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.
Molecular Regulation Of Haematopoiesis In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
The blood forming system coordinates production of cells that confer immunity to infection, transport oxygen and assist blood clotting. When the molecular mechanisms that control these functions go awry, diseases including leukaemia and autoimmunity result. This research will define fundamental molecular regulators of blood cell production and function, assess their role in blood cell diseases and explore their potential to provide leads for development of new therapeutics.
Assemble A Cross-disciplinary Team With Requisite Skill To Uncover New Molecular Pathways Regulating Haemopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$2,448,475.00
Summary
The major preoccupation of biology in the last decade has been the sequencing of the genomes of humans and important animal, plant, bacterial and viral organisms. With the completion of these projects, focus has shifted to understanding the molecular networks that regulate the biochemical, cellular and physiological processes that maintain health and the changes to these networks that lead to the onset and progression of disease. Within this fluid research landscape, my principal career goal ove ....The major preoccupation of biology in the last decade has been the sequencing of the genomes of humans and important animal, plant, bacterial and viral organisms. With the completion of these projects, focus has shifted to understanding the molecular networks that regulate the biochemical, cellular and physiological processes that maintain health and the changes to these networks that lead to the onset and progression of disease. Within this fluid research landscape, my principal career goal over the next 5 years is to ensure that, during a period of generational change at WEHI, its iconic molecular haematology team continues to flourish. Realizing this goal will allow us to use knowledge of the molecular determinants of health and disease to improve clinical outcomes of poorly treated conditions and in doing so improve the lives of patients and the health of the Australian economy.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
Dissecting The Role Of The IL-3 Receptor Alpha Subunit And Beta-catenin In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$583,312.00
Summary
Leukaemia is a devastating form of blood cancer affecting both young and old. We aim to understand the mechanisms of uncontrolled cell growth associated with acute myeloid leukaemia. We focus on the role of key growth regulators that are abnormally active in the critical leukaemia stem cells. Understanding the biological and molecular properties of these cells is of considerable importance for development of the next generation of leukaemia therapies.
Dissecting FLT3 Signalling In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$498,328.00
Summary
Each year approximately 6000 Australian adults and children are diagnosed with leukaemia, lymphoma or a related blood disorder, accounting for about 15% of all cancers. Acute Myeloid Leukaemia (AML) is the most common form of leukaemia in adults resulting from an accumulation of immature myeloid cells in the bone marrow and peripheral blood as a result of sustained, abnormal cell growth and survival together with a block in normal blood cell formation. There is still a major research effort aime ....Each year approximately 6000 Australian adults and children are diagnosed with leukaemia, lymphoma or a related blood disorder, accounting for about 15% of all cancers. Acute Myeloid Leukaemia (AML) is the most common form of leukaemia in adults resulting from an accumulation of immature myeloid cells in the bone marrow and peripheral blood as a result of sustained, abnormal cell growth and survival together with a block in normal blood cell formation. There is still a major research effort aimed at understanding the mechanisms that lead to AML formation and it is clear that multiple AML oncogenes and tumour suppressors remain to be identified. Identification of further events involved in AML is important as it will provide avenues for more specific and less toxic treatments. These are needed because current success rates for AML remain relatively poor. It is critical that research into the understanding of the pathways and events involved in AML keeps pace with the rapid development of new approaches for therapeutic agents. Together this will greatly increase the scope for therapeutic intervention over the next decade. In this application we investigate the role of a new molecular pathway in AML. Our studies have identified a gene of particular interest that we propose normally prevents AML formation and therefore is frequently turned off by the cellular changes that lead to AML. We propose that silencing of this gene is particularly important in those AML cases which have mutations in the cell surface receptor FLT3 (about 30% of AML cases). We will use a number of molecular and cell biology approaches to manipulate this gene in mouse cell lines, normal mouse cells and human AML cells. A better understanding of the role of this gene and the associated pathway involving FLT3 may generate new leads for therapeutic approaches.Read moreRead less
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.