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Spleen Tyrosine Kinase (Syk) As A Therapeutic Target In Antibody-dependent Transplant Rejection.
Funder
National Health and Medical Research Council
Funding Amount
$625,919.00
Summary
While kidney transplantation is a life saving treatment for those with end-stage kidney failure, a significant number of patients face long waits on dialysis because they have antibodies that would cause rejection of most potential donor kidneys. This project seeks to address this problem using a new strategy to treat antibody-mediated rejection and thereby enable such patients to receive a transplant without the fear of severe rejection.
Host-directed Therapy For Malaria: Host Cell Signalome As A Target
Funder
National Health and Medical Research Council
Funding Amount
$898,043.00
Summary
Malaria parasites kill 450,000 children a year and impact on the economic development of communities. Spreading drug resistant malaria parasites within Australia's South-East Asian neighbours creates an urgent and unmet need for new drug treatments. We will characterise host signals required for parasite survival in immature erythrocytes and identify host-directed, ready to develop, resistance-proofed drugs to kill malaria parasites.
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.
Sphingosine Kinase As A Target For Anti-cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$590,785.00
Summary
Sphingosine kinase is a protein involved in the development and progression of numerous types of solid tumors and leukaemias. We have recently made a major break-through by identifing how the cancer-inducing activity of sphingosine kinase is controlled. In this study we will target these control mechanisms to develop potential new anti-cancer therapies.
Targeting Necroptosis Signalling To Counter Stroke-induced Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,809.00
Summary
The origins of the brain injury that arises from stroke remain a matter of enormous interest. Our work suggests that a poorly understood form of cell death, termed necroptosis, contributes to injury to the brain following stroke. In addition to developing an advanced understanding of this process, we will use drugs developed at the Walter and Eliza Hall Institute to test whether blocking this process might be a plausible therapeutic strategy in stroke patients.
DYRK1A As A Novel Target For Glioblastoma Therapies
Funder
National Health and Medical Research Council
Funding Amount
$620,294.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called DYRK1A (using ‘DYRK1A inhibitors’) kills glioblastoma cells. This therapeutic advantage is even greater when combined with drugs approved for other cancers. This project will develop new DYRK1A inhibitors and examine a novel combination treatment for glioblastoma patients. This could initiate a novel therapy that could significantly extend patients’ lives.
Why Is The Hijacking Of A Human Erythrocyte Signalling Pathway Essential For Malaria Infection?
Funder
National Health and Medical Research Council
Funding Amount
$510,890.00
Summary
Malaria drug resistance is spreading and the world needs cost-effective new drugs. We found 2 human enzymes, known targets of cancer chemotherapy, to be key for parasite survival in red blood cells. We aim to understand why these human proteins are crucial for the parasite and to identify new human proteins hijacked by malaria. This will open exciting options for antimalarial drug discovery: to harness funds invested in cancer drugs by targeting proteins with dual roles in cancer and malaria.
Overcoming Receptor Tyrosine Kinase Mediated Resistance To BRAF Inhibitors In Metastatic Melanoma, Colorectal And Lung Cancers.
Funder
National Health and Medical Research Council
Funding Amount
$574,958.00
Summary
The drug Vemurafenib results in good responses in melanoma patients. However, patients become resistant to treatment. We have identified specific receptors that can cause Vemurafenib resistance, which can be overcome by combination treatment with drugs to these receptors. We will assess melanoma patient samples for expression of these receptors which will be highly beneficial for selecting combination treatments to prevent drug resistance and ensure better prolonged outcomes.
Isoform Selective PI3 Kinase Inhibitors For Cancer, Thrombosis And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$474,473.00
Summary
Inhibitors of the PI3 kinase family of enzymes have potential as therapeutics in diseases such as cancer, thrombosis and inflammatory disease. In this project the investigators will develop a new class of PI3 kinase inhibitors they have discovered, optimizing their pharmaceutical properties and evaluating them in models of disease. The aim is to develop a candidate for human clinical studies.
Chronic Myeloid Leukaemia: Changing The Treatment Paradigm
Funder
National Health and Medical Research Council
Funding Amount
$1,162,778.00
Summary
Most patients with chronic myeloid leukaemia achieve excellent responses to therapy but need therapy for life. We have pioneered the concept that some patients can cease their therapy and not relapse (treatment free remission –TFR). By studying the immune system and the leukaemic stem cells we will determine why TFR is possible for some, but not all patients. This holds the key to improving the rate of TFR, thus moving the CML goal from disease control to cure.