Colorectal cancer (CRC) is the 3rd most common cancer worldwide. 85% of CRC arises from mutations in the Wnt signalling pathway. We have shown that AZD1480, a drug that blocks Janus kinases (Jak) can prevent the appearance of Wnt mutant tumours and stop the growth of already established CRC in animal models. This project will test whether Jak inhibitors can improve treatment outcome and prolong disease free survival.
Investigating The Roles Of The Wnt And Notch Signalling Systems In Colon Cancer Crypt Biology
Funder
National Health and Medical Research Council
Funding Amount
$604,439.00
Summary
Colon cancer occurs because of mutations to a tumour suppressor gene. These mutations alter the growth and positional signals for the cancer cells. This project aims to produce a computer model of the regulatory processes in normal colonic cells, to discover why the mutations lead to cancer and to discover rational drug targets for interfering with the growth of colon cancer cells.
Defining The Molecular Effectors Of Gene/environment Interaction On Mouse Heart Development
Funder
National Health and Medical Research Council
Funding Amount
$749,271.00
Summary
One third of all birth defects involve the heart, and are the most common cause of infant death. Some defects are due to genetic factors, but others arise when the pregnant mother is exposed to environmental stress. We will examine how one stress (low oxygen levels) causes abnormal heart formation in the embryo, look at what causes this at a molecular level, and explore if such stress increases the risk of heart defects in families with a history of such abnormalities
SETD7-dependent Regulation Of Hippo/YAP And Wnt/beta-catenin Pathways In The Intestine
Funder
National Health and Medical Research Council
Funding Amount
$601,950.00
Summary
Colon cancer accounts for approximately 10% of all cancer-related deaths in Australia. One of the most common causes of colon cancer is a mutation in a signalling pathway called the Wnt/beta-catenin pathway. Despite this knowledge, there are currently no drugs that directly target this pathway to treat colon cancer. We have now identified a new way to control this pathway and have developed a potent and specific drug to block activation of this pathway.
The Role Of Meninges In Midbrain Dopamine Development
Funder
National Health and Medical Research Council
Funding Amount
$378,311.00
Summary
Dopamine neurons are important for the control of movement, emotion and cognitive function, and are affected in a number of disorders such as Parkinson’s disease. Instrumental in improving our knowledge of disease etiology and the development of new therapies will be a greater understanding of how these cells are initially born during development. This project examines the role of the brain’s meninges in dopamine development and repair and will identify proteins and signaling pathways involved.
Fzd receptors are often upregulated in gastric cancer, and recent studies have shown that targeting these receptors has be effective at reducing cancer cell growth in other cancers including prostate and breast. This project will use cutting edge technology to firstly determine the specific requirement for Fzd receptors during gastric cancer and then determine the therapeutic benefit of using an antibody to target these receptors in mouse models and human gastric cancer cells.
Sclerostin Is A Key Regulator Of Wnt Signalling In Bone And Cartilage Pathology In Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$590,945.00
Summary
Osteoarthritis (OA) is the most widespread bone and joint problem in Australia with has enormous social and economic consequences. We have identified Sclerostin (SOST) as a key regulator of the signalling pathway that drives the increase in production of bone and the erosion of cartilage in joints that are the hallmark of OA. The aims of the present project are to determine the effect altering SOST activity on the initiation and progression of OA.
Studying The Novel Role For G Protein-coupled Receptor Signalling In Leukaemia Development
Funder
National Health and Medical Research Council
Funding Amount
$373,144.00
Summary
Recent research has shown the clinical importance of abnormal stem cells (LSC) in acute myeloid leukaemia (AML). LSC are resistant to therapeutics suggesting that they could be a cause of relapse. Identifying signalling pathways that drive LSC development is essential to selectively eradicate LSC that could offer substantial therapeutic benefit. This proposal aims to identify and evaluate critical signalling pathways as a potential therapeutic target for developing effective novel LSC-targeted t ....Recent research has shown the clinical importance of abnormal stem cells (LSC) in acute myeloid leukaemia (AML). LSC are resistant to therapeutics suggesting that they could be a cause of relapse. Identifying signalling pathways that drive LSC development is essential to selectively eradicate LSC that could offer substantial therapeutic benefit. This proposal aims to identify and evaluate critical signalling pathways as a potential therapeutic target for developing effective novel LSC-targeted therapy in AML.Read moreRead less
Despite the high mortality associated with colon cancer only limited therapy options are available to treat these cancers. Here we propose a new strategy for inhibiting colon cancers driven by a specific type of mutations. Our preliminary data show that loss of DNA encoding a tumor suppressor gene creates a unique vulnerability in colon cancers. The aim of this proposal is to exploit this vulnerability as a strategy for combating colon cancer.
Wnt And MAPK Signalling In The Determination Of Colorectal Neoplasia Pathway
Funder
National Health and Medical Research Council
Funding Amount
$397,179.00
Summary
Polyps are growths in the bowel that may progress to become a bowel cancer. To prevent the development of cancer, these polyps must be removed by timely colonoscopy. There are many different types of bowel polyps, and these are associated with distinct genetic changes and likelihood of recurrence. This study aims to better understand the DNA changes that occur in bowel polyps and how these impact the clinical features of the polyps. In the future this will aid detection and surveillance strategi ....Polyps are growths in the bowel that may progress to become a bowel cancer. To prevent the development of cancer, these polyps must be removed by timely colonoscopy. There are many different types of bowel polyps, and these are associated with distinct genetic changes and likelihood of recurrence. This study aims to better understand the DNA changes that occur in bowel polyps and how these impact the clinical features of the polyps. In the future this will aid detection and surveillance strategies.Read moreRead less