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Myelodysplastic Syndrome And The Bone Marrow Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$562,654.00
Summary
We are interested in how myelodysplastic syndrome (MDS) affects the function of the bone marrow. We believe that changes associated with anaemia of MDS cause the bone marrow to be altered. This proposal addresses this question and explores new treatment approaches
Translation Of Genomic Findings To Improve Outcomes In Patients With Myeloid Blood Cancers
Funder
National Health and Medical Research Council
Funding Amount
$1,913,403.00
Summary
Changes within the DNA of blood cancer cells are responsible for causing cancer, but also control the progression through various stages of blood cancers and regulate the response of patients to treatment. It is fundamentally important to not only understand these genetic changes at the molecular level, but also to use these findings to rationally design clinical treatments that target these genetic changes to improve outcomes for patients with blood cancers.
Clonal Evolution In Myelodysplasia And Acute Myeloid Leukaemia Following Azacitidine
Funder
National Health and Medical Research Council
Funding Amount
$853,005.00
Summary
The myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) represent a spectrum of clinically heterogeneous malignancies that remain incurable in the vast majority of patients. Whilst the DNA mutations underpinning the initiation/maintenance of these malignancies are largely known we have little insight into how these mutations alter response to therapy. Using a range of sophisticated cutting edge technologies we will study how these DNA mutations evolve over the course of treatment.
Curing Blood Cancers: Rapid Translation From Target To Drug To Clinic
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Cure rates for many blood cancers have not improved over the last 20 years. We will use patient samples and mouse models of blood cancers to identify and test novel therapies. In particular, we will test the efficacy of a new drug developed by my laboratory in conjunction with a large team of Australian chemists. In collaboration with MERCK, this work will be the prelude to the first human trials in 2018. If successful, this will provide new hope for cure of a broad range of blood cancers.
A Novel Molecular Mechanism Controlling Myelopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$878,439.00
Summary
The immune system is comprised of many different cell types, each with a specialised function. Many are short-lived and must be continually replenished throughout life. Abnormalities in this process underlie many human diseases, including immunodeficiency, autoimmunity and cancer. We have discovered a novel molecular mechanism that is critical for the production of immune cells. This project will investigate how this mechanism is controlled and the impacts on myelodysplastic syndromes.
Anaemia In The Elderly: Epidemiology, Causes, Consequences And Optimal Transfusion Strategies
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Anaemia in the elderly (AE) is a common and increasing issue, which is often treated with blood transfusions. This project aims to investigate the causes and risk factors of patients who develop AE, and the impact of AE on health outcomes. The results will help define appropriate haemoglobin thresholds for AE, and provide information to develop appropriate guidelines for AE and transfusion management in the elderly.
Investigating The Molecular Basis For Drug Resistance And Disease Relapse In Myelodysplastic Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$722,557.00
Summary
Myelodysplastic Syndromes (MDS) are a group of blood stem cell disorders that result in low blood counts and leukemia especially in the elderly. Azacitidine (AZA) is a drug that improves blood counts and delays progression to leukemia and is the treatment of choice. However, only half the patients treated with AZA ever respond and half of the responders relapse within a year. We will describe the origins of MDS and the basis for drug response, resistance and disease relapse.
Regulation Of Red Blood Cell And Platelet Formation By BHLH Proteins
Funder
National Health and Medical Research Council
Funding Amount
$422,600.00
Summary
Continuous production of normal blood cells by the bone marrow is a process critical to human life. Disruption of this process leads to diseases such as leukemia, aplastic anemia and myelodysplasia which have devastating consequences for affected patients. Pivotal to understanding these diseases is a knowledge of the regulation of normal blood production. Our laboratory works on a gene known as SCL that is critical for blood formation. We have recently shown that loss of SCL in adult bone marrow ....Continuous production of normal blood cells by the bone marrow is a process critical to human life. Disruption of this process leads to diseases such as leukemia, aplastic anemia and myelodysplasia which have devastating consequences for affected patients. Pivotal to understanding these diseases is a knowledge of the regulation of normal blood production. Our laboratory works on a gene known as SCL that is critical for blood formation. We have recently shown that loss of SCL in adult bone marrow leads to abnormalities in two types of blood cells, the red blood cells and the platelets. This grant will extend this important observation to understand how the production of these cells is altered and what is its consequence. Our studies will help clarify the basis of blood cell formation and may impact on how we diagnose and treat a wide variety of blood disorders.Read moreRead less
Myelodysplastic syndromes (MDS) are disorders of blood-forming stem cells characterised by low blood counts and progression to acute leukaemia. Epigenetics refers to changes in gene expression without changing the underlying DNA sequence. More than half of MDS have mutation/s in epigenetic regulators, providing evidence that epigenetics is an important contributor to the disease. The goal of this project is to better understand how epigenetics contribute to MDS and discovery of new therapies.
Molecular Analysis Of Myelodysplasia In The Nup98HoxD13 Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$351,502.00
Summary
Myelodysplastic syndrome is a preleukemic condition which is poorly understood and occuring at an increasing frequency. Unfortunately no targeted therapy exists. Two features of the disease are abnormal gene expression and abnormal cell death. We have a uniquely accurate model of this disease, and we plan to use it to investigate these two phenomena which will lead to greater understanding of the disease and new molecular targets for therapeutic agents to be developed and tested in our model.