‘Transcriptional Tumour Suppression’ By Pax5 And Ikaros In B Progenitor Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$558,927.00
Summary
B-progenitor acute lymphoblastic leukaemia (B-ALL) is the most common cancer in children. The genes Pax5 and Ikaros are frequently mutated in B-ALL, but how this contributes to leukaemia development and treatment resistance remains unclear. We have recently produced new B-ALL models driven by reversible suppression of Pax5 or Ikaros activity, and propose to use these models to uncover how these genes control leukaemia differentiation and regression.
Mechanism Of Leukaemia Suppression By The Transcription Factor Ikaros
Funder
National Health and Medical Research Council
Funding Amount
$655,630.00
Summary
A subset of acute lymphoblastic leukaemias are characterised by mutations in the Ikaros gene. These leukaemias respond poorly to chemotherapy and require novel therapeutic approaches. We have discovered a new function of Ikaros in regulating leukaemia cell death. This project investigates how Ikaros regulates cell death and whether this is a general mechanism. Understanding Ikaros function is a step toward improved treatments for this aggressive type of leukaemia.
HIC1 Prevents Tumour Initiation By Maintaining Genomic Stability
Funder
National Health and Medical Research Council
Funding Amount
$531,681.00
Summary
Chromosomes are large structures that package the genome. Abnormalities in the structure and function of chromosomes are now recognised an in important driver of cancer. Using a genetically engineered mouse model this project seeks to understand how this process evolves from the very earliest stages in the evolution of a tumour.
Role Of MACROD2 Loss In DNA Repair, Chromosomal Instability And Development Of Colorectal Cancer: Clinical And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$772,871.00
Summary
The MACROD2 gene is deleted in one-third of human bowel cancers. We have discovered that MACROD2 deletion causes defective DNA repair and tumour chromosomal instability. Here, we will use novel laboratory models to show that MACROD2 loss actively promotes bowel cancer development. We will test the clinical implication of MACROD2 loss for predicting tumour therapy response and will investigate the potential of exploiting this deficiency for drug targeting.
Role Of PTEN Catalytic Function In Suppression Of Cancer And Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$758,319.00
Summary
PTEN mutations are frequently described in various types of cancer. This proposal outlines different experimental strategies to probe how modulation of distinct PTEN functions can affect signalling pathways and be responsible for oncogenic outcomes. We will use animal models and cell lines in culture to identify new signatures/biomarkers to stratifying patients on genetic and molecular bases, and to facilitate the design of tailored combinational therapies directed toward cancer eradication.
Investigation Of The Role Of PI3-kinase In The Regulation Of Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$837,660.00
Summary
The formation of blood vessels is critical for the development of embryos, but also after birth in processes such as wound healing. However, the uncontrolled formation of new blood vessels is also a feature of many human diseases such as cancer, and eye diseases that lead to blindness in adults or in premature infants. We propose to identify new regulators of blood vessel development, in order to improve current treatment therapies for these debilitating diseases.
Tumour Suppressive Mechanisms Of CEBP? And PU.1 In Acute Myeloid Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$497,827.00
Summary
Acute myeloid leukaemia (AML) is an aggressive leukaemia with poor overall responses to therapy. The transcription factors CEBPA and PU.1 are often lost during AML development, and therapies that can restore their normal functions hold great promise. By identifying the genes that these transcription factors regulate in normal and leukaemic white blood cells, this project aims to understand how AML develops and which genes represent rational drug targets for this disease.
Tumour Induced Innate Immune Responses That Control Breast Cancer Metastases
Funder
National Health and Medical Research Council
Funding Amount
$596,164.00
Summary
The mechanisms of breast cancer spread to bone are largely unknown. We have found that cross-talk between tumour cells and the immune system exists to induce anti-tumour immune responses. By decreasing the release of proteins known to activate immune responses (type I interferons), tumour cells can hide from such responses and spread to tissues such as bone. We aim to identify the immune responses activated by type I IFN and if restoration of these pathways can block breast cancer spread to bone ....The mechanisms of breast cancer spread to bone are largely unknown. We have found that cross-talk between tumour cells and the immune system exists to induce anti-tumour immune responses. By decreasing the release of proteins known to activate immune responses (type I interferons), tumour cells can hide from such responses and spread to tissues such as bone. We aim to identify the immune responses activated by type I IFN and if restoration of these pathways can block breast cancer spread to bone.Read moreRead less
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
The Oncogenic Function Of A Histone H3K9 Demethylase And Its Contribution To The Aggressive Malignant Phenotype Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$762,501.00
Summary
In contrast to the significant improvements in the treatment of acute lymphocytic leukaemia, advances in acute myeloid leukaemia (AML) therapy have been limited. The difficulty in treating AML is thought to arise from a drug-resistant subpopulation of leukaemic stem cells (LSC) that are capable of reinitiating disease after chemotherapy. This project will characterise a key regulator of LSC and provide insights into an important oncogenic process that gives rise to the aggressive and often fatal ....In contrast to the significant improvements in the treatment of acute lymphocytic leukaemia, advances in acute myeloid leukaemia (AML) therapy have been limited. The difficulty in treating AML is thought to arise from a drug-resistant subpopulation of leukaemic stem cells (LSC) that are capable of reinitiating disease after chemotherapy. This project will characterise a key regulator of LSC and provide insights into an important oncogenic process that gives rise to the aggressive and often fatal AML.Read moreRead less