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
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.
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.
Bioengineering Synthetic Elastin Conduits For Arterial Revascularisation
Funder
National Health and Medical Research Council
Funding Amount
$624,776.00
Summary
An arterial substitute with both physical and biological properties that mimic those of the human vasculature has long been the holy grail of vascular tissue engineering. We propose synthetic elastin can form the basis of a durable, clinically effective small diameter vascular graft and fill a significant unmet need for a biocompatible vascular substitute.
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.
The Role Of The MicroRNA Let 7 In Diabetic Proliferative Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$674,084.00
Summary
Cardiovascular complications remain the major cause of mortality in diabetes and our current treatment strategies are insufficient to reduce this burden. We have obtained extensive data to show that a novel molecule (the micro RNA, let 7b) has antiproliferative and vasculoprotective effects in diabetes. Thus, we propose that modulation of micro RNA let 7b specifically in vascular smooth muscle cells within the vascular wall represents a promising target to combat cardiovascular disease, in parti ....Cardiovascular complications remain the major cause of mortality in diabetes and our current treatment strategies are insufficient to reduce this burden. We have obtained extensive data to show that a novel molecule (the micro RNA, let 7b) has antiproliferative and vasculoprotective effects in diabetes. Thus, we propose that modulation of micro RNA let 7b specifically in vascular smooth muscle cells within the vascular wall represents a promising target to combat cardiovascular disease, in particular in diabetes.Read moreRead less
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.
Uncovering A Novel Genetic Interaction That Governs Blood Vessel Development In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$626,557.00
Summary
Blood vessels are a vital component of the cardiovascular system. Abnormalities in the growth and development of blood vessels are associated with human disorders including cardio-vascular disorders, cancer and inflammatory diseases. The focus of this application is to determine the molecular events that direct the construction of the blood vascular tree, with the aim of identifying targets to which novel therapeutics for the treatment of blood vascular diseases could be generated.