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.
We want to understand more about the control of blood cell formation and the development of leukemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukemia, and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to take these observations further so that we can ultimately understand how a gene important in blood cell formati ....We want to understand more about the control of blood cell formation and the development of leukemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukemia, and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to take these observations further so that we can ultimately understand how a gene important in blood cell formation can also be important in causing leukemia. Here we propose to use genetic engineering approaches to generate mice in which the function of this gene is ablated or removed in a controlled and regulated fashion.Read moreRead less
Analysis Of The Hematopoietic Function Of Endophilin And MASH Proteins
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
We want to understand more about the control of blood cell formation and the development of leukaemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukaemia and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to understand how a gene important in blood cell formation can also be important in causing leukaemia. To address ....We want to understand more about the control of blood cell formation and the development of leukaemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukaemia and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to understand how a gene important in blood cell formation can also be important in causing leukaemia. To address this we will study a new molecule with which it partners, and two molecules via which it exerts its actions.Read moreRead less
Molecular Regulation Of Blood Cell Production And Function
Funder
National Health and Medical Research Council
Funding Amount
$18,333,174.00
Summary
The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinica ....The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinical strategies for fighting these lethal diseases. This program is conducted by a large, established team of investigators that have made world-class contributions to understanding blood cell formation and function for more than 30 years. Their work established the modern era of molecular haematology via discovery and analysis of blood cell hormones (colony-stimulating factors or CSFs), their receptors and intracellular mediators, which resulted in development of treatments for millions of cancer patients. The program is a multidisciplinary, team approach to fundamental biological questions with a focus on potential clinical and commercial outcomes involving collaborations with clinical medicine and the pharmaceutical industry. Research will focus on meshing novel genetic approaches in mice with translation studies in humans to identify new validated targets for therapeutic intervention in blood cell diseases, as well as building on the team s expertise in cytokine action with emphasis on the actions of the suppressor of cytokine signalling (SOCS) molecules, a key family of proteins that controls cytokine actions.Read moreRead less