Choi-Fong Cho, PhD, of the Department of Neurosurgery, knows that not everything in life goes as planned. She started out studying cancer and ended up in neuroscience. She thought she’d never leave her home country in Canada and ended up in Boston. She created a modeling tool that was intended for studying cancer drug delivery and ended up with a technology that can be widely applicable to all areas in neuroscience. Straying from the plan has led to new collaborations and successes, making open-mindedness an essential part of Cho’s professional life.
Cho’s focus at the Brigham is on testing and developing therapeutics for brain cancer. One of her more recent advances is the development of a robust and high-throughput model for testing the delivery of therapeutics into the brain outside of a living system. When treating brain cancer, clinicians face a unique challenge: the blood-brain barrier. Everywhere else in the body, blood vessels allow diffusion. Within the blood-brain barrier, the blood vessels are surrounded by an additional barrier, a wall, that prevents most molecules from moving from the blood stream into the brain. While the blood-brain barrier is critical for protecting the brain from potentially harmful toxins, it’s a major hurdle for delivering therapeutics when it comes to treating diseases in the brain. The barrier is equipped with tight junctions and efflux pumps that serve as “security guards,” of sorts. One of Cho’s goals is to develop smart agents that can trick the guardians of the blood-brain barrier into allowing them to cross into the brain like a Trojan Horse invading Troy.
“Being able to model the blood-brain barrier in a culture dish allows us to test many different drugs at the same time in a high-throughput fashion,” said Cho. “Most importantly, the model needs to be predictive because we want to determine which drugs are most likely to be able to cross the blood-brain barrier in animals and, later, in humans.”
Cho’s group is culturing multi-cellular organoids (miniaturized and simplified versions of an organ) that can closely reproduce the structure and function of the blood-brain barrier outside of a living brain. These organoids, made up of little spheroids of cells less than half a millimeter in diameter, are composed of three different cell types— brain endothelial cells, pericytes and astrocytes—which are major components of the blood-brain-barrier. These three cell types organize to form one structure with a surface that acts as the barrier. The molecules under investigation are placed outside the spheroid, which represents the “blood” and researchers can observe if they can pass the spheroid surface and travel into the core, which represents the “brain.” Using that information, researchers can predict if the drug will pass through the blood-brain barrier in a living organism. This research was published in Nature Communications in June 2017 and has received a lot of attention in the brain research community and beyond.
To pursue her fascination with the brain, Cho trained in biochemistry, oncology, and molecular imaging before coming to the Brigham for her post-doctoral work in brain cancer research. Though brain cancer remains a focus, the multidisciplinary, collaborative environment in the Brigham’s Building for Transformative Medicine and the research community opened her eyes to various types of other translational research.
Reflecting on her field and the progression of her interests, Cho thought back a few years. “When I started, I was mainly focused on doing this to investigate brain cancer drugs. But in fact, this technology can also be used to address a wide range of other brain diseases,” said Cho. “Now, we are aiming to use this platform to answer broader questions that can help the neuroscience community and make a bigger impact on brain healthcare.”
Cho is working to improve and advance this model so that researchers from a variety of fields can implement the technology. Cho hopes that investigators studying anything from neurodegenerative disease to cancer to psychiatry will be able to utilize this platform.
“It’s a whole learning process for me too. I’ve learned not to be closed minded—especially in the field of research. When you open your mind, doors with great opportunities awaiting on the other side will start to open too,” said Cho.
Cho sees lab experience as valuable exposure for trainees to network and learn to become the highly integrative and collaborative professionals needed in today’s research world. Cho’s face lit up talking about her trainees. “I absolutely enjoy mentoring my students, and when they do very well, I’m so proud of them,” said Cho.
Cho has recently embraced the role of a faculty member, after years of having received mentorship and training herself. She particularly values mentors who take the time to support and guide their trainees, provide constructive feedback and create a positive energy in the research space. Cho cited several mentors not limited to Antonio Chiocca, MD, PhD (her current mentor), and Sean Lawler, PhD (her post-doctoral mentor), both in the Department of Neurosurgery, as well as Bradley Pentelute, PhD, a collaborator at Massachusetts Institute of Technology (MIT) as a few who have advised her throughout her professional career and helped create that positive work atmosphere. “To be a good mentor, it’s so important to have good advisors to begin with because as scientists, we’re not exactly tutored how to mentor others during our training. My views and approach on teaching are shaped through following the examples set by my own mentors in the past. It’s inspiration in itself.”
Antonio Chiocca, MD, PhD, chair of the Department of Neurosurgery, noted that there is no magic formula for mentorship, but in Cho’s case it means acting as a sounding board for objectives and how they can be achieved. With a wider range of projects and growing responsibilities, Cho sees motivation and positive attitude as assets especially as she works to grow the lab.
Cho also sets an example for her mentees of the power of collaboration. While her team focuses on developing brain cancer treatments, they are also collaborating with other groups to address other brain pathologies. Overall, Cho intends for her team’s platform to help advance neuroscience research and lead to the discovery of new and better drugs to treat a wide range of central nervous system diseases.
“Science has to be multidisciplinary because we won’t grow otherwise,” said Cho. “The more we collaborate, the more we learn, and the more we can accomplish together. I think that’s very important.”