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The Role Of The Pro-survival Bcl-2 Family Member A1 In The Development And Sustained Growth Of Lymphomas.
Funder
National Health and Medical Research Council
Funding Amount
$628,459.00
Summary
The death of cells, which is regulated by a complex interaction between cell survival and killer proteins, is an important mechanism to prevent cancer. In this proposal we aim to understand the function of one of the cell survival proteins in cancer development and maintenance. This will help to develop novel therapeutic drugs specifically targeting this cell survival protein, thereby eliminating specifically the cancer cells and minimizing collateral damage of healthy tissues.
A Novel Approach For Treating B-cell Lymphoma By Inhibition Of The E3 Ligase E6AP
Funder
National Health and Medical Research Council
Funding Amount
$624,846.00
Summary
B-cell lymphoma is the most common type blood cancer diagnosed in Australia, and Australia's fifth most common cancer. Despite remarkable advances in diagnosis and treatment, lymphoma continues to rank as a leading cause of cancer-related mortality. Our pilot studies reveal a novel approach to treatment of B-cell lymphoma by inhibiting an enzyme that destroys our natural mechanism of defense against cancer. In this study we will test the efficacy of this novel treatment.
Antigen Receptor As Oncogene: Understanding CARD11 Mutations In B Cell Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$607,395.00
Summary
More than 5000 Australians are newly diagnosed as lymphomas. Recent technology identified many candidate genes for lymphomas, however it still remains unclear how each mutated gene distorts signalling molecules inside tumours cells. By introducing one of recurrent mutated genes, CARD11 into mouse B cells, we will examine how this mutation affects normal signalling pathways and B cell functions. We hope this project will provide a guidance to use forthcoming drugs to target specific molecules.
Activation And Suppression Of Oncogenic Translocation By Uracil-DNA Glycosylases
Funder
National Health and Medical Research Council
Funding Amount
$513,000.00
Summary
The AID enzyme is implicated in cancer in B lymphocytes and prostate cells. AID causes DNA damage normally recognised by repair enzymes UNG and MutS?, among others. The repair processes these factors initiate involve a DNA break that, if incorrectly re-joined, destabilises the genome, causing cancer. Understanding the function of AID, UNG and MutS? in B cell lymphomas and prostate cancer will provide fundamental insights into cancer and may identify targets for new therapeutics.
Follicular Cytotoxic T Cell Differentiation And Function In Infection And B-cell Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$963,892.00
Summary
Cytotoxic T cells eliminate infected or cancerous cells, constituting a major arm of the immune defence. In this study, we will investigate a subset of cytotoxic T cells that particularly migrate into B cell follicles to control infection and malignancy. Understanding of the differentiation and function of this subset, termed as follicular cytotoxic T (TFC) cells, will help us to develop new strategies to treat EBV and HIV infections as well as B cell lymphomas.
A Phase I Study Of PiggyBac CD19 Specific Chimeric Antigen Receptor T-cells For Therapy Of Persistent And Relapsed B-cell Leukaemia And Lymphoma Post Allogeneic Stem Cell Transplantation (The CARTELL Study).
Funder
National Health and Medical Research Council
Funding Amount
$357,590.00
Summary
Most people with relapsed leukaemia and lymphoma after bone marrow transplant die of their disease. Inserting special genes into immune cells can enable them to kill leukaemia and lymphoma and has led to dramatic cures, but there is little experience in bone marrow transplant patients. We will make leukaemia and lymphoma specific immune cells from normal bone marrow transplant donors, then administer the immune cells to transplant patients to assess their safety and effectiveness.
Towards A Functional Cure For HBV: Exploiting Lessons From HBV-HIV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$913,551.00
Summary
Hepatitis B virus (HBV) infection can be treated, but therapy is usually lifelong and has side effects, so a cure for HBV is very important. We work closely with colleagues in Asia where both HBV and HIV are common so this provides a unique opportunity to study HBV. We will investigate how an effective immune response against the 2 main HBV proteins is developed. If we can understand how the immune response works against HBV, this could be used to develop new therapies to develop a cure for HBV
Understanding The Role Of Host Arih2 In Defence Against Viral Infection And Disease Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$537,737.00
Summary
A set of proteins, called E3 ligases, modulate many aspects of immunity. Arih 2 is a novel E3 ligase that limits immune cell activation to maintain the immune system in a quiescent state. The details of how Arih2 functions and its role in immunity to chronic overwhelming infection are the focus of this study. The insights gained from these studies have important implications for our understanding of how immune responses can be promoted during infection or halted in autoimmunity.
A Theoretical Framework For Chemotherapy And Immunosuppression
Funder
National Health and Medical Research Council
Funding Amount
$561,028.00
Summary
The team has discovered that potential alternative cell fates behave like autonomous timers, and are in competition in every cell. Variation in selected times within each cell alters the proportion that that die, divide or change into another cell type. The team have produced computational models of cell growth applicable to the immune response and cancer. Here they will apply their discovery to measure the effects of chemotherapeutic drugs and develop new protocols for enhancing the use of such ....The team has discovered that potential alternative cell fates behave like autonomous timers, and are in competition in every cell. Variation in selected times within each cell alters the proportion that that die, divide or change into another cell type. The team have produced computational models of cell growth applicable to the immune response and cancer. Here they will apply their discovery to measure the effects of chemotherapeutic drugs and develop new protocols for enhancing the use of such drugs in the clinic.Read moreRead less
Cell Cycle Tracking Of B Cell Differentiation And Mutation
Funder
National Health and Medical Research Council
Funding Amount
$719,666.00
Summary
Antibody-mediated immunity to infectious diseases requires the proliferation of infection-specific antibody-producing B cells. The fate of responding B cells is linked to this proliferation according to a poorly understood division-based “map”. This project will track B cell fates in vivo using advanced imaging techniques. We will define differences between B cells from young versus old individuals that may explain why the effectiveness of the immune system declines with age.