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.
A Critical New Signaling Axis In Lymphatic Vascular Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$700,784.00
Summary
The lymphatic vasculature is a crucial part of our vascular system required for tissue fluid drainage and maintenance of fluid homeostasis. Lymphatic vessels play major roles in vascular pathologies and in the spread of solid tumours during cancer progression. We have discovered a new molecular regulator controlling the formation of lymphatic vessels. This project will determine the signalling pathway employed by this new regulator and potential for future therapeutic applications.
Coupling The Mechanical, Signalling And Transcriptional Mechanisms That Initiate Pathogenesis Of Cerebral Cavernous Malformation
Funder
National Health and Medical Research Council
Funding Amount
$1,228,364.00
Summary
Cerebral cavernous malformations (CCMs) are thin walled, vascular malformations in the brain found in 1/200-250 individuals. They can cause migraine, neurological deficits or stroke. This disease can be inherited due to damaging mutations in any of three CCM genes. The project will investigate the molecular control of CCM pathogenesis in animal models. We aim to uncover the molecular cause of these vascular malformations and in doing so identify new therapeutic strategies.
Defining The Role Of VEGF And Vascular Formation In Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$636,417.00
Summary
Aberrant neural crest cell development gives rise to common congenital malformations such as cleft lip and/or palate and cardiac outflow tract defects that effect over 1% of all births. As the aetiology of these disorders are largely unknown it is critical to understand the cell and molecular mechanisms coordinating NCC development such that alternative therapies may be devised to target the underlying pathological defects and to provide definitive diagnostic / prognostic tools.
Defining The Role Of The Ubiquitin Protein Ligase Nedd4 In Vascular Development.
Funder
National Health and Medical Research Council
Funding Amount
$702,166.00
Summary
Blood and lymphatic vessels are vital components of the cardiovascular system. Abnormalities in the growth and development of these vessels are associated with human disorders including cancer and cardiovascular disease. The focus of this application is to characterise the role of the ubiquitin protein ligase Nedd4 in vascular development, with the aim of identifying targets to which novel therapeutics for the treatment of blood and lymphatic vascular diseases could be generated.
Modulation Of Vegfc/Vegfr3 Signaling At The Extracellular Matrix During Embryonic Lymphangiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$570,928.00
Summary
Lymphatic vessels play important roles in vascular diseases and cancer. However, we are yet to understand how they form during development and disease. We recently identified the gene CCBE1, essential for the formation of lymphatic vessels and responsible for lymphatic dysplasia in humans. This study aims to understand the molecular pathway in which CCBE1 acts. This work aims to characterize new molecular pathways in lymphatic vessels in order to identify new therapeutic targets in lymphatic dis ....Lymphatic vessels play important roles in vascular diseases and cancer. However, we are yet to understand how they form during development and disease. We recently identified the gene CCBE1, essential for the formation of lymphatic vessels and responsible for lymphatic dysplasia in humans. This study aims to understand the molecular pathway in which CCBE1 acts. This work aims to characterize new molecular pathways in lymphatic vessels in order to identify new therapeutic targets in lymphatic disease and cancer.Read moreRead less
Regulation Of VEGFR Trafficking And Signal Transduction By The Ubiquitin Ligase Nedd4
Funder
National Health and Medical Research Council
Funding Amount
$388,347.00
Summary
Our recent work has discovered that the Nedd4 gene is crucial for the growth and development of blood vessels and lymphatic vessels. Our data suggest that Nedd4 controls vessel growth by regulating the levels and signalling activity of the key vascular growth factor receptors VEGFR-2 and VEGFR-3. The goals of this proposal are to define precisely how Nedd4-1 regulates the activity of these receptors and how VEGFR signalling could be better targeted to treat vascular disorders.
A Novel Pathway For The Regulation Of Vascular Tone
Funder
National Health and Medical Research Council
Funding Amount
$596,550.00
Summary
The regulation of blood pressure is complex involving the nervous system, kidneys and local pathways that generate blood vessel relaxing and constricting factors. We recently discovered a novel local pathway that becomes induced during inflammation and generates a relaxing substance from the amino acid tryptophan. The present project will identify the active substance and characterize how it causes blood vessel relaxation and thus contributes to the regulation of blood pressure.
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.