CELL DEATH PATHWAYS AND TYPE 1 DIABETES
Grant number: 466658 | Funding period: 2007 - 2012
Loss of insulin-producing beta cells leads to type 1 diabetes and rejection of allogeneic islet transplants. The aim of this program is to discover ways of protecting beta cells from damage. We will do this by investigating whether blocking crucial regulators of cell death can protect mouse and human beta cells from destruction in vitro and in vivo. In doing so, we aim to prevent diabetes in mice and potentially improve the survival of islet grafts after transplantation.
Related publications (12)
Loss of NF-kappa B1 Causes Gastric Cancer with Aberrant Inflammation and Expression of Immune Checkpoint Regulators in a STAT-1-Dependent Manner
Lorraine A O'Reilly, Tracy L Putoczki, Lisa A Mielke, Jun T Low, Ann Lin, Adele Preaudet, Marco J Herold, Kelvin Yaprianto, Lin Tai, Andrew Kueh, Guido Pacini, Richard L Ferrero, Raffi Gugasyan, Yifang Hu, Michael Christie, Stephen Wilcox, Raelene Grumont, Michael DW Griffin, Liam O'Connor, Gordon K Smyth
Polymorphisms in NFKB1 that diminish its expression have been linked to human inflammatory diseases and increased risk for epithel..
Loss of c-REL but not NF-kappa B2 prevents autoimmune disease driven by FasL mutation
LA O'Reilly, P Hughes, A Lin, P Waring, U Siebenlist, R Jain, DHD Gray, S Gerondakis, A Strasser
FASL/FAS signaling imposes a critical barrier against autoimmune disease and lymphadenopathy. Mutant mice unable to produce membra..
Activation of the NLRP3 Inflammasome Complex is Not Required for Stress-Induced Death of Pancreatic Islets
Jibran A Wali, Esteban N Gurzov, Stacey Fynch, Lorraine Elkerbout, Thomas W Kay, Seth L Masters, Helen E Thomas
Loss of pancreatic beta cells is a feature of type-2 diabetes. High glucose concentrations induce endoplasmic reticulum (ER) and o..
The proapoptotic BH3-only proteins Bim and Puma are downstream of endoplasmic reticulum and mitochondrial oxidative stress in pancreatic islets in response to glucotoxicity
JA Wali, D Rondas, MD McKenzie, Y Zhao, L Elkerbout, S Fynch, EN Gurzov, S Akira, C Mathieu, TWH Kay, L Overbergh, A Strasser, HE Thomas
Apoptosis of pancreatic beta cells is a feature of type 2 diabetes and its prevention may have therapeutic benefit. High glucose c..
Granzyme B Is Dispensable in the Development of Diabetes in Non-Obese Diabetic Mice
Zia U Mollah, Kate L Graham, Balasubramanian Krishnamurthy, Prerak Trivedi, Thomas C Brodnicki, Joseph A Trapani, Thomas W Kay, Helen E Thomas
Pancreatic beta cell destruction in type 1 diabetes is mediated by cytotoxic CD8(+) T lymphoctyes (CTL). Granzyme B is an effector..
Defects in the Bcl-2-Regulated Apoptotic Pathway Lead to Preferential Increase of CD25(low)Foxp3( ) Anergic CD4( ) T Cells
Yifan Zhan, Yuxia Zhang, Daniel Gray, Emma M Carrington, Philippe Bouillet, Hyun-Ja Ko, Lorraine O'Reilly, Ian P Wicks, Andreas Strasser, Andrew M Lew
Defects in the Bcl-2-regulated apoptotic pathway inhibit the deletion of self-reactive T cells. What is unresolved, however, is th..
Glucose Induces Pancreatic Islet Cell Apoptosis That Requires the BH3-Only Proteins Bim and Puma and Multi-BH Domain Protein Bax
Mark D McKenzie, Emma Jamieson, Elisa S Jansen, Clare L Scott, David CS Huang, Philippe Bouillet, Janette Allison, Thomas WH Kay, Andreas Strasser, Helen E Thomas
OBJECTIVE: High concentrations of circulating glucose are believed to contribute to defective insulin secretion and beta-cell func..