The overall incidence of primary brain tumours in the Western world is 10 per 100,000 people. Unlike many other tumours, these occur in patients of all ages and comprise the second most common tumour type among children and young adults. Most brain tumours remain incurable. We are using our expertise in the field of neural stem cell research to characterise tumour cells responsible for resistance to treatment, with the final goal of identifying new targets for therapeutic intervention.
Improving The Assessment Of Brain Tumour Treatment Outcome Using 18F-FDOPA PET-MRI Fusion
Funder
National Health and Medical Research Council
Funding Amount
$660,666.00
Summary
The mortality rate within the first year of diagnosis for high-grade brain tumours is approximately 80%. A major factor contributing to poor outcome measures is the limitation of current neuroimaging techniques. In a novel approach we propose to combine the information available from MRI and PET images to better define the extent of the tumour and provide markers of early treatment response. This improved diagnostic information should improve survival rates.
Radiotherapy Vs Chemotherapy For Low-grade Gliomas Stratified For Genetic 1p Loss: Efficacy And Quality Of Life Benefits
Funder
National Health and Medical Research Council
Funding Amount
$410,316.00
Summary
Low-grade glioma is an uncommon malignant brain tumour. Surgery, radiotherapy and chemotherapy delay growth of this tumour, but cure is uncommon. Currently the goal of treatment is to control tumour growth for as long as possible whilst maintaining quality of life. This study compares treatment with radiotherapy with a new form of chemotherapy to see which treatment controls tumour growth most effectively, which produces the least side effects and which results in the better quality of life.
Truncating Presenilin Mutations And Their Effects On Gamma-secretase Activity, Tau And Beta-catenin
Funder
National Health and Medical Research Council
Funding Amount
$414,005.00
Summary
Alzheimer's disease (AD) and cancer are increasingly important both in terms of human suffering and the burden of care it imposes on society and the economy. Sporadic (non-inherited) AD is the most common form of dementia but is poorly understood. The PRESENILIN genes, PSEN1 and PSEN2, are the major sites for mutations causing inherited AD and are also implicated in cancer. Using the zebrafish embryo model we have discovered that, contrary to current thought, mutations that truncate presenilin p ....Alzheimer's disease (AD) and cancer are increasingly important both in terms of human suffering and the burden of care it imposes on society and the economy. Sporadic (non-inherited) AD is the most common form of dementia but is poorly understood. The PRESENILIN genes, PSEN1 and PSEN2, are the major sites for mutations causing inherited AD and are also implicated in cancer. Using the zebrafish embryo model we have discovered that, contrary to current thought, mutations that truncate presenilin proteins potently suppress normal presenilin activity. (They are so called, dominant negatives). This means that they are lethal for embryo development and explains why such mutations have never been found in inherited AD. Notably, this discovery could only be made using a subtle form of gene manipulation that is possible in zebrafish embryos. Our work has also established the first assay for the non-apoptotic (non-cell death) function of PSEN2 and has shown that PSEN2 activity is inhibited by truncated PSEN1. This is the first indication of possible interaction between PSEN1 and PSEN2 proteins at normal physiological expression levels. Loss of presenilin activity promotes cancer. Truncated presenilin proteins could be produced by errors in gene transcription (aberrant transcript splicing) common in cancerous cells. This suggests that truncated, dominant negative forms of presenilin produced through aberrant splicing (or mutation in precancerous cells) might be common in tumour formation. The proposed research will define the region of PSEN1 in which truncation leads to dominant negative activity. This will allow further examination of the role of presenilins in the cell signalling pathways involved in AD and cancer. We will also investigate the role that age-related truncation of presenilins in human cells can play in the formation of sporadic AD. This may reveal a common molecular link between the inherited and sporadic forms of this disease.Read moreRead less
A Novel Tumour-targeting Nanoliposome Drug Delivery System For The Treatment Of Malignant Gliomas
Funder
National Health and Medical Research Council
Funding Amount
$445,097.00
Summary
Most patients with malignant brain tumours die within a year after diagnosis due to the difficulty in effectively delivering drugs to the tumour cells. We aim to develop a safe and novel drug delivery system to effectively deliver anticancer drugs and novel anticancer agents to brain tumour cells that remain in normal brain after surgery. The success of this project will bring us a step forward in our efforts to significantly improve the survival rate and quality of life of such patients.
Genes Important For Early Brain Development Are Also Important For Adult Brain Disease
Funder
National Health and Medical Research Council
Funding Amount
$850,346.00
Summary
I committed to understanding of how the brain develops, grows and regenerates. My laboratory is active in finding a cure for brain injury following brain trauma or brain ischemia. I have discovered that the genes that drive neuron migration and wiring in the fetus also function in the adult brain to improve neuron survival and regeneration. Probing the function of these genes will deliver twin benefits in preventing brain disorder in the newborn and treating brain disease in the adult.
Investigating Immune Regulation In The Tumour Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$288,650.00
Summary
Suppressive factors made by cells of the immune system or cancers themselves and immune regulatory T cells inhibit an effective anti-tumour response. My project aims to investigate the mechanism by which these factors and cells mediate their suppressive function. Understanding these processes in the cancer environment will allow the design of more effective cancer therapies.