Pre-hospital Antifibrinolytics For Traumatic Coagulopathy And Haemorrhage (The PATCH Study)
Funder
National Health and Medical Research Council
Funding Amount
$1,668,152.00
Summary
About 2500 Australians die annually from severe injuries. Bleeding is exacerbated by early-onset clotting defects, which are associated with high mortality. The antifibrinolytic agent tranexamic acid has been shown to reduce mortality due to bleeding when given in hospital in less developed trauma systems, but its usefulness as a pre-emptive strike at the scene of injury in developed systems is unknown. Building on our prehospital clinical trials expertise, we will conduct a trial to assess its ....About 2500 Australians die annually from severe injuries. Bleeding is exacerbated by early-onset clotting defects, which are associated with high mortality. The antifibrinolytic agent tranexamic acid has been shown to reduce mortality due to bleeding when given in hospital in less developed trauma systems, but its usefulness as a pre-emptive strike at the scene of injury in developed systems is unknown. Building on our prehospital clinical trials expertise, we will conduct a trial to assess its effect on 6-month death and disability.Read moreRead less
Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.
Development Of Reversible Inhibitors Of Factor XIa
Funder
National Health and Medical Research Council
Funding Amount
$444,318.00
Summary
Blood usually clots in response to injury, but unwanted clots can cause thrombosis, as well as leading to stroke and heart disease. Existing drugs to treat thrombosis suffer from drawbacks such as invasive monitoring, interaction with diet and other medicines, and bleeding complications. New drugs are clearly needed. Our expert group of researchers will discover new anti-thrombotic compounds based upon our previous identification of natural products with anticoagulant properties.
A Newly Identified Role For 14-3-3zeta Protein In Thrombosis And Platelet Procoagulant Activity
Funder
National Health and Medical Research Council
Funding Amount
$556,327.00
Summary
Cardiovascular disease, including heart attack and stroke is the major cause of death globally, and is responsible for the death of 50,000 Australians each year. Platelet activation and blood coagulation play an important role in these diseases and we have discovered that a protein called 14-3-3 zeta is important in the processes that result in thrombosis. We are studying the mechanisms by which this protein contributes to life-threatening platelet activation with the aim of developing new and m ....Cardiovascular disease, including heart attack and stroke is the major cause of death globally, and is responsible for the death of 50,000 Australians each year. Platelet activation and blood coagulation play an important role in these diseases and we have discovered that a protein called 14-3-3 zeta is important in the processes that result in thrombosis. We are studying the mechanisms by which this protein contributes to life-threatening platelet activation with the aim of developing new and more effective anti-thrombotic drugs.Read moreRead less
RZR-alpha In The Control Of Proliferative Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$521,706.00
Summary
Four million Australians have cardiovascular disease accounting for 35% of all deaths. CVD is the most expensive disease burden and a National Health Priority. Smooth muscle cell growth is a cause of CVD. However, the mechanisms controlling SMC hyperplasia are poorly understood. This project will provide key insights on the role of RZR-alpha in the pathogenesis of blood vessel disease, and develop novel gene-targeting approaches for new opportunities to control complications of CVD.
Therapeutic Potential Of Transforming Growth Factor-beta Proteins For The Diagnosis And Treatment Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$942,961.00
Summary
We discovered and manufactured a growth factor produced uniquely by the egg. We named this growth factor cumulin. It is a powerful regulator of ovarian function and egg quality. This project will study the basic mechanisms of how cumulin works in the ovary. We will then develop an assay to measure it as a biomarker of human egg quality and quantity. New approaches in fertility preservation for cancer survivors will be developed using cumulin.
Mapping The TNF Pathway: A Qualitative And Quantative Molecular Analysis Of The Components And Post-translational Modifications Involved In Physiological And Pathological TNFR1 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$636,258.00
Summary
TNF is a master regulator of the inflammation response and dysregulated TNF signalling causes many human diseases. We will use a cutting edge mass spectrometry technique that we have developed to analyse molecules required for TNF signalling. Understanding how the TNF signalling works in all cell types and with different forms of ligands will open up therapeutic opportunities to selectively target TNF signalling in inflammatory diseases, such as Rheumatoid Arthritis and Cancer.
Activation Of GDF9 Regulates Human Folliculogenesis
Funder
National Health and Medical Research Council
Funding Amount
$531,690.00
Summary
GDF9 is a key regulator of fertility in female mammals, as it controls the process of folliculogenesis. In this grant, we will demonstrate the importance of GDF9 in human folliculogenesis, determine the mechanisms that activate GDF9 and show why aberrant GDF9 activation leads to ovarian disorders. Collectively, the outcomes of this proposal will increase our understanding of the fundamental mechanisms that regulate ovarian folliculogenesis and provide new avenues to manipulate this process.
Characterising Signals Important For Lymphangiogenesis During Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$604,938.00
Summary
Lymphatic vessels are a vital component of the cardiovascular system. Abnormalities in the growth and development of lymphatic vessels are associated with human disorders including cancer, lymphoedema and inflammatory diseases. The focus of this application is to characterise signals that direct the construction of lymphatic vessels, with the aim of identifying targets to which novel therapeutics for the treatment of lymphatic vascular diseases could be generated.
We will investigate how the master control gene, Kruppel-like factor 1, orchestrates production of red blood cells. We will use genetic and cell biology approaches to determine exactly how this factor interprets the genome blueprint in a cell specific manner. We will also determine how mutations in KLF1 cause human diseases such as congenital dyserythropoietic anemia and hereditary persistence of fetal haemoglobin. This has implications for reactivation of HbF in adults with sickle cell disease.