Investigation Of Activating Signals Transmitted During Platelet Aggregation
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
The blood platelet is a specialized adhesive cell that plays a critical role in the normal blood clotting process through its ability to rapidly adhere to sites of vascular damage. Upon injury to a blood vessel, platelets undergo a number of internal signalling process and strucural changes that allow them to rapidly adhere to the area of damage. Following this initial adhesion process, platelet-platelet interactions occur leading to the development of a stable blood clot. Our research studies a ....The blood platelet is a specialized adhesive cell that plays a critical role in the normal blood clotting process through its ability to rapidly adhere to sites of vascular damage. Upon injury to a blood vessel, platelets undergo a number of internal signalling process and strucural changes that allow them to rapidly adhere to the area of damage. Following this initial adhesion process, platelet-platelet interactions occur leading to the development of a stable blood clot. Our research studies are aimed at understanding more closely the factors that regulate platelet-platelet interactions during the course of blood clot formation, since this is an important determinant not only of normal clot formation, but also in the development of harmful blood clots (thrombi) associated with the onset of diseases such as heart attack and stroke. Our particular focus is on the way in which platelets communicate to one another during the course of platelet thrombus development. Particulary, we are interested in the role of calcium as a signal mediating platelet-platelet communication. We believe that the transmission of these calcium signals may be the key signaling mediator of blood clot formation and normal haemostasis.Read moreRead less
My research focuses on understanding the molecular regulation of blood cell production and function in health and disease with the ultimate goal of discovery of new treatments for blood cell diseases including leukaemia and autoimmunity.
Tetraspanins Serve As Molecular Facilitators To Regulate Platelet Thrombus Formation
Funder
National Health and Medical Research Council
Funding Amount
$589,544.00
Summary
Platelets are small fragments of megakaryocytes that circulate in the blood stream. They play an important role in preventing excessive blood loss at sites of tissue injury by sticking together and forming a haemostatic plug. Excessive platelet clumping in diseased blood vessels can lead to blockages and cause thrombotic diseases such as heart attack and stroke. We have discovered that tetraspanins serve to regulate platelet glycoproteins including integrin alphaIIbbeta, P2Y12 and thrombosis.
We propose to use a number of genetic approaches to identify key mutations involved in Polycythemia vera. We will analyse patient material, use cell lines and mouse models to investigate any new mutations. We also aim to dissect the role of an important blood cell surface receptor and its cooperation with the mutation in JAK2 recently shown to be important in this disease. These approaches will lead to better understanding of the disease and potential new diagnostic and drug strategies.
The Role Of Ap2a2 In Self-renewal Of Haematopoietic And Leukemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$579,171.00
Summary
The daily replenishment of the blood system is dependent on the blood stem cell. A unique property of these stem cells is self-renewal where the stem cell function is preserved, whilst other daughter cells continue to divide. Our research investigates the molecular mechanisms that regulate stem cell self-renewal. This work has potential clinical application on at least two levels: expansion of stem cells for transplantation, and for attacking abnormal cancer cell self-renewal pathways.
Role Of The Hypoxia-inducible Transcription Factor HIF-1a In Controlling Haematopoietic Stem Cell Fate
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
Haematopoietic stem cells (HSCs) reside in the bone marrow (BM) and make all immune and blood cells. We have found that, in the areas of the BM where HSC normally live, the level of oxygen is very low (hypoxia) and decreases even further when HSC are forced to move into the blood in order to be collected for transplantation. This project is to better understand how oxygenation of the BM controls HSC behaviour and properties, and to evaluate its impact on HSC transplantation.