The Oncogenic Function Of A Histone H3K9 Demethylase And Its Contribution To The Aggressive Malignant Phenotype Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$762,501.00
Summary
In contrast to the significant improvements in the treatment of acute lymphocytic leukaemia, advances in acute myeloid leukaemia (AML) therapy have been limited. The difficulty in treating AML is thought to arise from a drug-resistant subpopulation of leukaemic stem cells (LSC) that are capable of reinitiating disease after chemotherapy. This project will characterise a key regulator of LSC and provide insights into an important oncogenic process that gives rise to the aggressive and often fatal ....In contrast to the significant improvements in the treatment of acute lymphocytic leukaemia, advances in acute myeloid leukaemia (AML) therapy have been limited. The difficulty in treating AML is thought to arise from a drug-resistant subpopulation of leukaemic stem cells (LSC) that are capable of reinitiating disease after chemotherapy. This project will characterise a key regulator of LSC and provide insights into an important oncogenic process that gives rise to the aggressive and often fatal AML.Read moreRead less
Mechanisms Of PTEN Regulation By Ndfip1 And Their Biological Consequences For Neuron Survival During Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$686,640.00
Summary
We have discovered a new protein (Ndfip1) that protects brain cells from death after brain injury from trauma and stroke. We will investigate why this protein is activated only in some, but not in other, brain cells after injury. In this application, we will study the mechanisms behind neuron protection, and use this information to explore how to increase the number of brain cells activating Ndfip1.
Reactivities Of CD8 T Cells To Mutated Neo-antigens In Lung Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$661,979.00
Summary
Tumours express mutated proteins (called ‘neo-antigens’) which can be targets of powerful killer T cells which can destroy cancer cells. To understand why these cells fail to cure most cancers we will study neo-antigens identified by modern DNA sequencing methods to identify these neo-antigens & the responses to them. Then it will be possible to design trials in individual patients, e.g. personalised vaccines to ‘force’ the immune system to attack cells bearing these neo-antigens.
Defining The Role Of Microphthalmia-associated Transcription Factor (MITF) In Melanoma Heterogeneity By Real-time Cell Cycle Imaging
Funder
National Health and Medical Research Council
Funding Amount
$613,705.00
Summary
Metastatic melanoma is highly therapy-resistant. Modern targeted therapy is promising but suffers from rapid onset of drug resistance. Tumours consist of zones of fast growing cells next to zones of dormant cells. This tumour heterogeneity is one of the reasons for cancer drug resistance, as cells in different growth states respond differently to drugs. By understanding the causes of tumour heterogeneity we will set the basis for innovative clinical approaches against this devastating disease.
Adoptive Cell Transfer Incorporating Vaccination (ACTIV) Therapy For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$601,950.00
Summary
We have made a breakthrough in a new treatment for cancer that can destroy large tumours in mice. The treatment involves a transfusion of white blood cells and an injection of a vaccine. In this project, we will seek to understand how the treatment works, and apply it to human white blood cells in preparation for a clinical trial in cancer patients.
Molecular Pathways Mediating The Anti-tumour Activity Of WIF1
Funder
National Health and Medical Research Council
Funding Amount
$462,342.00
Summary
Osteosarcoma is the most common bone cancer. Treatment often entails aggressive surgery with intensive chemotherapy, although one third of those diagnosed will still die from this disease. We have found that the molecule WIF1 can suppress osteosarcoma growth. In this project we aim to identify genetic modifiers of WIF1, potential WIF1 interactors and define active domains of WIF1 for the development of more effective targeted therapeutics for osteosarcoma.
Improving Anti-cancer Therapy By Stromal Targeting And Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$673,742.00
Summary
We have developed a new drug which binds to abnormal cancer blood vessels. Upon binding, shape and tone of cancer vessels are restored and they become tighter. Our research will now test whether combining this new drug with current standard-of-care therapies such as chemo- and immunotherapy, will improve cytotoxic drugs and also make the immune system work better to fight the cancer. We also expect that tightening of blood vessels will stop cancer cells from spreading throughout the body.
Aberrant Transcriptional Signalling In The Progression And Metastasis Of Melanoma.
Funder
National Health and Medical Research Council
Funding Amount
$353,033.00
Summary
There are currently no treatments that have any impact on decreasing mortality from metastatic melanoma. We have found 2 new variants in melanoma that may control the tumour growing and invading around the body. This study will examine the protein containing these changes with the aims of finding how they function differently, to identify their roles in the formation of melanoma, as well as to identify new targets for prevention and treatment of metastatic disease.
This study investigates how much an individual's genes and environment account for the wide variation in brain structure and function. Using brain imaging we examine in what way the connectivity of the brain of identical and non-identical twins is the same or different from that of their co-twin, and carry out analysis of their DNA to identify some of the genes involved. This will provide fundamental information on genetic mechanisms influencing variation in brain structure and function.
Exploiting The Cross Talk Between Tuft Cells And Group 2 Innate Lymphoid Cells For Tissue Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$831,162.00
Summary
The project investigates the cellular cross talk within the gastric mucosa between tuft cells, a rare epithelial cell type, and tissue-resident group 2 innate lymphoid cells (ILC2). The tuft cell/ILC2 axis is driven by the two cytokines interleukin (IL)-25 and IL-13 and is required for tissue homeostasis but turns pro-tumourigenic in the context of chronic inflammation. Our investigation will dissect the underlying mechanisms using a combination of mouse models, immunology and bioinformatics.