Inherited heart disease research in Singapore
Much of Professor Stuart Cook's work is based on international collaborations. He tells Sarah Brealey how his work in Singapore, looking at the role of genes in heart and circulatory disease, could help patients around the world.
Stuart Cook is Professor of Clinical and Molecular Cardiology at Imperial College London, but his office is on a medical campus in Singapore.
The professor is Director of the National Heart Research Institute Singapore, as well as Senior Consultant Cardiologist and Director of the Clinical Cardiac MRI Service at the National Heart Centre Singapore. Much of his research is based on international collaborations.
My work here benefits my post at Imperial, and vice versa
His biography certainly has an international tone: he grew up in Kenya, studied medicine in London and did his post-doctoral training at Harvard (during which his daughter was born). He returned to London, where he established his research career alongside his work as a cardiologist, and became a professor at Imperial College in 2010. In 2012, his work became more international.
“A chance came up to work in Singapore,” says Professor Cook. “It has a huge patient base which was very important for the work I wanted to do. My work here benefits my post at Imperial, and vice versa.”
Exploring the role of genes in heart disease
Professor Cook leads a research team trying to understand more about the role of genes in heart and circulatory disease, improve diagnosis and develop new treatments. “We do a combination of genetic and human imaging,” he says. “If we find something interesting in human studies we take it back to the science lab to study it in more detail, with the ultimate aim to diagnose and treat disease.”
International collaboration is vital here. Researchers may need data from tens of thousands of patients, or even more, to spot genetic patterns – it’s difficult to do that in a single study.
One of Professor Cook’s team’s biggest findings is the role of a gene that instructs the body to create a protein called titin in heart failure. With the help of BHF funding, they have shown that a difference in this gene is the most common cause of dilated cardiomyopathy.
If we find something interesting in human studies we take it back to the science lab to study it in more detail
“This titin truncation, or difference, is present in about one per cent of the population,” Professor Cook says. “If you have it, your heart is primed to fail. It can function perfectly well, but it will be predisposed to get heart failure in certain circumstances that put it under strain, such as a viral infection, chemotherapy, or drinking too much alcohol.”
The team discovered that the titin gene is involved in many cases of peripartum cardiomyopathy – a rare type of heart failure that strikes women in late pregnancy or after childbirth. Its cause has been unexplained, and it is difficult to diagnose, but this discovery could help with both these issues.
Professor Cook’s team went on to develop a blood test for the titin gene difference. Family members of people affected can now discover their risk. In future, the test could potentially be used more widely, for example when planning a pregnancy, or before chemotherapy.
“Maybe people with this gene difference would respond to different drugs,” says Professor Cook. “We could give tailored lifestyle advice.”
The research was an international collaboration and was funded internationally, too, including by the BHF, the National Medical Council Singapore, the UK Medical Research Council, and others.
Testing for gene mutations and preventing atrial fibrillation
The BHF also helped fund work by Professor Cook’s team that led to a simple blood test that could diagnose all known inherited heart conditions. This means that in future, family members of people affected could be much more easily tested to see if they have a gene mutation, which will improve their care. This research was based on patient volunteers in both Singapore and London.
In the heart, the scarring disrupts the normal function of the muscle
Professor Cook’s team is also looking at scarring in the heart. Scarring can be caused by a heart attack or other things such as high blood pressure or genetic problems. “It is like when you cut yourself: you will get a scab and then a scar,” says Professor Cook. “In the short term that is a useful thing, but if there is chronic scarring then it can create more of a problem. In the heart, the scarring disrupts the normal function of the muscle.”
Chronic scarring can lead to problems such as atrial fibrillation (AF), the most common abnormal heart rhythm. AF affects more than 30 million people worldwide and can be difficult to treat. Professor Cook and his researchers are trying to control the scarring process, to reduce scarring and stop people developing AF in future.