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.
Preclinical Evaluation Of A Novel Allosteric IL-1R Inhibitor (rytvela) For The Prevention Of Perinatal Inflammation-induced Fetal Injury
Funder
National Health and Medical Research Council
Funding Amount
$1,377,827.00
Summary
Interleukin-1 (IL-1) is a potent inflammatory protein involved in many inflammatory disorders, including preterm birth (PTB). Blocking the actions of IL-1 in pregnancies at risk of delivering preterm may protect the fetus from PTB and the long-term harm of exposure to inflammation before birth. Using four different models of antenatal inflammation, we will explore the use of a new IL-1 inhibitor to see if it blocks inflammation ‘in utero’ and improve neonatal health and development.
Peri-conception Determinants Of Reproductive And Pregnancy Health
Funder
National Health and Medical Research Council
Funding Amount
$3,560,520.00
Summary
Reproductive and pregnancy disorders are common in Australian men and women, with 6% couples seeking infertility services and another 30% experiencing recurrent miscarriage, preeclampsia or preterm birth, often resulting in life-time health problems for children, and sometimes stillbirth. This research will investigate the immune causes of these conditions, and the results will contribute to new health tools, diagnostics and medical treatments to support maternal and infant health.
Predicting Renal, Ophthalmic, And Heart Events In The Aboriginal Community – THE PROPHECY Study
Funder
National Health and Medical Research Council
Funding Amount
$2,574,486.00
Summary
Up to 30% of adult Aboriginal people have diabetes yet our knowledge of the causes and predictors of complications remain incomplete. We have established the PROPHECY Study to assess the levels of complications in Aboriginal people with diabetes; to understand the way that these complications occur, and identify what clinical, social and genetic factors could predict who will get those complications to guide clinical management and prevention.
Role For Zinc And ZIP2 In The Action Of Nitric Oxide And In Vascular Protection Against Cigarette Smoke And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$685,941.00
Summary
The NO/cGMP signalling pathway, which is central to cardiovascular physiology and protection against disease, is only fully effective when there are adequate levels of zinc in the vascular endothelium. This is especially important where zinc stores are depleted (elderly, smokers, diabetics and kidney disease). There is an urgent clinical need to implement strategies to monitor vascular Zn status. This application will explore the underlying science and translate these to the clinic.
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.
Vascular Contributions To Dementia: Prevention In Those At High-risk
Funder
National Health and Medical Research Council
Funding Amount
$718,105.00
Summary
10,000 older adults undergo surgeries on their heart every year. These adults are at high risk for dementia, as the factors that bring them to cardiovascular surgery are the same as those that associate with dementia: hypertension, type II diabetes, etc. This population is in fact not only at increased risk of dementia due to vascular ill-health, but also because of undergoing the surgery itself. This project aims to prevent dementia in this vulnerable group.
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.
A Genome-wide Association Scan To Identify Genetic Risk Factors For Sight Threatening Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$982,203.00
Summary
Diabetic eye disease is an important complication of diabetes that can lead to blindness. Very little is known about how diabetes causes eye disease, but genetics is known to play a role. We aim to identify genes that contribute to eye disease in diabetes patients. We will compare genes between patients with diabetes with and without severe diabetic eye disease using cutting edge genomic technology. We hope to be able to better predict risk of blindness and to move towards novel treatments.