Research: Having research in the blood

By Anne Loh, Assistant Director, Communications & Outreach

A living laboratory mouse with what looked like a human ear growing out of its back. That was the Vacanti mouse image from the late 1990s that grabbed Nanyang Assistant Professor Christine Cheung's imagination when she was young, and ran away with it. Although this controversial image was later revealed to be a grafted ear using cow cartilage in a biodegradable mould and never intended for human use, yet this was Asst Prof Cheung's first notion of regenerative medicine and it ignited her interest in science, leading her to participate actively in various science and engineering competitions. She was thus motivated to pursue a research career.

The moment of realisation that she had made the right career decision was when Asst Prof Cheung, now 34 years old, was a student intern at the Agency for Science, Technology and Research (A*STAR) in 2007. "I went into the laboratory one day and saw beating cells in my cell culture dish. I was absolutely fascinated that I could make beating heart cells from human stem cells. This has certainly piqued my interest in stem cell research," she reminisced.   

Building upon this interest, Asst Prof Cheung proceeded to specialise in vascular biology, undertaking her PhD training at the University of Cambridge, where she invented methods to convert human stem cells into blood vessel cells, resembling those found in the brain and heart. "There is a saying that 'a man is as old as his arteries'. Blood vessel ageing underlies the crux of many health conditions. Now we can use that to make blood vessel cells from specific individuals in order to study their vascular health more closely," said Asst Prof Cheung.

In August 2018, she was named an Honouree of Medical Innovation at the Junior Chamber International (JCI) Ten Outstanding Young Persons (TOYP) Singapore Award show – the only woman honoured, and awarded the L'Oréal Singapore Science National Fellowship in November.

Her work has caught the attention of an international audience. In March, the mother of one also won the prestigious Human Frontier Science Program Young Investigator Grant to study how the human brain's structure is assembled during the embryonic stage and the role that blood vessels play in that process. The grant will fund this research for US$250,000 per year for a period of three years. This is the only grant awarded to Singapore from a field of 814 submissions from 60 countries. In this international study, she will be collaborating with Assistant Professor of Developmental Biology at Stanford Medicine, USA, Kyle Loh.

In the same month, Asst Prof Cheung was conferred the NTU Provost's Chair in Medicine. These are additions to her ever-growing list of accolades.

All these aren't enough to make her rest on her laurels though. Even when Asst Prof Cheung is off the clock, going about her life, there's a part of her mind constantly ticking, turning over possibilities, putting them down or shelving them for closer scrutiny at the next available window of opportunity to do so. "For me, failures precede success. I have way more rejected grants and fellowships than awarded ones. I learnt and kept trying," she added.

Asst Prof Cheung's on-going research projects also include one on the restoration of ageing blood vessels. "We are studying why certain people are genetically predisposed to vascular diseases. Through creating personalised blood vessel models, we can capture the complex genetics of patients and investigate how risk genotypes are linked to a person's underlying vascular health. We are working towards genetic testing to predict risk of developing certain diseases due to dysfunctional blood vessels."

Learning to ask the right questions is something that her generation has been trained to do. "I am not surprised that we still do not have more answers than questions. Artificial intelligence is powerful and can help us with data mining, but not all answers are factual. We still need human to contextualise and synthesise the right answers," said Asst Prof Cheung. "Standing on the shoulders of giants in the field of developmental biology, we learn about the processes by which organisms grow to give rise to tissues and organs. This collective knowledge has enlightened us on how to guide stem cells to become functional vascular cells using chemical factors."

Advances in techniques and tools have also allowed those working in this area to make huge leaps forward. Improved gene-editing tools and single-cell sequencing have made precision and resolution in our understanding of how genetic mutations affect vascular function, says Asst Prof Cheung, but she is still not yet close to answering the holy grail question in her field.

"Blood vessels were once thought to be passive conduits for transporting oxygen and nutrients to different parts of our body. Now we are beginning to recognise the unexpected role of vascular cells in the organisation of certain tissues' spatial architecture. While the notion that blood vessels could constitute a source of signals for tissue patterning is new, this topic opens up a new direction to better understand how blood vessels crosstalk with other organs," she said.  

What she enjoys most about her work is catching up with her team of researchers and students. "Sometimes they can become one of my best teachers. They educate me about the latest findings in the field, as well as their imaginations on alternative hypotheses."

Working in research has also coloured her life view. "When one door closes, another door opens. Research taught me resilience and versatility. If not for so many failed experiments, I would not have learned to look at problems from different perspectives," she asserts.

Biomedical research generates real impact on healthcare to benefit humanity, which is what drives Asst Prof Cheung, but she acknowledges that fund-raising for it is challenging. "Since funding is finite, I would shift a few large grants into many small grants so that the wider scientific community can benefit. Many breakthroughs are serendipitous findings and more opportunities should be given to seed more ideas," she said.

Counting her family, mentors and students as people who motivate her, Asst Prof Cheung has this advice for those thinking of a career in research, "It is important to have mentors. And research is hard work, which may not necessarily translate into success but without it, you won't get anywhere. In order to sustain your passion, do one thing well at a time and find a purpose in what you aspire to do."

And would she want her two-year-old daughter to follow in her footsteps? "I would rather place more emphasis on the essential soft skills, and hope she can learn to be appreciative and take failures in her stride."