Professor Wang Yibin, right, accepts the Basic Research Prize from the Association's President Joseph Wu, left

For his work on some of the smallest culprits behind one of the biggest killer diseases, cardiovascular scientist Professor Wang Yibin received the Basic Research Prize from the American Heart Association (AHA) during the Presidential Session of the Association's Scientific Sessions on 12 November.

The award, which is presented annually to an individual for their outstanding contributions to the advancement of cardiovascular science and who currently runs an exceptional basic science laboratory, is recognition of the impact of Prof Wang's research into the fundamental molecular and genetic mechanisms of cardiovascular physiology and cardiometabolic diseases, including heart failure. In addition to being a principal investigator, Prof Wang is the director of the Cardiovascular and Metabolic Disorders Programme at Duke-NUS.

In particular, his focus on a previously little studied aspect of metabolism enabled him and his team to identify a new hallmark of heart failure: the suppression of the breakdown of branched-chain amino acids in the heart. When these amino acids and related metabolites build up, they impair heart function and drive oxidative stress, leading to heart failure. From this discovery, Prof Wang and his team were able to develop a new drug candidate that has since progressed to phase I clinical trials backed by a global pharmaceutical company.

"This recognition is for all the team members and our collaborators over the years, who have devoted their talents and hard work in order to uncover new knowledge that can one day lead to new therapies for people with heart disease. I am very grateful to each of them and will use this award as a constant reminder that heart disease is still the number one killer and a challenge we must overcome with more research and better knowledge," said Prof Wang.

But the award holds a deeper—and personal—significance for Prof Wang: "I'm truly humbled by this award from the Association, an organisation that I am very fortunate to call home since the very beginning of my academic career."

"When I was a junior investigator, the AHA offered crucial funding and access to a community of researchers and physicians for me to interact with, be supported by, learn from and to be inspired. Then, when I was a junior and mid-career faculty, the Association offered critical funding for new ideas and opportunities for networking among the professionals. It also connected me with patients and advocates, enabling me to recognise the relevance of our research output in patient care and impact."

Prof Wang and his team made their seminal discovery at a time when amino acid metabolism in heart failure and other metabolic disorders was unchartered territory. Previous efforts had focused on the role of fatty acid and glucose utilisation, which is a common feature of heart failure.

"We were just beginning to discover how cells respond to changes in the environment internally through signalling pathways," said Prof Wang in an interview with MEDICUS.

But he soon realised that this was only part of the picture: "We missed a very important equation in our original understanding of heart failure. It turned out that one major, major change in patients was their metabolism—they are unable to utilise energy optimally. Particularly in heart failure patients with preserved ejection fraction who are often old, and suffering from other complications, such as obesity and diabetes, as well as hypertension. Because of the stiffened muscles in their left heart chamber, they are unable to pump sufficient blood around the body," he told the magazine. "And every standard therapy we tried with them didn't work."

And this is not the only project that has achieved translational success. Prof Wang's wider work on precision genome editing and systems genetic tools to investigate stress signalling pathways in the heart have also yielded drug candidates that have been licensed to pharmaceutical companies and are undergoing clinical development.

"Dr Yibin Wang was selected for this prize because of his commitment to learning more about the genetic, molecular and cellular mechanisms behind cardiovascular disease," said the Association's 2023-2024 volunteer President Joseph Wu in a statement to announce this year's recipient. "Additionally, his research applies discoveries made about stress signalling networks to new methods of treatment for heart disease and the management of heart failure."

Adding his congratulations, Duke-NUS Senior Vice-Dean for Research Professor Patrick Tan said, "This award is highly deserved for Yibin whose rigorous scientific approach and experimental courage have led him to investigate basic biologic mechanisms overlooked by others at the time, thereby creating new treatment approaches that will bring hope to millions of patients affected by cardiovascular diseases."

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