A5026404773- Neuroinflammation and Neurodegeneration Mechanisms
- RNA regulation and disease
- RNA modifications and cancer
- Immune cells in cancer
- Multiple Sclerosis Research Studies
- RNA Research and Splicing
- Immune Response and Inflammation
- MicroRNA in disease regulation
- interferon and immune responses
- Adenosine and Purinergic Signaling
- Neurogenesis and neuroplasticity mechanisms
- Vaccine Coverage and Hesitancy
- Pancreatitis Pathology and Treatment
- CRISPR and Genetic Engineering
- Amyotrophic Lateral Sclerosis Research
- Cytomegalovirus and herpesvirus research
- Inflammation biomarkers and pathways
- SARS-CoV-2 and COVID-19 Research
- Biochemical effects in animals
- Alzheimer's disease research and treatments
- RNA and protein synthesis mechanisms
- Phagocytosis and Immune Regulation
- Mechanical Circulatory Support Devices
- NF-κB Signaling Pathways
- Mesenchymal stem cell research
McGill University
2014-2023
McGill University Health Centre
2020-2023
Biogen (United States)
2022
Leipzig University
2022
Children's Mercy Hospital
2022
University of Missouri–Kansas City
2022
University of Mary
2020
Montreal Neurological Institute and Hospital
2014-2016
University of Antwerp
2016
Queen's University
2015
To investigate and measure the functional significance of altered P2Y12 expression in context human microglia activation.We performed vitro situ experiments to how can influence disease-relevant properties classically activated (M1) alternatively (M2) inflamed brain.We demonstrated that compared resting microglia, is increased under conditions. In response ADP, endogenous ligand P2Y12, M2 have ligand-mediated calcium responses, which are blocked by selective antagonism. antagonism was also...
Abstract Multifocal inflammatory lesions featuring destruction of lipid-rich myelin are pathologic hallmarks multiple sclerosis. Lesion activity is assessed by the extent and composition uptake myeloid cells present in such lesions. In inflamed CNS, comprised brain-resident microglia, an endogenous cell population, monocyte-derived macrophages, which infiltrate from systemic compartment. Using microglia isolated adult human brain, we demonstrate that phagocytosis dependent on polarization...
Dimethyl fumarate (DMF), a therapy for relapsing-remitting multiple sclerosis (RRMS), is implicated as acting on inflammatory and antioxidant responses within both systemic immune and/or central nervous system (CNS) compartments. Orally administered DMF rapidly metabolized to monomethyl (MMF). Our aim was analyze the impact of fumarates antiinflammatory profiles human myeloid cells found in compartment (monocytes) inflamed CNS (blood-derived macrophages brain-derived microglia).We analyzed...
<h3>Objective</h3> To expand the phenotypic spectrum of severity POLR3-related leukodystrophy and identify genotype-phenotype correlations through study patients with extremely severe phenotypes. <h3>Methods</h3> We performed an international cross-sectional on genetically proven atypical phenotypes to 6 children, 3 males females, phenotype compared that typically reported. Clinical, radiologic, molecular features were evaluated for all patients, functional neuropathologic studies 1 patient....
Leukodystrophies are a class of rare inherited central nervous system (CNS) disorders that affect the white matter brain, typically leading to progressive neurodegeneration and early death. Hypomyelinating leukodystrophies characterized by abnormal formation myelin sheath during development. POLR3-related or 4H (hypomyelination, hypodontia, hypogonadotropic hypogonadism) leukodystrophy is one most common types hypomyelinating for which no curative treatment disease-modifying therapy...
Abstract RNA polymerase III (Pol III)-related hypomyelinating leukodystrophy (POLR3-HLD), also known as 4H leukodystrophy, is a severe neurodegenerative disease characterized by the cardinal features of hypomyelination, hypodontia and hypogonadotropic hypogonadism. POLR3-HLD caused biallelic pathogenic variants in genes encoding Pol subunits. While approximately half all patients carry mutations POLR3B subunit B, there no vivo model based on mutation this subunit. Here, we determined impact...
