Dr. Yi Liu, Scientist in the Regenerative Medicine Program and the Neuroscience Program at the Ottawa Hospital Research InstituteDr. Yi Liu, Scientist in the Regenerative Medicine Program and the Neuroscience Program at the Ottawa Hospital Research InstituteDr. Yi Liu, Scientist in the Regenerative Medicine Program and the Neuroscience Program at the Ottawa Hospital Research Institute (OHRI) and Assistant Professor at the University of Ottawa, is uncovering how brain cells know which genes to turn on or off and what happens when that process goes wrong. From growing mini-brains in the lab to exploring gene-based therapies, his research sheds light on conditions like Rett syndrome and autism, with the goal of improving care for patients with both brain and heart disorders.
Read his Q&A to dive into the most mysterious organ and see what’s next for his research.
Can you describe your research and your goals?
My research explores how brain cells know which genes to turn on or off and what happens when that control goes wrong in conditions like Rett syndrome and autism. Using human stem cells, we grow miniature models of the brain to watch how neurons form, communicate and interact with immune cells. With powerful imaging and genomic tools, we study how a key protein called MECP2 helps organize the cell’s DNA and regulate gene activity. Uncovering what goes awry in these processes will hopefully pave the way for gene-based treatments that can restore healthy brain function. In the long run, our goal is to translate these discoveries into more precise therapies for both brain and heart disorders.
What inspired you to pursue this area of research?
The human brain has always amazed me, with nearly 100 billion neurons, each forming thousands of connections that work together to create our thoughts, memories, movements and emotions. I was drawn to the mystery of how this immense network arises from a simple genetic code. Every neuron follows a precise molecular script: genes switch on and off in carefully timed sequences to guide their growth, connections and responses to experience. What also fascinates me is how dynamic this program is. The environmental factors — influenced by early life experiences, stress or injury — can subtly rewrite these gene expression patterns, changing how neurons communicate and how the brain adapts or fails to recover. My work aims to decode these molecular instructions, to understand how they give rise to the most complex human functions and how their disruption can lead to neurodevelopmental disorders. To me, uncovering this interplay between genes and external signals is one of the most profound scientific frontiers: it connects who we are, how we learn and how we age.
What’s the biggest challenge you face in your research?
One of the biggest challenges in my research is capturing the complexity of the human brain in a dish. Even with the most advanced stem cell models, we can only recreate fragments of the intricate system that neurons experience in a living brain, including the electrical activity, immune signals and cell-cell interactions that shape development and behavior.
Gene regulation adds another layer of complexity. Every neuron in the brain shares the same DNA, yet they interpret it differently depending on how their genes are switched on or off. Decoding these dynamic gene expression patterns, especially how they respond to external influences like stress or injury, is both technically demanding and conceptually vast.
But this challenge is also what makes the work exciting.
Each experiment feels like uncovering one small piece of a much larger puzzle that could eventually help us understand not just disease, but what makes the human brain so remarkably adaptive.
What drew you to the Ottawa Hospital Research Institute?
What drew me to the OHRI was the people and its defining collaborative culture. OHRI brings together scientists, clinicians and engineers who share a common goal: translating discoveries into real benefits for patients. That sense of purpose creates an environment where ideas move quickly from basic research to clinical application. For me, OHRI represents the kind of research ecosystem where curiosity-driven science and translational impact truly come together.
After five amazing yet hectic years in Boston, where my wife and I both completed deeply rewarding postdoctoral fellowships at MIT, we decided it was time to bring our research and our lives back home to Canada, this time with our soon-to-arrive daughter. Ottawa feels like the perfect place to put down roots, a city that blends science, nature and community.
How does your work connect to patient care or real-world impact?
My work begins with patients. We use stem cells reprogrammed from individuals with neurodevelopmental disorders, such as Rett syndrome, to generate human neurons, brain organoids and other models. These systems allow us to study how genes and chromatin are regulated in health and disease. By recreating the cellular environment of the human brain, we can observe how specific genetic mutations alter the development and communication of neurons. This helps us uncover the fundamental principles of gene regulation that underlie learning, memory and cognition. From a translational perspective, these humanized models can be directly used to screen potential therapies or gene-editing approaches. The goal is to bridge the gap between molecular understanding and meaningful treatment, bringing discoveries made in the lab closer to improving the lives of patients.
What’s next for your research?
The next step for my research is to scale up discovery. We are building high-throughput and semi-self-driving experimental systems that can generate vast amounts of data on how genes are regulated in different cell types and disease conditions. By combining automated stem cell differentiation, imaging and molecular profiling, we can systematically map how neuronal genes and chromatin respond to specific perturbations or therapeutic candidates. All of this information will feed into a growing database designed for machine learning and AI-assisted analysis. The goal is to train algorithms that can recognize molecular patterns, predict disease outcomes, and even suggest new therapeutic strategies. Ultimately, I see this as a way to move from descriptive biology toward predictive biology, where we not only observe what happens in cells, but can also anticipate and design the next steps in restoring healthy function.
