My research has always been focused on the gastrointestinal tract. For my PhD, I did a comparative study of the fermentative organs of marsupials (kangaroos & possums) and placental mammals (sheep & rabbits). Gratifyingly, my papers on butyrate are still being cited. As a postdoc, I began studies on the physiological mechanisms underlying dietary and hormonal control of intestinal development. This area continued to be a major focus for the next 35 years, with a gradual shift to molecular and cellular aspects. Along the way I pursued some interesting side projects, namely the development of hunger and satiety mechanisms and the intestine as a site for gene therapy.
In the last 15 years, we turned to studies of intestinal stem cells (ISCs). Our work using side population (SP) sorting was the first successful generation of a fraction enriched in ISCs. After that there was an explosion of interest in ISCs with the development of multiple lines of EGFP reporter mice which allowed easy isolation of ISCs. However, we chose to remain focused on methods that could be used with wild-type mice, in the belief that these would be translatable to human intestine. To this end we used microarray analysis of our SP cells to identify CD24 as a membrane marker which can be used for isolation of epithelial stem cells from both small intestine and colon. These techniques allowed studies of the regenerative response of the intestine after various challenges, including intestinal resection and damage by the chemotherapeutic drug doxorubicin.
Beyond my 50+ years of research, my greatest professional satisfaction has been mentoring the next generation of scientists and physician-scientists – both those who worked in my own lab as well as others in the various training programs with which I have been associated. The stream of young folk whose careers I have influenced has included: undergraduates, graduate students, medical students, postdocs, and junior faculty. As I face retirement (Sept 2019), watching their own careers flourish gives me ongoing optimism and joy.
Education and Training
- Undergraduate University of Melbourne
- PhD University of Melbourne
- Postdoctoral Stanford University