The Regulation Of Aromatase In The Context Of Obesity And Postmenopausal Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$436,601.00
Summary
Current hormone therapy for breast cancer using inhibitors of oestrogen formation results in serious side-effects including bone loss, joint pain and possibly cognitive issues. Our current work is aimed at understanding how oestrogen formation is regulated with the goal of developing breast-specific inhibitors of oestrogen formation to obviate these problems. In addition, this work is aimed at devising therapeutic intervention to break the linkage between obesity and breast cancer.
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
The Ghrelin Axis As A Target For Prostate Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$585,497.00
Summary
Prostate cancer affects one in nine Australian men in their lifetime, and although there have been great advances in treatments, advanced prostate cancer remains incurable. Current treatments often lead to side effects which affect quality of life. We have found that the appetite hormone, ghrelin, stimulates prostate cancer cell growth and may be a useful target for prostate cancer therapy. We predict that targeting the ghrelin axis will prevent some of the side effects of other treatments that ....Prostate cancer affects one in nine Australian men in their lifetime, and although there have been great advances in treatments, advanced prostate cancer remains incurable. Current treatments often lead to side effects which affect quality of life. We have found that the appetite hormone, ghrelin, stimulates prostate cancer cell growth and may be a useful target for prostate cancer therapy. We predict that targeting the ghrelin axis will prevent some of the side effects of other treatments that reduce quality of life for patients.Read moreRead less
HEREDITARY ENDOCRINE CANCER: A MODEL BASED ON PHAEOCHROMOCYTOMA- PARAGANGLIOMA SYNDROMES
Funder
National Health and Medical Research Council
Funding Amount
$875,894.00
Summary
Phaeochromocytomas and paragangliomas are tumours remarkable for their very high heritability. They have a high burden of disease themselves, and their associated hereditary syndromes include risks for other malignancies. Our study will rationalize the pathological approach to diagnosing these hereditary syndromes, find new therapeutic targets for metastatic disease, and provide a template for other cancers with high heritable component.
A Multi-ethnic Cohort And Intervention Trial To Identify Early Biomarkers For Type 2 Diabetes And Customise Individualized Environments For Disease Prevention
Funder
National Health and Medical Research Council
Funding Amount
$597,376.00
Summary
Diabetes is often called a lifestyle disease, however, large clinical studies have shown that diabetes cannot always be prevented through lifestyle modification. This collaborative study between Shanghai Institutes of Biological Science and Sydney University will identify biomarkers that predict the development of type 2 diabetes. Using this knowledge, the best interventions (including diet, exercise and medications) to improve an individual’s risk profile for type 2 diabetes will be identified.
Investigating The Novel Role Of SEPS1 In The Prevention Of Islet Beta Cell Failure And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$535,804.00
Summary
SEPS1 is an important glucose-regulated protein whose function is to protect tissues from oxidative stress. Inhibition of SEPS1 by hyperglycaemia, is a mechanism for progression of Type 1 and Type 2 diabetes once hyperglycaemia supervenes. The overall aim of the project is to investigate the function of the novel SEPS1, using transgenic and knockout approaches.
Testosterone Intervention For The Prevention Of Diabetes Mellitus In High Risk Men: A Randomised Trial
Funder
National Health and Medical Research Council
Funding Amount
$5,054,654.00
Summary
Type 2 diabetes (T2DM) is increasingly common, costly and deadly. Some men at risk of T2DM have low testosterone (T) levels. Our preliminary data suggests that T treatment may prevent the development of T2DM, and improve cardiovascular and sexual function, body composition and bone density, and mood. This remains to be fully tested in a randomized placebo-controlled trial, and this project will do so in a 2-year study of T treatment compared to placebo in men at risk of T2DM participating in a l ....Type 2 diabetes (T2DM) is increasingly common, costly and deadly. Some men at risk of T2DM have low testosterone (T) levels. Our preliminary data suggests that T treatment may prevent the development of T2DM, and improve cardiovascular and sexual function, body composition and bone density, and mood. This remains to be fully tested in a randomized placebo-controlled trial, and this project will do so in a 2-year study of T treatment compared to placebo in men at risk of T2DM participating in a lifestyle program.Read moreRead less
Analysis Of Effect Of Different Treatment Targets On Maternal And Child Health Outcomes In Gestational Diabetes Mellitus (GDM), Review Of Specific Treatments And Development Of Clinical And Biochemical Predictors.
Funder
National Health and Medical Research Council
Funding Amount
$122,686.00
Summary
This research aims to analyse newly proposed treatment targets for Gestational Diabetes Mellitus (GDM) and the effect this will have on maternal and child health outcomes, via comparison of data from two large Australian health services using the traditional and newly proposed critiera. The research will also investigate current effective interventions for GDM, including the impact of early antenatal lifestyle interventions, and formulation of a clinical and biochemical risk prediction model.