NEW INVESTIGATOR AWARD 2021 WINNER
Dr. Lisa Julian, Assistant Professor, Department of Biological Sciences, Simon Fraser University
Grant Project: Investigating lysosome activation as a driver of pediatric epilepsy using human cell models
Lisa Julian, PhD is an Assistant Professor at Simon Fraser University (SFU) in the Department of Biological Sciences. She is a Tier II Canada Research Chair in Developmental Origins of Stem Cell Fate, and a Michael Smith Foundation for Health Research/ Parkinson Society BC Scholar. After BSc and MSc degrees in Biochemistry at Western University, Dr. Julian completed her PhD at the University of Ottawa (2013) in developmental neuroscience. Subsequently, she held a Banting Postdoctoral Fellowship at the Ottawa Hospital Research Institute, where she focused on engineering humanized models of the neurodevelopmental epilepsy disorder tuberous sclerosis. Since opening her own research laboratory in the fall of 2020, Dr. Julian has focused on studying the cellular processes that give rise to altered brain development and function in epilepsy disorders. Her lab does this largely by producing and studying brain cells and tissues “in a dish” that are derived from human cells (from non-invasive sources), specifically from patients who suffer from rare genetic epilepsy disorders. Personal experiences with neurological disease and epilepsy, as well as the relationships she continues to build with rare disease patients and families who suffer from these devastating conditions, are strong motivators for Dr. Julian to conduct this important work. Her ultimate goal is to identify effective biomarkers of epilepsy disorders to allow for staging and tracking of disease progression and treatment responses, and to uncover novel therapeutic strategies to cure this devastating disease.
Dr. Julian’s work has revealed that abnormal regulation of organelles, which are sub-cellular structures important for proper cell health and function, during the production of brain stem cells and neurons is linked to the establishment of epileptic brain circuits. Through this Epilepsy Canada/ CURE Epilepsy New Investigator Award funding, her group will now be able to investigate how, at a molecular level, stem cells with dysfunctional organelles contribute to the development of hyper-active epileptic neuron and glial cell networks. In patients with tuberous sclerosis and other similar conditions, epileptic foci contain not only dysfunctional neurons and glia, but also highly atypical neural stem cells. This project will establish the first human cell-based models of epileptic networks containing all three relevant cell types. This will finally allow us to understand the role of these aberrant stem cells in controlling epileptic activity, importantly in the context of human tissue.
Combining these engineered epilepsy models with SFU’s renowned high throughput pharmaceutical compound and functional screening facility, Dr. Julian’s group will also initiate chemical screens to identify and validate novel therapeutic strategies to prevent and inhibit epileptic activity. Establishment of these defined multicellular models of human epileptic tissue will yield patient-centered impacts in important ways: an increased understanding of the molecular processes that lead to epileptic disorders, from the earliest stages, therefore emphasizing both prevention and disease management. Additionally, they will uncover new therapeutic strategies to address both prevention and treatment of epilepsy, which balance finding a cure with an emphasis on minimizing side effects to patients. Importantly, this project aims to develop reproducible and measurable cell models of epileptic tissue from a patient’s own cells; thus, it will establish a critical first stage to enable patient-specific modeling and personalized therapeutics. Over the long-term, this will impact individuals with not only tuberous sclerosis but many other genetic epilepsy conditions as well.