To Determine The Means By Which Plasminogen Activators Modulate Integrity Of The Blood Brain Barrier
Funder
National Health and Medical Research Council
Funding Amount
$523,084.00
Summary
Tissue-type plasminogen activator (t-PA) is used clinically to remove blood clots. However, t-PA can also cause brain injury and influence the blood brain barrier (BBB) which has implications for the treatment of patients with ischaemic stroke. This project will use in vitro and in vivo models to understand the mechanism by which t-PA modulates the BBB. A novel tPA variant will also be created that ultimately may be of benefit for patients with ischaemic stroke.
Molecular Analysis Of Myelodysplasia In The Nup98HoxD13 Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$351,502.00
Summary
Myelodysplastic syndrome is a preleukemic condition which is poorly understood and occuring at an increasing frequency. Unfortunately no targeted therapy exists. Two features of the disease are abnormal gene expression and abnormal cell death. We have a uniquely accurate model of this disease, and we plan to use it to investigate these two phenomena which will lead to greater understanding of the disease and new molecular targets for therapeutic agents to be developed and tested in our model.
Characterisation Of CBF Acute Myeloid Leukaemia By MicroRNA Profiling
Funder
National Health and Medical Research Council
Funding Amount
$118,956.00
Summary
Recent studies have demonstrated the existence of small pieces of previously undescribed genetic material, known as microRNAs (miRNAs), which are thought to have critical functions across various biological processes and regulatory pathways in cells. This project aims to examine the role of these miRNAs in the development of abnormal cellular proliferation that leads to leukaemia, by examining the expression of all known miRNAs in the abnormal cells of our patients with leukaemia.
Molecular Pathways Mediating Quiescence And Resistance In Leukaemia Stem Cells In Acute Myeloid Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$100,381.00
Summary
Acute myeloid leukaemia (AML) is a devastating cancer of the blood and bone marrow which is rapidly fatal unless effectively treated with chemotherapy. AML is caused by genetic events that alter normal blood stem cells to give them a growth and survival advantage and also may confer resistance to chemotherapy in some cases. We will evaluate and target the mechanism of this resistance in laboratory models. This information can then be used to design new treatments to improve outcomes in AML.
The mechanisms regulating expression and function of surface receptors on blood platelets are critical for understanding cardiovascular diseases involving aberrant platelet function, not only thrombotic diseases such as heart attack or stroke, but other pathology involving platelets including coagulopathy and autoimmune thrombocytopenia caused by anti-platelet antibodies. Improved diagnosis and therapeutic targeting of platelet-specific receptors mediating arterial thrombosis can save many lives ....The mechanisms regulating expression and function of surface receptors on blood platelets are critical for understanding cardiovascular diseases involving aberrant platelet function, not only thrombotic diseases such as heart attack or stroke, but other pathology involving platelets including coagulopathy and autoimmune thrombocytopenia caused by anti-platelet antibodies. Improved diagnosis and therapeutic targeting of platelet-specific receptors mediating arterial thrombosis can save many lives given the prevalence and severity of disease.Read moreRead less
Eradicating Leukaemic Stem Cells By Targeting The Arginine Methyltransferase PRMT5
Funder
National Health and Medical Research Council
Funding Amount
$770,950.00
Summary
Acute leukemia is a devastating cancer arising from primitive cells in the bone marrow called stem cells. We have identified a protein (PRMT5) that is highly expressed in leukemia stem cells. Our preliminary experiments suggest that blocking the function of this protein with a novel drug can stop the growth of these cells. This project will use a variety of mouse models of acute leukemia to determine how PRMT5 keeps stem cells alive and whether this drug will be a valuable new treatment.
Investigating A Potential New Treatment For Stroke
Funder
National Health and Medical Research Council
Funding Amount
$878,522.00
Summary
Blood clots blocking blood flow to the brain (stroke) are a major cause of death and disability. Safety concerns limit approved therapies to a small subset of patients, highlighting an urgent need for safer, more effective drugs. Our studies show that inhibitors of the enzyme PI3Kbeta increase blood clot permeability, increasing clot ‘dissolvability’, without increased bleeding. This raises the possibility that PI3Kbeta inhibitors may represent a safe and effective adjuvant therapy for stroke.