April 2016 | Issue 23
Research shorts

Advancing frontiers in mental health

On 25 February, the highly anticipated Frontiers in Mental Health Symposium kicked off at the Institute of Mental Health’s Lecture Hall. With a stellar line-up of international and local speakers, places at the two-day event were snapped up in no time.

Co-organised by LKCMedicine and Institute of Mental Health (IMH), the symposium was jointly opened by Toh Kian Chui Distinguished Professor and LKCMedicine Professor of Developmental Biology Philip Ingham FRS, and National Healthcare Group Deputy Group CEO for Education and Research Associate Professor Lim Tock Han.

IMH CEO Associate Professor Chua Hong Choon and LKCMedicine Dean Professor James Best then delivered their welcome address. Prof Best took the opportunity to outline the research goals that LKCMedicine is pursuing in the area of neuroscience and mental health.

Segmented across four thematic sessions, experts shared their insights and latest research on mental health. Among the speakers from IMH, University of Oxford, Imperial College London and Harvard University were LKCMedicine Neuroscience & Mental Health Scientific Director and Professor of Translational Neuroscience Balázs Gulyás and Visiting Associate Professor Tan Hao Yang, who talked about molecular neuroimaging in psychiatry research and computational neuropsychiatry and imaging genetics respectively.

The Frontiers in Mental Health Symposium featured a stellar line-up of international and local speakers

After much stimulating discussion and lively exchanges of ideas, LKCMedicine Vice-Dean for Research Professor Russell Gruen brought the symposium to a close, saying, “This is a special day, in particular for us, as an open and outward expression of our partnership and joint commitment to improve the lives of Singaporeans who are burdened by mental illness. We have demonstrated that the best hope rests in the combination of outstanding science, excellent education and committed clinical care.”

New avenue for more effective diabetes treatment

Patients diagnosed with diabetes face a complicated life-long regimen of medications and monitoring to manage their blood sugar levels. Some of these treatments, recent data suggest, are even harmful to patients’ remaining insulin-producing beta cells.

Beta cells sit in islets embedded within the pancreas, and hold the key to insulin production. They are notoriously difficult to study, and so far, in vitro experiments have not been successful at recapitulating fully functioning beta cells for regenerative diabetes therapy.

But now, scientists from LKCMedicine have developed a new method that allows them not only to grow beta cells in a living animal, but also to easily observe them as they grow over time. This method offers the first glimpse of a novel approach to treating diabetes.

LKCMedicine Assistant Professor of Metabolic Disease Yusuf Ali together with Senior Research Fellow Dr Juan Diez found that implanting a small number of pancreatic progenitor cells into the anterior chamber of the eye stimulates blood vessel growth in these cells, providing, for the first time, a glimpse of how these cells differentiate into functioning beta cells within a living organism.

Asst Prof Yusuf said, “This transplant method allows us to visualise and understand how pancreatic beta cells are formed after progenitor cell transplantation into a living organism. Prior to this paper, this information was a black box.”

Growing islet cells in the eye could provide a natural source of blood sugar regulating hormones and could offer a new approach to treatment. The findings were published in the prestigious journal Diabetologia online in February.

“This technical achievement will allow a much more comprehensive view of how our beta cells develop and the underlying regulatory mechanisms,” said LKCMedicine Visiting Professor Per-Olof Berggren, who pioneered the living window approach.

Next, Asst Prof Yusuf plans to investigate whether pancreatic progenitor cells derived from human embryonic and induced pluripotent stem cells can be implanted and stimulated to produce pancreatic hormones during starvation and fed states. If successful, this could pave the way for an autologous diabetes treatment that does away with daily insulin injections and constant blood sugar monitoring.

Scientists find key to non-alcoholic fatty liver disease

Excess fat in the liver, known as a fatty liver, was once considered a disease of middle-aged heavy drinkers. But nowadays, fatty liver affects more young people who drink little or no alcohol.

Known as non-alcoholic fatty liver disease (NAFLD), it is the most frequent cause of liver disease in the Western world. About one in five people with NAFLD develop a progressive form of the disease, where the fatty liver becomes inflamed. This inflammation can lead to permanent scarring and hardening of the liver, known as cirrhosis.

To understand the mechanisms that lead to fat build up in the liver, an international team of scientists from
LKCMedicine and France’s National Institute of Agricultural Research (INRA) has been studying the key molecular pathways that regulate fat storage in the liver. They have now identified a key protein responsible for this process, a finding which was recently published in the journal GUT.

The scientists engineered a mouse model that lacked the peroxisome proliferator-activated receptor known as PPARα in the liver cells and found that the mice quickly accumulated fat in their livers, regardless of the type of diet they were on. In addition, the mice developed NAFLD without being overweight or diabetic, two of the traditional risk factors for developing the condition.

“Already we know that 80 per cent of obese people and 70 per cent of diabetic people have fatty liver disease. Our findings show that this is likely just the tip of the iceberg. With this discovery, we may have not only a new drug target, but the key to prevent NAFLD in the first place,” said LKCMedicine Professor of Metabolic Medicine Walter Wahli.


 ​Natural wonders


This zebrafish
glitters because of its
reflective iridophore
cells. Factors that
are essential to the
formation of these
cells also cause certain
lymphomas, and are
thus used as a screen
for anti-cancer agents.

Courtesy of LKCMedicine Assistant Professor Tom Carney