The discoveries made to date and the proposed studies point to an intrinsic role for vitamin D compounds in skin in providing protection from sun damage. As a result of sun exposure, increased concentrations of vitamin D compounds in skin will be generated and this is likely to provide protection against further UV damage, in much the same way as increased pigmentation and increased thickness of the outer layer of skin. Furthermore, the studies are designed to test whether vitamin D compounds wh ....The discoveries made to date and the proposed studies point to an intrinsic role for vitamin D compounds in skin in providing protection from sun damage. As a result of sun exposure, increased concentrations of vitamin D compounds in skin will be generated and this is likely to provide protection against further UV damage, in much the same way as increased pigmentation and increased thickness of the outer layer of skin. Furthermore, the studies are designed to test whether vitamin D compounds which have minimal effects on serum calcium, could nevertheless be used topically in association with a sunscreen or moisturizer to add to sun protection. As Australia has the highest skin cancer rates in the world, this would be of significant health and economic value.Read moreRead less
How Intra-abdominal Transplantation Of Subcutaneous Adipose Tissue Prevents High-fat Diet-induced Insulin Resistance And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$358,465.00
Summary
In obese humans, storing excess fat within the abdomen is associated with the development of adult-onset diabetes and cardiovascular disease. However, the mechanisms linking intra-abdominal fat accumulation with these diseases are not well understood. We have studied intra-abdominal fat accumulation in mice using a transplant model, and we have found that transplanting subcutaneous fat intra-abdominally prevents diet-induced obesity and glucose intolerance. We aim to investigate the underlying m ....In obese humans, storing excess fat within the abdomen is associated with the development of adult-onset diabetes and cardiovascular disease. However, the mechanisms linking intra-abdominal fat accumulation with these diseases are not well understood. We have studied intra-abdominal fat accumulation in mice using a transplant model, and we have found that transplanting subcutaneous fat intra-abdominally prevents diet-induced obesity and glucose intolerance. We aim to investigate the underlying mechanisms.Read moreRead less
The effects of therapeutic glucocorticoid doses on carbohydrate and energy metabolism and cardiovascular risk have not been fully clarified. This PhD thesis will be based around two studies aiming to: 1.) Define mechanisms underlying the adverse effects of low dose prednisolone in patients with inflammatory rheumatologic disease and 2.) Improve treatment of prednisolone-induced hyperglycaemia in hospitalized patients.
Thyroid-sympathoadrenal Regulation Of Human Brown Fat
Funder
National Health and Medical Research Council
Funding Amount
$447,141.00
Summary
This project aims to determine how hormones influence the growth and activity of brown fat in humans. Majority of fat cells in the body are white fat cells, which store fat, and cause obesity when in excess. Brown fat cells function like generators. They burn fat and release energy as heat. Humans with lots of brown fat are lean. What controls brown fat activity is currently unknown in humans. This project investigates how hormones influence brown fat activity and may shed light on the therapeut ....This project aims to determine how hormones influence the growth and activity of brown fat in humans. Majority of fat cells in the body are white fat cells, which store fat, and cause obesity when in excess. Brown fat cells function like generators. They burn fat and release energy as heat. Humans with lots of brown fat are lean. What controls brown fat activity is currently unknown in humans. This project investigates how hormones influence brown fat activity and may shed light on the therapeutic potential of brown fat in obesity treatment.Read moreRead less
Is CYP11A1 Critical For The Vitamin D Photoprotective System In Skin?
Funder
National Health and Medical Research Council
Funding Amount
$517,567.00
Summary
Sunlight produces DNA damage. When inadequately repaired, this damage produces skin cancer. The vitamin D system in skin helps protect against this skin damage, but the vitamin D compounds involved and how they work is unclear. Recent data shows new vitamin D compounds with photoprotective activity and that vitamin D compounds increased expression of DNA repair proteins. These studies may enable pharmacological enhancement of protection from sunlight.
The Role Of Grb10 In The Regulation Of Muscle Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$624,960.00
Summary
Obesity increases the risk of metabolic diseases such as type 2 diabetes. Muscle is a key tissue for balancing whether energy is used or stored as fat and as we age, muscle mass normally decreases making maintaining a healthy metabolism even more difficult. We have discovered that removing the Grb10 gene from mice produces bigger muscles. This project will investigate the mechanisms of this effect so that strategies can be developed to regulate muscle mass and improve metabolic health
Androgen Receptor Signalling In Development And Progression Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$753,420.00
Summary
Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because pr ....Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because prostate cells are dependent on testicular androgens for their growth and survival, surgical or medical castration results in an initial tumour regression. However, tumours inevitably develop resistance to androgen ablation therapy and regrow. In this study we aim to provide the most comprehensive analysis to date of the role of androgen signalling in the initiation and progression of prostate cancer. This will enable us to identify the most effective means of eliminating androgen-dependent prostate tumours and identify tumours with high metastatic potential. Our studies will indicate whether treatments targeting androgen signalling are a more effective strategy to inhibit prostate cancer growth while minimising undesirable side effects.Read moreRead less
Role And Mechanism Of Connective Tissue Growth Factor In Diabetic Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$382,820.00
Summary
Diabetic cardiomyopathy is a condition where the heart muscle is directly damaged by diabetes. It is being recognised as a prominent cause of both acute and chronic heart failure in diabetes. It is common and occurs in up to 60% of diabetic patients . At present however, no treatments are available to directly treat the cardiomyopathy. This condition can also occur in people with diabetes who have high blood pressure and-or coronary artery disease and may combine with these problems to worsen pa ....Diabetic cardiomyopathy is a condition where the heart muscle is directly damaged by diabetes. It is being recognised as a prominent cause of both acute and chronic heart failure in diabetes. It is common and occurs in up to 60% of diabetic patients . At present however, no treatments are available to directly treat the cardiomyopathy. This condition can also occur in people with diabetes who have high blood pressure and-or coronary artery disease and may combine with these problems to worsen patient outcomes. We have generated data in experimental diabetes in rodents that strongly implicates a heart growth factor in causing diabetic cardiomyopathy. This protein, called connective tissue growth factor (CTGF), is increased in diabetic cardiomyopathy, and is elevated by high glucose and other factors in diabetes. We have published data showing that CTGF causes tissue scarring like that which occurs in cardiomyopathy, by affecting signals in cells called fibroblasts. It increases the laying down of extracellular matrix (ECM) and also inhibits the degradation of ECM by the proteins that break down matrix, known as the MMPand PAI systems. Such accumulation of ECM is thought to be a major factor leading to abnormal muscle function in cardiomyopathy. We now plan to block CTGF in this diabetic heart model to determine if we can prevent diabetic cardiomyopathy. We have generated two methods to inhibit CTGF in the animal model. Echocardiography (a heart ultrasound test), and molecular analysis of the heart tissue will determine if we can prevent the otherwise adverse functional and structural changes of diabetes in the heart. We will also study our baboon model of diabetes to determine if diabetic cardiomyopathy with increased heart CTGF is present in the primates. Cell culture studies from rat heart fibroblasts and myocytes will determine how CTGF has the effect on cells to cause cardiomyopathy and how we might further prevent this condition developing in diabetes.Read moreRead less