Microenvironmental Impact In The Treatment Of Acute Lymphoblastic Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$621,458.00
Summary
Acute lymphoblastic leukemia remains one of the leading causes of death in children and outcomes for adults with this disease remain poor. This project examines how manipulation of the environment where leukemia arises can be used to therpaeutic advancage. Acute lymphoblastic leukemia cells are highly dependent on the support provided by bone marrow cells but the mechanisms are not well understood. Disrupting signals from the bone marrow cells has potential as a therapeutic strategy.
Is Hypoxia Inducible Factor 2 The Trigger Of The Angiogenic Switch And A Driver Of Disease Progression In Myeloma?
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Multiple myeloma (MM) is a fatal cancer of plasma cells (PC). PC migrate to the bone marrow, which compared with other organs is low in oxygen (hypoxic). In response to this hypoxia, the cancer cells turn on the expression of genes called hypoxia-inducible factors (HIF). HIFs activate the expression of genes that encourage blood vessel formation, which in turn stimulates greater tumour growth and disease progression. This proposal will investigate the role of HIFs in the progression of MM.
Harnessing RNA Interference In Gene Therapy Vectors For ?-thalassaemia
Funder
National Health and Medical Research Council
Funding Amount
$719,188.00
Summary
There is an urgent need to develop safe and effective treatments for ?-thalassaemia. We anticipate that ?-globin-specific RNAi sequences will synergise with ?-globin transgene expression to achieve balanced ?-/?-globin ratio in a clinical setting. Given that one of the major issues with current gene therapy vectors is achieving high levels of expression, we believe this will be a more effective gene therapy strategy than ?-globin transgene expression alone.
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.
A Newly Identified Role For 14-3-3zeta Protein In Thrombosis And Platelet Procoagulant Activity
Funder
National Health and Medical Research Council
Funding Amount
$556,327.00
Summary
Cardiovascular disease, including heart attack and stroke is the major cause of death globally, and is responsible for the death of 50,000 Australians each year. Platelet activation and blood coagulation play an important role in these diseases and we have discovered that a protein called 14-3-3 zeta is important in the processes that result in thrombosis. We are studying the mechanisms by which this protein contributes to life-threatening platelet activation with the aim of developing new and m ....Cardiovascular disease, including heart attack and stroke is the major cause of death globally, and is responsible for the death of 50,000 Australians each year. Platelet activation and blood coagulation play an important role in these diseases and we have discovered that a protein called 14-3-3 zeta is important in the processes that result in thrombosis. We are studying the mechanisms by which this protein contributes to life-threatening platelet activation with the aim of developing new and more effective anti-thrombotic drugs.Read moreRead less
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 Zeb2/Sip1 In Leukaemic Stem Cell Formation And Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$655,174.00
Summary
T-cell acute lymphoblastic leukaemia (T-ALL) results from the abnormal development of T cells that are an important cell type in the body's immune system. Although the prognosis for T-ALL has improved remarkably over the last decade, for one out of five T-ALL cases the underlying genetic defects remain unresolved and are refractory to current therapies. This project aims to use both novel mouse models and human patient cell lines to better understand this disease and discover novel targets for f ....T-cell acute lymphoblastic leukaemia (T-ALL) results from the abnormal development of T cells that are an important cell type in the body's immune system. Although the prognosis for T-ALL has improved remarkably over the last decade, for one out of five T-ALL cases the underlying genetic defects remain unresolved and are refractory to current therapies. This project aims to use both novel mouse models and human patient cell lines to better understand this disease and discover novel targets for fighting this disease.Read moreRead less
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.