Understanding Autophagy In Haematopoiesis And Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$500,813.00
Summary
Blood cancers such as leukaemia are among the most deadly types of cancer and new treatments are desperately needed to improve survival. We have identified a new pathway that is activated when cells undergo stress. This pathway controls the survival of normal blood cells and also appears to be very important in the way cancer cells respond to chemotherapy. We will characterize this pathway in normal blood cells and use this information to develop new treatments to target and eliminate the leukae ....Blood cancers such as leukaemia are among the most deadly types of cancer and new treatments are desperately needed to improve survival. We have identified a new pathway that is activated when cells undergo stress. This pathway controls the survival of normal blood cells and also appears to be very important in the way cancer cells respond to chemotherapy. We will characterize this pathway in normal blood cells and use this information to develop new treatments to target and eliminate the leukaemia cells.Read moreRead less
Genome Engineered, Preclinical Models Of Serrated Colorectal Cancer To Fast-track A High Sensitivity, Early Detection Test
Funder
National Health and Medical Research Council
Funding Amount
$593,854.00
Summary
1 in 12 Australians will develop colorectal cancer. Here we use information about changes to the genetic (inherited) material of these cancers to develop new, complex models of this disease. This teaches us about what those changes do, and highlights important targets for future drug therapies. We are also developing a better test to detect hidden pre-cancers that are not well detected by our current population screening strategy, to help reduce deaths from this disease.
Role Of A DNA Helicase, Recql4, In Haematopoiesis, Skeletal Biology And Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$750,701.00
Summary
We are interested in understanding how a gene involved in familial cancer works. Mutations in this gene cause patients to develop a range of cancers in their blood and skeleton. We are seeking to understand how this gene functions so that we can understand how the cancers form in these families and also how sporadic cancer forms.
Mechanisms Of Resistance To Immunological Targeting Of Primary And Metastatic Colorectal Cancers
Funder
National Health and Medical Research Council
Funding Amount
$612,828.00
Summary
The immune system influences the outcome in patients with cancer. We have been early adopters of immunotherapy approaches to target cancer cells using the novel approaches to enhance immune attack on cells that aberrantly express cancer regulators. These represent drivers to which cancer cells are addicted. A central tenant of optimizing immunotherapies has been to employ immune stimuli in concert with removing immune blocking systems. Our research plan is to improve immunotherapy efficiency.
EphA3 Is A Marker Of Glioma Stem/progenitor Cells And A Potential Target For Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
EphA3 is a cell surface marker which is enriched on glioma ‘propagating’ stem cells (GSCs) and furthermore has a functional role in regulating GSC differentiation and fate determination. EphA3 therefore provides a novel therapeutic target for high-grade glioma.
The Microniche: A Novel In-vitro And In-vivo Prostate Cancer Model System
Funder
National Health and Medical Research Council
Funding Amount
$561,012.00
Summary
Maintaining primary prostate cancer cells (PCa) in vitro remains an enormous challenge for the field, and this obstructs efforts to systematically characterize cell behaviour and quantify drug response. Our group recently developed a 3-demsensional (3D) organoid culture system that does maintain PCa in vitro, and here we will integrate this technology with our 3D bone maorrow niche model system to better characterize PCa bone metastases and identify new clinical treatment regimes.
Tapping The Power Of Pluripotency: The Role Of HMGA1 In Stem Cell Self-renewal And Cell Fate Transitions
Funder
National Health and Medical Research Council
Funding Amount
$520,314.00
Summary
Stem-cell-based therapies have great potential as new treatments for degenerative and genetic diseases. However, to ensure we move in the right direction, we need a detailed understanding of stem cell properties. We have recently identified a novel mechanism for controlling stem-cell-like properties in both normal and cancer stem cells. In this project, we will further investigate this new means of controlling stem cells, which could revolutionise future therapeutic strategies for many diseases.
Mab Immunotherapies For Myeloid Leukemia Patients With Germline Or Somatic RUNX1 Mutations.
Funder
National Health and Medical Research Council
Funding Amount
$766,995.00
Summary
This proposal presents preliminary evidence and proposes to confirm that 2 cell surface molecules, CD11a (ITGAL) and IL3RA (CD123) are direct (probably repression) targets of RUNX1 in HSCs, and are dysregulated in RUNX1 mutated AML. Monoclonal antibody therapies that target these two surface molecules have already passed different clinical trial phases for different diseases. We plan to show these antibodies are effective in RUNX1 positive AML in preclinical models and then clinical trials.
The Role Of The Asymmetric Cell Division Regulator GPSM2 In Mammary Gland Development And Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
Tissues are built by small populations of progenitor cells which divide unequally to generate different cell types. Recent studies suggest defective progenitor cells are founders of some breast cancers and that progenitor-like cancer cells resist therapy to regenerate tumours. We have shown a progenitor division regulator called GPSM2 controls these cells and inhibits breast cancer. Examination of this new anti-tumour pathway promises to identify therapeutic targets for breast cancer recurrence.
Regulatory Interactions Between YAP And Beta-catenin In Normal Epidermal Homeostasis And In Skin Cancer
Funder
National Health and Medical Research Council
Funding Amount
$396,157.00
Summary
Australia has the highest skin cancer incidence in the world. We found that oncoprotein YAP activates stem cell proliferation in the skin through activation of the Wnt pathway, and we have evidence that YAP is hyperactivated in human skin cancer. We will map out the molecular nature of the interaction between YAP and the Wnt pathway in normal epidermal homeostasis and in skin cancer. This study will provide novel insights for development of therapeutic avenues for human skin cancer and other reg ....Australia has the highest skin cancer incidence in the world. We found that oncoprotein YAP activates stem cell proliferation in the skin through activation of the Wnt pathway, and we have evidence that YAP is hyperactivated in human skin cancer. We will map out the molecular nature of the interaction between YAP and the Wnt pathway in normal epidermal homeostasis and in skin cancer. This study will provide novel insights for development of therapeutic avenues for human skin cancer and other regenerative dermatological disorders.Read moreRead less