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.
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.
Preclinical Evaluation Of The Novel Therapeutic Compound APP96-110 In An Ovine Model Of Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$874,734.00
Summary
Traumatic brain injury (TBI) is a significant cause of death and disability, and yet there are currently no effective treatments to improve outcome following such an insult. Our laboratory has developed a novel therapeutic compound, by identifying an endogenous neuroprotective molecule, in the amyloid precursor protein and then identifying the active site and modifying it to improve its efficacy. We will be testing this compound in our sheep model of TBI.
An Examination Of The Relationship Between Alcohol-related Injury (ARI) And Licensed Premises
Funder
National Health and Medical Research Council
Funding Amount
$78,686.00
Summary
There is growing interest in acute alcohol-related problems, and especially injuries. These are often experienced by young people, frequently as a consequence of intoxication or drinking in unsafe settings. Little work has been undertaken in Australia to systematically examined alcohol-related injuries (ARIs). This study will examine ARIs, identify the frequency with which such problems present to a local hospital, record the nature of the injuries, details of the person sustaining it, and the d ....There is growing interest in acute alcohol-related problems, and especially injuries. These are often experienced by young people, frequently as a consequence of intoxication or drinking in unsafe settings. Little work has been undertaken in Australia to systematically examined alcohol-related injuries (ARIs). This study will examine ARIs, identify the frequency with which such problems present to a local hospital, record the nature of the injuries, details of the person sustaining it, and the drinking location. Characteristics of drinking locations and drinking settings, in particular licensed premises, will be examined to determine their association with ARIs. Then an intervention will be undertaken in conjunction with local police, to address the conditions of the drinking environment with the aim of reducing ARIs and other alcohol-related problems stemming from licensed premises. The intervention will form part of a randomised controlled trial where licensed premises, identified through monthly police data as hot spots, receive either an intervention or act as a control. In the following month, controls receive the intervention (a cross-over design). The intervention was established in 1998 by Gold Coast police and involves police, fire and liquor licensing officers undertaking an on-site inspection and taking prescribed actions. It is hypothesised that this action should result in a decreased level of ARIs being generated from premises which receive the intervention, compared to those that do not. This is an intersectoral, collaborative project aimed at improving community safety through a concerted effort by police, health and the licensees.Read moreRead less
A New Target For Allergic Inflammation: The Sphingolipid Pathway
Funder
National Health and Medical Research Council
Funding Amount
$588,617.00
Summary
Collectively, allergic diseases contribute immensely to the burden of health care in Australia. Notably, allergic reactions are symptomatic responses to a normally innocuous environmental antigen. Allergic diseases include asthma, hay fever, food allergy, anaphylaxis, insect sting and drug allergy. This project aims to understand the underlying mechanisms associated with allergic reactions such that it may aid in the identification of novel targets for the development of new treatments.
Addressing significant product safety knowledge gaps for older Australians . This project addresses significant gaps in contemporary knowledge of consumer product safety risks for older persons, with 25 years since the last Australian product safety research found older persons are at high risk of product-related injury/death. Products have evolved substantially and aged care models have changed in that time. This project generates contemporary knowledge of unsafe products causing injuries/death ....Addressing significant product safety knowledge gaps for older Australians . This project addresses significant gaps in contemporary knowledge of consumer product safety risks for older persons, with 25 years since the last Australian product safety research found older persons are at high risk of product-related injury/death. Products have evolved substantially and aged care models have changed in that time. This project generates contemporary knowledge of unsafe products causing injuries/deaths, risk factors/behaviours, and human rights issues. Outcomes benefiting the Australian community are improved prediction/characterisation of product safety issues for older Australians informing safer product design and use, targetted regulatory responses, ageing-in-place strategies, and creating safer home environments.Read moreRead less