A Study Of The Origins Of Macrophages In Healthy And Atherosclerotic Vasculature Focusing On A Novel Population Of Resident Adventitial Macrophage Progenitor Cells (AMPCs)
Funder
National Health and Medical Research Council
Funding Amount
$465,345.00
Summary
White blood cells (macrophages) play a key role in the development of atherosclerosis, the underlying cause of most heart attacks and strokes. We have made new discoveries to show that there are stem (progenitor) cells for macrophages that exist within the outer lining of blood vessels. This project will study whether these local progenitor cells, called AMPCs, are a source of macrophages in atherosclerosis and in turn could lead to new treatment approaches for cardiovascular disease.
Targeting Renal And Vascular Inflammation In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$781,589.00
Summary
Inflammation is a hallmark of high blood pressure (A.K.A. hypertension) and underlies clinical complications of the condition such as kidney failure and blood vessel disease. This project will investigate whether a recently described signaling complex termed the 'inflammasome' is a trigger of inflammation in hypertension in the hope of identifying it as a target for new drugs that are more effective in the treatment of hypertension and its complications.
The Cardiomyocyte Mineralocorticoid Receptor Plays A Critical Role In Cardiac Disease.
Funder
National Health and Medical Research Council
Funding Amount
$613,477.00
Summary
Drugs that block the mineralocorticoid receptor (MR), which responds to adrenal hormones, protect against heart disease and hypertension. We have shown that this effect is in part due to MR blockade in heart muscle cells. This novel finding is being explored further to understand the precise role of the MR in heart muscle cells in normal physiology and in disease. An understanding of the role of the MR in different tissues will enable development of tissue specific treatments for heart disease.
The Relationship Between Vascular Remodelling And Mast Cells In Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$353,253.00
Summary
It is known that the airwalls of asthmatics have increased numbers of small blood vessels which can contribute to poor lung function in asthma. The proposed research uses a novel sheep model for chronic asthma to investigate the progressive changes to the blood vessels in the airway walls of asthmatic lungs. The information gained from our sheep model will assist the understanding of blood vessel growth and thus ulitmately help in devising new strategies to treat the effects of asthma.
Regulator Of G Protein Signalling-5 Loss And Gain Of Function In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$625,428.00
Summary
Cancer and cardiovascular diseases are amongst the largest causes of morbidity and mortality in Western populations. We have identified a molecule, called Regulator of G protein signalling 5 (RGS5), which is involved in vessel remodelling in both diseases. This molecule is a prime candidate for drug development. We will study the precise role of RGS5 in sophisticated preclinical models which will create future opportunities for urgent therapy.
Regulator Of G-protein Signalling-5: A Key Modulator Of Vascular Maturation And The
Funder
National Health and Medical Research Council
Funding Amount
$548,396.00
Summary
Tumours progressively grow in part because they escape destruction by the immune system. New blood vessels grow inside tumours by a process called angiogenesis, which in turn stops disease-fighting cells in their tracks. However, we have now discovered that it is possible to reverse angiogenesis by normalising the blood vessels. This effectively means the barriers are broken down and the tumour can be opened to the immune system or cancer fighting drugs. Furthermore, we have identified a protein ....Tumours progressively grow in part because they escape destruction by the immune system. New blood vessels grow inside tumours by a process called angiogenesis, which in turn stops disease-fighting cells in their tracks. However, we have now discovered that it is possible to reverse angiogenesis by normalising the blood vessels. This effectively means the barriers are broken down and the tumour can be opened to the immune system or cancer fighting drugs. Furthermore, we have identified a protein which appears to be very important for normalisation, a process which is currently not well understood. This proposal continues our pioneering work on vessel normalisation and will use models of highest clinical relevance to study the dynamics of vessel remodelling in tumours. Our approach is different to current angiogenesis research which simply tries to block or destroy the blood vessels that feed tumours. We expect our findings to lead to highly specific and effective anti-tumour therapies. Moreover, vessel growth in tumours has striking parallels to other vascular processes in the body, which have important implications for major and common human diseases such as high blood pressure and atherosclerosis. We now have the tools to study these processes and their abnormalities in our newly established disease model. By gaining insight into these disorders we will be able to develop novel approaches to stop disease progression.Read moreRead less
B Cell Activation Generates Antibodies To Promote Vascular And Renal Inflammation, Remodelling And Dysfunction In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$327,193.00
Summary
Hypertension is a major contributor to chronic cardiovascular and renal diseases, with recent literature suggesting the pathogenesis is similar to that of autoimmune diseases. This fellowship will enhance the current understanding of the pathogenesis of hypertension and the associated inflammation of the kidneys and vasculature. It will also assess the therapeutic potential of drugs that dampen the immune response in several animal models of hypertension.
Cancer causes significant morbidity and mortality in Australia’s aging population. There is strong evidence that abnormal blood vessels in tumours limit drug access and drive metastases. We have identified a molecule which controls vessel remodelling in tumours. In this proposal we will study mechanisms on how the molecule itself is regulated with the aim to normalize blood vessels for improved therapy.