Role Of ZEB/NuRD Interactions In Haematopoiesis And Lymphoid Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$810,497.00
Summary
Cancers of the blood arise from (epi)genetic changes that enable blood cells to bypass normal survival and growth checkpoints, leading to accumulation of additional mutations that drive full-scale transformation. This grant aims to understand the role of specific transcription factors (that control disease causing genes to be expressed) and how we can use a novel class of epigenetic drugs together with inhibition of these factors to selectively get rid of cancer causing blood cells in the body.
Developing Mouse Models Of Diffuse Large B Cell Lymphoma For Therapeutic Discovery
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Diffuse large B cell lymphomas are aggressive cancers of white blood cells. Gene mutations play significant yet poorly understood roles in the cause of these lymphomas and their resistance to drug treatments. I plan to develop new mouse models of lymphoma to identify factors that cause lymphoma to develop in living organisms and factors that cause them to resist drug treatment. I will also test if combinations of multiple drugs can effectively and safely treat these lymphomas.
Roles Of The EMT Transcription Factors In Epigenetic Remodelling And Myeloid Cell Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$809,520.00
Summary
This project is based upon our novel discoveries that identified ZEB2 and SNAI1 as novel genes involved in the development of aggressive forms of blood cancer. During the course of this proposal we will find new drug targets and new drug treatment options using existing drugs that will specifically target cancer initiating cells in order to kill aggressive forms of blood cancers that are currently refractory to treatment.
‘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.
Role Of Erg In B-cell Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$749,034.00
Summary
Acute lymphoblastic leukaemia (ALL) is a lethal blood cancer for which current treatments are suboptimal. Over-expression of the ERG gene has been associated with the poor prognosis B cell ALL called Ph+ B-ALL. We have recently shown that loss of Erg prevents disease development in disease models. We hypothesise that expression of ERG is a key driver of Ph+ B-ALL and propose to define this role and identify new opportunities for development of specific novel therapeutics.
Transposon Mutagenesis For Discovery Of Disease Causing Genes And Their Cooperative Interactions In Acute Myeloid Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$659,302.00
Summary
The emergence of cancer is caused by multiple mutations in normal cells. Recent progress has allowed the detection of virtually all mutations in a cancer genome. Although this has been enormous progress, it has become increasingly evident that only rare mutations are responsible for sustained tumour growth and treatment failure, while the majority of mutations are without effect. Our research will assist identification of the genetic changes essential to leukemia development, which will help dev ....The emergence of cancer is caused by multiple mutations in normal cells. Recent progress has allowed the detection of virtually all mutations in a cancer genome. Although this has been enormous progress, it has become increasingly evident that only rare mutations are responsible for sustained tumour growth and treatment failure, while the majority of mutations are without effect. Our research will assist identification of the genetic changes essential to leukemia development, which will help develop new cancer therapies.Read moreRead less
EphA3, A Novel Target For Leukaemia Stem Cell Therapy
Funder
National Health and Medical Research Council
Funding Amount
$616,992.00
Summary
Patients with acute myeloid leukaemia often respond to therapy, but many relapse due to “leukemic stem cells” (LSC), the few cells in the original leukaemia which survive therapy. We focus on a protein (EphA3) which sits on LSCs and helps them interact with their environment. Disrupting this interaction may make these cells vulnerable to therapy. We aim to determine the function of EphA3 on LSCs and optimise the therapeutic use of an antibody against EphA3 which is currently in clinical trial.
Targeting Sphingosine Kinase 1 To Sensitise Acute Myeloid Leukaemia To BH3 Mimetic Therapy
Funder
National Health and Medical Research Council
Funding Amount
$670,005.00
Summary
Acute Myeloid Leukaemia (AML) patients are currently treated with chemotherapeutics and despite their success at achieving disease remission these responses are often short lived, resulting in relapse and death. We have identified sphingosine kinase 1 as a new drug target in AML. This proposal aims to examine the role of targeting sphingosine kinase 1 in combination with new targeted therapies in patient samples and preclinical mouse models of AML.
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.