Proatherogenic CD4 NKT Cells And Atherosclerosis: Molecular Mechanisms And Therapeutic Strategies For Suppression
Funder
National Health and Medical Research Council
Funding Amount
$504,348.00
Summary
Immune cells called CD4+ iNKT cells are known to be activated by lipids which initiate development of atherosclerosis, a disorder of blood vessels which is responsible for most heart attacks and strokes. We aim to investigate how these cells contribute to the development of this important blood vessel disoder and examine potential ways of inhibiting their activation to prevent heart attacks and strokes.
Natural Killer (NK) Cells And Development Of Atherosclerosis: Cellular And Molecular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
Atherosclerosis, the accumulation of fat and white cells in the blood vessel wall is the major cause of heart attacks, stroke and death. Cholesterol lowering drugs reduce the risk by only 40%. Targeting cells that promote inflammation is one approach to further reduce risk. We have shown that a specific cell type called a natural killer (NK) cells contributes greatly to development of atherosclerosis. Our aim is to understand how these cells promote development of atherosclerosis.
Understanding And Applying Macrophage-mediated Effects On Liver Progenitor Cells To Treat Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$628,109.00
Summary
As liver cancer risk correlates with increased liver stem/progenitor cell numbers, therapies that reduce their numbers will reduce cancer development. On the contrary, therapies to increase progenitor cell numbers will assist their use in cell therapy-based approaches or artificial liver devices to treat chronic liver disease. This project will determine how to use inflammatory cells to manipulate progenitor cell numbers.
We are studying human amnion epithelial cells (AECs) as a new therapy for stroke. Here if we find the protective effects of AECs are unaffected by a 'clot-buster' drug,we will broaden our planned Phase II trial of AECs to include patients that have received clot lysis therapy. Further, as we suspect that AECs exert their effects via release of nanoparticles called 'exosomes', we will test whether exosomes given intravenously or intranasally are similarly protective.
The Role Of Necroptosis In Inflammatory Skin Diseases
Funder
National Health and Medical Research Council
Funding Amount
$548,690.00
Summary
Diseases associated with exaggerated inflammation account for a large toll of human disease. We have recently described how mice with a mutation in the Sharpin gene, that causes the chronic proliferative dermatitis phenotype (cpdm), can be rescued by crossing these mice to TNF (Tumor Necrosis Factor) knock-out mice. Our findings suggest that TNF induced cell death, rather than TNF induced cytokine production, may be at the root of many inflammatory diseases and we aim to test this hypothesis in ....Diseases associated with exaggerated inflammation account for a large toll of human disease. We have recently described how mice with a mutation in the Sharpin gene, that causes the chronic proliferative dermatitis phenotype (cpdm), can be rescued by crossing these mice to TNF (Tumor Necrosis Factor) knock-out mice. Our findings suggest that TNF induced cell death, rather than TNF induced cytokine production, may be at the root of many inflammatory diseases and we aim to test this hypothesis in this proposal.Read moreRead less
Generating Tumour-Specific Dendritic Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Therapies using the immune system are showing promise for cancer treatment, particularly for melanoma, but complete durable responses are few and improvements are needed. We believe that such immunotherapies, in their current form, fail to sufficiently mimic a natural immune reaction to disease, and therefore fall short of effectively controling cancer. In particular, an alarm (danger signal) is not produced within tumour as it would be when the body is challenged by infectious agents. Such dang ....Therapies using the immune system are showing promise for cancer treatment, particularly for melanoma, but complete durable responses are few and improvements are needed. We believe that such immunotherapies, in their current form, fail to sufficiently mimic a natural immune reaction to disease, and therefore fall short of effectively controling cancer. In particular, an alarm (danger signal) is not produced within tumour as it would be when the body is challenged by infectious agents. Such danger signals are critical for the immune system to respond effectively and for white blood cells of the immune system to find their way to the disease organism and eliminate it. The strongest danger signals are produced by a type of white blood cell known as a dendritic cell (DC). These cells detect infectious agents and produce biochemical alarm molecules that alert the entire immune system to the danger resulting in powerful action against the disease. However, tumours are really just a part of our own body and no danger signal is produced. It is our aim to use genetic modification to make DC see tumours as a threat and produce danger signals. These gene-modified DC either alone, or in combination with other immunotherapies, may lead to destruction of tumours.Read moreRead less
Elucidating The Role Of Mast Cell Tryptases In Chronic Obstructive Pulmonary Disease And Crohn's Disease
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
Smoking leads to inflammation that causes emphysema and inflammation in the lung and gut, which are major health problems. Once induced, there is a progressive decline in health and there are no effective treatments. Particular proteins and small genes have been discovered that control inflammation in these diseases. We may be able to control these proteins/genes and stop the progression of emphysema and gut inflammation. This project may lead to a completely new way of preventing and treating t ....Smoking leads to inflammation that causes emphysema and inflammation in the lung and gut, which are major health problems. Once induced, there is a progressive decline in health and there are no effective treatments. Particular proteins and small genes have been discovered that control inflammation in these diseases. We may be able to control these proteins/genes and stop the progression of emphysema and gut inflammation. This project may lead to a completely new way of preventing and treating these diseases.Read moreRead less
Chemokine Receptors And The Control Of Th17-mediated Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$801,229.00
Summary
Controlling persistent inflammation in autoimmune diseases is a major challenge and current therapeutics have significant side effects. Thus, novel targets must be identified. We have discovered a previously unknown level of control of autoimmune inflammation that may represent a more specific and effective means of controlling ongoing inflammation in these diseases.
Dissecting Immune Responses To Salmonella Infection
Funder
National Health and Medical Research Council
Funding Amount
$415,797.00
Summary
Successful treatment of Salmonella infections requires a detailed understanding how Salmonella growth is controlled. This project will examine the role of white blood cells, will reveal how they contribute to the control of Salmonella infections and will test novel treatment options. The outcome of this project will significantly advance our understanding of immune responses against Salmonella.