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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
Investigating The Contribution Of Distinct Mitochondrial Cell Death Pathways To Platelet Survival And Function
Funder
National Health and Medical Research Council
Funding Amount
$635,247.00
Summary
Platelets are small blood cells that form clots to stop bleeding. We have found new and unexpected roles for 2 distinct pathways that regulate cell death in the process of blood clot formation. We will study the precise role of these pathways in blood clot formation, and determine whether they may also regulate the survival of platelets stored by the blood bank for transfusion. These studies will provide new insight into the role of cell death pathways in blood clot formation, and may help to im ....Platelets are small blood cells that form clots to stop bleeding. We have found new and unexpected roles for 2 distinct pathways that regulate cell death in the process of blood clot formation. We will study the precise role of these pathways in blood clot formation, and determine whether they may also regulate the survival of platelets stored by the blood bank for transfusion. These studies will provide new insight into the role of cell death pathways in blood clot formation, and may help to improve current protocols for storing plateletsRead moreRead less
Redirecting T-cells For Immunotherapy Of Leukaemia And Lymphoma By The Expression Of A CD19-specific Chimeric Antigen Receptor Using The PiggyBac Transposon Gene Modification System
Funder
National Health and Medical Research Council
Funding Amount
$374,876.00
Summary
Most lymphomas respond to therapy but then relapse. Immune cells can attack and kill virus related lymphomas. However, most lymphomas are NOT virus related. We will create immune cells targeting these virus negative lymphomas by inserting artificial receptors into the immune cells. These receptors attach to the lymphoma and activate the immune cells. The immune cells will home to the lymphoma, kill lymphoma cells and persist in the body for many years, preventing lymphoma relapse.
We will investigate how the master control gene, Kruppel-like factor 1, orchestrates production of red blood cells. We will use genetic and cell biology approaches to determine exactly how this factor interprets the genome blueprint in a cell specific manner. We will also determine how mutations in KLF1 cause human diseases such as congenital dyserythropoietic anemia and hereditary persistence of fetal haemoglobin. This has implications for reactivation of HbF in adults with sickle cell disease.
Mechanisms Underlying The Effects Of TNFalpha In Bone And Haemopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$589,425.00
Summary
Recent studies have identified that bone plays an important role in blood cell production. We have discovered that elevated levels of TNF alpha (which increases with ageing and can negatively impact on health) contributes to a blood cell disorder that can progress to leukaemia. There are also reduced numbers of blood stem cells and bone in this mouse model. In these studies we will determine how TNFalpha contributes to blood and bone defects, which may lead to better treatment of such diseases.
KLFs are master control genes that regulate the expression of many target genes to determine cell fate and to convert one cell fate to another. Mutations in KLFs cause human diseases. This grant will focus on the founding member of the KLF family, KLF1. We will use genomics techniques and animal models to determine how KLF1 works in normal blood cell production and in disease
Regulation Of The Haemostatic Activity Of Plasma Von Willebrand Factor
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
Our genes encode proteins that perform the tasks of life. Most proteins are chemically modified after they are made to control how, when, and where they function. Prof Hogg discovered a new chemical modification of proteins that is important in health and disease. He will apply this discovery to develop new diagnostics and therapies for heart attacks and stroke. Prof Hogg is one of the few Australians to take new diagnostics and therapies developed in the lab to evaluation in patients.