Hepatic Oxidative Stress, PTPs & STAT Signalling In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$1,086,547.00
Summary
Obesity is increasing at an alarming rate worldwide and is a leading cause of morbidity and mortality. Obesity is causally linked to the development of insulin resistance, a prelude to type 2 diabetes. In this proposal we will define a novel liver centric mechanism by which insulin resistance and oxidative stress may promote the development of morbid obesity, type 2 diabetes and liver disease.
There are ~1.6 billion overweight adults worldwide & this is predicted to rise to 2.3 billion by 2015. In Australia > 2/3 of adults are overweight or obese. Obesity is a key factor in the progression of many human malignancies. Obesity poses the greatest risk for the development hepatocellular carcinoma (HCC), a deadly cancer refractory to nearly all available anti-cancer therapies. This application will delineate the molecular mechanisms by which obesity promotes HCC development.
New Insights Into Mechanisms That Coordinate Kinase Signalling And Molecular Motors In Mitosis: A Novel Role For The Protein Scaffold WD-repeat Protein 62 (WDR62).
Funder
National Health and Medical Research Council
Funding Amount
$529,122.00
Summary
Proteins perform all functions within a cell. Commonly, different proteins are assembled into large complexes to carry out processes, such as cell division, with significant implications for human health. Scaffold proteins facilitate the proper assembly of large complexes but are a poorly understood protein class. We will perform molecular analysis of a newly discovered scaffold, WDR62, to define how it drives cell division and reveal how this can be exploited to develop new anti-cancer drugs.
Trafficking Mechanisms Governing Receptor Availability For Signalling
Funder
National Health and Medical Research Council
Funding Amount
$526,978.00
Summary
Receptors on the cell surface allow cells to respond to their environment. We have recently discovered a new pathway for controlling the amount of receptors displayed on the cell surface, errors within which will lead to defects in development and diseases like cancer. We are studying how this new pathway controls the balance between how much receptors are destroyed after being activated and how much are recycled back for re-use.
Role Of Macrophages In Lipotoxic Beta Cell Failure
Funder
National Health and Medical Research Council
Funding Amount
$612,736.00
Summary
Type 2 diabetes (T2D) affects 7% of Australians and is a major cause of morbidity and mortality. A failure of insulin secretion contributes to T2D, and this is linked to the inability of insulin producing ?-cells to use lipids appropriately (lipotoxicity). Here we will study the role of the immune system and how this inhibits insulin secretion in T2D
Antioxidant Enzymes Counter Reactive Oxygen Species From Steroidogenic Cytochrome P450 Enzymes In The Ovary To Limit Aneuploidy Of Embryos
Funder
National Health and Medical Research Council
Funding Amount
$536,978.00
Summary
Many birth defects are due to damage sustained by the eggs before ovulation. Aging allows more damage, hence the advice to have babies earlier in life. However, we believe we have identified a source of damage that happens during late development of the follicle in the weeks before ovulation. Proving this will enable us define when an egg is most at risk of damage and to devise strategies to lower the risk.
Investigating New Pathways In Acute Kidney Injury That Are Regulated By CD47
Funder
National Health and Medical Research Council
Funding Amount
$508,848.00
Summary
Acute kidney injury (AKI) is a widespread problem affecting both native and transplanted kidneys. Studies indicate that the incidence has increased more than 200-fold in the last decade, as has mortality. AKI also predisposes to the development of chronic kidney disease. There is no effective therapeutic for treatment or prevention of AKI. This project will investigate new cell signalling pathways regulating AKI with a view to developing these as novel clinical therapies.
Endosomal Reactive Oxygen Species In Tumour Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$633,739.00
Summary
Cancer claims more lives worldwide than any other disease affecting millions of people annually. Tumours grow and spread in the body by acquiring their own blood vessels that provide them with nutrients and oxygen. We have identified a new protein called NADPH oxidase that promotes the development of these new blood vessels in tumours. We propose to test new drugs that block NADPH oxidase activity to stop the development of new blood vessels for the potential treatment of cancer
A New Strategy To Prevent Anthracycline-induced Cardiotoxicity While Improving Anti-cancer Activity
Funder
National Health and Medical Research Council
Funding Amount
$318,034.00
Summary
The anthracycline-based drugs such as doxorubicin currently used for cancer treatment have a major side effect in that they induce heart damage. We have shown that doxorubicin action can be modified to result in greater tumour cell kill, but also with reduced death of cardiac cells. We now aim to develop a molecular understanding of this process in order to allow better design of chemotherapy regimes that include the anthracyclines.
This proposal utilises forefront technologies to identify and characterise fundamental biological processes influenced by toxic free radicals that are triggered by viruses such as the flu and HIV. The approach is a synergistic collaboration between researchers with unique and complementary expertise across disciplines and across Australian and Irish universities to ultimately identify future drugs to treat viral disease.