Characterising Signals Important For Lymphangiogenesis During Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$604,938.00
Summary
Lymphatic vessels are a vital component of the cardiovascular system. Abnormalities in the growth and development of lymphatic vessels are associated with human disorders including cancer, lymphoedema and inflammatory diseases. The focus of this application is to characterise signals that direct the construction of lymphatic vessels, with the aim of identifying targets to which novel therapeutics for the treatment of lymphatic vascular diseases could be generated.
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.
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.
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
Priming The Maternal Immune Response To Resist Inflammatory Disorders Of Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$920,972.00
Summary
Preeclampsia and preterm birth are common conditions affecting >15 million pregnancies annually. An underlying cause is the mother’s immune response, which can react adversely to the fetus causing an inflammatory reaction. This project seeks to find ways to strengthen the maternal immune system beginning before conception. The work will provide insights upon which to advise intending parents and will inform development of new treatments options to protect susceptible women.
Personalised Medicine Markers Of Anti-EGFR Antibody Therapy In Metastatic Colorectal Cancer: Accelerating Clinical Translation With Collaborative Meta-analyses Based On Individual-participant Data
Funder
National Health and Medical Research Council
Funding Amount
$300,953.00
Summary
When selecting cancer therapy we take into account ‘biomarkers’, biological cancer characteristics that predict treatment success. We will work with an international group, the Advanced Colorectal Cancer Database, to analyse individual patient clinical trial data. We intend to validate biomarkers used to select treatment with cetuximab or panitumumab. Cancer genes called KRAS, NRAS, PTEN, PIK3CA, EREG and BRAF will be examined. Our study will provide best evidence for personalised treatment.
Pushing AR Toward Better Outcomes In Breast And Prostate Cancers
Funder
National Health and Medical Research Council
Funding Amount
$998,754.00
Summary
Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives ....Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives.Read moreRead less
Revolutionising The Diagnosis And Monitoring Of CF Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$818,391.00
Summary
Cystic fibrosis (CF) lung disease starts early in childhood and relentlessly progresses, with early death a common outcome. There is currently no method capable of detecting very early disease onset nor directly assessing the effectiveness of putative treatments. This project will apply our globally unique X-ray imaging tools, which are capable of imaging lung function at any point across the entire lung, for the very early detection of CF and assessment of clinically applicable treatments.
Exploiting Increased Autophagy In Bronchial Epithelial Cells: A New Therapeutic Approach For Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$724,161.00
Summary
COPD is incurable, a leading cause of death, and new therapies are urgently needed. Autophagy is a cell response to cell stress conditions, however increased autophagy is harmful. We will investigate the association of increased autophagy with COPD and smoking and evaluate therapies that can reduce autophagy, including zinc-related drugs and novel antibiotics that have been modified to lose their anti-bacterial activity.
A Randomised Controlled Trial (RCT) Of Azithromycin Versus Doxycycline For The Treatment Of Rectal Chlamydia Infection In Men Who Have Sex With Men.
Funder
National Health and Medical Research Council
Funding Amount
$797,906.00
Summary
Rectal chlamydia is very common among gay men; it can exist for long periods without symptoms leading to ongoing transmission. Azithromycin (1 gram single dose) or 7 days doxycycline (100mg twice daily) are the two recommended treatments globally. But, there is concern about rectal chlamydia treatment with reports of up to 22% failure following azithromycin. We will conduct a randomised trial to compare these treatments for rectal chlamydia and determine which drug works better.