Overcoming Breast Cancer Heterogeneity And Resistance Using A Novel Therapeutic Approach Targeting The Metastasis Suppressor NDRG1.
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Breast cancer (BrCa) is the leading cause of cancer death in women and current treatments suffer from development of resistance, leading to metastatic progression. I will assess a novel treatment strategy for BrCa, targeting a gene that is able to inhibit multiple key drivers of BrCa, using a novel potent and selective anti-cancer agent. This approach has the potential to overcome resistance to current therapies and alleviate the onset of metastasis, to improve prognosis for BrCa patients.
TACI: A Novel Immune Checkpoint In Chronic Lymphocytic Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$874,462.00
Summary
Chronic Lymphocytic Leukemia (CLL) is a very common blood cancer. CLL cells actively shut down immune defenses in patients. Moreover, current as well as emerging more targeted therapies suppress immunity and over a quarter of patients will die from an infection despite a good response to cancer treatments. Our laboratory has gained new understanding in the mechanism of action of a new treatment for CLL called Ibrutinib. This information allows us to design improved treatment options for CLL.
Relaxin Receptor Structural Determination To Aid Therapeutic Development
Funder
National Health and Medical Research Council
Funding Amount
$1,249,114.00
Summary
The receptor for the peptide hormone relaxin, RXFP1, is being targeted by numerous drug companies for the treatment of cardiovascular disease. However, the lack of molecular detail of how relaxin binds and activates RXFP1 is hindering new drug development. We will determine the structure of the complex of relaxin bound to RXFP1 and the mechanism by which this activates cells. The knowledge gained will aid in the design of new drugs targeting RXFP1 for the treatment of cardiovascular disease.
Glucocorticoids (or 'steroids') are among the most commonly used drugs in the world, chiefly used for inflammatory diseases. However, they have major predictable side effects that have been known for over 60 years. Science has, til now, failed to deliver an alternative that delivers the effects of steroids without the side effects. This application is for funds to support the development of the discovery of the protein known as GILZ towards a treatment to help patients.
Targeting The Complement Cascade: A Novel Therapeutic Strategy For Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$546,496.00
Summary
The incidence of melanoma is increasing world-wide, and Queensland has the highest rate of melanoma in the world. Despite advances in treatment, the 3-year survival rate for metastatic melanoma remains extremely low. This project builds on our recent research demonstrating a role for a key component of the innate immune system (complement C3a) in melanoma growth. Specifically we seek to investigate the potential of C3a as a therapeutic target for metastatic melanoma.
Molecular Toxinology Of Australian Box Jellyfish Venoms
Funder
National Health and Medical Research Council
Funding Amount
$283,110.00
Summary
Box jellyfish are an ongoing cause of illness and death for coastal communities and tourist regions in northern Australia. As well as creating a significant medical problem, the resulting closure of beaches during boxjellyfish 'season' results in an enormous loss of tourism income and threatens Australia's reputation as a safe destination. The jellyfish venoms contain toxins with potentially lethal effects on humans. For the first time, using pure venoms derived from the specialised stinging cel ....Box jellyfish are an ongoing cause of illness and death for coastal communities and tourist regions in northern Australia. As well as creating a significant medical problem, the resulting closure of beaches during boxjellyfish 'season' results in an enormous loss of tourism income and threatens Australia's reputation as a safe destination. The jellyfish venoms contain toxins with potentially lethal effects on humans. For the first time, using pure venoms derived from the specialised stinging cells (i.e. nematocytsts), we will isolate and characterize the major toxins from four species of box jellyfish. Their mechanism of action will be determined and the effect of various treatments such as antivenom will be investigated. This will also lead to the discovery of toxins with potentially novel targets and modes of action and increase our understanding of proposed treatments and prevention of stings.Read moreRead less
Immunotherapy has recently shown promise in bone cancer. We have found that while immune modulators Il-6 and Ifn?? contribute to tumour suppression Il-23 promotes the growth of radiation-induced bone cancer. We have generated mouse models of bone cancer to investigate tumour growth and immune surveillance in immune competent mice with an overall aim of identifying therapeutic targets in this disease.
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.
INFLAMMASOMES AND INTERLEUKIN-18 SIGNALLING: NOVEL BIOMARKERS AND THERAPEUTIC TARGETS FOR KIDNEY DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$1,003,340.00
Summary
Chronic kidney disease (CKD) is a major health problem. There is no cure for CKD and current therapies merely slow its progression. Thus for many patients, dialysis or kidney transplant is an inevitable outcome. We have evidence that a protein called interleukin-18 (IL-18) is a key mediator of kidney damage in CKD. Here we will explore how IL-18 causes kidney damage and whether IL-18 may be used as a diagnostic for early detection of CKD, and a target for more effective therapies to treat CKD.
Delivering On The GWAS Promise: From Genetic Discoveries To Novel Drug Targets For Asthma
Funder
National Health and Medical Research Council
Funding Amount
$697,605.00
Summary
The aim of this study is to identify new drug targets for asthma. This is important because for 6 in 10 asthma patients, current treatments do not adequately control disease symptoms and so these individuals are at a higher risk of having severe exacerbations. I propose that identifying asthma risk genes represents our best chance to identify novel drug targets for asthma. In this study, I will identify new asthma risk genes and test whether blocking these genes can alleviate disease symptoms.