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.
The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
We recently discovered a new way to treat melanoma by inhibiting a protein called MDM4 that is important in promoting tumor growth in ~2/3 of melanomas. In this proposal, we will extend this work to see if anti-MDM4 therapy is effective in laboratory models that are more relevant to patients and in combination with other melanoma therapies. We will also explore additional ways of inhibiting MDM4 that may make anti-MDM4 therapy even more potent.
Regulating Gene Expression Changes In Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$690,754.00
Summary
Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression.
Correlating Multiple Sclerosis Risk SNPs With Immune Cell Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$789,386.00
Summary
In Multiple Sclerosis (MS), the immune system repeatedly attacks the brain and spinal cord. In the last three years, rapid progress has been made in understanding genetic risk factors for MS, and more than 20 are known, but their function is not understood. The proposed study will recruit patients with MS and healthy controls to isolate five major immune cell types, and will assess how risk genes influence these cells. We hope to obtain a much better picture of how genetic risk factors for MS ac ....In Multiple Sclerosis (MS), the immune system repeatedly attacks the brain and spinal cord. In the last three years, rapid progress has been made in understanding genetic risk factors for MS, and more than 20 are known, but their function is not understood. The proposed study will recruit patients with MS and healthy controls to isolate five major immune cell types, and will assess how risk genes influence these cells. We hope to obtain a much better picture of how genetic risk factors for MS actually work.Read moreRead less
Targeting The Oncoprotein MDMX As A Novel Treatment For Triple Negative Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$561,672.00
Summary
Breast cancer (BrCa) is a leading cause of cancer death in women worldwide. BrCas unable to respond to current therapies have the worst outcomes. We propose a novel strategy to treat these cancers, based on our new findings. Our two protein targets are: (1) MDMX, that we found drives BrCa with its partner, (2) mutant p53, which causes cancer spread. We plan to directly target these drivers of aggressive BrCas, using new drugs that individually show great promise in trials in a number of cance
Cyclotherapy: A New Approach To Stop The Side Effects Of Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$565,847.00
Summary
Cyto-toxic chemotherapy is a widely used treatment for cancer but is associated with significant side effects for the patient. These are due to the chemotherapy killing normal dividing cells in the gut, bone marrow and hair follicles. We will determine the potential of cyclotherapy in preventing these side effects. In cyclotherapy a pre-treatment temporarily stops normal cells from dividing and therefore protects them from the damage of subsequent chemotherapy.
Over half of all cancers contain mutations in a gene called TP53, also known as the “guardian of the genome”. Mutation of TP53 provides tumour cells with a growth advantage, and leads to resistance to chemotherapy and poor outcomes for patients. We have identified a potential “Achilles heel” in cancers with TP53 mutations. In this project we will establish a new paradigm for treating tumours with TP53 mutations that will be applicable to a large number of patients across all types of cancer.
Elucidating The Cellular Processes That Are Critical For P53 Mediated Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$1,016,108.00
Summary
p53 is a tumour suppressor gene that is mutated in ~50% of human cancers. Mutations in p53 cause development of cancer and render malignant cells resistant to chemotherapy. We have identified genes regulated by p53 that appear critical for its tumour suppressive function. In this project, we will use innovative novel genetic tools to discover the cellular and biochemical functions of these genes. The ultimate goal of our studies is to identify novel targets for anti-cancer therapy.
Mechanisms Of Cytokine Independence During The Development Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
Signals from growth factors such as cytokines and hormones are required for cell survival. In their absence cells activate an in-built self-destruct process. Determining how cytokines regulate cell death will provide novel targets so that unwanted cells (like cancer cells) can be triggered to die and needed cells (such as brain cells) can survive.