“New insights into Type 1 diabetes development and therapy”

Professor Chris Parish, John Curtin School of Medical Research, Australian National University

Date: Friday 26 July 2013, 2 pm

Venue: James Cook University(JCU), Cairns A21.002 Videolinked to JCU Townsville Social Sciences room 225

Download a flyer

Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing beta cells in the pancreas are destroyed by the immune system, although the molecular basis of this autoimmune destruction is unclear. We have recently reported that mouse islets express extraordinarily high levels of the glycosaminoglycan heparan sulfate (HS) intracellularly and are also surrounded by a basement membrane (BM) rich in HS. In fact, beta cells are exquisitely dependent on intracellular HS for their survival, with in vitro addition of HS or related molecules maintaining beta cell viability and rendering the cells highly resistant to damage by reactive oxygen species. Furthermore, we have found in vivo that destructive insulitis is associated with high level expression by leukocytes of enzymatically active heparanase, an endoglycosidase that degrades HS. In addition, in vivo treatment with several heparanase inhibitors significantly protected NOD mice from clinical diabetes. Based on these data we propose that initially leukocyte-derived heparanase degrades HS in the islet BM, allowing leukocyte entry into islets. Thereafter, heparanase-mediated degradation of beta cell-associated HS results in a novel mechanism of beta cell death. Recent studies using an acute T1D model in heparanase knock out mice has confirmed the importance of heparanase in T1D development, with heparanase expression by several different cell types being important. Thus heparanase inhibition, possibly combined with HS replacement in beta cells, has great therapeutic promise for treating T1D patients at an early stage of the disease and, potentially, for the prevention of T1D in "at risk" individuals.

Professor Chris Parish received his undergraduate training at the University of Melbourne and then gained a PhD degree in immunology at The Walter & Eliza Hall Institute, Melbourne. He is currently the Director of the John Curtin School of Medical Research, ANU. Chris Parish is an immunologist and cancer biologist with a research career spanning 40 years. He is recognised as a world leader in studies of immune regulation and the role of heparanase and heparan sulfate in cell migration. He has also developed several carbohydrate-based drugs, such as PI-88 (Muparfostat), that inhibit inflammation, tumour metastasis and angiogenesis and has developed immunotherapeutic cancer vaccines. His research findings underpin six Australian biotechnology companies. In recognition of his scientific achievements in 2005 he was awarded the Clive and Vera Ramaciotti Medal for Excellence in Biomedical Research and in 2011 he was elected a Fellow of the Australian Academy of Technological Sciences and Industry and became an Honorary Life Member of the Australasian Society for Immunology.


web design by precedence