Bone Marrow Endothelial Stem Cells Have The Capacity To Form Both The Endothelial And Haemopoietic Hierarchies
Funder
National Health and Medical Research Council
Funding Amount
$1,452,856.00
Summary
Blood cell formation is hierarchically organised; with hemopoietic stem cells (HSC) responsible for producing mature circulating blood cells. HSC reside in marrow near blood vessel cells. Although these play a key role in HSC regulation their origin in adults is poorly understood. We have demonstrated the existence of adult marrow vessel stem cells at the apex of a parallel hierarchy. Our objective is to characterise these in mice and humans and determine their role in blood malignancies.
Understanding The Role Of Cell Death In Blood Vessel Regression And Regrowth
Funder
National Health and Medical Research Council
Funding Amount
$468,059.00
Summary
Blood vessels are essential to distribute oxygen and nutrients throughout our bodies, and as such, disruptions to normal blood vessel behaviour can have significant impacts on health. This research is aimed at understanding how blood vessel networks can regrow after damage in order to maintain healthy blood supply to a tissue. This work will be particularly relevant to diseases where blood vessel loss or inappropriate blood vessel growth occur.
Pulmonary hypertension is a disease affecting the blood vessels in the lungs that causes severe shortness of breath and early death. Genetic mutations are known to cause this disease but the precise link between these mutations and the changes in the lungs are poorly understood. If we could understand this process better, we could design better treatments. This project will look at how the cells in the lungs communicate with each other and how this process is disturbed in pulmonary hypertension.
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.
Endothelial Development From Pluripotent Stem Cells As A Means To Study Pathology In Pulmonary Artery Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Pulmonary artery hypertension (PAH) is a fatal disease primarily affecting young adults. It is caused by a defect in cells that form the vessel that carries blood from the heart to the lungs. We will use stem cells made from the skin of PAH patients to examine why the blood vessel cells from these patients fail to function normally.
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
Expansion Of TGF-beta-Smad Signaling Network And Intrinsic Epithelial-mesenchymal-endothelial Transition
Funder
National Health and Medical Research Council
Funding Amount
$557,297.00
Summary
The majority of tumor death occurs due to tumor metastasis. Both tumor growth and tumor spread require angiogenesis, which is thought to be driven by tumor but originated from host endothelial cells. Could tumor cells behave and function like endothelial cells? This application aims to detect the transition of adult epithelial cells to endothelial cells through a transient mesenchymal state. Our studies should reveal both the molecular and cellular causes of vasculogenic mimicry, thus establishi ....The majority of tumor death occurs due to tumor metastasis. Both tumor growth and tumor spread require angiogenesis, which is thought to be driven by tumor but originated from host endothelial cells. Could tumor cells behave and function like endothelial cells? This application aims to detect the transition of adult epithelial cells to endothelial cells through a transient mesenchymal state. Our studies should reveal both the molecular and cellular causes of vasculogenic mimicry, thus establishing a new paradigm in understanding tumor growth and metastasis. Such novel molecular understanding will open up new anti-tumor therapeutic opportunities.Read moreRead less
Imaging Neutrophil And Endothelial Function In Acute Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$545,517.00
Summary
The glomerulus is a group of small blood vessels which form the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response during which white blood cells accumulate in the glomerular blood vessels and cause damage. In this project, we will visualise the blood vessel lining of the glomerulus in order to understand how white blood cells damage this region and cause leakage of protein leak into the urine.
Modulation Of Endothelial Junctions As Selective Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$911,387.00
Summary
We have developed a new drug (CD5-2) that targets the junctions of endothelial cells, the cell that lines all vessels. CD5-2 reduces oedema in diseases such as diabetic retinopathy and tumours. Thus it has potential as a new therapeutic in chronic inflammatory diseases where leaky blood vessels are central to the pathology. This grant will provide fundamental understanding of how CD5-2 induces such profound effects to alter the levels of oedema and alter inflammatory cell infiltrates in tissues.
Microparticles Are Pathogenic Elements In The Pathophysiology Of Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$605,205.00
Summary
Cerebral malaria (CM) is still a world health problem. We aim to better understand its mechanisms by deciphering the role of small blood elements called microparticles (MP). We discovered elevated numbers of MP in CM patients and demonstrated that preventing MP overproduction in mice protects against this fatal disease. Our research will investigate the mechanisms of action and the fate of MP in the blood vessels during CM and allow us to identify strategies for patientÍs treatment and care.