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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. Thomas HE, McKenzie MD, Angstetra E, Campbell PD, Kay TW. Beta cell apoptosis in diabetes. Apoptosis 14:1389-1404 (2009)
  3. 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)
  4. 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)
  5. 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)
  6. 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)
  7. Trivedi PM, Fynch S, Kennedy LM, Chee J, Krishnamurthy B, O’Reilly LA, Strasser A, Kay TWH, Thomas HE. Soluble FAS ligand is not required for pancreatic islet inflammation or beta-cell destruction in non-obese diabetic mice. Cell Death Discov. 5:136 (2019)
  8. Sutherland APR, Graham KL, Aston MP, Jhala G, Trivedi P, Catterall T, Fynch S, Kay TWH, Thomas HE. IL-21 regulates SOCS1 expression in autoreactive CD8+ T cells but is not required for acquisition of CTL activity in the islets of non-obese diabetic mice. Sci Rep, 9:15302 (2019)
  9. Ge T, Jhala G, Fynch S, Akazawa S, Litwak S, Pappas EG, Catterall T, Vakil I, Long A, Olson LM, Krishnamurthy B, Kay TW, Thomas HE The JAK1 selective inhibitor ABT 317 blocks signaling through interferon and common gamma chain cytokine receptors to reverse autoimmune diabetes in NOD mice. Front Immmunol. 11:588543 (2020)
  10. Akazawa S, Mackin L, Jhala G, Fynch S, Catterall T, Selck C, Graham KL, Krishnamurthy B, Pappas EG, Kwong C-TJ, Kay TWH, Brodnicki TC, Thomas HE Deficiency of the innate immune adaptor STING promotes autoreactive T-cell expansion in NOD mice. Diabetologia 64:878-889 (2021)