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UP

Prof Tom Kay

Research Unit

Immunology

Information

Director
Unit Head, Immunology and Diabetes

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

89-94  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    JDRF 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 began 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 beta 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-gamma-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. Angstetra E, Graham KL, Emmett S, Dudek NL, Darwiche R, Ayala-Perez R, Allison J, Santamaria P, Kay TWH, Thomas HE. In vivo effects of cytokines on pancreatic beta-cells in models of type 1 diabetes dependent on CD4+ T lymphocytes. Immunol Cell Biol, 2009: 87:178-85 (2009)
  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. O’Connell PJ, Holmes-Walker JD, Goodman D, Hawthorne WJ, Loudovaris T, Gunton JE, Thomas HE, Grey ST, Drogemuller CJ, Ward GM, Torpy DJ, Coates PT, Kay TW, On behalf of the Australian Islet Transplant Consortium. Multicenter Australian Trial of Islet Transplantation: Improving Accessibility and Outcomes Am. J. Transplant. 13:1850-8 (2013)
  10. Coppieters KT et al (2012) Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. J Exp Med 209:51-60
  11. 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 61:425-35 (2012)
  12. Graham KL, Krishnamurthy B, Fynch S, Mollah ZU, Slattery RM, Santamaria P, Kay TW, Thomas HE Autoreactive cytotoxic T lymphocytes acquire higher expression of cytotoxic effector markers within the islets of NOD mice after priming in the pancreatic lymph nodes. Am. J. Pathol. 178:2716-25 (2011)
  13. Chee J*, Ko H-J*, Skowera A, Jhala G, Catterall T, Graham KL, Sutherland RM, Thomas HE, Lew AM, Peakman M,  Kay TWH, Krishnamurthy B Effector memory T cells develop in islets and report islet pathology in type 1 diabetes. J. Immunol 192:572-80 (2014)