A5056706108- Muscle Physiology and Disorders
- Neurogenetic and Muscular Disorders Research
- Cardiomyopathy and Myosin Studies
- Inflammatory Myopathies and Dermatomyositis
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Hereditary Neurological Disorders
- RNA modifications and cancer
- Myasthenia Gravis and Thymoma
- RNA Research and Splicing
- Genomics and Rare Diseases
- Metabolism and Genetic Disorders
- Nuclear Structure and Function
- Caveolin-1 and cellular processes
- Genetics and Neurodevelopmental Disorders
- Eosinophilic Disorders and Syndromes
- Ubiquitin and proteasome pathways
- Cellular Mechanics and Interactions
- Protein Tyrosine Phosphatases
- Glycogen Storage Diseases and Myoclonus
- Galectins and Cancer Biology
- Neurological diseases and metabolism
- Genomic variations and chromosomal abnormalities
Children's Hospital of Eastern Ontario
2020-2025
University of Ottawa
2020-2025
University of Duisburg-Essen
2018-2025
Ottawa Hospital
2021-2025
Düsseldorf University Hospital
2024-2025
Essen University Hospital
2020-2025
Heinrich Heine University Düsseldorf
2024-2025
Zentrum für Kinderheilkunde
2025
BG University Hospital Bergmannsheil Bochum
2022-2024
Ruhr University Bochum
2022-2024
Dermatomyositis is an acquired auto-immune disease characterized by skin lesions and muscle-specific pathological features such as perifascicular muscle fibre atrophy vasculopathy. patients display upregulation of type I interferon-inducible genes in fibres, endothelial cells, peripheral blood. However, the effect interferon on tissue has not yet been determined. Our aim was to study pathogenicity vitro evaluate efficacy pathway blockade for therapeutic purposes. The activation...
Intracellular accumulations of mutant, misfolded proteins are major pathological hallmarks amyotrophic lateral sclerosis (ALS) and related disorders. Recently, mutations in Sigma receptor 1 (SigR1) have been found to cause a form ALS frontotemporal lobar degeneration (FTLD). Our goal was pinpoint alterations modifications SigR1 determine how these changes contribute the pathogenesis ALS. In present study, we that levels protein were reduced lumbar patient spinal cord. abnormally accumulated...
Abstract Cysteine modifications emerge as important players in cellular signaling and homeostasis. Here, we present a chemical proteomics strategy for quantitative analysis of reversibly modified Cysteines using bioorthogonal cleavable-linker switch technique (Cys-BOOST). Compared to iodoTMT total analysis, Cys-BOOST shows threefold higher sensitivity considerably specificity precision. Analyzing S-nitrosylation (SNO) S-nitrosoglutathione (GSNO)-treated non-treated HeLa extracts identifies...
Silver–Russell syndrome (SRS) is a heterogeneous disorder characterised by severe intrauterine and postnatal growth retardation, limb body asymmetry, typical facial appearance less common dysmorphisms. Recently, epimutations maternal duplications affecting the short arm of chromosome 11 have been shown to crucial role in aetiology disease. Disturbances same genomic region cause overgrowth Beckwith–Wiedemann (BWS). In BWS, mutations telomeric as well centromeric imprinting centres (ICR1 ICR2)...
Charcot–Marie–Tooth disease type 4C (CMT4C) is an early-onset, autosomal recessive form of demyelinating neuropathy. The clinical manifestations include progressive scoliosis, delayed age walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity. gene mutated in CMT4C disease, SH3TC2 / KIAA1985 , was recently identified; however, the function protein it encodes remains unknown. We have generated knockout mice where first exon Sh3tc2 replaced with enhanced GFP...
Patients with Charcot–Marie–Tooth neuropathy and gene targeting in mice revealed an essential role for the SH3TC2 peripheral nerve myelination. expression is restricted to Schwann cells nervous system, product, SH3TC2, localizes perinuclear recycling compartment. Here, we show that interacts small guanosine triphosphatase Rab11, which known regulate of internalized membranes receptors back cell surface. Results protein binding studies transferrin receptor trafficking are line a as Rab11...
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark ALS. Disruption functional interplay between protein degradation (ubiquitin proteasome system autophagy) RNA-binding homeostasis has recently been suggested as an integrated model that merges several ALS-associated into common pathophysiological pathway. The E102Q mutation...
Marinesco-Sjögren syndrome is a rare autosomal recessive multisystem disorder featuring cerebellar ataxia, early-onset cataracts, chronic myopathy, variable intellectual disability and delayed motor development. More recently, mutations in the SIL1 gene, which encodes an endoplasmic reticulum resident co-chaperone, were identified as main cause of syndrome. Here we describe results mutation analysis 62 patients presenting with cataracts myopathy or combinations at least two these. We...
