The Role Of Hox Genes In Myeloid Cell Development And Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$591,286.00
Summary
The transformation of normal white blood cells into leukaemic cells occurs as a result of changes to the genes of those cells. These changes are often characteristic of particular cancers and carry diagnostic and prognostic significance. This work will determine how critical some of the typical genetic changes of leukaemia are to the occurrence and persistence of cancer. Importantly, we will determine whether targeting these changes can provide new and effective approaches to treatment.
Develop New Approaches To Cancer Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$4,000,000.00
Summary
Apoptosis is the dominant focus of our planned studies, because its impairment is both a critical step towards malignancy and a barrier to effective treatment. Arguably, the laboratory heads within our division and our collaborators from the Structure Biology Division at WEHI constitute the world’s strongest group with this focus. Our accumulated experience in this field from its renaissance in 1988 and the many unique materials they have created superbly position us to answer the fundamental qu ....Apoptosis is the dominant focus of our planned studies, because its impairment is both a critical step towards malignancy and a barrier to effective treatment. Arguably, the laboratory heads within our division and our collaborators from the Structure Biology Division at WEHI constitute the world’s strongest group with this focus. Our accumulated experience in this field from its renaissance in 1988 and the many unique materials they have created superbly position us to answer the fundamental questions and translate them into new therapeutic approaches. Our team’s second focus, the links of stem cells to cancer, is also of great importance, because the rare stem cells in the tumour may dictate therapeutic outcome. This Fellowship aims to addresses fundamental issues with enormous potential for medicine. It builds on productive ongoing research by a team with diverse complementary expertise, a record of effective interaction, high momentum and a history of path-breaking discoveries. I plan to maintain and further develop our Division (the Molecular Genetics of Cancer Division at WEHI) as one of the strongest teams for cancer research and development of cancer therapies in the world. Our division contains several laboratories that are highly interactive and complimentary in their approaches and research interests. I plan to strengthen the already highly productive laboratories in our division and to develop some new ones (see below under ‘proposed team’). I plan to increase work of our division to also include studies on other solid tumours (e.g. colon cancer, lung cancer, prostate cancer). This Fellowships aims to greatly enhance cancer research and hopefully also clinical practice in Australia. This should enhance the reputation of Australia as a country with recognized excellence in medical research and clinical practice. I am also confident that our division will continue to educate outstanding PhD graduates and postdoctoral fellows who will in due course become independent researchers and develop into future leaders in medical research in Australia and-or overseas.Read moreRead less
The Role Of The PRB/E2F Pathway In Erythropoiesis And Cell Cycle Control
Funder
National Health and Medical Research Council
Funding Amount
$272,036.00
Summary
Circulating blood contains two major types of cells. Red blood cells supply the oxygen required by all cells in our body to survive and white blood cells protect our body from invasion by foreign organisms. The balance in the number of these cells in our blood is a carefully regulated process which, when disturbed, can lead to a number of life-threatening blood diseases. Uncontrolled overgrowth of blood cells results in a particular type of cancer known as leukaemia. In contrast, when there is a ....Circulating blood contains two major types of cells. Red blood cells supply the oxygen required by all cells in our body to survive and white blood cells protect our body from invasion by foreign organisms. The balance in the number of these cells in our blood is a carefully regulated process which, when disturbed, can lead to a number of life-threatening blood diseases. Uncontrolled overgrowth of blood cells results in a particular type of cancer known as leukaemia. In contrast, when there is an insufficient number of red blood cells, not enough oxygen reaches cells from the brain and other vital organs and results in a condition known as anaemia. We have genetically engineered a mouse that lack the protein known as E2F4 and is unable to produce enough red blood cells and suffers from anaemia. This protein, E2F4, controls genes essential for the decision of cells to start or stop growing and multiplying. The E2F4-deficient mice therefore provide a new and powerful model to understand the mechanism by which disturbance of red blood cell numbers can lead to diseases such as leukaemia and other diseases of the blood. Identification of the genes controlled by E2F4 may provide new targets for the development of therapeutic drugs to combat these diseases.Read moreRead less
Interactions Between Transcription Factor Networks And Cell Signaling Pathways During Early Blood Development
Funder
National Health and Medical Research Council
Funding Amount
$589,338.00
Summary
Cancer initiating cells acquire stem cell characteristics and self renew within a supportive environment that helps maintain and propagate malignant tumours. Identifying the normal hierarchy of gene regulation within blood stem cells and designing therapies that target key transcription factors (proteins that control other genes) that are over expressed in cancer stem cells is the ultimate goal.
