Antibody-based Inhibition Of ADAM10 As Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$652,788.00
Summary
Despite our advances in understanding the molecular basis of cancer, treatments for metastatic cancers are limited, emphasising an urgent need for strategies targeting several oncogenic pathways. We generated monoclonal antibodies effectively blocking the activity of ADAM10, an oncogenic cell surface protease that activates tumour growth, invasion and metastasis through multiple pathways. Here we describe the strategies that progress these antibodies as lead therapeutics for clinical testing.
Novel Dual Domain Targeting Strategies Against ErbB Receptors
Funder
National Health and Medical Research Council
Funding Amount
$711,216.00
Summary
This project will develop innovative strategies to treat cancer through novel antibodies to erbB growth factor receptors, and identify ways to improve conventional treatments.
Testing Novel Therapies Using Paediatric Brain Tumour Models
Funder
National Health and Medical Research Council
Funding Amount
$384,023.00
Summary
Brain tumours are the second most common childhood cancer, with 300 children affected in Australia each year. Many children with brain tumours continue to die of their disease, whilst survivors are often left with devastating life long side effects. Our goals are to harness the power of innovative model systems of childhood brain tumours, in order to test the effectiveness of new treatments for these devastating diseases, so that the most promising therapies can be taken through to the clinic.
Investigating The Role Of Mutant P53 And MCL-1 In The Sustained Growth Of MYC Lymphomas And Strategies For Targeted Therapy
Funder
National Health and Medical Research Council
Funding Amount
$616,940.00
Summary
A large number of human cancers have abnormal expression of a protein called MYC, leading to rapid growth. We found that when another protein called MCL-1 was inactivated, the lymphomas regressed. Importantly, mutations in the tumour suppressor gene called p53 are frequently found in cancer cells and we noticed that this could reduce the dependency on MCL-1. We aim to investigate this further in this grant proposal, in part using a novel drug that targets MCL-1.
Structural Investigations Of The Bax And Bak Cell Death Apparatus
Funder
National Health and Medical Research Council
Funding Amount
$275,509.00
Summary
Programmed cell death is a process by which the body keeps rogue cells in check. Cancer cells adapt to avoid this process and thus evade this important defence mechanism. This project seeks to understand the machinery that controls programmed cell death at the molecular level. It will provide the atomic details of how this machinery is regulated and how it functions to induce cell death. These insights will provide new avenues for targeting this machinery for a new generation of cancer therapeut ....Programmed cell death is a process by which the body keeps rogue cells in check. Cancer cells adapt to avoid this process and thus evade this important defence mechanism. This project seeks to understand the machinery that controls programmed cell death at the molecular level. It will provide the atomic details of how this machinery is regulated and how it functions to induce cell death. These insights will provide new avenues for targeting this machinery for a new generation of cancer therapeutics.Read moreRead less
The Axis Of Bcl-2, Plasmacytoid DCs And Lupus As A Basis For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$712,172.00
Summary
Systemic lupus erythematosus (SLE) affects 1 in 1000 Australians, mostly women. Here the immune system goes awry and makes antibodies against the body’s own components including the body’s DNA. This leads to damage to many parts of the body including kidneys, joints, brain and heart. It is incurable. A particular immune cell controls the development of this disease and we have found this cell is selectively killed by an inexpensive drug, which we hope will be a better way of treating SLE.
Examining The Contribution Of Mutant DNMT3a In The Development And Sustained Growth Of Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$820,880.00
Summary
Experimental models of Acute Myeloid Leukaemia (AML) have been valuable tools for studying this cancer. Recent analysis of human cancer genomes identified novel mutated gene products implicated in AML. To study the involvement of these genes in the development and sustained growth of AML, we will generate new experimental models that express the mutated forms of these newly described genes. These studies will assist in the development of improved treatments for patients with AML.
DOES BCL-G, A BH3-ONLY PROTEIN, PLAY A ROLE IN INFLAMMATION-ASSOCIATED COLON CANCER?
Funder
National Health and Medical Research Council
Funding Amount
$418,587.00
Summary
Deregulation of the function of several members of the Bcl-2 family has been shown to be an aggravating factor in autoimmune diseases and cancer. Bcl-G is a new and poorly characterized member of this family. We have produced essential tools to study the physiological function of Bcl-G, and discovered that it plays a role in inflammatory bowel disease. We now plan to investigate its possible role in inflammation-associated colon cancer.?
Understanding The Activation Of Pro-apoptotic Bcl-2 Family Proteins For The Development Of Modulators Of Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$627,805.00
Summary
Programmed cell death is a process by which the body protects against rogue cells, eg cells potentially cancerous or infected by viruses. Dysregulation of the process occurs in cancer and can also lead to degenerative diseases. This work will discover the molecular mechanisms by which key proteins control the life/death switch in cells and will develop compounds capable of regulating their activity, setting the foundation for developing therapeutics aimed at regulating these processes.
Dual Targeting Of Myc And Apoptosis Pathways For Improved Blood Cancer Treatment Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$754,685.00
Summary
Cancer cells frequently possess defects in genes called MYC and BCL-2 that control their growth and survival. Our preliminary studies have shown that combining novel reagents that specifically target MYC plus BCL-2 leads to enhanced lymphoma cell killing. In the proposed research, we will further develop these reagents and evaluate their ability to treat blood cancer in mice. We expect our approach will provide new avenues for treating cancer patients that respond poorly to current treatments.