I am on to something important, realised Josephine Hendrikson late one night while working in the Applied Human Genetics Laboratory at the National Cancer Centre Singapore (NCCS).

It was June 2018. Together with the team and her supervisor, Assistant Professor Johnny Ong, she had been tackling a particularly ambitious problem: to disrupt the reach of the cellular communication that enables some cancers to spread throughout the abdominal cavity.

As the results from the first plate appeared on the screen, Hendrikson knew at a glance that she had hit the jackpot.

“It was a Eureka moment for me,” recalled Hendrikson, who is now a second-year MD student at Duke-NUS.

A double-sided Eureka moment: one where she saw that their hypothesis held up and one that would alter the course of her life.

“When I saw that the experiment had worked and we could possibly help patients one day with this finding, I realised that combining science and medicine is something that I wanted to do in a long-term way.” - Josephine Hendrikson

Josephine Hendrikson, second from left, is now in her second year of medical school, has enjoyed the team-based learning approach adopted by Duke-NUS and made fast friends with her team members who have been together since the first year // Credit: Josephine Hendrikson
 

Simple experiments to tackle high-stakes questions

When she had first joined Ong’s lab as a research officer in December 2015, the Nanyang Technological University, Singapore Biological Sciences graduate imagined that the next step—in due course—would be to apply for a PhD. But working in the translational lab of Ong, she saw science in a new light. It was a lab where people dreamt big, took risks and weren’t afraid of failure. And Hendrikson’s project embodied all of that.

“Even among the wider department, many were doubtful whether we would be able to pinpoint anything conclusively,” said Ong, a clinician-scientist with the Department of Sarcoma Peritoneal and Rare Tumours or SPRinT in the Division of Surgery and Surgical Oncology at Singapore General Hospital and NCCS. He specialises in treating cancers that have spread from abdominal organs such as the colon, stomach, liver or ovaries throughout the abdominal cavity. Patients whose cancers have spread throughout this hollow space often experience bloating, caused by excess fluid flooding the cavity.

And it was this fluid and the signals it carries that Hendrikson and Ong were studying.

“No one thought we could stop the growth of cancers by targeting the fluid,” said Ong, who is also an assistant professor at Duke-NUS.

Hendrikson kept detecting this inhibitor in sample after sample–screening more than 150 patient samples by the end of the project But it was an inhibitor that had no known role in these advanced abdominal cancers.

Intrigued by the lack of information, Hendrikson combed through the literature for any hint about what this inhibitor might block, eventually finding that when it was present, it created an environment that allowed cancers’ cellular communication to spread far and wide.

“We did many experiments to make sure that our findings were true,” said Hendrikson. “But throughout, we always married the science with patients’ needs, a translational perspective that was quite different from what I would have done in a basic research lab.”

Adopting this translational perspective forced Hendrikson to think more clearly about what she wanted to find out.

“It also meant that I was able to complete more experiments in less time,” she added.

Josephine Hendrikson worked as a research officer for five years before starting medical school // Credit: Josephine Hendrikson

Even so, seeing her results published in Cell Reports Medicine would take another four years, during which she would be at medical school during the day and return to the lab at night—even though she was no longer a “current” member of team.

“Josephine still designed the experiments. Others would carry out the experiments during the day, and she would come back after hours to troubleshoot because she’d been so involved for so long that she really was the one who knew best,” said Ong.

And what they found was that in the samples with high levels of this inhibitor, the cancers spread fast. So, if they could block the inhibitor, they could potentially cut the communication line, preventing the fluid from broadcasting cancerous signals throughout the abdomen.

Prepping for med school

While lab work was always busy, Ong made sure to offer guidance and encouragement and involved Hendrikson in the everyday routines of a young doctor’s life as she explored different career options.

“Whatever came next, I was very clear in my mind that she should leave us on a better note—to pursue a PhD or to study medicine—and we supported her all the way,” said Ong.

Once Hendrikson was set on pursuing a Doctor of Medicine, she got time off to study for her Medical College Admission Test or MCAT, mentoring sessions and all the advice and insights she could ask for. And, of course, a big celebration from the team when her application to study at Duke-NUS was accepted.

“It was bittersweet,” said Hendrikson of the moment when the news sank in that after almost five years, she would be saying goodbye to the lab and the close-knit team she had been working with.

Johnny Ong (left) presents Josephine Hendrikson with a farewell gift from the whole lab team // Credit: Josephine Hendrikson
 
Now, Hendrikson is nearing the end of her second year of medical school and is once again preparing to head back to the lab for her third-year scholarly project. While she’s not going back to Ong’s lab, he’s keeping close tabs on her progress and helps her make the right connections.

“The clinician-scientist path is not an easy one, even in our AMC (SingHealth Duke-NUS Academic Medical Centre) ecosystem,” said Ong, who knows first-hand the pressure that comes from the personal need to excel in two different disciplines. “I want to make sure that I help her as much as I can along the way.”

Seeing her research through to publication while studying at medical school gave Hendrikson a taste of what her future might feel like. Yet, despite the tall demands on her time, she is still keen to pursue a clinician-scientist pathway.

Reflecting about her career choice, she said: “I saw how difficult the clinician-scientist journey can be and that it takes a certain character to go through this. I was lucky to meet Johnny early on, or else, I might not have considered this as a career option.

“And now, I am looking forward to picking up new research skills during my scholarly project including in areas such as bioinformatics so that I will be able to combine science and medicine throughout my career.”

This story was first published on MEDICUS 2022 - Issue 2.