Throughout our lives cells must die and be replenished. One way multicellular organisms remove unwanted cells is through a process called programmed cell death. This process eliminates redundant, damaged or infected cells by a program of cell suicide. We are studying the underlying molecular mechanisms of this cell suicide in order to design new pharmaceuticals to treat illnesses caused by a disruption in programmed cell death. The fine balance between living and dying cells must be maintained a ....Throughout our lives cells must die and be replenished. One way multicellular organisms remove unwanted cells is through a process called programmed cell death. This process eliminates redundant, damaged or infected cells by a program of cell suicide. We are studying the underlying molecular mechanisms of this cell suicide in order to design new pharmaceuticals to treat illnesses caused by a disruption in programmed cell death. The fine balance between living and dying cells must be maintained and if this balance is lost then disease may result. A reduced level of cell death may result in cancers while too many dying can contribute to degenerative diseases such as Alzheimer's disease and stroke. Currently many of these diseases do not have effective treatments. We will determine the three-dimensional structures of key proteins involved in programmed cell death and use this information to design drugs that can interfere with the molecular processes involved in signalling cell death. Such drugs may prove useful new therapies in a wide range of diseases caused by a breakdown in the biochemical paths to cell death.Read moreRead less
Characterisation Of Novel Regulators Of The Haemopoeitic System.
Funder
National Health and Medical Research Council
Funding Amount
$381,680.00
Summary
All of the circulating blood cells (including red cells and white cells) develop from a single cell type, called the haemopoietic stem cell (HSC), found in the adult bone marrow. Normally, HSCs are gradually restricted to become only one cell type and once they have started down that pathway can no longer generate cells of another pathway (e.g. once HSC begin to develop into red blood cells, they cannot normally change their direction to become white cells). There are a few examples of mature ce ....All of the circulating blood cells (including red cells and white cells) develop from a single cell type, called the haemopoietic stem cell (HSC), found in the adult bone marrow. Normally, HSCs are gradually restricted to become only one cell type and once they have started down that pathway can no longer generate cells of another pathway (e.g. once HSC begin to develop into red blood cells, they cannot normally change their direction to become white cells). There are a few examples of mature cells, however, that have changed pathways. We have use one of these, the mouse J2E red cell changing into macrophages, to identify the genes involved in this process. Two of the genes we found, HLS5 and HLS7, are potentially important in lineage determination and normal blood development as well as the formation of blood cancers. This project aims to investigate the roles these genes play in blood development. Much of our work to date has focused on HLS7. The human equivalent of HLS7 was found by an American group independently of us as a gene which causes one type of blood cancer. We have shown HLS7 has dramatic effects on normal blood development and, together, these results clearly show the importance of this gene. Through our studies on how HLS7 works, we have identified another gene, M44, which may be important in regulation of HLS7 and also plan to investigate is function. Finally, HLS5 has similarities to a group of molecules called transcription factors which are known to be key regulators blood development. Clearly, analysis of this gene will further our knowledge in this field.Read moreRead less
Transcriptional Regulation Of Haematopoietic Stem Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$566,470.00
Summary
Cancer initiating cells acquire stem cell characteristics and self renew within a supportive environment that helps maintain and propagate malignant tumours. Identifying the normal hierarchy of gene regulation within blood stem cells and designing therapies that target key transcription factors (proteins that control other genes) that are over expressed in cancer stem cells is the ultimate goal.