Prorenin And The Prorenin Receptor In Diabetic Retinopathy: Involvement Of The Wnt Pathway And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$580,042.00
Summary
Diabetic retinopathy is the leading cause of blindness in people of working age. The World Health Organization predicts that by 2030 more than 300 million people will have diabetes. Given the prevalence of diabetic retinopathy and the lack of effective treatments, there is an urgent need to identify the factors that contribute to its development. This project will determine the role of components of a hormonal system, prorenin and its receptor, in diabetic retinopathy and whether they are new ta ....Diabetic retinopathy is the leading cause of blindness in people of working age. The World Health Organization predicts that by 2030 more than 300 million people will have diabetes. Given the prevalence of diabetic retinopathy and the lack of effective treatments, there is an urgent need to identify the factors that contribute to its development. This project will determine the role of components of a hormonal system, prorenin and its receptor, in diabetic retinopathy and whether they are new targets for its treatment.Read moreRead less
Interactions Between Vasoactive, Epigenetic And Immunogenic Pathways In The Development Of Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$664,584.00
Summary
In our community, diabetic retinopathy is the leading cause of vision loss in people of working age. As the prevalence of diabetic retinopathy increases, there is an urgent need to understand the factors that cause its development in order to develop new treatments. This proposal will explore the contribution of hormones, the memory of retinal cells to high glucose and stress, and the immune system to diabetic retinopathy. The goal is to develop new and improved treatments for Australians.
Fenofibrate And Microvascular Events In Type 1 Diabetes (FAME 1) Trial
Funder
National Health and Medical Research Council
Funding Amount
$2,883,529.00
Summary
Diabetes is one of the commonest cause of blindness in adults. Vision loss, which is irreversible, is a most feared complication of diabetes. A blood fat lowering drug called fenofibrate, available in Australia, has been shown to reduce eye damage in people with Type 2 diabetes by 35-40%, and to prevent eye damage in Type 1 diabetic animal models. This study will evaluate the potential benefits of fenofibrate in 450 adults with Type 1 diabetes who have early diabetic eye damage.
Omega 3 Polyunsaturated Fatty Acid Analogues In The Treatment Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$418,446.00
Summary
Treatment of diabetes has become an even greater challenge to our community today. The ill health from diabetes arises from the high blood sugar levels. Treatment of diabetic complications such as kidney damage has now become a major goal. This research addresses this problem by trying to find out if a group of novel polyunsaturated fatty acids can target the process initiated by high blood sugar responsible for kidney damage.
The Nuclear Growth Hormone Receptor- Its Actions And Mechanism Of Nuclear Translocation
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
We and others have found that cell surface receptors for growth factors such as EGF, FGF and growth hormone can be found in the nucleus of proliferating cells. We have shown that many cancers have elevated nuclear GH receptor including leukemia, breast and colon cancer. If we artificially target the GH receptor to the nucleus, the resulting cells are tumorigenic when injected into immunocompromised mice, rapidly form ing metastasising tumours. To create more effective inhibitors of this tumourog ....We and others have found that cell surface receptors for growth factors such as EGF, FGF and growth hormone can be found in the nucleus of proliferating cells. We have shown that many cancers have elevated nuclear GH receptor including leukemia, breast and colon cancer. If we artificially target the GH receptor to the nucleus, the resulting cells are tumorigenic when injected into immunocompromised mice, rapidly form ing metastasising tumours. To create more effective inhibitors of this tumourogenesis, and to define the physiological roles of nuclear GH receptor, we will define the transport process which carries the receptor to the nucleus and block it. We will also seek to define how the receptor in the nucleus interacts directly with DNA to inhibit programmed cell death. To carry out these projects we will use sophisticated proteomics -mass spectrometry to identify the proteins interacting with the receptor in the transport and gene activation processes. The role of candidates will be tested by preventing their expression or by direct inhibition of their action using drugs or dominant negative versions. These approaches will provide leads to new anti-cancer therapeutics, and therapies for blocking diabetic blindness and kidney failure.Read moreRead less
Validating A New Model For Growth Hormone Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$472,500.00
Summary
Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its anabolic actions. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and ageing. The hormone exerts these actions through its receptor, which is a class1 cytokine receptor, similar to many receptors important in regulating immunity, inflam ....Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its anabolic actions. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and ageing. The hormone exerts these actions through its receptor, which is a class1 cytokine receptor, similar to many receptors important in regulating immunity, inflammation, metabolism and cancers. In principle, if we can find out how the GH receptor works, this information would help in designing drugs to treat many immune and inflammatory disorders. With current NHMRC support we have developed a model which describes how GH activates the receptor at a molecular level. The model involves two pre-associated receptors at the cell surface binding to the hormone, with the result that the receptors are rotated relative to each other, and this brings the two JAK2 signalling units attached tothe receptor inside the cell into alignment, so they can activate each other. We can activate the receptor without hormone by artificially rotating it. This model is a prediction based on several techniques, but lacks proof of rotation. There are also a number of issues relating to the need for rigidity in the receptors, so the torque can be transmitted into the cell, since many believe there is no rigidity just above the membrane. We predict there is , but need to prove this. This information is vital for designing small orally active mimics of growth hormone, and for developing GH antagonists, likely to be useful for breast and colon cancer. Finally, we have evidence that the specificity of receptor signalling can be changed by mutating the outer part of the receptor (novel). We believe this can be used to change the activity spectrum of GH, hence decrease side effects, by developing analogs which activate one pathway or the other.Read moreRead less
Intervention To Reduce The Risk Of Diabetic Retinopathy And Early Adverse Retinal Changes In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,294,846.00
Summary
The long term effects of young onset T1D may be devastating: diabetes is the leading cause of visual loss in young adults in Australia and other countries. We have the unique opportunity to investigate whether ACEI and statins will modify retinopathy through our collaboration with an already funded international multicentre trial. This study will treat adolescents for 4 years and will follow them for the next 5-10 years. We will use novel measures of retinal blood vessels size and fractals.
Diabetes affects over one million Australians and is an increasing health problem in Australia and worldwide. Diabetes can damage small blood vessels, harming the kidneys and eyes and large blood vessels leading to heart attack, stroke and leg amputation. The research team leading this Centre for Clinical Research Excellence (CCRE) has wide experience in diabetes research and includes experts in diabetes management in hospitals and in the community setting of general practice. There is special e ....Diabetes affects over one million Australians and is an increasing health problem in Australia and worldwide. Diabetes can damage small blood vessels, harming the kidneys and eyes and large blood vessels leading to heart attack, stroke and leg amputation. The research team leading this Centre for Clinical Research Excellence (CCRE) has wide experience in diabetes research and includes experts in diabetes management in hospitals and in the community setting of general practice. There is special expertise in eye disease and in dietary management of diabetes. The research team will conduct research into diabetes, both type 1 diabetes, which usual starts in childhood, and type 2 diabetes that generally affects middle aged or older people, although increasingly is occurring in younger adults as the population becomes more obese. We will focus on the complications, which are common to both types of diabetes, looking for ways to detect them early and prevent them. Our studies will involve groups of up to 10,000 people with diabetes, sometimes followed over 5 or more years. Indigenous Australian groups will be included in the studies as they have a high rates of diabetes and its complications. We will also study ways in which people with type 2 diabetes can be more involved in improving the management of their illness. An exciting part of the study program will involve patients having transplants of insulin producing human islet cells. Although this treatment will be available for only a few patients, it is an important advance towards future treatments using human cells. The CCRE will have a very strong focus on recruiting and training the next generation of doctors and other clinicians involved in diabetes research, including nurses, dietitians and optometrists.Read moreRead less