Shir Lin Koh
University of Melbourne, VIC
Rotary District 9640
Bowel Cancer
Shir Lin Koh was born in Malaysia. She came to Australia in 2001 and completed a Biomedical Science degree at the University of Melbourne majoring in molecular biology of the cell in health and diseases. During her final year she participated in two research projects: investigating malaria (Professor Geoff McFadden, Department of Botany) and examining colorectal and jejunal distension (Professor John Furness and Dr. Anthony Shafton, Department of Anatomy and Cell Biology).
In 2005 Shir Lin was awarded the Sir John Eccles Vacation Scholarship and participated in a summer research project examining serotonin receptors in the intestine (Department of Anatomy and Cell Biology, University of Melbourne). This work confirmed her desire to build a career in research and she pursued an honours degree in the same area.
Shir Lin joined the Department of Surgery, Austin Health, University of Melbourne in 2006. Under the guidance of Professor Christopher Christophi, she was put in charge of a project utilising hyperbaric oxygen therapy to treat acute pancreatitis in a rat model. Her research was presented at the prestigious Austin Health Research Week in 2006, 2007 and 2008 and at the International Hepato-Pancreato-Biliary Association Conference held in Mumbai, India (2008).
The University of Melbourne’s Department of Surgery at the Austin Hospital conducts cancer research that focuses on Shir Lin’s research interests. After consulting with Professor Christophi she was encouraged to do a PhD study on the spread of bowel cancer to the liver. In 2009 Shir Lin was awarded an Australian Rotary Health Funding Partner PhD Scholarship in conjunction with Rotary District 9640 and the University of Melbourne.
Shir Lin said “although the journey ahead may be challenging, I believe that my PhD research will not only carve the path of my career as a scientist, but it will further enrich me as a person and, I hope, will ultimately benefit our community”.
SUMMARY OF PROJECT:
The expression and role of the renin-angiotensin system in liver regeneration and tumour stimulation
Bowel cancer is a major health concern in Australia, resulting in more than 5,000 deaths every year. The spread of bowel cancer to the liver is responsible for over 70% of these deaths. Surgery to remove part of the liver containing tumour offers the best chance of cure. However, tumours recur after surgery in 60-80% of the patients. One of the possible explanations for this is that the molecules responsible for regeneration of the liver also stimulate the growth of small, undetected tumour cells left behind or shed into the circulation after surgery.
Although commonly associated with regulation of blood pressure, recent studies have confirmed the renin-angiotensin system (RAS) as a potential target to improve liver regeneration (3, 4). Preliminary work has shown that the RAS components are increased after partial removal of the liver. Shir Lin Koh’s hypothesis is that the rise in Ang II, a key effector peptide of the RAS, regulates the rate of liver regeneration by modulating the levels of key growth and blood vessel formation factors. In addition to its possible role in liver regeneration, there is strong evidence from the University of Melbourne’s Department of Surgery and international researchers that the RAS also regulates the growth and spread of cancer (1, 2, 5). Animal studies have shown that blocking the production or action of Ang II can inhibit the growth of some tumours, including bowel cancer that spreads to the liver (1). Thus, blockade of the RAS components might not only improve liver regeneration but may also simultaneously decrease tumour stimulation.
With extensively characterised mouse models of liver regeneration and bowel cancer that spreads to the liver, Shir Lin’s research aims to characterise the expression of the RAS after partial removal of the liver. Her team will also investigate the effects of the RAS blockade on liver regeneration and recurrent tumour growth after liver surgery. This project will elucidate the underlying mechanisms by which the RAS exerts its effects, and by doing so, will enable them to develop optimal strategies to target this system to improve patient outcomes.
Defining the relationship between the RAS, liver regeneration, tumour growth, and formation of new blood vessels, may improve liver regeneration and assist in the development of anti-cancer treatments. Due to its key role in both liver regeneration and tumour stimulation, the RAS offers a unique anti-cancer target for patients who have undergone surgery to treat liver tumours.