Synovial Macrophages And T-cells Are Therapeutic Targets In Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$658,761.00
Summary
Osteoarthritis (OA) is the most widespread musculoskeletal disease in Australia and there are currently no therapies that halt disease progression. Specific inflammatory events play a pivotal role in initiating and driving OA progression. In this study we will define the specific inflammatory cells involved in OA, how and why they change with time, and which can be targeted to stop disease onset and development. This will provide the platform for initiating human clinical trials.
Mechanisms Of Novel TLR9 Mediated Intraocular Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$442,244.00
Summary
Corneal opacities and scarring due to microbial and parasitic infections are a major cause of blindness globally. Novel studies in our lab have shown that topical application of bacterial/viral DNA alone to the cornea can cause previously unrecognised inflammation in the retina. Understanding the mechanisms of this retinal inflammation and how to block it may help in the design of novel treatments for a number of blinding conditions.
Investigating The Link Between Oxidative Stress And Biomechanical Integrin Activation In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Diabetes represents a serious healthcare problem globally. A large proportion of deaths associated with diabetes can be attributed to the development of blood clots in the circulation of the heart and brain (heart attack/stroke). The blood clotting mechanism is ‘hyperactive’ in diabetes, although the reason for this is not well defined. In this proposal we will investigate a new mechanism promoting blood clots, and will investigate innovative approaches to reduce this clotting mechanism.
A Nanomedicine Strategy For Detecting And Modulating Protease Activity In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$455,534.00
Summary
Protease enzymes are vitally important for normal bodily function but can play a deleterious role in many diseases such as cancer, aging diseases and eye diseases. The proposed research will provide a nanomedicine solution to the detection and therapeutic control of protease activity in vivo using nanoporous optical devices that are benign to the body. This general strategy for will be demonstrated in eyes with a view to detection and treating the eye disease uveitis.
Autoimmune-based thrombocytopenia can be a life-threatening adverse event associated with viral load, surgery, drug therapies or the use of the anticoagulant, heparin. This grant will define mechanisms of anti-platelet antibody-dependent platelet activation and assess shedding of platelet-specific glycoprotein (GP)VI as an immediate consequence of this activation, provide a new strategy for evaluating risk of thrombosis in HIT.
Macrophage Polarisation And Control Of Pulmonary Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$895,494.00
Summary
As key immune cells, macrophages are polarised to phenotypes that turn inflammation on or off. In cystic fibrosis, defective macrophage polarisation enhances inflammation and prevents lung repair. We are defining the molecules and cellular pathways that control this process and identifying targets for existing drugs that can be used to reprogram macrophages and restore lung repair to improve patient outcomes.
Investigation Of The Proinflammatory Function Of Platelets During Ischaemia-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$552,720.00
Summary
Platelets are important blood cells that stop bleeding. Platelets also regulate inflammation by modulating the function of white blood cells. Excessive stimulation of white cells by platelets may cause tissue damage relevant to a broad of cardiovascular diseases, including heart disease and stroke. This grant application aims to investigate the precise mechanism by which platelets promote inflammation during a heart attack or stroke.
The Dengue Virus Glycoprotein NS1 Binds Cholesterol And Mediates Cellular Activation
Funder
National Health and Medical Research Council
Funding Amount
$632,029.00
Summary
Cholesterol has been shown to play a vital role in the life cycle of many viruses. This project will investigate the basis of dengue virus interaction with this important host molecule and along with investigations of how dengue is able to stimulate host cells, will provide new insights into the way these viruses cause severe disease. Findings from this study will also aid in the development of new drug strategies for dengue and related viruses such as West Nile virus.
Defining The Role Of Kidney CD103+Dendritic Cells For Treatment Of Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$599,431.00
Summary
Chronic kidney disease (CKD) is a major cause of death and morbidity. Current treatments for CKD are not effective and new therapeutic approaches are needed. Dendritic cells (DCs) are key immune cells and play a central role in kidney disease. We recently found that a major DC subset called CD103+ DCs harmed the kidney in an animal model of human CKD. This study is to determine how CD103+ DCs cause kidney damage, and how to target CD103+ DCs for development of new therapies for human CKD.
Mineralocortioid Receptor-Mediated Injury In Progressive Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$707,008.00
Summary
Diabetes is the major cause of kidney failure. Activation of a hormone receptor (the mineralocorticoid receptor-MR) can promote kidney injury. Current drugs blocking MR can suppress diabetic kidney disease but are limited by their poor specificity and harmful side effects. Our study will help improve strategies for blocking MR by identifying the cell types responsible for MR-mediated injury and by examining whether a new class of drug targeting MR is a superior therapy to current MR inhibitors.