Diabetic Complications

Associate Professor Josephine Forbes
Head, Advanced Glycation
josephine.forbes@bakeridi.edu.au

Laboratory Research Overview

Research in the Advanced Glycation Lab focuses on kidney disease in diabetes, specifically, the effects of advanced glycation on the diabetic kidney. Kidney disease is one of the most important risk factors for heart attack and death from any cause.

Advanced glycation is a biochemical process brought on by an excess of sugar - we see it in the browning of fruit and the process is also apparent in the ageing of collagen, resulting in the gradual formation of wrinkles and lines on our skin as we grow older. Advanced glycation end products are also commonly consumed in the food of our western diet since they are made by modern processing techniques to give food taste, texture and properties such as longer shelf life. Glycation is a major problem in diabetes, and these molecules resulting from an excess circulating blood sugar have the capacity to do major damage to the organs of a diabetic person over several decades. Essentially, it speeds up the ageing process, and can lead to a "caramelisation" of major organs such as the kidney. Kidney disease is an important risk factor for heart attack. It is estimated that as many as 70 percent of people with diabetes die from heart attack or stroke.

One of the major research interests of this group is to better understand how advanced glycation occurs and the very process by which sugar attaches itself to proteins in the blood. They are trying to find out if they can inhibit the process once it has begun and crucially, whether it can be reversed. This is important since many people who present with kidney problems have been suffering from diabetes for many years but have not known it. As a result, their kidney dysfunction has not been addressed and is at an advanced stage. The challenge taken up by Josephine's team is to find some way of undoing the damage in these patients.

Dysfunction of the small power stations or the "mitochondria", within our cells is an extremely important step towards irreversible kidney damage. As our kidney cell energy levels are depleted, the cells slow down and eventually die. We have discovered that damage to other cell compartments by advanced glycation can cause and initiate mitochondrial damage and energy depletion from the outside. As current medicines do not address this pathway it is a novel new target for therapies in diabetic kidney disease.

Josephine's team is also looking at ways to predict who in the community might be at risk of developing diabetic complications. The main complications involve the eyes, heart, kidneys and nerves. By investigating genetic risk factors in people with diabetes who are as yet not suffering from any related health problems but have a diabetic relative with eye, kidney or heart disease, they hope to help prevent the progress of this disease in a new generation of sufferers.

Research Focus

• Diabetes
• Kidney disease
• Advanced glycation
• Mitochondrial dysfunction
• Food processing

Lab Head Profile

A/Prof Forbes completed her PhD in Nephrology in 1999 at Victorian Paediatric Renal Services, Royal Children's Hospital (Paediatrics, University of Melbourne). In 2002, she became the Group Leader for the Glycation and Diabetes Complications Laboratory at the Baker IDI Heart and Diabetes Research Institute. She is currently an NHMRC Career Development Fellow and currently holds research grants from NHMRC, Juvenile Diabetes Research Foundation (JDRF) and NIH (USA). She is a regular member of NHMRC review panels in addition to grant review panels for the JDRF international.

A/Prof Forbes' work to date has resulted in more than 80 publications in highly ranked diabetes and related journals with excellent citation rates. Her primary research focuses on the biochemical process of advanced glycation and its contribution to diabetes and its vascular complications, in particular nephropathy. She has received awards for her research including the Commonwealth Health Minister's Award for Excellence in Medical Research in 2010, an NHMRC Achievement Award as the highest ranked biomedical CDA Level 2 in 2009 and a Young Tall Poppy Award in 2008. A/Prof Forbes currently leads a team of 12 staff including three PhD students, in addition to being an Associate Professor in Immunology at Monash University, and a Principal Research Fellow in medicine at the University of Melbourne, Australia.

Achievements/Awards

Publication Highlights

• Forbes JM, Cooper ME, Thallas V, Burns WC, Brammar GC, Lee F, Grant S, Burrell LC, Jerums G, Osicka TM. Reduction of the accumulation of advanced glycation end products by angiotensin converting enzyme inhibition in experimental diabetic nephropathy. Diabetes 2002;51:3274-3282.
• Forbes JM, Thallas V, Thomas MC, Burns WC, Jerums G, Cooper ME. The breakdown of preexisting advanced glycation end products is associated with reduced renal fibrosis in experimental diabetic nephropathy. FASEB J 2003;17(12):1762-1764.
• Forbes JM, Thorpe SR, Thallas-Bonke V, Pete J, Coughlan MT, Thomas MC, Deemer ER, Bassal S, Long DM, Panagiotopoulos S, Jerums G, Osicka TM, Cooper ME. Angiotensin Converting Enzyme-1 Inhibition in diabetic nephropathy reduces the accumulation of advanced glycation end products via mediation of soluble RAGE. J Am Soc Nephrol 2005;16:2363-2372.
• Forbes JM, Coughlan MT, Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 2008;57:1-9.
• Coughlan MT, Thorburn DR, Penfold SA, Laskowski A, Harcourt BE, Sourris KC, Tan ALY, Thallas-Bonke V, Nawroth P, Brownlee M, Bierhaus A, Cooper ME, Forbes JM.AGE-RAGE-induced cytosolic oxidative disturbances amplify mitochondrial superoxide generation in diabetic nephropathy. J Am Soc Nephrol 2009;20:742-752.

Key Staff

Contact

Direct: +613 8532 1456
Email: josephine.forbes@bakeridi.edu.au