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.
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.
A Non-cytotoxic Approach To Reduce Ocular Fibrosis Following Surgery In Glaucoma
Funder
National Health and Medical Research Council
Funding Amount
$586,979.00
Summary
Glaucoma surgery often leads to scar formation and blindness. We have identified a novel protein (NADPH oxidase 4; Nox4) which promotes scar formation in the eye. Lack of Nox4 in a mouse models reduces scar formation. We have demonstrated that a ‘repurposed’ drug which is currently used to treat lung diseases can also block Nox4 in the eye. We aim to determine whether this drug can be used as a novel therapy for vision loss after glaucoma surgery.
When Prometheus Needs A Hand – How Human Amnion Epithelial Cells Resolve Fibrosis And Regenerate The Liver
Funder
National Health and Medical Research Council
Funding Amount
$530,653.00
Summary
Cirrhosis can progress to end stage disease for which transplantation provides the only hope for survival. Liver donors in Australia are scarce; the need for donor organs is increasing. Using stem cells to repair and regenerate damaged liver may provide an alternative to organ transplantation. We are studying placental stem cells that can decrease inflammation and increase progenitor cells to repair and regenerate liver. Our goal is to use these stem cells as treatment for human liver disease
VITAL: Vaccine Immunomodulation Throughout The Aging Lifespan
Funder
National Health and Medical Research Council
Funding Amount
$795,117.00
Summary
The elderly respond less well to vaccines than their younger counterparts. Flu is particularly dangerous to the elderly. In this proposal we will determine the likely immune mechanism undelying this difference, as well as specifically address the urgent issue of whether prior injection with a whooping cough vaccine makes Flu vaccines less likely to be effective.