Colorectal cancer is a common malignancy in Australia and the mutation of one gene (Apc) is implicated in >80% of the cases. We aim to understand Apc biochemistry in normal and colon cancer cells by integrating mathematics with our experimental biology program. The main outcomes for this project will be a better understanding of the regulatory systems perturbed in colon cancer. We believe that the insights gained by our research will point the way to more effective treatments of colon cancer.
Defining The Genetic Requirements For Maintenance Of Colorectal Cancer
Funder
National Health and Medical Research Council
Summary
Colorectal cancer is the second leading cause of cancer-related death worldwide because there are few effective treatments for people with aggressive disease. The goal of this project is to uncover how normal colon cells suppress cancerous changes and to identify the important factors that colon cancer cells depend on for survival and growth. With this knowledge we can begin to develop more effective cancer treatments with fewer side-effects.
The Therapeutic Value Of Targeting Wnt Signalling For The Treatment Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$561,535.00
Summary
Osteoarthritis (OA) affects 1.62 million Australians and imposes a significant burden on healthcare. It is characterised by damage to joint cartilage, and increased bone formation with formation of bone spurs. Our studies will determine the importance of the Wnt signalling pathway in mediating OA joint degeneration and identify mechanisms that regulate the activation of this pathway in OA. This will inform the development of novel therapeutic strategies which could halt joint damage in OA.
Investigating The Role Of The Notch4 Receptor In Blood Vessel Formation And Remodelling In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$653,086.00
Summary
We aim to understand how blood vessels form. This process is crucial for foetal development, and for injury repair in adults. When there is too much or too little blood vessel formation, diseases such as arthritis, blindness and osteoporosis can result. Also many tumours grow and spread by growing new blood vessels. We will study a signal that occurs between cells (Notch signalling) that is important in controlling the amount of blood vessel formation, by analysing in detail one component (Notch ....We aim to understand how blood vessels form. This process is crucial for foetal development, and for injury repair in adults. When there is too much or too little blood vessel formation, diseases such as arthritis, blindness and osteoporosis can result. Also many tumours grow and spread by growing new blood vessels. We will study a signal that occurs between cells (Notch signalling) that is important in controlling the amount of blood vessel formation, by analysing in detail one component (Notch4)Read moreRead less
Functional Analysis Of The Notch Signalling Pathway In The Differentiation And Maintenance Of Pituitary Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$421,320.00
Summary
Many of the processes that are essential for normal bodily function such as growth, the ability to cope with stress, sexual organ development, metabolism and milk production, are controlled by the pituitary gland. This organ is located at the base of the brain and regulates these bodily functions through the release of six different hormones. Formation of the pituitary gland occurs during development of the foetus. This process requires a specific set of genes that shape the pituitary and allow ....Many of the processes that are essential for normal bodily function such as growth, the ability to cope with stress, sexual organ development, metabolism and milk production, are controlled by the pituitary gland. This organ is located at the base of the brain and regulates these bodily functions through the release of six different hormones. Formation of the pituitary gland occurs during development of the foetus. This process requires a specific set of genes that shape the pituitary and allow the hormone secreting cells to arise. Changes in these pituitary formation genes results in underdevelopment of the pituitary in newborn babies. In severe cases, where the pituitary has failed to form completely (panhypopituitarism), these babies are extremely ill and in some instances do not survive. We are studying the genes that belong to the Notch signalling pathway. These genes are important regulators of cell differentiation during the development of the brain, skin, bone and many other tissues. However, the role of the Notch signalling genes in pituitary development is not known. We have shown for the first time that these genes are active during pituitary development. To test the function of these genes in the pituitary, we will generate mouse models that either lack or inappropriately activate these genes. Our results will provide insight into the role of Notch Signalling genes in pituitary development in mice and humans. In this project, we also hope to identify cells in the pituitary that are able to give rise to multiple hormone secreting cell types. These stem cells are of significant clinical importance as they provide an avenue for the development of novel therapies for pituitary disorders in humans, based on the replacement of defective pituitary tissue with functional stem cell derived tissue.Read moreRead less
Functions Of FZD7 In The Intestine And Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$644,761.00
Summary
Wnt proteins are a family of signaling molecules that are critical for the function of normal and cancerous epithelial cells in the gut. However, the cell surface receptor that transmits Wnt signals is not known. Our research strongly implicates one Wnt receptor (FZD7). Here we test this using innovative mouse and cell line models. We wish to understand how Wnt-driven processes are activated. This knowledge will lead to novel avenues to block aberrant activation of Wnt signalling in cancer cells
The Intersection Between Hedgehog And Notch Signalling In Medulloblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$620,647.00
Summary
Brain tumours are the second most common malignancy of childhood and the leading cause of cancer related death and disability in children. Medulloblastoma is the most frequent malignant childhood brain tumour, arising in the cerebellum. This application looks at the relationship between two genetic pathways responsible for medulloblastoma which are also drug targets. Understanding this interaction will lead to better treatment options for the disease.
The Contribution Of Gp130-Stat3 During Wnt-beta-catenin Induced Intestinal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$396,275.00
Summary
There is growing evidence that cancer is initiated and develops not by the deregulation of a single gene or signaling pathway, but by multiple events. We will study the co-operation between two pathways - gp130-Stat and Wnt. These signaling pathways are frequently deregulated in many types of cancer, however their interaction remains poorly understood. We shall explore their mechanism of interaction during intestinal cancer in order to develop a novel therapeutic target for this disease.
Osteoblast Control Of Mesenchymal Progenitor Cell Differentiation: The Role Of Glucocorticoids And Wnt Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$443,131.00
Summary
Osteoporosis is an important and growing health issue. Reduced ability to make new bone is an important cause of osteoporosis. In this project we will study how the immature cells which eventually make bone are recruited and controlled. In particular, we will study how genes coding for important growth factors are regulated so that the proper signals are sent to young cells to induce them to become bone-making rather than fat-making cells.