Close to Heart: Giving the Heart a RESET
Twenty-three people in Singapore die from cardiovascular disease every day1. The situation is expected to worsen from 482 cases of heart attacks per 100,000 population in Singapore in 2025 to 1,418 per 100,000 population by 2050, representing a nearly three-fold increase2.
Professor Roger Foo, Vice Dean (Research), Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) and Director of the Cardiovascular-Metabolic Disease Translational Research Programme at the National University Health System (NUHS), and his team are looking to slow down, and possibly reverse, the growth trajectory of cardiovascular disease in Singapore in an ambitious nationwide preventive heart health translational research programme—Project RESET.
With over two decades of clinical and research experience under his belt, the Corresponding Principal Investigator of Project RESET, Prof Roger Foo also holds concurrent portfolios as Head of the NUHS Clinician Scientist Academy, Director of the Cardiovascular Research Institute under the National University Heart Centre Singapore (NUHCS), as well as Senior Consultant in the Department of Cardiology at NUHCS, and the Zayed Bin Sultan Al Nahyan Professor in Medicine.
That is an impressive and illustrious list of professional appointments. Could you share more about your journey as a clinician scientist?
I always like to tell people that my journey is one that is unexpected, unintentional—but eventful and fulfilling. After completing my studies at NUS Medicine and serving the National Service, I went to the UK for my postgraduate clinical training. First at King’s College Hospital in London, then at Addenbrooke’s Hospital in Cambridge, and eventually, passing the Membership of the Royal Colleges of Physicians of the United Kingdom (MRCP(UK)) within a year. Having planned for a two-year no-pay leave originally, I had a year to spare—so my bosses suggested that I go into the lab and try my hand at bench research.
Joining the lab of the late David de Bono (British Heart Foundation, and Chair of Cardiology, University of Leicester) and working alongside the late Anthony Gershlick gave me first-hand exposure to what it would be like to pursue a career in research. Subsequent research stints in labs of Morris Brown (past president British Hypertension Society, and Professor of Clinical Pharmacology, Cambridge), and Martin Bennett (BHF Chair of Cardiovascular Sciences, Cambridge) further spurred my research interests. My research journey was further consolidated by a Wellcome Trust fellowship, which brought me to Albert Einstein College of Medicine in New York City, US, in the lab of Rick Kitsis (the Dr Gerald and Myra Dorros Chair in Cardiovascular Disease) for two years, and finally landed me back as a Consultant at Addenbrooke’s Hospital, and a British Heart Foundation Fellow at the University of Cambridge. Amid these unfolding events, I paid off my bond, finished my PhD, pursued my postdoctoral fellowship and started my research group as a new group leader at Cambridge.
What keeps you passionate about your work as a clinician scientist after all these years?
When I finally returned to Singapore in 2013, we were at a nascent stage in biomedical research and technology. The Foo lab was literally among the first to establish the mouse model of heart disease, training small animal surgeons to handle operations for mice, and setting up equipment like ultrasound for mice. Since then, we have been running fast. Our achievements are especially evident when we compare how research discoveries are made here. Many of our discoveries stem directly from the population through collecting and analysing human samples. In contrast to the convention of starting from the dish or smaller model organisms before being replicated to see if the same applies to humans. A significant contributor to our accomplishments today is the systematic and coordinated manner in which we drive research as a community. An example would be the PRECISE-SG100K project.
There is so much motivation in Singapore to do right by our population. As a result, every time we see patients, we are not only thinking about providing them with the best treatment, but also opportunities presented by new research findings. Coupled with exciting discoveries—like new genes and genetic pathways—in the research space every other day, it is hard to not get excited or be passionate. Imagine rewriting the heart’s gene programme such that cells in this non-self-healing organ can divide and regenerate new cells to heal scars from heart attacks—heart disease and heart failure could become something of the past!
And we are possibly getting nearer to that point—if the recently approved heart disease medicine, mavacamten, is any measure. Traditionally, all heart disease patients get the same medicine for their symptoms—and when one medicine doesn’t work, another medicine would be added, then another. As a result, many patients end up taking a large host of medicines for one disease. With mavacamten, a myosin activator, we are using molecular understanding to offer targeted treatment for the first time. As genetic discoveries reveal more underpinning basis, targeted treatments and medicines will increasingly become the norm for cardiovascular diseases. That means—patients get more efficacious medicines tailored for their genetic make-up.
Can you tell us more about Project RESET and its significance to improving our population’s cardiovascular health?
In relation to what I mentioned earlier about a molecular basis for treatment, it is important that we base our application on relevant and accurate information. But how can we do that if our development is derived from non-Asian sources? Did you know—the profile of heart failure patients in Singapore is actually quite different from heart failure patients in the US, UK and elsewhere in Europe?
Metabolic diseases such as diabetes are strong contributing factors for poor cardiovascular health here—not just blocked arteries. That is why our patients not only tend to present with heart failures at a younger age, but are also likelier to have metabolic diseases in the background of heart failure.
Through Project RESET, we are looking to gather health metrics and physical and lifestyle data of over 10,000 high-risk individuals between 40 and 70 years old from the general population. From there, we would select 3,000 participants for a five-year follow-up programme. We would make use of technology to track their sleeping habits and physical activities, study their lifestyle markers and genetics, and analyse the correlation of these with heart diseases—to obtain a full diagnostic picture of each patient.
And we are not going to stop there. Ultimately, like the PRECISE-SG100K project, we are working with the team to establish polygenic risk score assays that are reflective of our population and can be effectively deployed to healthy Singaporeans, and the wider Asian populations. The goal is to develop new innovative preventive strategies and make preventive heart health more accessible and relevant to individuals. To help with achieving this, we will leverage technologies such as artificial intelligence, mixed reality and wearables.
What are your hopes for the future of genetic cardiovascular diseases?
The science and technology landscape is moving rapidly—and at a complementary pace to each other. Correspondingly, opportunities for early intervention and precision medicine are also growing. These are all very exhilarating for clinicians and scientists. But at the same time, now more than ever, we confront the issue of ethics especially when we talk about CRISPR—short for “clustered regularly interspaced short palindromic repeats”—technology and gene editing. Where does gene editing stop and discrimination starts? And what should we do to ensure equality and ethicality? I hope we can collectively figure this out as a community soon.
Personally, I hope some of the genes my research team and I put out there can help drive better therapeutic outcomes—and we can contribute towards Healthier SG through providing more precise lifestyle or activity advice to individuals and enabling them to keep cardiovascular and other diseases at bay.
References
1 https://www.myheart.org.sg/health/heart-disease-statistics/
2 https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(23)00121-9/fulltext