Novel Role Of Innate Immune DNA Sensors In Promoting Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$774,025.00
Summary
Stomach cancer is the third most lethal cancer worldwide, and is strongly associated with inflammation (gastritis) caused by Helicobacter pylori bacterial infection. However it remains unknown how Helicobacter triggers gastritis and stomach cancer in people. Using a mouse model for gastritis-associated stomach cancer, our aim is to demonstrate the role of immune system proteins in the stomach which detect bacterial and host DNA to drive chronic inflammatory responses that lead to stomach cancer.
Individuals with stomach cancer, the second most lethal cancer world-wide, have a poor survival rate which is largely due to our poor understanding of the mechanisms which drive this deadly malignancy. Our aims are to identify how over-activation of a specific molecule of the immune system, called STAT3, in the mitochondria of cells promotes the growth of stomach tumours, and also examine whether blocking the actions of mitochondrial STAT3 can suppress the growth of gastric cancer cells.
Targeting PI3K-regulated Small Non-coding RNAs To Restore Cardiac Function
Funder
National Health and Medical Research Council
Funding Amount
$610,204.00
Summary
Heart failure affects approximately 2.4% of the adult population and over 11% of people over 80 years old. The majority of existing therapies slow, rather than reverse heart failure progression. The primary goal of this study is to determine whether regulating novel regulatory genes can enhance cardiac function in a setting of heart failure. Ultimately, technologies that target these genes may lead to innovative pharmacotherapies in the clinical management of heart failure.
Slowing Progression Of Alzheimer’s Disease By Modulating The Kynurenine Pathway
Funder
National Health and Medical Research Council
Funding Amount
$578,460.00
Summary
Chronic inflammation in the brain in known to be a factor in the progression of Alzheimer's disease. We are exploring if blocking a particular enzyme in a biochemical pathway involved in inflammation, can improve symptoms, or slow progression, of the disease in animal models of AD. If results are as expected, our proposal has the potential to generate a new a therapy for AD.
Nedd4-2: A New Player In Polycystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$671,995.00
Summary
Polycystic kidney disease (PKD) is a life threatening disorder affecting over 12 million people worldwide. This project is based on our discovery of a new gene that controls PKD. Using kidney specific gene knockout, biochemical and cellular approaches we will now address how this gene controls PKD. The results from this study will lead to better understanding of the underlying mechanisms that cause PKD, thus providing possible new targets for therapeutic interventions.
Targeting A New Regulator Of Cardiac Pathology To Protect The Heart From Cardiac Dysfunction And Arrhythmia
Funder
National Health and Medical Research Council
Funding Amount
$717,857.00
Summary
Heart failure is associated with high mortality, and treatment of this condition represents a major unmet need. We recently reported that specific lipid species are elevated in hearts of mice with heart failure. The goal of this study is to comprehensively examine the therapeutic potential of targeting these lipid species with drugs.
Novel Treatment Approaches To Prevent Joint Fusion In Ankylosing Spondylitis
Funder
National Health and Medical Research Council
Funding Amount
$477,440.00
Summary
Ankylosing spondylitis (AS) is a form of arthritis targeting the spine and pelvis that causes uncontrolled bone formation resulting in complete joint fusion, severe disability and even death for which no therapies are currently available. Using a mouse model that closely replicates the human disease we will characterise the changes causing this joint fusion and identify possible new targets to develop novel treatments.
Cellular Contributions To PAR-2's Essential Role In Periodontal Disease
Funder
National Health and Medical Research Council
Funding Amount
$648,786.00
Summary
Periodontal disease is a disease of the gums, which ultimately causes loss of teeth. It is a debilitating condition affecting about 20% of Australian adults. PAR-2, a receptor for protein-degrading enzymes, which is present on cells in the gums, is known to be required for development of the disease. This project will investigate the mechanism of PAR-2’s involvement in periodontal disease and provide ideas for development of treatments.
Molecular Dissection Of Aberrant IL6/gp130 And TGF? Signaling In The Pathogenesis Of Interstitial Pneumonitis
Funder
National Health and Medical Research Council
Funding Amount
$590,009.00
Summary
Interstitial pneumonia (IP) is frequently observed in the group of lung diseases which affect the transfer of oxygen from inhaled air into the bloodstream. Current treatments for these diseases only effectively manage patient’s symptoms but don’t cure patients of IP. We have developed a strategy to identify the exact cell type responsible for an acute IP and the molecular intermediates that may offer novel treatments and pave the way for a possible cure for this disease.
The Role Of Reduced Phagocytosis In The Pathogenesis Of Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$786,742.00
Summary
Understanding the underlying mechanisms which lead to age-related macular degeneration (AMD) is critical if we are to ultimately develop novel treatments. We hypothesise that there is a defective ability to remove debris that accumulates in the retina as we age and this is a crucial step in the development of AMD. We will investigate this hypothesis in an AMD cohort and in a pre-clinical model where we will test the efficacy of an intervention that improves the ability to clear debris.