About
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Our Lab Aims
The Zandee Lab at the Montreal Neurological Institute (The Neuro), McGill University, investigates the cellular and molecular mechanisms that drive lesion formation and evolution in Multiple Sclerosis (MS). MS is a chronic autoimmune and neurodegenerative disease of the central nervous system (CNS), affecting an estimated 97,300 Canadians. It is thought to be initiated by the migration of immune cells across the blood-brain barrier (BBB) or blood-cerebrospinal fluid barrier (BCSFB), triggering the formation of CNS lesions. However, we still do not fully understand how lesions form, why they form in specific locations, or what determines their timing and progression.
Our overarching goal is to uncover the mechanisms that control the initiation, progression, and repair of MS lesions using single-cell and spatial transcriptomics, proteomics, and machine learning (ML) approaches. We believe that deeper insight into these processes will not only advance basic science but also identify new therapeutic targets and biomarkers to improve care for people living with MS.
Why the research matters
Despite decades of research, we still lack effective tools to predict where and when MS lesions will form, or how they will progress. Current blood-based biomarkers often fail to reflect what is happening inside the brain. By studying lesions directly within the CNS and using cutting-edge computational tools, we aim to change that.
Our lab brings together neuroimmunology, systems biology, and data science to build a more complete picture of MS pathology; one that moves us closer to personalized treatment strategies, better disease monitoring, and ultimately, improved outcomes for patients.
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Our research is supported by the Ludmer Centre for Neuroinformatics and Mental Health and Healthy Brains for Healthy Lives (HBHL).
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Research Focus Areas
Lesion Pathology at single-cell resolution
We use single-cell RNA sequencing, spatial transcriptomics, bulk RNA sequencing and multiparameter flow cytometry to study MS lesions in detail. A major focus of the lab is the complement system, a key component of the innate immune response, which we investigate in the context of neuroinflammation and demyelination. We also study the role of the anti-inflammatory cytokine IL-37 in CNS immune regulation and lesion dynamics.
Spatial & Temporal Mapping of lesions
Using spatial transcriptomics and multi-parameter fluorescent imaging, we generate high-resolution 2D maps of gene and protein expression in MS lesions across different anatomical regions (cortical, periventricular, deep white and grey matter) and lesion stages. We also perform 3D lesion profiling with confocal and light sheet microscopy to visualize immune cell infiltration, cell-cell interactions, and tissue structure at unprecedented depth.
Mechanistic Studies in Human Glial cells
To validate molecular findings, we use primary human brain cells and induced pluripotent stem cell (iPSC)-derived glia to model inflammation in the CNS. These experiments allow us to explore how candidate pathways affect glial cell function and how inflammation alters gene and protein expression in CNS-resident cells.
Machine Learning for lesion classification nd biomarker discovery
We are pioneering the use of machine learning in MS neuropathology to integrate multi-modal data, including clinical profiles, molecular signatures, and imaging data. Our goal is to develop ML models that can classify lesion types, identify spatial patterns, and predict lesion evolution. This approach aims to discover novel biomarkers and therapeutic targets, especially for CNS-compartmentalized inflammation, which is a major contributor to long-term disability in MS.