Phospholipase Cbeta 1b, A Target To Limit Atrial Dilatation
Funder
National Health and Medical Research Council
Funding Amount
$544,847.00
Summary
We have identified a heart specific protein that is involved in perpetuating dilatation of the upper chambers of the heart and thereby contributing to cardiac disease. Inhibitors of this protein provide a suitable target for therapy to limit heart disease. The current studies aim to test such inhibitors in vivo as proof-of-concept that such treatment effectively limits cardiac dysfunction.
Pre-clinical Assessment Of The Therapeutic Potential Of Targeting The Hippo Pathway In Muscle Wasting & Muscle-derived Cancer
Funder
National Health and Medical Research Council
Funding Amount
$621,979.00
Summary
Recent findings have identified the Hippo signalling pathway as an important regulator of processes in muscle fibres and muscle progenitor cells. This project will look at the significance of the Hippo pathway in the development of muscle wasting caused by statin administration, and in the genesis of muscle derived tumors (rhabdomyosarcoma). The studies will determine if interventions that regulate the Hippo pathway could provide new therapies for these important muscle-related diseases.
Location, Location, Location: Sub-cellular Specific Targeting Of JNK As A Novel Therapy In Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$633,755.00
Summary
The ‘triple negative’ breast cancer subtype is the most aggressive form of breast cancer, and unlike other subtypes, there are no drugs to specifically this subtype. While many potential drug targets have been identified, they cannot be utilised clinically because of other beneficial roles within the body. We are now deploying our innovative experimental platforms to specifically target the tumour promoting functions of a protein known as ‘JNK’, whilst retaining its beneficial functions.
GTPase Regulation Of The Hippo Organ Size-control Pathway
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which two proteins, Pix and Git, control tissue growth by regulating the Hippo pathway. These studies will be performed in flies. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
We have identified a microRNA (miRNA) which can elicit the functional outcome of the anti-inflammatory cytokine IL-10. miRNAs constitute a novel mechanism used by cells to regulate gene expression and have shown much promise as a therapeutic tool. Our finding suggests that modulation of miRNAs through the use of miRNA mimics or antisense technology may serve as an alternative and/or synergistic approach for the use of IL-10 as therapy in chronic inflammation.
Male fertility requires sufficient production of healthy sperm in the testis. We discovered that cells in the adult testis communicate via the Hedgehog (Hh) signalling pathway as sperm develop. We propose to use a highly specific drug to inhibit Hh activity in order to delineate the precise steps in sperm production affected by Hh signalling. We will study the importance Hh in maintenance of spermatogonial stem cells and create mouse models to learn how it is controlled.
Targeting The JNK-JUN Pathway To Overcome Therapy Resistance In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$694,729.00
Summary
Melanoma patients can display remarkable responses to targeted and immunotherapies. However most patients progress rapidly on targeted therapies and only a small proportion respond to immunotherapies. We have found that combination treatment with JNK inhibitors can overcome therapy resistance. We will determine the most efficacious JNK inhibitors available, and the optimal dosing and scheduling of combination treatment for evaluation in patients to improve responses, outcomes and survival.
Despite aggressive treatment, the survival rate for high-risk neuroblastoma patients is below 50%. We recently found that these poor-outcome neuroblastomas have a defect in a key drug response pathway, called the JNK pathway. Standard-of-care neuroblastoma drugs all require the JNK pathway to kill neuroblastoma cells, although we have now identified alternative drugs that do not require JNK. We now plan to demonstrate the efficacy of these drugs in neuroblastomas with a defective JNK pathway.
Studying The Novel Role For G Protein-coupled Receptor Signalling In Leukaemia Development
Funder
National Health and Medical Research Council
Funding Amount
$373,144.00
Summary
Recent research has shown the clinical importance of abnormal stem cells (LSC) in acute myeloid leukaemia (AML). LSC are resistant to therapeutics suggesting that they could be a cause of relapse. Identifying signalling pathways that drive LSC development is essential to selectively eradicate LSC that could offer substantial therapeutic benefit. This proposal aims to identify and evaluate critical signalling pathways as a potential therapeutic target for developing effective novel LSC-targeted t ....Recent research has shown the clinical importance of abnormal stem cells (LSC) in acute myeloid leukaemia (AML). LSC are resistant to therapeutics suggesting that they could be a cause of relapse. Identifying signalling pathways that drive LSC development is essential to selectively eradicate LSC that could offer substantial therapeutic benefit. This proposal aims to identify and evaluate critical signalling pathways as a potential therapeutic target for developing effective novel LSC-targeted therapy in AML.Read moreRead less
Cellular Regulation Of Receptor Signalling And Cytokine Responses
Funder
National Health and Medical Research Council
Funding Amount
$859,288.00
Summary
Cell surface receptors and signalling pathways elicit the release of cytokines, or chemical messengers, to control inflammation, which is the body’s response to infection or danger. We have discovered a new signalling pathway that can turn off inflammation and help prevent inflammatory disease. Our studies will now define the molecular details of this pathway and show how new and existing drugs targeting this pathway can be optimally used to treat inflammation and cancer.