Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase ....Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase 3 (HDAC3) as potentially involved in promoting colon cancer. The current proposal will now extend and validate this finding in mice. Importantly, drugs which inhibit HDAC3 have recently been developed for the treatment of cutaneous T-cell lymphoma. Defining the role HDAC3 plays in colon cancer will justify testing these drugs in colon cancer patients.Read moreRead less
Molecular signals that regulate the regenerative properties of intestinal epithelial cells. Most cancer deaths are due to the cancer spreading to other organs. Cancer is much more difficult to treat once it has spread to other organs in the body where the cancer cells can exist in a dormant state. Dormant cancer cells evade conventional anticancer treatment and can remain dormant for a very long time before they change back to a 'tumour-growing' state. An understanding of how the cancer initiati ....Molecular signals that regulate the regenerative properties of intestinal epithelial cells. Most cancer deaths are due to the cancer spreading to other organs. Cancer is much more difficult to treat once it has spread to other organs in the body where the cancer cells can exist in a dormant state. Dormant cancer cells evade conventional anticancer treatment and can remain dormant for a very long time before they change back to a 'tumour-growing' state. An understanding of how the cancer initiating (stem cell) property of tumour cells is maintained offers potential novel avenues to eliminate persistent cancer cells. This knowledge will ultimately lead to better management and treatment of cancer, and increase survival. An understanding of stem cell behaviour is also central to the control of degenerative conditions.Read moreRead less
The role of retinoic acid signalling in the development of the oesophageal epithelium. Oesophageal adenocarcinoma (OAC) is a disease with increasing incidence. The majority of patients with OAC are diagnosed when the cancer is at a late stage and therefore treatment options are limited, meaning the disease is almost invariably fatal. OAC arises from the precancerous condition, Barrett's oesophagus, which occurs as a consequence of chronic reflux, although the key processes driving its developmen ....The role of retinoic acid signalling in the development of the oesophageal epithelium. Oesophageal adenocarcinoma (OAC) is a disease with increasing incidence. The majority of patients with OAC are diagnosed when the cancer is at a late stage and therefore treatment options are limited, meaning the disease is almost invariably fatal. OAC arises from the precancerous condition, Barrett's oesophagus, which occurs as a consequence of chronic reflux, although the key processes driving its development are unknown. This project aims to better understand the critical first step in the progression to cancer and thus expand the scope for the development of therapies, particularly those aimed at early intervention, and tools that predict progression.Read moreRead less