Research Groups

Seminars & Meetings


	Member Profiles: Group Leader: Prof Tom Kay Lab Heads: Dr Janette Allison Dr Helen Thomas Dr Stuart Mannering Research Scientists: Dr Balasubramanian Krishnamurthy Dr Kate Graham Dr Zia Mollah Dr. Yuxing Zhao Dr Thomas Loudovaris (Islet Isolation Manager)

Laboratory Members

Prof Tom Kay

Director
Immunology and Diabetes Unit
St Vincent's Institute

Telephone: +61 3 9288 2480
Facsimile: +61 3 9416 2676
Email: tkay@svi.edu.au

Other Positions:

Endocrinologist, St. Vincent's Hospital
Professorial Associate, Department of Medicine, University of Melbourne
Head, Tom Mandel Islet Transplant Program

Education:

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

Awards:

1989-1994	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

Scientific Involvement:

	Bio21 Scientific Advisory Committee
	VBCRC Scientific Advisory Committee
	National Serology Reference Laboratory, Management Committee
	Juvenile Diabetes Research Foundation Medical and Scientific Review Committee
	St. Vincent's Hospital Research Development Committee
	St. Vincent's Hospital Medical Executive Committee
	Editorial Board, Autoimmunity
	Editorial Board, Journal of Molecular Endocrinology
	Editorial Board, Endocrinology

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.

Publications:

Kay TWH, Parker JL, Stephens LA, Thomas HE and Allison J. RIP-beta 2-microglobulin transgene expression restores insulitis, but not diabetes, in beta 2-microglobulin null nonobese diabetic mice. J. Immunol.1996; 157:3688-3693.
French MB, Allison J, Cram DS, Thomas HE, Dempsey-Collier M, Silva A, Georgiou HM, Kay TWH, Harrison LC and Lew AM. Transgenic expression of mouse proinsulin II prevents diabetes in nonobese diabetic mice. Diabetes, 1997; 46:34-39.
Thomas HE, Parker JL, Schreiber RD and Kay TWH. IFN-gamma action on pancreatic beta cells causes class I MHC upregulation but not diabetes. J. Clin. Invest. 1998; 102:1249-1257.
Alexander WS, Starr R, Fenner JE, Scott CL, Handman E, Sprigg NS, Corbin JE, Cornish AL, Darwiche R, Owczarek CM, Kay TWH, Nicola NA, Hertzog PJ, Metcalf D and Hilton DJ. SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell 1999; 98:597-608.1999
Chong MMW, Cornish AL, Darwiche R, Stanley EG, Purton JF, Godfrey DI, Hilton DJ, Starr R Alexander WS, Kay TWH. Suppressor of Cytokine Signaling-1 is a Critical Regulator of Interleukin-7-Dependent CD8+ T cell Differentiation. Immunity 2003; 18:475-8.
Darwiche R, Chong MM, Santamaria P, Thomas HE, Kay TWH. Fas is detectable on beta cells in accelerated, but not spontaneous, diabetes in nonobese diabetic mice. J. Immunol. 2003;170:6292-6297
Thomas HE, Irawaty W, Darwiche R, Brodnicki TC, Santamaria P, Allison J, Kay TWH. IL-1 receptor deficiency slows progression to diabetes in the NOD mouse. Diabetes 2004; 53: 113-121
Chong MMW, Chen Y, Darwiche R, Irawaty W, Santamaria P, Allison J, Kay TWH, Thomas HE. Suppressor of cytokine signaling-1 overexpression protects pancreatic beta cells from CD8+ T cell-mediated autoimmune destruction. J. Immunol. 2004; 172: 5714-21
Chong MM, Metcalf D, Jamieson E, Alexander WS, Kay TWH. Suppressor of cytokine signaling-1 in T cells and macrophages is critical for preventing lethal inflammation. Blood. 2005 106: 1668-75
Jamieson E, Chong MMW, Steinberg GR, Jovanovska V, Fam BC, Bullen DVR, Chen Y, Kemp BE, Proietto J, Kay TWH, Andrikopoulos S. SOCS1 deficiency enhances hepatic insulin signalling. J. Biol. Chem. 2005; 280: 31516-31512
Sutton VR, Estella E, Li C, Chen M, Thomas HE, Kay TWH, Trapani JA. A critical role for granzyme B, in addition to perforin and TNF alpha, in alloreactive CTL-induced mouse pancreatic beta cell death. Transplantation 2006; 81(2): 146-154
Estella E, McKenzie MD, Catterall T, Sutton VR, Bird PI, Trapani JA, Kay TWH, Thomas HE. Granzyme B-mediated death of pancreatic beta cells requires the pro-apoptotic BH3-only molecule Bid. Diabetes 2006 (in press)
McKenzie MD, Dudek NL, Mariana L, Chong MMW, Trapani JA, Kay TWH, Thomas HE. Perforin and Fas induced by interferon-gamma and tumor necrosis factor-alpha mediate beta-cell death by OT-I cytotoxic T lymphocytes. International Immunology (in press)
Dudek NL, Thomas HE, Mariana L, Sutherland RM, Allison J, Estella E, Angstetra E, Trapani JA, Santamaria P, Lew AM, Kay TWH. Cytotoxic T cells from T-cell receptor transgenic NOD8.3 mice destroy beta cells via the perforin and Fas pathways. Diabetes (in press)
Krishnamurthy B, Dudek NL, McKenzie MD, Purcell AW, Brooks AG, Gellert S, Colman PG, Harrison LC, Lew AM, Thomas HE, Kay TWH. Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP. J Clin Invest 2006; 116:3258-65
Steinberg GR, Michell BJ, van Denderen BJ, Watt MJ, Carey AL, Fam BC, Andrikopoulos S, Proietto J, Gorgun CZ, Carling D, Hotamisligil GS, Febbraio MA, Kay TWH, Kemp BE. Tumor necrosis factor alpha-induced skeletal muscle insulin resistance involves suppression of AMP-kinase signaling. Cell Metab. 2006; 4: 465-74
Barral AM, Thomas HE, Ling EM, Darwiche R, Rodrigo E, Christen U, Ejrnaes M, Wolfe T, Kay TWH, von Herrath MG. SOCS-1 protects from virally-induced CD8 T cell mediated type 1 diabetes. J Autoimmun 2006; 27:166-73.
Londrigan SL, Brady JL, Sutherland RM, Hawthorne WJ, Thomas HE, Jhala G, Cowan PJ, Kay TWH, OConnell PJ, Lew AM. Evaluation of promoters for driving efficient transgene expression in neonatal porcine islets. Xenotransplantation 2007; 14(2):119-25
Croom HA, Izon DJ, Chong MM, Curtis DJ, Roberts AW, Kay TWH, Hilton DJ, Alexander WS, Starr R. Perturbed thymopoiesis in vitro in the absence of suppressor of cytokine signalling 1 and 3. Mol Immunol 2008; 45: 2888-96
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
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 beta cells. Diabetes 2008; 57: 1284-92
Campbell PD, Estella E, Dudek NL, Jhala G, Thomas HE, Kay TWH, and Mannering SI. Cytotoxic T-lymphocyte-mediated killing of human pancreatic islet cells in vitro. Hum Immunol 2008; 69:543-51
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