Epigenetic Reprogramming Of Calcified Vascular Smooth Muscle Cells As A Treatment For Vascular Calcification
Funder
National Health and Medical Research Council
Funding Amount
$1,285,195.00
Summary
Pathological hardening of blood vessels, or vascular calcification, is a frequent and deadly complication of many cardiovascular disorders. It is caused by the irreversible change in mature vascular smooth muscle cells (the main cell type in the blood vessel walls) to a bone-forming cell type. We have now identified a new gene that can potentially revert calcified vascular cells back to their physiological state. This represents a promising new approach for treatment of vascular calcification.
Understanding How GATA2 Controls Lymphatic Vessel Valve Development
Funder
National Health and Medical Research Council
Funding Amount
$697,942.00
Summary
Mutations in the GATA2 gene cause human lymphoedema as a result of the crucial role that GATA2 plays in controlling the expression of genes important for building functional lymphatic vessels. Here we aim to gain a complete picture of the cellular and molecular events that are controlled by GATA2 in lymphatic vessels and in particular, in lymphatic vessel valves.
Defining The Role Of GATA2 In Lymphatic Vascular Development As A Means To Understanding How GATA2 Mutations Predispose To Human Lymphedema.
Funder
National Health and Medical Research Council
Funding Amount
$718,890.00
Summary
We have discovered that mutations in the transcription factor GATA2 result in human primary lymphedema, a debilitating disorder resulting from the failure of lymphatic vessels to return tissue fluid to the bloodstream. The goal of this application is to define the role of GATA2 in lymphatic vessels, in order to understand how GATA2 mutations cause lymphedema. Ultimately, we aim to identify targets to which desperately needed therapeutics for the treatment of lymphedema could be generated.
Characterisation Of A Newly Identified, Indispensible, Transcriptional Regulator Of Lymphangiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$535,224.00
Summary
Lymphatic vessels form via lymphangiogenesis: growth of lymphatics from pre-existing vessels. This process is amenable to therapeutic intervention during metastasis because lymphatics support tumour spread. We discovered a gene that is essential for lymphangiogenesis to occur. We will investigate the control of lymphangiogenesis by this new factor. We aim to understand how it controls lymphatic vessel formation and identify genes within this pathway that have novel therapeutic potential.
This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less
Heme-oxidised Soluble Guanylyl Cyclase, A Mechanism-based Target For Vascular Diagnostics And Vasoprotective Therapy
Funder
National Health and Medical Research Council
Funding Amount
$524,456.00
Summary
Nitric oxide is produced in the inner lining of blood vessels and maintains blood flow via binding to a specific protein, sGC. In disease, sGC is defective and can be targeted by a novel group of drugs which are more active in diseased versus normal blood vessels. This project will examine the use of these drugs as markers of cardiovascular disease and in the treatment of high cholesterol and may lead to the development of new diagnostic tools and therapies for vascular complications.
Role Of Indoleamine 2,3-dioxygenase In Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$271,500.00
Summary
Atherosclerosis and its clinical presentation including heart attack and stroke represent a major source of morbidity and mortality in the developed world, including Australia. Atherosclerosis involves the accumulation of lipid-laden cells in the wall of arteries that generates plaques resulting in a decrease in the lumen of the affected vessel that can impede or block blood flow resulting in clinical complications. The cellular events involved in atherosclerosis are complex. However, increasing ....Atherosclerosis and its clinical presentation including heart attack and stroke represent a major source of morbidity and mortality in the developed world, including Australia. Atherosclerosis involves the accumulation of lipid-laden cells in the wall of arteries that generates plaques resulting in a decrease in the lumen of the affected vessel that can impede or block blood flow resulting in clinical complications. The cellular events involved in atherosclerosis are complex. However, increasing information indicates that atherosclerosis involves an inappropriate response of the immune and inflammatory systems. This proposal plans to investigate the role of a protein, indoleamine 2,3-dioxygenase (IDO) that is increased during inflammation and is important for the regulation of the host's immune system. We propose that increasing IDO activity in inflammatory cells will attenuate the degree of vascular disease by decreasing the overall level of immune activation and inflammation in the blood vessels. We will test this by modulating the expression and activity of this protein in animal models of vascular disease, measure the extent of disease and then elucidate the mechanisms by which the protein acts. The significance of these studies is that they will provide useful information on the inflammatory and immune processes involved in the progression of atherosclerosis and may identify a potential novel target for therapeutic intervention.Read moreRead less
Molecular Mechanisms In Pregnancy-indcuded Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$649,668.00
Summary
Approximately 5-10% of pregnancies are complicated by hypertension with associated health risks for both mother and child. To keep blood pressure at normal levels during pregnancy requires active regulation, but underlying processes are not yet fully understood. We have identified a molecule which crucially controls blood pressure during pregnancy. In this proposal we will study how the molecule remodels blood vessels in pregnant females to optimize pharmacological intervention and pregnancy out ....Approximately 5-10% of pregnancies are complicated by hypertension with associated health risks for both mother and child. To keep blood pressure at normal levels during pregnancy requires active regulation, but underlying processes are not yet fully understood. We have identified a molecule which crucially controls blood pressure during pregnancy. In this proposal we will study how the molecule remodels blood vessels in pregnant females to optimize pharmacological intervention and pregnancy outcomes in humans.Read moreRead less