Anti-synthetase syndrome (ASyS)-associated myositis is a major subgroup of the idiopathic inflammatory myopathies (IIM) and characterized by disease chronicity with musculoskeletal, dermatological pulmonary manifestations. One eight autoantibodies against aminoacyl-transferase RNA synthetases (ARS) detectable in serum affected patients. However, disease-specific therapeutic approaches have not yet been established.To obtain deeper understanding underlying pathogenesis to identify putative...
To characterize morphological and molecular underpinnings of polymyositis with mitochondrial pathology (PM-Mito) in comparison sporadic inclusion body myositis (IBM) to define common distinct pathophysiologic features a focus on interferon (IFN)-associated inflammation T-cell response.In this cross-sectional study, skeletal muscle biopsy samples clinical laboratory data from patients PM-Mito IBM were analyzed at Charité university hospital Berlin, Germany. All available samples, an equal...
Abstract The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also many cases post-infectious syndromes, colloquially referred to as “long COVID”. Due the heterogeneous nature symptoms and scarcity available tissue samples, little is known about underlying mechanisms. We present an in-depth analysis skeletal muscle biopsies obtained from eleven patients suffering enduring fatigue post-exertional malaise after infection with SARS-CoV-2. Compared two...
Inclusion body myositis (IBM) is unique across the spectrum of idiopathic inflammatory myopathies (IIM) due to its distinct clinical presentation and refractoriness current treatment approaches. One explanation for this resistance may be engagement cell-autonomous mechanisms that sustain or promote disease progression IBM independent activity. In study, we focused on senescence tissue-resident cells as potential driver disease. For purpose, compared patients non-diseased controls...
Abstract Background Analysis of muscle biopsies allowed to characterize the pathophysiological changes Duchenne and Becker muscular dystrophies (D/BMD) leading clinical phenotype. Muscle tissue is often investigated during interventional dose finding studies show in situ proof concept pharmacodynamics effect tested drug. Less invasive readouts are needed objectively monitor patients' health status, quality, response treatment. The identification serum biomarkers correlating with function...
Extracellular small RNAs (sRNAs), including microRNAs (miRNAs), are promising biomarkers for diseases such as Duchenne muscular dystrophy (DMD), although their biological relevance is largely unknown. To investigate the relationship between intracellular and extracellular sRNA levels on a global scale, we performed sequencing in four muscle types serum from wild-type, dystrophic mdx, mdx mice which dystrophin protein expression was restored by exon skipping. Differentially abundant sRNAs...
Abstract Transport And Golgi Organization protein 2 (TANGO2) deficiency has recently been identified as a rare metabolic disorder with distinct clinical and biochemical phenotype of recurrent crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias, encephalopathy cognitive decline. We report nine subjects from seven independent families, we studied muscle histology, respiratory chain enzyme activities in skeletal proteomic signature fibroblasts. All carried autosomal recessive...
Abstract Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the DMD gene leading to lack of dystrophin. Variability disease course suggests that other factors influence progression. With this study we aimed identify genetic may account for some variability clinical presentation. We compared whole-exome sequencing (WES) data 27 patients with extreme phenotypes candidate could affect Validation SNPs was performed two independent cohorts including 301 (BIO-NMD cohort) and 109...
Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6-months of age. RIRCD associated with the homoplasmic m.14674T>C DNA mutation; however, only ~ 1/100 carriers develop disease. We studied 27 affected and 15 unaffected individuals from 19 families found additional heterozygous mutations nuclear genes interacting mt-tRNAGlu including EARS2 TRMU majority individuals,...
Duchenne muscular dystrophy (DMD) is a severe progressive muscle disease that mainly affects boys due to X-linked recessive inheritance. In most affected individuals, MLPA or sequencing-based techniques detect deletions, duplications, point mutations in the dystrophin-encoding DMD gene. However, small subset of patients clinically diagnosed with DMD, molecular cause not identified these routine methods. Evaluation 60 our center revealed three cases without known genetic cause. DNA samples...
Abstract Myotonic dystrophy type 2 (DM2) is an autosomal-dominant multisystemic disease with a core manifestation of proximal muscle weakness, atrophy, myotonia, and myalgia. The disease-causing CCTG tetranucleotide expansion within the CNBP gene on chromosome 3 leads to RNA-dominated spliceopathy, which currently untreatable. Research exploring pathophysiological mechanisms in myotonic 1 has resulted new insights into identified mitochondrial dysfunction as promising therapeutic target. It...