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.
I am a physiologist and my diabetes research involves a preclinical approach to address the issue of diabetes and its major renal and cardiovascular complications
Prof Cooper’s diabetes research encompasses basic mechanisms through to translational research and major clinical trials in order to address the issue of diabetes and in particular the prevention and management of its major renal and cardiovascular complications.
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
Role Of Vasoactive Hormones And Cytokines In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$361,650.00
Summary
Kidney disease is a major cause of disability and premature death in the Australian population. In diabetic kidney disease a major factor which accelerates the progression of this disorder is the presence of hypertension. Indeed international and national organisations now recommend aggressive blood pressure treatment in the diabetic patient. This proposal aims to optimise blood pressure treatment in diabetes and evaluate novel more potent blood pressure lowering agents which block within the ki ....Kidney disease is a major cause of disability and premature death in the Australian population. In diabetic kidney disease a major factor which accelerates the progression of this disorder is the presence of hypertension. Indeed international and national organisations now recommend aggressive blood pressure treatment in the diabetic patient. This proposal aims to optimise blood pressure treatment in diabetes and evaluate novel more potent blood pressure lowering agents which block within the kidney important hormonal pathways implicated in diabetic kidney disease. This approach will assist in determining key factors which mediate the damage to the kidney induced by elevated blood pressure. It is anticipated that these studies will lead to more rational, targeted and powerful antihypertensive agents which will retard or prevent the development of diabetic nephropathy.Read moreRead less
Progressive Renal And Vascular Disease: Pivotal Role Of The AT2 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$283,875.00
Summary
Diabetes and renal disease are commonly associated with a range of vascular complications. I have been investigating a particular hormone system known as the renin-angiotensin system in promoting kidney and vascular complications in various diseases including diabetes. This system is a pathway which ultimately generates a hormone called angiotensin II which has many actions which could be harmful to the kidney and blood vessels. The importance of this hormone system has been demonstrated by the ....Diabetes and renal disease are commonly associated with a range of vascular complications. I have been investigating a particular hormone system known as the renin-angiotensin system in promoting kidney and vascular complications in various diseases including diabetes. This system is a pathway which ultimately generates a hormone called angiotensin II which has many actions which could be harmful to the kidney and blood vessels. The importance of this hormone system has been demonstrated by the beneficial effects particularly on the kidney of drugs which block this pathway. It has been demonstrated that angiotensin II acts via 2 different receptors, the AT1 and AT2 subtypes. Initially the AT1 receptor was viewed to mediate most of the biological effects of angiotensin II. However, as demonstrated by our own and other groups, the AT2 receptor may play a role in mediating various effects of angiotensin II particularly in disease states. We have identified expression of this receptor in the adult kidney and in the vessel wall which may be upregulated in various disease states. The status of the AT2 receptor is not well characterised in diabetes and many other kidney diseases and this proposal will address this issue in a comprehensive manner by evaluating various sites of injury in diabetes including the kidney and vascular tree. This proporsal includes different approach to moduate this receptor involving drug blockers and animal model where this receptoris either deleted or overexpressed. These studies potentially have major implications for the management of diabetic and renal complications. It remains to be determined if the AT2 receptor confers beneficial or deleterious effects in diabetic nephropathy or other renal diseases, if these effects vary among the various organs to be studied and whether AT2 receptor antagonists may themselves be of therapeutic value in individuals at high risk of kidney and vascular disease such as people with diabetes.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
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.
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.
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.