I am a lipid biochemist-cell biologist determining the molecular mechanisms of disorders of lipid metabolism and developing treatments for such disorders. The diseases where lipid metabolism plays a key role include cardiovascular diseases (such as coronary artery disease), metabolic disorders (such as diabetes), some infectious diseases (such as HIV) and neurological disorders (such as Alzheimer disease).
The Interactive Effects Of Dietary Saturated Fat And Apolipoprotein-E Genotype On Peripheral Metabolism Of Lipoprotein-amyloid And Neurovascular Integrity.
Funder
National Health and Medical Research Council
Funding Amount
$637,536.00
Summary
This project is based on a remarkable discovery which suggests that in some individuals, Alzheimer's disease may be a consequence of corruption of microscopic blood vessels that supply brain, damaged as a consequence of exaggerated exposure in blood to a protein produced principally in liver. The project will explore this pathway further in subjects at heightened risk of Alzheimer's disease and in humanised animal models. The findings may provide new opportunities for prevention and treatment.
Molecular Mechanisms Of Inherited Hypocholesterolaemias: Impact Of APOB And MTTP Mutations On Lipoprotein Assembly And Secretion
Funder
National Health and Medical Research Council
Funding Amount
$200,213.00
Summary
Inherited low cholesterol levels can be caused by mutations in either of two genes: APOB and MTTP. These genes encode proteins that are critical for the assembly of fat particles in the body. We plan to use cell lines to study how single amino acid changes out of the 4500 in ApoB and the 900 in the MTTP protein affect protein production, binding with other proteins, and fat particle assembly.
Addressing Residual CV Risk In Diabetes: Focus On Lp(a) Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$367,864.00
Summary
High postmeal lipid levels and fatty liver occurs commonly in Type 2 Diabetes and is associated with increased risk of cardiovascular disease. In addition to the standard risk factors of triglycerides and cholesterol, other factors, including a small protein called Lp(a) increase cardiovascular disease risk. Few therapies reduce Lp(a) and this study will examine the effect of niacin on reducing the concentration of this protein. A positive result may expand treatment choices for diabetics in red ....High postmeal lipid levels and fatty liver occurs commonly in Type 2 Diabetes and is associated with increased risk of cardiovascular disease. In addition to the standard risk factors of triglycerides and cholesterol, other factors, including a small protein called Lp(a) increase cardiovascular disease risk. Few therapies reduce Lp(a) and this study will examine the effect of niacin on reducing the concentration of this protein. A positive result may expand treatment choices for diabetics in reducing the risk of heart disease.Read moreRead less
Pathophysiology And Therapeutics Of Lipoprotein Disorders In Humans
Funder
National Health and Medical Research Council
Funding Amount
$451,716.00
Summary
Lipid disorder is the major casual factor that contributes to the development of cardiovascular disease, the leading cause of death in Australia. My research has provided new knowledge that has significant impact upon the treatment strategy of lipid disorder and cardiovascular risk. My vision for the next four years is to develop a comprehensive program in understanding lipid transport and translating the knowledge into clinical practice.
PCSK9 is an inhibitor of the receptor that is responsible for removing LDL (the bad cholesterol) from the circulation. We will study the molecular mechanisms that inhibit PCSK9 at the protein level. This study is needed to understand if drugs that inhibit PCSK9 will diminish the risk of developing heart disease in patients who do not respond well to existing treatments, for example those who already had a cardiovascular event or those with familial hypercholesterolemia.
Postprandial Lipid Metabolism In Familial Hypercholersterolaemia: Mechanisms And Effects Of Omega-3 Fatty Acid Ethyl Esters
Funder
National Health and Medical Research Council
Funding Amount
$616,344.00
Summary
Familial hypercholesterolaemia (FH) is the most common genetic condition known to cause premature coronary heart diseaseis (CHD). The increasd CHD risk in FH may be in part due to accumulation of fat in blood. Fish oil supplementation may be a new target, additional to standard best therapy, for reducing CHD risk in FH. Our results will add value to the science behind and clinical therapy for lipid disorders in FH, and will establish a key role for fish oils.
Insulin As A Regulator Of Postprandial Lipaemia In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$226,097.00
Summary
People who are overweight often develop cardio- and peripheral-vascular disease. The reasons are multifactorial but usually involve disturbances in the metabolism of fats. Overweight subjects have a tendency to accumulate energy rich lipids in blood derived from the gut or from the liver. Chronic arterial exposure to these lipids leads to an accumulation of certain types of fats in the wall of blood vessels, which if unabated ultimately leads to an impediment in blood flow. Ongoing studies in ou ....People who are overweight often develop cardio- and peripheral-vascular disease. The reasons are multifactorial but usually involve disturbances in the metabolism of fats. Overweight subjects have a tendency to accumulate energy rich lipids in blood derived from the gut or from the liver. Chronic arterial exposure to these lipids leads to an accumulation of certain types of fats in the wall of blood vessels, which if unabated ultimately leads to an impediment in blood flow. Ongoing studies in our laboratory have found that in obesity the production of these fats and the clearance is disturbed probably because of an inability to properly respond to insulin. The hormone insulin critically regulates synthesis, secretion and clearance of lipids, however, in obese subjects the concentration of insulin is abnormally elevated. We have explored the impact of sustained weight reduction on the production and clearance of lipids from blood. Collectively, weight loss leads to an improvement in fat metabolism because of increased sensitivity to the normal effects of insulin. However, weight reduction alone is rarely able to fully correct the disturbances in fat metabolism and it is likely that the individuals are still at risk of developing vascular disease. In this proposal, we wish to explore the efficacy of two agents which could potentially ameliorate lipid disturbances in diabetes by enhancing the regulatory effects of insulin. We believe that long term correction of the lipid abnormalities in obesity will reduce the frequency and progression of cardio- and peripheral-vascular disease.Read moreRead less
Novel Apolipoprotein A-I Mimetic Peptides: A Research Tool And A Therapeutic Agent To Study And Treat Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$266,387.00
Summary
Drugs affecting lipid metabolism have revolutionized the treatment of heart diseases. There is, however, an urgent need for further reduction of high remaining risk. A most promising direction is increasing levels of _good cholesterol�. A new type of such therapy are simple compounds mimicking structure of good cholesterol. We have synthesized new such compounds that are even more active than good cholesterol. Now we will test these compounds in animals and in clinical trial.