Dr. Carol Chen, one of the DMCBH’s newest faculty members, is on a mission to illuminate the intricate mechanisms underlying brain cancer and neurodevelopmental syndromes.
She earned her PhD from the University of British Columbia, focusing on chromatin modifications—the chemical changes that can affect gene expression and ultimately influence health and disease. She then completed a valuable postdoctoral fellowship at McGill University.
“I fell in love with the idea that simple chemical modifications in your genome can change and significantly alter the phenotype of disease,” she recalls. In 2019, a research team led by her postdoctoral supervisor, Dr. Nada Jabado, made a significant scientific breakthrough by linking specific mutations in histone proteins to highly aggressive pediatric brain tumours.
If you were to stretch out all the DNA in a single human cell, it would measure about two metres in length—impressive for something so microscopic. To pack this information efficiently, DNA wraps around proteins called histones, much like thread on spools. This wrapping condenses the genetic material into a structure known as chromatin, providing essential support and organization.
“Histones are fundamental components of our DNA, and they have remained unchanged over five million years of evolution,” Dr. Chen explains. “Yet in certain forms of pediatric brain cancer, they have these specific point mutations.”
DNA and histones can be modified through epigenetic regulation, which is the process that controls gene activity without changing the DNA sequence. This process allows cells to turn genes on or off based on factors like environment and lifestyle, playing a crucial role in growth, development, and disease. If mutations occur in histones or the proteins that modify them, it can sometimes lead to issues that contribute to cancer or neurodevelopmental disorders.
“In a sense, it all started with researching histones,” she reflects. “It has since evolved into an investigation into how epigenetics affects disease.”
Mutations in histone proteins can drive deadly brain cancers like high-grade gliomas, which are a leading cause of death in children and young adults. These aggressive cancers spread rapidly and are often difficult to treat. During her postdoctoral fellowship, Dr. Chen discovered that they originate from specific neurons with abnormal chromatin structures. These differences increase the risk of cancer by improperly activating a particular gene. Targeting this gene with certain drugs could provide better treatment options for patients in the future.
The Chen lab
Established in 2020, the Chen lab focuses on investigating the epigenetic mechanisms underlying brain cancer and neurodevelopmental syndromes. Their research aims to unravel how these diseases come to be, potentially leading to new therapeutic approaches.
To achieve these goals, the lab employs a variety of advanced experimental methods, including patient-derived samples, cerebral organoids and transgenic animal models. By using cerebral organoids, which mimic the structure and function of the human brain, researchers can uniquely study cancer mechanisms. A cerebral organoid from the Chen lab is pictured to the right.
“This approach lets us cultivate three-dimensional mini brains in petri dishes that can mimic the structure of a primitive fetal brain,” Dr. Chen explains. “Using this model is incredibly powerful, as it provides a controlled environment to study brain development and the mechanisms underlying brain disorders.”
Additionally, the use of transgenic animals allows for the exploration of gene function and interaction in vivo. Coupled with state-of-the-art sequencing technologies to profile the genome, epigenome and transcriptome, these methods enhance the lab’s ability to dissect the complex interactions driving brain cancer and neurodevelopmental disorders.
Mentorship and personal life
Dr. Chen reflects on the impact that mentorship has had on her career to date.
“There have been fantastic moments when I’ve made unexpected scientific discoveries, but the most rewarding experiences come from watching the people I’ve mentored exceed my own abilities.”
She is amazed by the rapid advancement of new techniques and technologies and watching the next generation of scientists excel has been incredibly rewarding. When asked about advice for aspiring researchers, she emphasizes the importance of determination and hard work.
“I always echo UBC’s motto: Tuum Est, meaning ‘it is yours.’ You have to be driven. No amount of handholding or negotiating can replace the drive of someone who is self-motivated. My biggest advice for young scientists is to find what you’re passionate about and pursue it because you genuinely want to – It’s crucial for building a fulfilling career. Additionally, surround yourself with people who will champion your dreams—you can’t do it alone.”
Work-life balance is also important for Dr. Chen. When she’s not in the lab, she spends time with her dog Lucy, going for walks, hiking and cooking for her lab friends.
Dr. Chen, pictured with her lab members.
