Epithelial Regeneration Laboratory

Head: Dr Helen Abud

We are interested in:-

1. The cellular changes involved in the initiation of colorectal cancer.
2. Differentiation of stem cells
3. Gut development

The intestinal epithelium or bowel lining is a regenerative tissue that is constantly renewed throughout life via a small population of stem cells. The bowel lining forms a barrier between the contents of the bowel and the rest of the body. Despite the rapid turnover of cells, the lining of the gut is normally maintained as a perfect, unbroken layer with a constant number of epithelial cells. In order to achieve this, an exquisite balance between the production of new cells and the differentiation and death of older cells needs to be maintained. Defects in the homeostasis of the intestinal epithelium can have dramatic consequences for human heath. Conditions such as short bowel syndrome and inflammatory bowel disease show loss of the epithelial cell lining. Colon cancer can result when unrestricted growth occurs.

Colorectal cancer is currently the most common cancer in Australia with around 1 in 20 Australians developing the disease in their lifetime. There is also a high mortality rate where just under half of those people diagnosed with colorectal cancer will die of the disease.

We are interested in how growth and differentiation of intestinal epithelial cells is regulated during development and the initiation of cancers. We utilize differentiation of mouse embryonic stem (ES) cells to study the genes which control initial differentiation of intestinal lineage cells. We study how potential cancer-causing genes disrupt the development and biology of intestinal epithelial cells using organ culture, transgenic and knockout mouse models. Changes in cell behaviour can be observed in our unique organ culture system where gene constructs can be introduced into live epithelial cells and changes in cell growth, shape and migration visualized using live cell microscopy.