Just as cells are the building blocks of life, research institutes are the building blocks of scientific networks. For Wanjin Hong, Executive Director of A*STAR’s Institute of Molecular and Cell Biology (IMCB) and Professor at the National University of Singapore (NUS), his journey that contributed towards the building of Singapore’s thriving landscape of biomedical research began in 1989 when he joined IMCB, the first institute devoted towards the field in Singapore.
For his years of dedication to cutting-edge molecular and cell biology research at IMCB; his nurturing of local scientific talents; and his critical efforts to forge collaborative partnerships with higher learning institutes, hospitals and industry partners across the country’s biomedical research ecosystem, Hong was recently conferred the 2022 President’s Science and Technology Medal, one of three awards from the President’s Science and Technology Awards (PSTA).
Since 2009, the PSTA have represented the highest national honours conferrable on exceptional scientists or engineers in Singapore. The awards recognise individuals or teams who have made invaluable contributions to the country’s vibrant R&D landscape.
On the global stage, research by Hong’s team has contributed significantly to new understandings of cellular transport pathways, and the role of the Hippo signalling pathway in human cancers. Hong also oversaw IMCB’s development of diagnostics across two historic pandemics: SARS in 2003, and COVID-19 in 2020.
In this interview with A*STAR Research, Hong discusses his team’s work in the molecular development of cancers; IMCB and A*STAR’s growth as key contributors to Singapore’s global excellence in biomedical science; and his advice for young talents in STEM on creating impactful research.
Q: What sparked your interest in cancer signalling pathways?
Simply put, if you can understand the molecular mechanisms behind how and why cancers develop, you can look for targets in those mechanisms that might, if drugged, stop those cancers.
When I first came to Singapore, I spent the first 20 years mainly exploring cell structure and function, particularly the mechanics of the secretory pathway. Understanding its components and their interactions, and how proteins are made and transported within and beyond the pathway, helped build our basic understanding of what makes healthy cells tick.
Later, my colleagues and I developed an interest in figuring out how cancer overcomes those ordinary functions in a cell, causing it to proliferate aggressively. We started by looking at the structure of β-catenin—a protein often mutated in liver cancers—and found it had a certain motif that only occurred in its mutated form. We went looking for other proteins which had the same motif. This led to us finding more proteins and genes that, when mutated, are likely to trigger cancers.
Those components—genes like WWTR1, and proteins like TAZ, YAP and TEADS—are all part of the Hippo signalling pathway, which regulates how cells multiply or self-destruct. The Hippo pathway is an increasingly fascinating area of study not only because it’s a point of convergence for so many other signalling pathways, but it also seems to play a role in drug resistance. We’ve been researching this pathway for the last 15 years, uncovering things like YAP’s crystal structure and the TAZ-TEADS complex.
One of our biggest findings was a druggable hydrophobic pocket in the structure of TEAD proteins. Since then, there’s been a wave of translational research by academic institutes, biotech and pharma into small molecules that might bind that pocket and inhibit TEAD, which could lead to new cancer treatments. A few such candidates are already in phase 1 clinical trials.
Q: Throughout your career, what challenges have stood out?
One would be the increasing level of talent competition. When IMCB was initially established, it was the only biomedical institute in Singapore for 15 years. Since then, the national research ecosystem has grown and matured tremendously. It now includes autonomous universities, academic medical centres, clinical research centres, corporate labs and startups.
Regardless, A*STAR today is well connected and has strong collaborations within this ecosystem. We hope to attract international STEM talent to Singapore to complement our talent base. Through this exchange of knowledge and expertise, we aim to create impactful scientific outcomes for the nation.
Q: Having been with A*STAR (formerly NSTB) since 1989, how has your research approach changed?
In the early days of the biomedical field in Singapore, the emphasis was on conducting research. When IMCB first started at the National University of Singapore (NUS) in 1985, there was a very strong focus on basic research. Our main goals were to put Singapore’s academic research on the global map and to train more young talents in the field.
As Singapore’s needs evolved, A*STAR, including IMCB, reviewed how our strong foundation in basic research could be better applied and translated into real-world applications. A*STAR was also no longer the only ‘kid on the block’ when it came to biomedical research; new institutes such as the Research Centres of Excellence, Duke-NUS Medical School and the Lee Kong Chian School of Medicine began building up their capacities. It was therefore key to understand our clinical partners and work closely with them to translate our upstream discoveries to benefit patients.
Q: With young talents, how do you approach mentorship?
I do my best to create a conducive environment for my students. I want to provide them with an environment where they feel free to explore their interests and research ideas with my strategic direction yet without my direct intervention. I hope to train my students to be independent researchers.
Giving them this independence empowers them to become more confident in their abilities as academics and researchers. It also allows them to freely collaborate with other colleagues and institutes who can share different perspectives and skills, helping them improve both their basic research and its transition toward application.
Q: What advice do you have for young researchers in the field?
Depending on your interests and where you are in your career, you have to shift your mindset towards how the research you are passionate about can be harnessed for greater outcome and impact, and applied to real-world challenges. It’s important to consider how your work fits into A*STAR’s mission, which is to enhance economic growth and improve lives. Whether within yourself or among the people you work with, that change in mindset can be challenging, but it’s possible through proactive collaboration.
Basic research continues to be important because of the foundation it provides us to build on when we tackle big ideas and challenges. Few are approachable by a single team’s efforts; it’s important to cultivate a collaborative spirit with your fellow scientists, as well as experts from other institutes and industries, which will bring together the different skills needed to transform your research into actionable results and tangible solutions.