Grant: CIHR Fellowship

The brain is the most complex part of the human body. It comprises billions of cells that constantly communicate with each other at every stage of our lives. The brain cells that are responsible for this communication are called neurons. Neurons make extensions to connect to each other with great precision and to form proper brain wiring. However, when neurons make mistakes in their connections, it often results in brain disorders that affect children. Examples of this include intellectual disability and autism spectrum disorders. What interests me is how these neuronal connections get miswired causing children's brains to not function properly. For this purpose, I study a receptor called EPHB2, that is present on the surface of neurons. It instructs neurons whether to connect with other neurons or not. Recently, our group found that this receptor interacts with a protein called MYCBP2. What is striking about that is that our neurologist collaborators identified several children with brain defects that have mutations in either of these two molecules. Here, I propose that these two molecules, the EPHB2 receptor and the MYCBP2 protein work together to wire our brains. In this proposal, I describe a series of cutting-edge experiments that will examine how these two molecules work to direct the formation of neuronal connections, and what happens when these molecules are mutated. For my experiments, I will use mice and human neurons made from stem cells, which will allow me to model how neuronal connections are perturbed in these neurodevelopmental disorders. With my research, I aim to facilitate early diagnosis of specific brain defects in children, which is key to effective therapy and symptom management. Insights from this work may aid the development of new therapeutics that target EPHB2 receptor in neurons, a subject of many current clinical trials.