Rob Ramsay has had a long standing research commitment to understanding bowel and breast cancer using mouse models with defined genetic defects. These sophisticated models replicate various stages of cancer development and some have profound effects on normal tissue biology. He also uses molecular tools to investigate how genes are controlled. These approaches are providing direct input into the development of therapeutic agents for cancer treatment.
Defining The Role Of Reserve Stem Cells In Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$563,739.00
Summary
Over 800,000 deaths from stomach cancer occur annually. This often fatal disease is caused by chronic inflammation of the stomach lining. This proposal will investigate how stomach inflammation ‘reprograms’ a new type of 'cancer stem cell' to form tumours and evaluate ways to therapeutically target these cells to prevent disease. Collectively, these studies will inform new approaches for stomach cancer prevention and treatment.
Understanding the mechanisms in the development of mutations in cancers will assist in development of targeted therapies to overcome chemotherapy resistance. The recently discovered TMPRSS2:ERG fusion in prostate cancer is unique as dominant fusion translocations are uncommon in solid organ malignancy. Activation induced cytidine deaminase (AID) is thought to play a role. Understanding the role of AID and downstream DNA repair pathways may be a target for future therapies in cancer.
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.
Fighting Epidermal Skin Cancers By Targeting Epidermal Clones That Accumulate Mutations
Funder
National Health and Medical Research Council
Funding Amount
$1,149,373.00
Summary
Common skin cancers such as basal and squamous cell carcinomas (BCC and SCC) are by far the most frequent cancer worldwide and require over a million interventions per year in Australia. This project will identify the skin cells that are most susceptible to give rise to cancer if excessively exposed to the sun and explores ways to prevent cancer formation. This will inform on new strategies to prevent new skin cancer development.
The Microenvironmental Niche In Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
It is well accepted that the cells in the local environment of cancers can help to promote the growth and spread of tumour cells. We have shown that a cell type known as the pericyte previously thought to be involved in controlling tumour expansion by affecting new blood vessel formation, may directly influence tumour growth, a notion that will be tested in human skin and ovarian cancer models. We will also test if pericyte markers can predict those cancer patients at greater risk of relapse.
There are ~1.6 billion overweight adults worldwide & this is predicted to rise to 2.3 billion by 2015. In Australia > 2/3 of adults are overweight or obese. Obesity is a key factor in the progression of many human malignancies. Obesity poses the greatest risk for the development hepatocellular carcinoma (HCC), a deadly cancer refractory to nearly all available anti-cancer therapies. This application will delineate the molecular mechanisms by which obesity promotes HCC development.
Therapeutically Exploiting Non-oncogene Addiction And Defining Genetic Interactions For Disease Progression In A Preclinical Model Of Inflammation-dependent Gastric Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$624,960.00
Summary
Cancers of the stomach are often associated with chronic inflammation and represent a major health burden with little treatment options available. We propose to test whether drugs undergoing clinical testing for other diseases may have beneficial effects in a preclinical model of gastric cancer, and establish the genetic interaction required for gastric cancer progression. The study outcomes may highlight novel therapeutic opportunities for the clinic.
Cellular And Molecular Aspects Of Mammographic Density As A Predictor Of Breast Cancer Risk In Pseudo-orthotopic Mammatrophic Environment
Funder
National Health and Medical Research Council
Funding Amount
$113,322.00
Summary
High mammographic density (MD), or denser breast tissue on mammogram, is associated with greater breast cancer risk. Despite this, the basis for its increased risk is poorly understood. This study assesses the effect of high density breast tissue transferred from high risk women at time of mastectomy into tissue engineering chambers in mice. Changes in the connective tissue harvested from the chamber were examined with specialized imaging, laboratory stains and molecular analysis.
Role Of Chromatid Cohesion In Colon Biology And Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$628,422.00
Summary
Rad21 is a gene, present in many species and essential for accurate chromosome separation and DNA damage repair. Based on its known function in different species, we predict that its� dysfunction fuels cancer progression by promoting genetic instability, which is commonly associated with human cancers. This study will use unique mouse mutant models to investigate the function of this potential cancer-causing gene in colon cancer.