My research focuses on the mechanisms responsible for diabetic kidney and heart complications with an emphasis on identifying novel targets as the basis for developing new treatment to reduce the burden of these complications. It is hypothesised that diabetic complications arise as a result of a number of key factors, the most important being chronic elevation of blood glucose.
Characterisation Of Novel AGE Binding Proteins: Implications For Diabetic Vascular Complications.
Funder
National Health and Medical Research Council
Funding Amount
$210,990.00
Summary
This project will explore a process known as advanced glycation and in particular how this may lead to organ injury in diabetes. Diabetes is characterised by sustained elevation of blood glucose levels which interact with proteins to generate products known as advanced glycation end-products (AGEs). These AGEs bind to other proteins some of which have been isolated and are considered receptors. Our own group has identified a new family of proteins known as ERM proteins which bind to AGEs. This i ....This project will explore a process known as advanced glycation and in particular how this may lead to organ injury in diabetes. Diabetes is characterised by sustained elevation of blood glucose levels which interact with proteins to generate products known as advanced glycation end-products (AGEs). These AGEs bind to other proteins some of which have been isolated and are considered receptors. Our own group has identified a new family of proteins known as ERM proteins which bind to AGEs. This is a highly novel finding which now needs to be examined in more detail. The ERM proteins which include ezrin, radixin and moiesin are found at many sites of diabetic complications including the kidney, retina and blood vessel wall. They have a number of functions including effects on cell adhesion and cell structure. This is important in diabetes where changes in cells including altered structure have been observed. This grant will characterise the interactions between AGEs and ERM proteins at the molecular and cellular level. It will define how AGEs influence cells via interactions with ERM proteins. These studies have the potential to lead to treatments that may modulate the AGE-ERM interactions, thereby retarding or preventing diabetic vascular complications. These complications are of important clinical significance since they are the major cause of morbidity and mortality in the diabetic population. Furthermore, diabetes is a major cause of premature atherosclerosis in our community, diabetic kidney disease is the leading cause of end-stage renal failure in the Western world and diabetic retinopathy (eye disease) is the main cause of blindness in the working age population.Read moreRead less
E-PREDICE Early Prevention Of Diabetes Complications In Europe
Funder
National Health and Medical Research Council
Funding Amount
$917,400.00
Summary
The e-PREDICE study will randomise 3000 people aged 45-74 with mild hyperglycaemia or early diabetes to treatment with intensive lifestyle modification alone, or plus metformin, or sitagliptin, or liraglutide, aiming to reduce diabetes eye, kidney and nerve damage. The Australian arm will be co-ordinated by the University of Sydney and other sites include Baker IDI Heart and Diabetes Institute, Royal Melbourne Hospital, St Vincent’s Hospital Melbourne and Royal Brisbane and Womens Hospital
The Role Of Angiotensin Converting Enzyme 2 In Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$453,144.00
Summary
Most heart attacks and strokes arise from narrowing of the arteries. This process is regulated by a number of hormonal pathways. One of the most important is the renin angiotensin system. Our group has demonstrated important changes in this pathway which play a pivotal role in regulating the development of atherosclerosis and its response to treatment. It is predicted that these studies will provide critical information to develop innovative treatment strategies for cardiovascular disease.
Epigenetic Determinants Of Nephropathy In Adults With Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$532,118.00
Summary
The prevention and successful management of diabetic complications are issues of utmost importance for the health of Australians. We hypothesize that epigenetic pathways partly determine why some individuals with diabetes develop complications of their disease, while others do not, despite a similar duration of diabetes, treatment intensity and mean glucose exposure.
Targeting Epigenetic Pathways That Lead To Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$989,948.00
Summary
Glucose remains the major cause of complications in diabetes with prior episodes of high glucose having long lasting effects on blood vessels leading to heart attacks, kidney disease and blindness. We have identified an enzyme Set7 which plays a key role in promoting glucose induced injury. By validating this target using drug and molecular approaches we will strengthen the rationale to develop potent inhibitors of this enzyme in order to reduce the major burden of diabetes, its complications.
JDRF/NHMRC Diabetes Complications Centre Of Research Excellence
Funder
National Health and Medical Research Council
Funding Amount
$2,607,291.00
Summary
Despite intensive intervention some individuals with type 1 diabetes develop complications. There remains an urgent need for means to identify patients at risk of complications and new targets and therapies for preventing, arresting, treating and reversing them. The primary objective of the Diabetes Complications Centre of Research Excellence (DC-CRE) is to translate novel experimental findings into preventive/treatment strategies for the management of diabetes and its complications.
RAGE And ACE2 Shedding As Therapeutic Targets In Diabetes And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$748,447.00
Summary
We have previously demonstrated the pivotal role of two shed proteins, Receptor for Advanced Glycation End-products (RAGE) and Angiotensin Converting Enzyme Receptor 2 (ACE2) in heart disease and diabetic complications. In this project, we will use a novel technologies to modify shedding of these proteins from the cell surface and alter their ability to cause disease.
NOX Isoforms In Diabetes Associated Vascular Injury: Implications For Therapeutic Strategies
Funder
National Health and Medical Research Council
Funding Amount
$441,511.00
Summary
These studies will investigate the role of oxidative stress and enzymes involved in oxidative stress production in diabetes associated blood vessel injury and kidney damage, leading to heart attacks, stroke and kidney failure. We will use unique knockout animal models and novel drug treatments. Ultimately, we aim to develop novel treatments to better treat and prevent diabetes related complications.
Epidemiological And Molecular Risk Factors For Diabetic Retinopathy Blindness.
Funder
National Health and Medical Research Council
Funding Amount
$61,988.00
Summary
Diabetic retinopathy (DR) is the leading cause of blindness in working age adults, affecting 30% of Australians with diabetes. Patients at most risk of blindness are the focus of this project. We aim to (1) investigate why some people are more likely to develop blinding DR by looking at genetic difference between diabetic patients with and without DR; and, (2) help to understand why Indigenous Australians are so over represented in this subset of diabetic patients going blind from DR.