Identification Of A New Thrombosis Mechanism Triggered By Dying Platelets
Funder
National Health and Medical Research Council
Funding Amount
$608,742.00
Summary
A severe reduction in blood flow (ischemia) to the intestines can trigger blood clot formation (thrombosis) in multiple organs, including the lungs. We have identified a new thrombosis mechanism that is triggered by the clumping of white blood cells in the intestines, leading to widespread thrombosis in the lung. Here we will investigate the mechanisms triggering this thrombosis mechanism with the ultimate aim of identifying more effective antithrombotic approaches.
Investigation Of A New Leukocyte Recruitment Mechanism At Sites Of Vascular Injury
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
Blood clots formed at sites of small vessel injury can cause damage of vital organs by obstructing blood flow and promoting a proinflammatory response by efficiently recruiting and activating leukocytes. The molecular mechanisms responsible for the latter event are poorly defined. We have established a new mouse model, gained novel insights into the leukocyte recruitment by blood clots, and aim to define the precise mechanism for this process in this application.
Microparticles Are Pathogenic Elements In The Pathophysiology Of Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$605,205.00
Summary
Cerebral malaria (CM) is still a world health problem. We aim to better understand its mechanisms by deciphering the role of small blood elements called microparticles (MP). We discovered elevated numbers of MP in CM patients and demonstrated that preventing MP overproduction in mice protects against this fatal disease. Our research will investigate the mechanisms of action and the fate of MP in the blood vessels during CM and allow us to identify strategies for patientÍs treatment and care.
Regulation Of Megakaryocyte And Platelet Survival In Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$536,914.00
Summary
In this grant we will investigate how blood cells called platelets are produced in normal conditions and during disease. Platelets are blood cells that stop us from bleeding when we get a cut. When too many platelets accumulate, there is an increased risk of blood clots forming. This project grant will help us learn how platelet numbers swell in response to some blood and ovarian cancers, and the mechanisms that control cell death in platelets and the cells that produce them.
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.
Regulation Of Receptors That Control Platelet Function Under Shear Stress
Funder
National Health and Medical Research Council
Funding Amount
$507,273.00
Summary
Specialized human blood cells that control blood loss and clotting (platelets) are currently difficult to test in the clinical laboratory, meaning patients are at risk of excessive bleeding or serious clot formation during disease or treatment. The aim of this proposal is to use our new reagents and assays to develop more reliable methods for evaluating relative bleeding or clotting risk in individuals.
Defining The Function Of The Thrombin Receptor, PAR4, On Human Platelets
Funder
National Health and Medical Research Council
Funding Amount
$541,402.00
Summary
Inappropriate blood clot formation is the cause of most heart attacks and strokes, and platelets are the cells in the blood which form these clots. Drugs that block platelet function, such as aspirin, are used to prevent heart attack and stroke but are frequently ineffective. We will study the signals which control platelet incorporation into clots in order to discover improved therapeutic strategies for heart attack and stroke prevention.
Heparin-induced Thrombocytopenia And Thrombosis: Better Understanding Of Pathogenesis And Improving Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$653,137.00
Summary
Heparin, a widely used drug, can cause an adverse effect which results in a fall of the platelet count and the development of serious thrombosis. This drug complication is mediated by an immune mechanism. This proposal aims to provide a better understanding of the disease mechanism. It also aims to develop a new test that will improve the diagnosis, and to produce a novel drug that will effectively suppress the immune reaction and improve the treatment.
Activated Platelets As Unique Targets For Early Imaging And Site-directed Therapy Of Cardiovascular And Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$846,979.00
Summary
Heart attack and inflammatory diseases such as rheumatoid arthritis und multiple sclerosis either kill or severely disable people. We use the presence of platelets early on in these diseases to develop methods for early diagnosis as well as potential drugs for site-directed therapy. We have developed new biotechnological tools to perform novel high sensitivity imaging in Positron Emission Tomography (PET) and laser light imaging as well as a localised anti-inflammatory therapy.
Investigating The Formation And Utility Of The Prenatal Platelet Forming System
Funder
National Health and Medical Research Council
Funding Amount
$793,442.00
Summary
A major challenge to regenerative medicine is discovering how to produce useful cell types in the laboratory. Particularly urgent is the need to generate large numbers of platelets, the building blocks of the clotting system, for clinical use. Current laboratory methods are woefully inefficient, thus cannot meet demand. This project aims to discover how platelets are made in nature. With this information we will be able to devise better platelet production strategies in the laboratory.