TWH. Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice. J Immunol 2008; 180: 4458-4464
  7. McKenzie MD, Carrington EM, Kaufmann T, Strasser A, Huang DCS, Kay TWH, Allison J, Thomas HE. Pro-apoptotic BH3-only protein Bid is essential for death receptor-induced apoptosis of pancreatic b cells. Diabetes 2008; 57: 1284-92
  8. Kay TWH, Krishnamurthy B, Brodnicki TC, Mannering SI. Insulin teaches a new lesson in tolerance. The EMBO Journal 28(18):2687-8 (2009)
  9. McKenzie MD, Jamieson E, Jansen ES, Scott CL, Huang DCS, Bouillet P, Allison J, Kay TWH, Strasser A, Thomas HE. Glucose induces pancreatic islet cell apoptosis that requires the BH3-only proteins Bim and Puma and multi-BH domain protein Bax. Diabetes 59(3):644-52 (2009)
  10. Thomas HE, McKenzie MD, Angstetra E, Campbell PD, Kay TW. Beta cell apoptosis in diabetes. Apoptosis 14:1389-1404 (2009)
  11. Thomas HE, Trapani, JA, Kay TW. The role of perforin and granzymes in diabetes. Cell Death Differ 17(4):577-85 (2010)
  12. Krishnamurthy B, Chee J, Jhala G, Fynch S, Graham KL, Santamaria P, Morahan G, Allison J, Izon D, Thomas HE, Kay TW. Complete diabetes protection despite delayed thymic tolerance in NOD8.3 TCR transgenic mice due to antigen-induced extrathymic deletion of T cells. Diabetes (2011) [Epub ahead of print]