Role Of Ferroptosis In The Lipid Metabolism Of Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$238,792.00
Summary
Conventional cancer treatments are becoming increasingly ineffective as cancers mutate to protect cells from drug-activated death. To combat this, new ways to selectively kill cancer cells must be found and therapeutically exploited. This research will study how ferroptosis, a recently discovered form of cell death that is distinct from other killing mechanisms, can be used to target cancer and provide avenues for next-generation cancer treatments.
I am a cell /whole body integrative biologist determining the cellular and molecular mechanisms that lead to insulin resistance in insulin sensitive tissues such as skeletal muscle, liver and adipose tissue. My work primarily focuses on targeting inflammatory signalling cascades that lead to impaired insulin action, and pathways that enhance energy utilization.
Therapeutically Targeting The Major Genetic Risk Factor Of Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$530,069.00
Summary
The second greatest risk factor for Alzheimer’s disease (after age) is genetic variation in a protein called APOE, however it is unknown why APOE increases the risk of disease. We have new clinical and laboratory evidence that APOE incresase risk of Alzheimer’s disease by manipulating iron pathways in the brain. We plan to examine these pathways and apply a new theraputic we have developed that targets these pathways in animal models of Alzheimer’s disease.
Mammalian Endotoxin: Characterisation Of Highly Inflammatory Endogenous Material
Funder
National Health and Medical Research Council
Funding Amount
$915,859.00
Summary
Inflammation drives development of many common diseases including heart disease, cancer, Alzheimer's disease and diabetes. We understand how bacterial molecules initiate inflammation during infections, but the nature of inflammatory stimuli that promote degenerative diseases of ageing has been elusive. In this project we will identify highly inflammatory molecules that have become altered in cells under stress. Knowledge of these pathways will promote new treatments for chronic diseases.
Novel Interplay Of Oestrogen And Growth Hormone In Regulating Lipid Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$673,045.00
Summary
These studies provide insights into the mechanisms and role of oestrogen in regulating whole body and liver fat metabolism. Oestrogen-related medications that modify the action or tissue availability of oestrogen are widely used therapeutics and can predispose to obesity and fat accumulation in the liver. Whether the effect is direct or through interplay with other metabolic hormones is unknown. This proposal examines their metabolic consequences and impact on obesity and liver health.
Lipoprotein Oxidation, Antioxidants And Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$281,812.00
Summary
We are studying how major blood vessels harden. This process (called atherosclerosis) is the major underlying cause of heart disease, the major single cause of death of Australians. Our research focusses on the 'Oxidation Theory', one of the most common theories of how atherosclerosis develops. Accordingly, fats in fat-carrying particles (called lipoproteins) penetrate the walls of blood vessels, where they cause disease as a result of going rancid. This is a primary reason for the general publi ....We are studying how major blood vessels harden. This process (called atherosclerosis) is the major underlying cause of heart disease, the major single cause of death of Australians. Our research focusses on the 'Oxidation Theory', one of the most common theories of how atherosclerosis develops. Accordingly, fats in fat-carrying particles (called lipoproteins) penetrate the walls of blood vessels, where they cause disease as a result of going rancid. This is a primary reason for the general public's interest in antioxidant supplements to combat heart disease. However, it is not clear at present whether rancid fats is a cause or consequence of atherosclerosis, and we recently showed that the two processes can be dissociated in an animal model of the disease. This application addresses the question of whether the process of fats going rancid can be generally dissociated from atherosclerosis, using several different animal models of the disease. We will distinguish different chemical pathways that give rise to different types of rancid fats, and between rancid fats and 'rancid' proteins. Such studies have not been carried out to date. Our underlying hypothesis is that the process of lipoprotein fat going rancid is a consequnece rather than a cause of atherosclerosis and heart disease. By testing this hypothesis, we will provide a rationale for whether antioxidant supplements aimed at preventing rancid fats from accumulating are likely of benefit in terms of preventing heart disease. This is of direct interest to public health. Our studies also address the issue of how antioxidants (if not through preventing fats from going rancid) attenuate atherosclerosis. We will focus on a particular synthetic antioxidant for which there is strong evidence that it is beneficial in preventing the re-narrowing of blood vessels in humans undergoing coronary angioplasty. These studies have the potential to provide new clues for the development of novel drugs against heart disease.Read moreRead less
Factors Controlling Lipid Accumulation In Non-adipose Tissues
Funder
National Health and Medical Research Council
Funding Amount
$463,500.00
Summary
The fat cells of the body are designed to store excess fuel for use when supply from the diet is low, or in situations like exercise, demand is high. Fat also accumulates to some extent in the cells of other tissues types, but in some people the accumulation is excessive. This can have a number of serious effects. In the liver and muscle it can interfere with the ability of insulin to properly regulate the amount of glucose present in the blood, contributing to the development of diabetes. In th ....The fat cells of the body are designed to store excess fuel for use when supply from the diet is low, or in situations like exercise, demand is high. Fat also accumulates to some extent in the cells of other tissues types, but in some people the accumulation is excessive. This can have a number of serious effects. In the liver and muscle it can interfere with the ability of insulin to properly regulate the amount of glucose present in the blood, contributing to the development of diabetes. In the liver, fat accumulation can also lead to cirrhosis and liver failure. Cardiovascular complications, resulting in premature death, are also likely. However despite these devastating consequences it is not clear what the underlying cause of the over-accumulation of fat is not known. In this project we will investigate in detail several aspects of fat metabolism that we think are important in controlling how tissues take up fat from the circulation and whether it is subsequently stored or burnt for energy. We will study the amount of fat that is taken up by different tissues of the body under a range of conditions including fed, and short- and long-term fasting. We will also use drugs to inhibit or promote the amount of fat that is burnt, to see if this changes the rate at which fat is taken up by different tissues. In addition we will accelerate, by genetic manipulation, the rate at which some key enzymes of fat metabolism are produced, to determine their effect on the amount of fat that is stored by different tissue types. Our aim is to determine the metabolic processes that influence fat accumulation in those adversely affected tissues such as liver, heart and skeletal muscle. The identification of the most important processes will contribute significantly to the targeting of therapies aimed at preventing excess fat accumulation and its associated diseases.Read moreRead less