Immunology and Diabetes - Islet Biology Laboratory headed by A/Prof Helen Thomas

Islet Biology Laboratory headed by A/Prof Helen Thomas

Research Overview

Our research is focused on understanding how the immune system causes beta-cell damage and finding ways to protect beta cells as a potential therapy for type 1 diabetes. We want to understand how the immune effectors of pancreatic beta-cell death, CD8+ and CD4+ T cells and macrophages, kill beta cells, and how this can be prevented. In the NOD mouse model of type 1 diabetes and in humans, there is good evidence that beta cells are destroyed by apoptosis. We have studied beta-cell apoptosis induced by perforin/granzymes, Fas/FasL and inflammatory cytokines in mouse models and human islets. We are also studying proteins within the beta cell that either promote or reduce cell death. Our work is being applied to humans through the transplantation of human islets from organ donors to reverse diabetes in severe cases.

Research Themes

Human islet biology in transplantation and type 1 diabetes

The role of perforin and granzymes in type 1 diabetes

Staff

A/Prof Helen Thomas
Dr Yuxing Zhao
Dr Mugdha Joglekar
Dr Zia Mollah
Cameron Kos
Stacey Fynch
Jibran Wali
Lorraine Elkerbout
Prerak Trivedi
Allison Irvin
Joshua Szanyi

Publication Highlights

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)

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)

Estella E, McKenzie MD, Catterall T, Sutton VR, Bird PI, Trapani JA, Kay TW and Thomas HE. Granzyme B-mediated death of pancreatic beta cells requires the pro-apoptotic BH3-only molecule Bid. Diabetes, 55:2212-9 (2006)

McKenzie MD, Carrington EM, Kaufmann T, Strasser A, Huang DCS, Kay TWH, Allison J, and Thomas HE Pro-apoptotic BH3-only protein Bid is essential for death receptor-induced apoptosis of pancreatic cells. Diabetes, 57:1284-92 (2008)

McKenzie MD, Jamieson E, Jansen ES, Scott CL, Huang DCS, Bouillet P, Allison J, Kay TWH, Strasser A, Thomas HE Glucose induces pancreatic islet cell apoptosis that requires the BH3-only proteins Bim and Puma and multi-BH domain protein Bax. Diabetes, in press (2010)

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, 87:178-85 (2009)

Campbell PD, Estella E, Dudek NL, Jhala G, Thomas HE, Kay TW, and Mannering SI Cytotoxic T-lymphocyte mediated killing of human pancreatic islet cells in vitro. Human Immunology 69: 543-51 (2008)

Thomas HE, McKenzie MD, Angstetra E, Campbell PD, Kay TW Beta cell apoptosis in diabetes. Apoptosis 14:1389-1404 (2009)

Thomas HE, Trapani, JA, Kay TW The role of perforin and granzymes in diabetes. Cell Death Differ, in press (2010)