A5078709967- Peroxisome Proliferator-Activated Receptors
- Retinoids in leukemia and cellular processes
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Adenosine and Purinergic Signaling
- interferon and immune responses
- Immune cells in cancer
- RNA regulation and disease
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Retinal Development and Disorders
- Tryptophan and brain disorders
- Cancer-related gene regulation
- Eicosanoids and Hypertension Pharmacology
- Neuroinflammation and Neurodegeneration Mechanisms
- Circular RNAs in diseases
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Retinal Diseases and Treatments
- Nuclear Receptors and Signaling
- Open Source Software Innovations
- Metabolism and Genetic Disorders
- Innovation and Socioeconomic Development
McGill University Health Centre
2019-2025
McGill University
2012-2025
Peroxisome biogenesis disorders (PBD) are a group of conditions caused by partial or generalized defect in peroxisome biogenesis. They encompass two phenotypic groups: 1. the Zellweger spectrum (ZSD) including severe, intermediate and milder forms [previously known respectively as syndrome (ZS), Neonatal Adrenoleukodystrophy (NALD) Infantile Refsum Disease (IRD)] 2. Rhizomelic Chondrodysplasia Punctata type 1 (RCDP1), well variant phenotypes now being described for both groups. PBD represent...
Zellweger Spectrum Disorder (ZSD) is caused by defects in PEX genes, whose proteins are required for peroxisome assembly and function. Peroxisome dysfunction ZSD causes multisystem effects, with progressive retinal degeneration (RD) among the most frequent clinical findings. However, much remains unknown about how deficiency RD. To study RD pathophysiology ZSD, we used PEX1-p.Gly844Asp (G844D) mouse model, which represents common human PEX1-p.Gly843Asp allele. We previously reported...
Peroxisomal biogenesis disorders (PBDs) are genetic of peroxisome and metabolism that characterized by profound developmental neurological phenotypes. The most severe class PBDs—Zellweger spectrum disorder (ZSD)—is caused mutations in peroxin genes result both non‐functional peroxisomes mitochondrial dysfunction. It is unclear, however, how defective contribute to impairment. In order understand the molecular basis this inter‐organellar relationship, we investigated fate peroxisomal mRNAs...
ABSTRACT Introduction Zellweger spectrum disorder (ZSD) is an autosomal recessive caused by mutations in any of 13 PEX genes encoding proteins required for peroxisome assembly and function. Chronic liver disease one the major clinical manifestations patients impacts quality life survival. However, pathophysiology ZSD remains largely unknown, current interventions are limited. To further study mechanism, we use PEX1-Gly844Asp (G844D) mouse model mild ZSD, which was previously shown to develop...
Abstract Zellweger spectrum disorder (ZSD) results from biallelic mutations in PEX genes required for peroxisome biogenesis. PEX1‐G843D is a common hypomorphic allele the patient population that associated with milder disease. In prior work using PEX1‐G843D/null fibroblast line expressing green fluorescent protein (GFP) reporter peroxisome‐targeting signal (GFP‐PTS1), we demonstrated treatments chemical chaperone betaine and flavonoid acacetin diacetate recovered functions. To identify more...
Patients with Zellweger spectrum disorder (ZSD) commonly present vision loss due to mutations in PEX genes required for peroxisome assembly and function. Here, we evaluate PEX1 retinal gene augmentation therapy a mouse model of mild ZSD bearing the murine equivalent (PEX1-p[Gly844Asp]) most common human mutation. Experimental adeno-associated virus 8.cytomegalovirus.human PEX1.hemagglutinin (AAV8.CMV.HsPEX1.HA) control AAV8.CMV.EGFP vectors were administered by subretinal injection...
The immune response is essential for survival by destroying microorganisms and pre-cancerous cells. However, inflammation, one aspect of this response, can result in short- long-term deleterious side-effects. Mclk1+/− mutant mice be long-lived despite displaying a hair-trigger inflammatory chronically activated macrophages as high mitochondrial ROS generation. Here we ask whether phenotype beneficial or simply tolerated. We used models infection Salmonella serovars found that mutants mount...
Abstract Peroxisome Biogenesis Disorders-Zellweger Spectrum (PBD-ZSD) are a heterogenous group of autosomal recessive disorders caused by defects in PEX genes whose proteins required for peroxisome assembly and function. Peroxisomes ubiquitous organelles that play critical role complex lipid metabolism. Dysfunctional peroxisomes ZSD cause multisystem effects, with progressive retinal degeneration (RD) leading to childhood blindness being one the most frequent clinical findings. Despite...
Abstract Background Zellweger Spectrum Disorder (ZSD) is caused by bi-allelic defects in any of 13 PEX genes, resulting failure to form functional peroxisomes. Individuals manifest a wide spectrum clinical phenotypes and severity, but almost all have retinal degeneration leading blindness. The onset, extent progression findings has not been well-described there are no therapies for treating vision loss. With expanding research trials on gene therapy genetic disorders, it now crucial...
Abstract Peroxisomal Biogenesis Disorders (PBDs) are a class of inherited metabolic disorders with profound neurological and other phenotypes. The most severe PBDs caused by mutations in peroxin genes, which result nonfunctional peroxisomes typically through impaired protein import. In order to better understand the molecular causes Zellweger Spectrum Disease (ZSD) -the -, we investigated fate peroxisomal mRNAs proteins ZSD model systems. We found that loss import has no effect on mRNA...
Background: Zellweger spectrum disorder (ZSD) is an autosomal recessive disease caused by mutations in any one of 13 PEX genes whose protein products are required for peroxisome assembly. Retinopathy leading to blindness the major handicaps faced affected individuals, but treatment this supportive only. To test whether we could improve visual function ZSD, performed a proof-of-concept trial PEX1 gene augmentation therapy using Pex1-G844D mouse model, which bears equivalent common human...
Background: Zellweger spectrum disorder (ZSD) is an autosomal recessive disease caused by mutations in any one of 13 PEX genes whose protein products are required for peroxisome assembly. Retinopathy leading to blindness the major untreatable handicaps faced patients with ZSD but not well characterized, and requirement peroxisomes retinal health unknown. To address this inform future therapeutic studies, we examined progression retinopathy our murine model common PEX1-G843D allele. Methods:...