Combining PI3K, CDK4/6 Pathway Inhibitors And Immunotherapies In Triple-negative Breast Cancer (TNBC): A Novel Therapy Combination
Funder
National Health and Medical Research Council
Funding Amount
$626,345.00
Summary
Triple-negative breast cancer (TNBC) has the worst prognosis of all breast cancer subtypes, classically affecting young women and characterized by a lack of effective therapies. We show that blocking both PI3K and CDK4/6 pathways together effectively reduces TNBC growth in mice and can enhance anti-tumour immune responses. We aim to understand how these drugs work together and if adding immunotherapy can improve responses. Our project could provide a new treatment approach for TNBC patients.
Characterisation Of Two Novel Markers Of Osteosarcoma Metastasis As Potential Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$624,500.00
Summary
Osteosarcoma (OS) is the most common bone tumour in children and adolescents. In spite of aggressive chemotherapy, OS tumours that metastasise to the lungs result in dismal long-term survivals of only 10-20%. For these patients, new treatment options are desperately needed. In this proposal we show compelling data identifying two new markers of OS metastasis. This research aims to validate the suitability of these novel markers as therapeutic targets to prevent OS metastasis.
Understanding The Role Of The Essential Regulator WalKR In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$555,239.00
Summary
Staphylococcus aureus is one of the most common human bacterial pathogens. This project aims to characterise an important global control system in S. aureus, and determine if chemical inhibitors of this control system could be used to treat S. aureus disease in the future.
For 60 years, we have had only 3 effective cancer treatments: surgery, radiation and chemotherapy, often used in combination.The last 5 years have produced a powerful fourth treatment: the patient's own immune system.The long standing collaborations and synergies of our multi-disciplinary teams have already underpinned many recent advances in immune-based therapies: we are now poised to develop several further immunotherapies and on track to test them in patients during the term of this grant.
The Role Of Stem-progenitor Cells In Regeneration Of Mouse Endometrium.
Funder
National Health and Medical Research Council
Funding Amount
$311,938.00
Summary
The endometrium (lining of the uterus) undergoes breakdown and re-growth each month as part of the menstrual cycle. This restorative process is not well understood. For the first time stem cells have been identified within human endometrium that are likely to be responsible for its remarkable regeneration. The aim of this project is to identify stem cells within the mouse endometrium, to use as a model to understand how the endometrium restores each month after menstruation.
We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Central Neural Circuits Subserving Nutrient–activated Thermogenesis - The Basis Of Post Prandial Energy Expenditure
Funder
National Health and Medical Research Council
Funding Amount
$766,207.00
Summary
Studies of “energy burning” brown fat, including its importance in the determination of obesity in humans and the potential to increase its capacity by turning white fat into brown-like fat are currently foremost in obesity research. Here we study the detail of brain pathways that dictate brown fat activity after a meal resulting in the burning of ingested calories and reduction of body weight. The results will give us a better idea of how we can harness brown fat to combat obesity.
Identifying Target Genes For Novel Anti-epileptic Therapies In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$469,802.00
Summary
Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not respo ....Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not responding to current therapy. This project is designed to identify new biologic pathways which may be interrupted with drugs to prevent seizures in people with epilepsy. This project uses a procedure to induce mutations into genes in mice and then screens for mice which do not seize when challenged with a drug which generates seizures in mice. Genetic studies will identify the mutated genes and these will be used as potential targets for new therapies or will identify new biological pathway which should expand the use of future anti-epileptic drugs.Read moreRead less
Central Neural Regulation Of Brown Fat Function – Glucose Sensing And CNS Pathways
Funder
National Health and Medical Research Council
Funding Amount
$761,942.00
Summary
Our research aims to identify how specific brain cells detect changes in glucose levels and how ageing and diet affect their function. We identified a subset of nerve cells that detect changes in glucose and the “hunger” hormone ghrelin, their ability to do so adapting with age and nutritional status. This project will investigate the potential of these nerve cells as targets for therapeutic and diet- intervention strategies to target obesity, diabetes and promote healthy ageing.
Deadly Commute - Targeting The Trafficking Mechanisms That Licence Inflammatory Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$774,544.00
Summary
MLKL is a protein naturally found inside cells. MLKL is activated by inflammation. Once activated, MLKL relocates to the outer periphery of cells and kills them. Gut cells are especially vulnerable to death-by-MLKL and this problem causes Inflammatory Bowel Disease. Using cutting edge microscopy, we have discovered how MLKL moves to the periphery of cells prior to killing them. We will test if blocking this movement of MLKL to the cell periphery stops gut death and Inflammatory Bowel Disease.