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Prof Helen Thomas

Research Unit

Islet biology

Information

Senior Research Officer
Head, Immunology and Diabetes Unit

Professional Experience

1988        BSc (Hons), University of Western Australia
2000        PhD, Walter and Eliza Hall Institute of Medical Research

Achievements

2019       Professorial Fellow, The University of Melbourne
2013       NHMRC Senior Research Fellowship
2011       JDRF Macquarie Group Foundation Diabetes Research Innovation Award
2010       Editorial Board of the journal Diabetes
2005       NHMRC RD Wright Career Development Award
2004-      Senior scientist, Tom Mandel Islet Transplant Program
2001       JDRF Advanced Postdoctoral Fellowship

Research Interests

My research is focused on preventing pancreatic beta cell destruction to preserve beta cell mass 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 they 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 their interaction with the immune system in type 1 diabetes, and the intracellular apoptotic signalling pathways in type 2 diabetes. In the next 5 years, I plan to test inhibitors of JAK1/JAK2 in clinical trials for type 1 diabetes, conduct pre-clinical tests on drugs to repurpose for type 1 diabetes, conduct basic research to understand the early events in diabetes development, and understand the apoptosis mechanisms activated in beta cells. Our work is being applied to humans through the transplantation of human islets from organ donors to reverse diabetes in severe cases.

Selected Publications

  1. Thomas HE, Parker JL, Schreiber RD, Kay TWH. IFN- action on pancreatic beta cells causes class I MHC upregulation but not diabetes. J. Clin. Invest. 102:1249-1257 (1998)
  2. Chong MM, Chen Y, Darwiche R, Dudek NL, Irawaty W, Santamaria P, Allison J, Kay TW, Thomas HE. Suppressor of cytokine signaling-1 overexpression protects pancreatic cells from CD8+ T cell-mediated autoimmune destruction. J. Immunol, 172:5714-5721 (2004)
  3. Thomas HE, McKenzie MD, Angstetra E, Campbell PD, Kay TW. Beta cell apoptosis in diabetes. Apoptosis 14:1389-1404 (2009)
  4. 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)
  5. Quah HS, Miranda-Hernandez S, Khoo A, Harding A, Fynch S, Elkerbout L, Brodnicki TC, Baxter AG, Kay TWH, Thomas HE*, Graham KL* Deficiency in type I interferon signaling prevents the early interferon-gene signature in pancreatic islets but not type 1 diabetes in non-obese diabetic mice. Diabetes 63:1032-40 (2014)
  6. 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 pro-apoptotic 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. 5:e1124 (2014)
  7. Zhao Y, Scott NA, Fynch S, Elkerbout L, Wong WW-L, Mason KD, Strasser A, Huang DC, Kay TWH, Thomas HE Autoreactive T cells induce necrosis and not BCL-2-regulated or death receptor-mediated apoptosis or RIPK3-dependent necroptosis of transplanted islets in a mouse model of type 1 diabetes. Diabetologia 58:140-8 (2015)
  8. 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)
  9. Wali JA, Galic S, Tan CYR, Gurzov EN, Frazier AE, Connor T, Ge J, Pappas EG, Stroud D, Varanasi LC, Selck C, Ryan MT, Thorburn DR, Kemp BE, Krishnamurthy B, Kay TWH, McGee SL, Thomas HE. Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation, reduces adiposity and improves insulin sensitivity in mice. Cell Death Differ, 25:217-225 (2018)
  10. Irvin AE, Jhala G, Zhao Y, Blckwell TS, Krishnamurthy B, Thomas HE, Kay TWH. NF-kB is weakly activated in the NOD mouse model of type 1 diabetes. Sci Rep 8:4217 (2018)
  11. Scott NA, Zhao Y, Krishnamurthy B, Mannering SI, Kay TW, Thomas HE. IFNg-induced MHC class II expression on islet endothelial cells is an early marker of insulitis but is not required for diabetogenic CD4+ T cell migration. Frontiers Immunol. 9:2800 (2018)