Modulation Of TGF-beta Signaling By CDA1 In The Diabetic Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$524,004.00
Summary
Cell Division Autoantigen 1 (CDA1) is a molecule we identified several years ago. Recently we found that CDA1 played an unique role in causing blood vessels to scar and become stiff by hijacking and controlling the existing transforming growth factor-beta (TGF-beta) signaling pathway. We will explore the possibility to use this unique property of CDA1 to treat the blood vessel hardening and related diseases such as atherosclerosis and heart attacks, particularly in the setting of diabetes.
INFLAMMASOMES AND INTERLEUKIN-18 SIGNALLING: NOVEL BIOMARKERS AND THERAPEUTIC TARGETS FOR KIDNEY DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$1,003,340.00
Summary
Chronic kidney disease (CKD) is a major health problem. There is no cure for CKD and current therapies merely slow its progression. Thus for many patients, dialysis or kidney transplant is an inevitable outcome. We have evidence that a protein called interleukin-18 (IL-18) is a key mediator of kidney damage in CKD. Here we will explore how IL-18 causes kidney damage and whether IL-18 may be used as a diagnostic for early detection of CKD, and a target for more effective therapies to treat CKD.
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.
Regulatory T Cells And Cardiac Fibrosis In Hypertensive Heart Disease: Cellular And Molecular Mechanisms Of Suppression
Funder
National Health and Medical Research Council
Funding Amount
$715,316.00
Summary
Excessive accumulation of collagen in the heart, cardiac fibrosis is a major factor causing heart failure and sudden death. How collagen accumulation occurs in the heart still needs to be elucidated but recent studies in humans and animal models of cardiac fibrosis indicate a significant role for inflammation. The proposed studies are to address this issue and how to regulate inflammation in the heart to suppress cardiac fibrosis, using immune cells called regulatory T cells that suppress inflam ....Excessive accumulation of collagen in the heart, cardiac fibrosis is a major factor causing heart failure and sudden death. How collagen accumulation occurs in the heart still needs to be elucidated but recent studies in humans and animal models of cardiac fibrosis indicate a significant role for inflammation. The proposed studies are to address this issue and how to regulate inflammation in the heart to suppress cardiac fibrosis, using immune cells called regulatory T cells that suppress inflammation.Read moreRead less
The Brain As A Therapeutic Target For Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$923,432.00
Summary
In heart failure there is a large increase in sympathetic nerve activity to the heart that leads to damage to the heart and sudden death. We have shown that lesion of the area postrema, a brain nucleus that senses hormones in the blood, reduces nerve activity to the heart and, importantly, improves cardiac function. We aim to translate these findings into a treatment that can be used clinically, which our findings compellingly indicate should improve cardiac function in heart failure
Atherosclerosis: Molecular Action And Suppression Of NKT Cell Subsets
Funder
National Health and Medical Research Council
Funding Amount
$458,815.00
Summary
Atherosclerosis, or hardening of large arteries, is the underlying cause of up to 50% of deaths in Western communities from heart attacks and strokes. Today it is considered a chronic inflammatory disease arising from the influx of fats such as cholesterol into the inner liming of arteries that provide blood supply to organs such as the heart and the brain. However, the exact role that inflammation plays in the development of this blood vessel disease is poorly understood. This study is directed ....Atherosclerosis, or hardening of large arteries, is the underlying cause of up to 50% of deaths in Western communities from heart attacks and strokes. Today it is considered a chronic inflammatory disease arising from the influx of fats such as cholesterol into the inner liming of arteries that provide blood supply to organs such as the heart and the brain. However, the exact role that inflammation plays in the development of this blood vessel disease is poorly understood. This study is directed towards understanding the role of a subset of while blood cells known as NKT cells in the inflammatory process. In particular we will examine whether the activity of NKT cells in promoting atherosclerosis can be controlled either by the administration of drugs that deprive them of molecules that stimulate their activity and-or by the injection of another population of white blood cells known as regulatory T cells that may to limit their activity. Our preclinical study of atherosclerosis in mice has potential for extension to the control of atherosclerosis in humans. Successful translation in this way can be expected to provide a significant health benefit.Read moreRead less