A5001333839- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Neurogenesis and neuroplasticity mechanisms
- Phagocytosis and Immune Regulation
- Immune Response and Inflammation
- Adenosine and Purinergic Signaling
- Nuclear Receptors and Signaling
- MicroRNA in disease regulation
- Multiple Sclerosis Research Studies
- interferon and immune responses
- S100 Proteins and Annexins
- Lysosomal Storage Disorders Research
- Retinal Diseases and Treatments
- Single-cell and spatial transcriptomics
- Chemokine receptors and signaling
- melanin and skin pigmentation
- Tryptophan and brain disorders
- Advanced Glycation End Products research
- Parkinson's Disease Mechanisms and Treatments
- Cellular transport and secretion
- Extracellular vesicles in disease
- Autophagy in Disease and Therapy
- Neuropeptides and Animal Physiology
Montreal Neurological Institute and Hospital
2021-2025
McGill University
2021-2025
Memorial University of Newfoundland
2023
HEC Montréal
2023
Université de Montréal
2019-2021
Abstract Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases activated microglia mouse brain disease models does not change a non-human primate model or common human describe genetic divergence the gene promoter, consistent with...
Abstract Aging affects all cell types in the CNS and plays an important role diseases. However, underlying molecular mechanisms driving these age-associated changes their contribution to diseases are only poorly understood. The white matter aging brain as well diseases, such Multiple sclerosis is characterized by subtle abnormalities myelin sheaths paranodes, suggesting that oligodendrocytes, myelin-maintaining cells of CNS, lose capacity preserve a proper structure potentially function age...
Microglia are tissue resident macrophages with a wide range of critically important functions in central nervous system development and homeostasis.In this study, we aimed to characterize the transcriptional landscape ex vivo human microglia across different developmental ages using cells derived from pre-natal, pediatric, adolescent, adult brain samples. We further confirmed our observations ELISA RNAscope.We showed that pre-natal have distinct regulatory signature relative their post-natal...
In multiple sclerosis (MS), microglia and macrophages within the central nervous system (CNS) play an important role in determining balance among demyelination, neurodegeneration, myelin repair. Phagocytic regenerative functions of these CNS innate immune cells support remyelination, whereas chronic maladaptive inflammatory activation promotes lesion expansion disability, particularly progressive forms MS. No currently approved drugs convincingly target CNS, contributing to lack therapies...
Abstract Background Astrocytes are the most numerous glial cell type with important roles in maintaining homeostasis and responding to diseases brain. Astrocyte function is subject modulation by microRNAs (miRs), which short nucleotide strands that regulate protein expression a post-transcriptional manner. Understanding miR profile of astrocytes disease settings provides insight into cellular stresses present microenvironment may uncover pathways therapeutic interest. Methods Laser-capture...
Mer tyrosine kinase (MerTK) is a receptor that mediates non-inflammatory, homeostatic phagocytosis of diverse types cellular debris. Highly expressed on the surface microglial cells, MerTK importance in brain development, homeostasis, plasticity and disease. Yet, involvement this clearance protein aggregates accumulate with ageing neurodegenerative diseases has yet to be defined. The current study explored function uptake alpha-synuclein fibrils which play causative role pathobiology...
Abstract Efforts to understand microglia function in health and diseases have been hindered by the lack of culture models that recapitulate situ cellular properties. In recent years, use serum‐free media with brain‐derived growth factors (colony stimulating factor 1 receptor [CSF1R] ligands TGF‐β1/2) favored for maintenance rodent as they promote morphological features observed situ. Here we study functional transcriptomic impacts such on human (hMGL). Media formulation had little impact...
Abstract Background Induced pluripotent stem cell-derived microglia (iMGL) represent an excellent tool in studying microglial function health and disease. Yet, since differentiation survival of iMGL are highly reliant on colony-stimulating factor 1 receptor (CSF1R) signaling, it is difficult to use study dysfunction associated with pathogenic defects CSF1R. Methods Serial modifications existing protocol were made, including but not limited changes growth combination drive differentiation,...
Abstract In subretinal inflammation, activated mononuclear phagocytes (MP) play a key role in the progression of retinopathies. Little is known about mechanism involved loss photoreceptors leading to vision impairment. Studying retinal damage induced by photo-oxidative stress, we observed that cluster differentiation 36 (CD36)-deficient mice featured less MP accumulation and attenuated photoreceptor degeneration. Moreover, treatment with CD36-selective azapeptide ligand (MPE-001) reduced...
The retinal pigment epithelium (RPE) performs many functions that maintain photoreceptor health. Oxidative damage to the RPE is a critical component in pathogenesis of eye diseases such as age‐related macular degeneration (AMD). Ligands cluster differentiation 36 (CD36) have previously preserved integrity mouse models AMD. cytoprotective effect CD36 ligand MPE‐001 on cells has now been elucidated employing model oxidative stress. Sodium iodate (NaIO 3 ) induced formation reactive oxygen...
Abstract In multiple sclerosis (MS), microglia and macrophages within the central nervous system (CNS) play an important role in determining balance between myelin repair demyelination/neurodegeneration. Phagocytic regenerative functions of these CNS innate immune cells support remyelination, whereas chronic maladaptive inflammatory activation promotes lesion expansion disability, particularly progressive forms MS. No currently approved drugs convincingly target CNS, contributing to critical...
ABSTRACT Synucleinopathies are characterized by the accumulation and propagation of α-synuclein (α-syn) aggregates throughout brain, leading to neuronal dysfunction death. Understanding how these propagate from cell in a prion-like fashion thus holds great therapeutic promises. Here, we focused on understanding cellular processes involved entry pathological α-syn aggregates. We used an unbiased FACS-based genome-wide CRISPR/Cas9 knockout (KO) screening identify genes that regulate preformed...
Abstract MerTK is a receptor tyrosine kinase that mediates the immunologically silent phagocytic uptake of diverse types cellular debris. Highly expressed on surface microglial cell, importance in brain development, homeostasis, plasticity, and disease. Yet, involvement this clearance protein aggregates accumulate with aging neurodegenerative diseases has yet to be defined. The current study explored function alpha-synuclein fibrils which play causative role pathobiology synucleinopathies....
Abstract Increasing evidence indicates heterogeneity in functional and molecular properties of oligodendrocyte lineage cells both during development under pathologic conditions. In multiple sclerosis, remyelination grey matter lesions exceeds that white matter. Here we used derived from versus regions surgically resected human brain tissue samples, to compare the capacities A2B5-positive progenitor mature oligodendrocytes ensheath synthetic nanofibers, relate differences profiles these...
Abstract Efforts to understand microglia function in health and diseases have been hindered by the lack of culture models that recapitulate situ cellular properties. In recent years, use serum-free media with brain-derived growth factors (CSF1R ligands TGF-β1/2) favored for maintenance rodent as they promote morphological features observed . Here we study functional transcriptomic impacts such on human microglia. Media formulation had little impact transcriptome assessed RNA sequencing which...
Abstract Background Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a primary microgliopathy caused by pathogenic variants in the colony-stimulating factor 1 receptor ( CSF1R ) gene. Since signaling crucial for microglia development, survival function, induced pluripotent stem cell-derived (iMGL) represent an excellent tool studying microglial defects ALSP patient-specific variants. Methods Serial modifications to existing iMGL protocol were made, including...