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.
B1a B Cells: Atheroprotective Mechanisms And Therapeutic Application
Funder
National Health and Medical Research Council
Funding Amount
$547,180.00
Summary
Atherosclerosis-related heart attacks and strokes remain leading causes of global deaths despite use of potent lipid-lowering drugs. Thus, another therapeutic option is urgently needed. Our laboratory found that B1a B cells protect against atherosclerosis. We will study the therapeutic efficacy of expanding B1a cells by different approaches in atherosclerosis. Our proposal for clinical translation is to reduce mortality from atherosclerosis-based heart attacks and strokes.
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.
Bioengineering Endovascular Prostheses With Proactive Biocompatibility
Funder
National Health and Medical Research Council
Funding Amount
$627,950.00
Summary
Metallic cardiovascular implants, such as stents, used in the treatment of heart disease are not compatible with blood. They cause inflammation at the site of implantation and increase the risk of blood clots forming. We have developed a unique method of binding bioactive protein layers to the surface of metal alloys, and shown a significant improvement in their compatibility. Stents coated using our technology stand to dramatically improve the treatment of cardiovascular disease.
Childhood Lymphatic Malformations: The Mechanism Of Rapamycin In Controlling Growth
Funder
National Health and Medical Research Council
Funding Amount
$456,579.00
Summary
Lymphatic malformations (also known as cystic hygromas or lymphangiomas) cause deformity and pain which can last lifelong. Current treatments help but do not fix all the symptoms. Rapamycin, a drug used for many years in children and adults with kidney transplants, may be useful for treating children with lymphatic malformations. We aim to understand how the drug works on the cells of lymphatic malformations in culture and in an animal model, to develop new and more effective treatments.
The health benefits of consuming fruits and vegetables can in part be attributed to their high content of polyphenolic compounds such as flavonoids. These substances can improve functioning of blood vessels and have the potential to reduce the risk of heart disease. This project will examine one of the most common flavonoids in the diet to try and understand how it works and better understand the protective effects.
Characterising Signals Important For Lymphangiogenesis During Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$604,938.00
Summary
Lymphatic vessels are a vital component of the cardiovascular system. Abnormalities in the growth and development of lymphatic vessels are associated with human disorders including cancer, lymphoedema and inflammatory diseases. The focus of this application is to characterise signals that direct the construction of lymphatic vessels, with the aim of identifying targets to which novel therapeutics for the treatment of lymphatic vascular diseases could be generated.
Role Of Epigenomic Changes In Conferring Hyperglycemic Memory
Funder
National Health and Medical Research Council
Funding Amount
$636,146.00
Summary
The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment h ....The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment has returned glucose levels towards normal.Read moreRead less
Dysfunctional blood vessel growth is an important mechanism of many congenital vascular diseases and other postnatal diseases such as ischemia and cancer. Cerebral cavernous malformations (CCMs) are common vascular disease in brain that cause strokes and seizures in midlife. Due to their location in the brain, CCMs are virtually untreatable, making the development of novel therapies a priority. This proposal aims to understand how the molecular players underlying this brain vascular disease cont ....Dysfunctional blood vessel growth is an important mechanism of many congenital vascular diseases and other postnatal diseases such as ischemia and cancer. Cerebral cavernous malformations (CCMs) are common vascular disease in brain that cause strokes and seizures in midlife. Due to their location in the brain, CCMs are virtually untreatable, making the development of novel therapies a priority. This proposal aims to understand how the molecular players underlying this brain vascular disease control blood vessel function and growth.Read moreRead less
Identification And Characterisation Of Novel RNAs Involved In Cardiovascular Cell (de)differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$632,701.00
Summary
Several recent breakthroughs have made us realise that there is a lot of plasticity in cellular development, and we can now harness this plasticity to create stem cells that may eventually be used to repair the damaged heart and blood vessels after heart attacks and stroke. Here we will use mouse stem cells to discover the genetic factors responsible for a cell’s plasticity and memory in order to create pure populations of heart and blood vessel cells that can be used in repair settings.