Activation of human skeletal muscle stem cells:role of Orai3 ans its partner AHNAK2 in physiological condition and in Duchenne Muscular Dystrophy
Prof. Maud Frieden, University of Geneva
Abstract
The regeneration process of skeletal muscle is induced after a lesion or an overloaded exercise and
relies on the presence of muscle stem cells, called satellite cells. Our laboratory has been working for
several years with an in vitro model of human muscle regeneration, where activated muscle stem cells
proliferate as myoblasts and differentiate into myotubes, but also reform a quiescent stem cell
population, called reserve cells. Serum stimulation triggered the re-entry into the cell cycle (activation)
of a subset of reserve cells, that is associated with an elevation of the cytosolic calcium concentration.
However, we showed that the activation is independent of the calcium signal while the migration of
reserve cells depends on calcium response. Surprisingly, we identified a calcium channel, Orai3, as
being a key player for reserve cell activation but independently from its calcium channel function.
Furthermore, we found out by a proximity protein assay, that AHNAK2, a large scaffold protein, is a
partner of Orai3. One aim of this project is to determine the role of Orai3 and AHNAK2 in the reserve
cell activation process and the interaction sites between both proteins. The second goal is to determine
the function of both proteins in the context of Duchenne muscular dystrophy. We postulate that these
proteins being overexpressed in the condition of reduced dystrophin expression might be involved in
the pathogenicity of DMD. Overall, this project will bring a better knowledge of the processes of human
muscle stem cell activation and the role of two new players in this process, namely a calcium channel
Orai3 and a scaffold protein AHNAK2. This knowledge will be extended to DMD, a very severe muscular
dystrophy.
Projekte
- Neue Forschungsprojekte ab 2024
- Die Bedeutung und die Erfolge der Forschung
- Finanzierte Projekte
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- Activation of human skeletal muscle stem cells:role of Orai3 ans its partner AHNAK2 in physiological condition and in Duchenne Muscular Dystrophy
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- Facilitating diagnosis of critical illness myopathy using muscle excitability testing
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- Can HDAC/DNA methyltransferase inhibitors improve muscle function in a congenital myopathy caused by recessive RYR1 mutations?
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- A multicenter cross-sectional and longitudinal study of the Swiss cohort of Merosin-negative congenital muscular dystrophy
- Targeting NADPH oxidase 4 in models of Duchenne muscular dystrophy
- Characterizing the role of ER stress in C9orf72-linked ALS pathology
- Inducing mitophagy with Urolithin A to restore mitochondrial and muscle function in muscular dystrophy
- Motor unit action potentials analysis in patients with myopathies with a new wireless portable and multichannel Surface EMG device (WPM-SEMG)
- Role and therapeutic potential of PLIN3 in neuromuscular diseases
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- Characterization of pathological pathways activated in muscles of patients with congenital myopathies with disturbed Ca2+ homeostasis
- Creation of a study team to conduct an SMA 1-clinical trial at the Centre for Neuromuscular Diseases of the University Children's Hospital Basel (UKBB)
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- Understanding the pathomechanisms leading to muscle alterations in Myotonic Dystrophy type I
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- Generation of uncommitted human IPSC derived muscle stem cells for therapeutic applications
- Transposable vectors for dystrophin-expression in a murine model for muscular dystrophy
- Cardiac involvement in patients with Duchenne/Becker Muscular Dystrophy; an observational study
- Deciphering the pathogenic mechanisms of C9ORF72 ALS
- Enhancing estrogenic signalling to fight muscular dystrophies: Mechanisms of action and repurposing clinically approved drugs
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- Triggering human myoblast differentiation: from EGFR to myogenic transcription factors
- Improving cellular therapies of muscle dystrophies by uncovering epigenetic and signaling pathways of muscle formation
- Protein engineering in an attempt to increase the mechanical, integrin dependent cytoskeleton-matrix linkage in muscle fibers
- Muscle velocity recovery cycles: a new tool for characterization of muscle disease in vivo
- Excessive neurotrypsin activation and agrin cleavage-a pathogenic condition leading to sarcopenia-like muscle atrophy?
- Evaluation of novel treatment strategies for dyspherlinopathies in mouse models
- Cell therapy of LGMD2D by donor HLA-characterized human mesoangioblasts (hMABs) produced in GMP conditions
- In search of small molecules targeting protein-RNA complex: a novel approach against Spinal Muscular Atrophy
- Restoration of autophagy as a new strategy for the treatment of congenital muscular dystrophies
- Development of magnetic resonance methods for functional imaging of the skeletal muscle
- Targeting ER stress response: a potential mechanism for neuroprotection in Amyotrophic Lateral Sclerosis
- Generation of uncommitted human IPSC derived muscle stem cells for therapeutic applications
- Projektbroschüre
- SEAL Therapeutics AG
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