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Role Of Epigenomic Changes In Conferring Hyperglycemic Memory
Funder
National Health and Medical Research Council
Funding Amount
$636,146.00
Summary
The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment h ....The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment has returned glucose levels towards normal.Read moreRead less
Angiotensin II AT2 Receptor In Diabetic Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$477,472.00
Summary
Activation of the angiotensin 2 receptor may have effects leading to large artery disease in diabetes. We will investigate the role of the AT2 receptor in diabetes using knockout animals, novel blockers and activators and most importantly the role of the AT2 receptor in macrophages in diabetes.
The Role Of The MicroRNA Let 7 In Diabetic Proliferative Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$674,084.00
Summary
Cardiovascular complications remain the major cause of mortality in diabetes and our current treatment strategies are insufficient to reduce this burden. We have obtained extensive data to show that a novel molecule (the micro RNA, let 7b) has antiproliferative and vasculoprotective effects in diabetes. Thus, we propose that modulation of micro RNA let 7b specifically in vascular smooth muscle cells within the vascular wall represents a promising target to combat cardiovascular disease, in parti ....Cardiovascular complications remain the major cause of mortality in diabetes and our current treatment strategies are insufficient to reduce this burden. We have obtained extensive data to show that a novel molecule (the micro RNA, let 7b) has antiproliferative and vasculoprotective effects in diabetes. Thus, we propose that modulation of micro RNA let 7b specifically in vascular smooth muscle cells within the vascular wall represents a promising target to combat cardiovascular disease, in particular in diabetes.Read moreRead less
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.
Modulation Of TGF-beta Signaling By CDA1 In The Diabetic Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$524,004.00
Summary
Cell Division Autoantigen 1 (CDA1) is a molecule we identified several years ago. Recently we found that CDA1 played an unique role in causing blood vessels to scar and become stiff by hijacking and controlling the existing transforming growth factor-beta (TGF-beta) signaling pathway. We will explore the possibility to use this unique property of CDA1 to treat the blood vessel hardening and related diseases such as atherosclerosis and heart attacks, particularly in the setting of diabetes.
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.
The Role Of Dicarbonyl-derived AGEs And RAGE In Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$470,617.00
Summary
Based on our pilot data we postulate that glucose derived molecules such as methylglyoxal (MGO) have effects on inflammation and oxidative stress leading to accelerated atherosclerosis in diabetes. Our studies aim to identify novel treatments which block these effects thus leading to superior protection and prevention of atherosclerosis in diabetes.
Inhibition Of Specific NOX Isoforms As A New Treatment For Hypertensive And Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$855,172.00
Summary
Almost all people with diabetes will develop some retinal disease (diabetic retinopathy, DR) and vision loss. Unfortunately, current treatments target the late stages of DR, do not prevent disease progression and can be damaging. This project will uncover the role of a fundamental process that occurs in DR, called oxidative stress. We will evaluate a major cause of oxidative stress called NOX, which exists in various forms. Animal models of diabetes in which NOXes have been manipulated as well a
Novel GPCR Transactivation Of Serine Kinases In Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$386,565.00
Summary
All of biology and disease is based on cells receiving signals from hormones and growth factors via cell surface receptors. Cells integrate these signals to give a response which may be cell growth or the secretion of further hormones and growth factors. Signals from receptors can intersect to modify the response. This project will explore a new interaction we have discovered where a hormone activates its receptor to cause the activation of a growth factor receptor potentially providing new drug ....All of biology and disease is based on cells receiving signals from hormones and growth factors via cell surface receptors. Cells integrate these signals to give a response which may be cell growth or the secretion of further hormones and growth factors. Signals from receptors can intersect to modify the response. This project will explore a new interaction we have discovered where a hormone activates its receptor to cause the activation of a growth factor receptor potentially providing new drug targets in cardiovascular disease.Read moreRead less
We have validated CDA1 as an effective target to retard kidney disease in diabetes using a mouse model where we deleted the CDA1gene. We have also developed a novel agent to inhibit CDA1 in order to retard diabetic kidney disease. In this application, we propose to confirm the efficacy of targeting CDA1 using various diabetes models and a range of strategies to target CDA1. We will also rigorously explore translation of these findings to a new treatment for diabetic renal disease.