My research is focused on preventing pancreatic beta cell destruction in diabetes. My lab has identified pathways of beta cell death in type 1 and 2 diabetes. We aim to understand how different effector mechanisms participate in diabetes development, and how these can be prevented.
The pathogenesis of type 1 and 2 diabetes is complex, with immune abnormalities in type 1 and insulin resistance in type 2 diabetes. However, beta cell deficiencies are required for both diseases, and this is the focus of the Islet Biology Laboratory.
My recent studies pinpoint ways of preventing beta cell death, by targeting interaction with the immune system in type 1 diabetes, and the intracellular apoptotic signalling pathways in type 2 diabetes. I am testing the JAK1/JAK2 inhibitor baricitinib in a clinical trial of participants with newly diagnosed type 1 diabetes, conducting pre-clinical tests on drugs to repurpose for type 1 diabetes, and conducting basic research to understand the early events in diabetes development.
Our lab’s work is being applied to humans through the transplantation of human islets from organ donors to reverse diabetes in severe cases and in the BANDIT clinical trial. I strive to have a positive impact on the young scientists that I supervise and mentor.
2019 The University of Melbourne; Professor (Medicine)
2013-2017 NHMRC Senior Research Fellow
2011 JDRF Macquarie Group Foundation Diabetes Research Innovation Award
2010-2012 NHMRC Career Development Award level 2 Fellow
2010 Editorial Board of the journal Diabetes
2005-2009 NHMRC RD Wright Fellow
Ge T, Phung A-L, Jhala G, Trivedi P, Principe N, De George DJ, Pappas EG, Litwak S, Sanz-Villanueva L, Catterall T, Fynch S, Boon L, Kay TW, Chee J, Krishnamurthy B, Thomas HE Diabetes induced by checkpoint inhibition in nonobese diabetic mice can be prevented or reversed by a JAK1/JAK2 inhibitor. Clin Transl Immunol, 2022, 11:e1425, doi: 10.1002/cti2.1425
Jhala G, Krishnamurthy B, Brodnicki TC, Ge T, Akazawa S, Selck C, Trivedi PM, Pappas EG, Mackin L, Principe N, Brémaud E, De George DJ, Boon L, Smyth I, Chee J, Kay TWH, Thomas HE. Interferons limit autoantigen-specific CD8+ T-cell expansion in the non-obese diabetic mouse. Cell Rep. 2022 Apr 26;39(4):110747. doi: 10.1016/j.celrep.2022.110747.
Akazawa S, Mackin L, Jhala G, Fynch S, Catterall T, Selck C, Graham KL, Krishnamurthy B, Pappas EG, Kwong CJ, Sutherland APR, Kay TWH, Brodnicki TC, Thomas HE. Deficiency of the innate immune adaptor STING promotes autoreactive T cell expansion in NOD mice. Diabetologia. 2021 Apr;64(4):878-889. doi: 10.1007/s00125-020-05378-z.
Ge T, Jhala G, Fynch S, Akazawa S, Litwak S, Pappas EG, Catterall T, Vakil I, Long AJ, Olson LM, Krishnamurthy B, Kay TW, Thomas HE. The JAK1 Selective Inhibitor ABT 317 Blocks Signaling Through Interferon-γ and Common γ Chain Cytokine Receptors to Reverse Autoimmune Diabetes in NOD Mice. Front Immunol. 2020;11:588543. doi: 10.3389/fimmu.2020.588543.
Wali JA, Rondas D, McKenzie MD, Zhao Y, Elkerbout L, Fynch S, Gurzov EN, Akira S, Mathieu C, Kay TW, Overbergh L, Strasser A, Thomas HE. The proapoptotic BH3-only proteins Bim and Puma are downstream of endoplasmic reticulum and mitochondrial oxidative stress in pancreatic islets in response to glucotoxicity. Cell Death Dis. 2014 Mar 13;5:e1124. doi: 10.1038/cddis.2014.88.
Thomas HE, Parker JL, Schreiber RD, Kay TW. IFN-gamma action on pancreatic beta cells causes class I MHC upregulation but not diabetes. J Clin Invest. 1998 Sep 15;102(6):1249-57. doi: 10.1172/JCI2899.
ORCID profile: https://orcid.org/0000-0001-6604-6640
Google Scholar profile: https://scholar.google.com.au/citations?user=p7L8c3YAAAAJ&hl=en