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.
Regulation Of Platelet Adhesion By The GPIbalpha Cytoplasmic Tail
Funder
National Health and Medical Research Council
Funding Amount
$516,014.00
Summary
Platelets are small blood cells that play an essential role in the normal blood clotting process that stops bleeding following an injury to a blood vessel. In addition to their important role in preventing bleeding, they are also responsible for the development of harmful blood clots which can sometimes result in a fatal outcome in the form of a heart attack or a stroke. When platelets stick to sites of blood vessel injury they must respond very rapidly to ensure the formation of a stable blood ....Platelets are small blood cells that play an essential role in the normal blood clotting process that stops bleeding following an injury to a blood vessel. In addition to their important role in preventing bleeding, they are also responsible for the development of harmful blood clots which can sometimes result in a fatal outcome in the form of a heart attack or a stroke. When platelets stick to sites of blood vessel injury they must respond very rapidly to ensure the formation of a stable blood clot. Our research studies are aimed at understanding more closely the factors that regulate the adhesiveness of platelets, since this is an important deteminant not only in normal blood clot formation but also in the development of harmful blood clots (thrombosis). A better understanding of these processes will add significantly to our knowledge of how blood clotting is controlled. This information is relevant to many human diseases including heart attack and stroke.Read moreRead less
The Biology And Clinical Manifestations Of Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$440,583.00
Summary
I am a haematologist studying the biology and clinical manifestations of chronic myeloid leukaemia with particular reference to the dynamics of response to kinase inhibitor therapy and the causes and clinical management of suboptimal response and drug res
Investigation Of The Role Of The GPIb/V/IX-filamin-1 Interaction In Regulating Platelet Function In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
Platelets play an essential role in blood clotting and blod vessel repair. Upon injury to a blood vessel, platelets rapidly adhere to the area of damage where they undergo dramatic changes in their shape and internal structure that facilitates spreading over the area of injury and subsequent formation of a stable blood clot. Our research studies are aimed at understanding more closely the factors that regulate the adhesiveness of platelets, since this is an important determinant not only in norm ....Platelets play an essential role in blood clotting and blod vessel repair. Upon injury to a blood vessel, platelets rapidly adhere to the area of damage where they undergo dramatic changes in their shape and internal structure that facilitates spreading over the area of injury and subsequent formation of a stable blood clot. Our research studies are aimed at understanding more closely the factors that regulate the adhesiveness of platelets, since this is an important determinant not only in normal blood clot formation but also in the development of harmful blood clots (thrombosis) associated with the development of diseases such as heart attack and stroke. Our particular focus is on the interaction between adhesion receptors on the surface of the platelet and components of the intracellular platelet structure referred to as the cytoskeleton and how this interaction might regulate the reactivity of platelets and their ability to adhere to blood vessels. We believe this may be an important mechanism that regulates platelet adhesion and notmal blood clotting.Read moreRead less
Use Of Retroviral Expression Libraries To Characterise Mechanisms Of Drug Resistance In Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$362,545.00
Summary
At present, treatment of leukaemia is based either on established chemotherapeutic drug treatment or newly identified inhibitor drugs currently being tested as part of clinical trials. Both these treatments are known to induce or select for resistance to the drugs in some cases. Resistance usually reduces the success rate of any further treatment with the same or similar drugs. To discover possible ways of overcoming drug resistance it is important to understand the mechanisms that are responsib ....At present, treatment of leukaemia is based either on established chemotherapeutic drug treatment or newly identified inhibitor drugs currently being tested as part of clinical trials. Both these treatments are known to induce or select for resistance to the drugs in some cases. Resistance usually reduces the success rate of any further treatment with the same or similar drugs. To discover possible ways of overcoming drug resistance it is important to understand the mechanisms that are responsible. To date a number of mechanisms that cause resistance are known, but there are still unidentified mechanisms that are associated with drug resistance. The aim of our work is to use a new method to identify unknown drug resistance mechanisms in leukaemia. Once a mechanism is identified, we will determine its relevance in leukaemia by screening a number of patients that have shown resistance to treatment. If identified as a common mechanism of resistance in leukaemic patients, we will test possible agents able to prevent drug resistance that could be used in conjunction with drug during treatment, and to screen new drugs for susceptibility to resistance mechanisms. Diagnostic tests to detect the presence of the known resistance mechanisms prior to treatment could be used in selection of the most appropriate drug combinations for individual patients. Some of the known drug resistance mechanisms that occur in leukaemia are also operative in other forms of cancer and the project is of general relevance to cancer chemotherapy.Read moreRead less