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. Our team also identified the primary role of autoimmune recognition of proinsulin in type 1 diabetes and we are developing antigen-specific therapies to prevent 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.
Key achievements
2020 Kellion Award, Australian Diabetes Society
2015 Convenor of Joint Congress of the International Pancreas and Islet Transplant Association and the Immunology of Diabetes Society
2013 Convenor of the 13th Congress of the Immunology of Diabetes Society
2004 JDRF International Mary Jane Kugel Award
2003 Diabetes Australia Millennium Grant Award
1997 JDRF Career Development Award
1995 Viertel Foundation Clinical Investigator Award
1992 Royal Australasian College of Physicians, Golden Jubilee Fellowship
1991 Endocrine Society (USA) New Investigator Award
1989-1994 Neil Hamilton Fairley Fellowship, NHMRC
Selected publications
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.
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.
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)
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)
Pathiraja V, Kuechlich JP, Campbell PD, Krishnamurthy B, Loudovaris T, Coates PTH, Brodnicki TC, O’Connell PJ, Kedzierska K, Rodda C, Bergman P, Hill E, Purcell AW, Dudek NL, Thomas HE, Kay TWH, Mannering SI Proinsulin specific, HLA-DQ8 and HLA-DQ8 transdimer restricted, CD4+ T cells infiltrate the islets in type 1 diabetes. Diabetes 64:172-82 (2015)
Jhala G, Chee J, Trivedi PM, Selck C, Gurzov EN, Graham KL, Thomas HE, Kay TW, Krishnamurthy B Perinatal tolerance to proinsulin is sufficient to prevent autoimmune diabetes. JCI Insight 1:e86065 (2016)
Trivedi PM, Graham KL, Scott NA, Jenkins MR, Majaw S, Sutherland RM, Fynch S, Lew AM, Burns CJ, Krishnamurthy B, Brodnicki TC, Mannering SI, Kay TW, Thomas HE. Repurposed JAK1/JAK2 inhibitor reverses established autoimmune insulitis in non-obese diabetic mice. Diabetes 66:1650-60 (2017)
So M, Elso CM, Tresoldi E, Pakusch M, Pathiraja V, Wentworth JM, Harrison LC, Krishnamurthy B, Thomas HE, Rodda C, Cameron FJ, McMahon J, Kay TWH, Mannering SI Proinsulin C-peptide is an autoantigen in people with type 1 diabetes. Proc Natl Acad Sci USA 115:10732-7 (2018)
Galligan A, Krishnamurthy B, Kay TW Comment on Trinh et al. Successful treatment of immune checkpoint inhibitor-induced diabetes with infliximab. Diabetes Care 43:e10 (2020)
Jhala G, Selck C, Chee J, Kwong C-TJ, Pappas E, Thomas HE, Kay TW, Krishnamurthy B Tolerance to proinsulin-1 reduces autoimmune diabetes in NOD mice. Front Immunol, 12:645817 (2021)