Phospholipase D (PLD) is a phospholipase enzyme responsible for hydrolyzing phosphatidylcholine into the lipid signaling molecule, phosphatidic acid, and choline. From therapeutic perspective, PLD has been implicated in human cancer progression as well target neurodegenerative diseases, including Alzheimer's. Moreover, knockdown of rescues ALS phenotype multiple Drosophila models (amyotrophic lateral sclerosis) displays modest motor benefits an SOD1 mouse model. To further validate whether...
RNA polymerase III (Pol III) is a critical enzymatic complex tasked with the transcription of ubiquitous non-coding RNAs including 5S rRNA and all tRNA genes. Despite constitutive nature this enzyme, hypomorphic biallelic pathogenic variants in genes encoding subunits Pol lead to tissue-specific features cause hypomyelinating leukodystrophy, characterized by severe permanent deficit myelin. The pathophysiological mechanisms POLR3- related leukodystrophy specifically, how reduced function...
Immunopanning is an efficient and reliable method for isolating primary cells from rodent brain tissue, making it a valuable tool researchers interested in vitro glial models. Here, we present immunopanning protocol optimized the isolation of Platelet-Derived Growth Factor Receptor Alpha positive (PDGFRα+) oligodendrocyte precursor (OPCs) mouse tissue that results high yield pure OPCs minimal quantities starting tissue.•The presented here PDGFRα-dependent selection using commercial antibody,...
Introduction Rare neurodevelopmental disorders, including inherited white matter disorders or leukodystrophies, often present a diagnostic challenge on genetic level given the large number of causal genes associated with range disease subtypes. This study aims to demonstrate challenges and lessons learned in investigations leukodystrophies through presentation series cases solved using exome genome sequencing. Methods Each six patients had leukodystrophy hypomyelination delayed myelination...
A middle-aged patient presented with mild facial dysmorphisms, small teeth enamel hypoplasia, progressive gait disturbances, memory problems, and history of syndactyly, corrected in early childhood. MRI showed a hypomyelination pattern compatible oculodentaldigital dysplasia (ODDD)1,2 (Figure 1). Ophthalmic findings revealed severe bilateral myopia. Exome sequencing heterozygous GJA1 missense variant ( p .Gly138Asp). The patient's mother (deceased) had developed slowly neurodegeneration,...
OBJECTIVE: To compare the in vivo and vitro effects of DMF MMF on human monocytes. BACKGROUND: therapy reduces relapse rates multiple sclerosis (MS). In experimental models, inhibits production pro-inflammatory molecules, induces anti-oxidant responses. vivo, is rapidly metabolized to MMF, thought be biologically active agent. Expression cytokine regulator microRNA-155 (miR-155) up-regulated monocytes untreated MS patients compared healthy controls. DESIGN/METHODS: Monocytes obtained from...
<h3>Objective:</h3> To characterize the role of RNA polymerase III (Pol III) in oligodendrocyte development. <h3>Background:</h3> Hypomyelinating leukodystrophies are a heterogeneous group rare, genetic white matter disorders characterized by insufficient myelin deposition They typically present early development and lead to progressive neurodegeneration premature death months years following onset. III-related hypomyelinating leukodystrophy (POLR3-HLD) is one most common arises from...
<h3>Objective:</h3> To develop the first model of RNA Polymerase III (Pol III)-Related Hypomyelinating Leukodystrophy (POLR3-HLD) based on a <i>POLR3B</i> mutation. <h3>Background:</h3> POLR3-HLD is devastating neurological disease characterized by severe diffuse hypomyelination and progressive functional decline leading to early death. It caused biallelic pathogenic variants in genes encoding Pol subunits. Patients are most commonly affected mutations <i>POLR3A</i> or <i>POLR3B</i>, but...
The Canadian government recently announced, to much fanfare, that they have begun procuring the supplies will be essential for mass vaccination against COVID-19, beginning with an agreement 75 million syringes, alcohol swabs and bandages. This is certainly good news, it absolutely worthwhile think about these possibly overlooked factors needed effectively vaccinate population. But what we them with? Dankner Michell-Robinson argue in current political climate, Government must act now invest...