A5048758770- Inflammation biomarkers and pathways
- Muscle Physiology and Disorders
- Autoimmune and Inflammatory Disorders Research
- Virus-based gene therapy research
- Single-cell and spatial transcriptomics
- Otitis Media and Relapsing Polychondritis
- Calpain Protease Function and Regulation
- CAR-T cell therapy research
- Gene Regulatory Network Analysis
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Kawasaki Disease and Coronary Complications
- Cell Image Analysis Techniques
- Microfluidic and Bio-sensing Technologies
- Hematopoietic Stem Cell Transplantation
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Hereditary Neurological Disorders
- Acute Myeloid Leukemia Research
- Immune Cell Function and Interaction
- Viral Infectious Diseases and Gene Expression in Insects
- Heat shock proteins research
- Digital Imaging for Blood Diseases
- Gene expression and cancer classification
École Pratique des Hautes Études
2014-2025
Université Paris Sciences et Lettres
2016-2025
Genethon (France)
2012-2024
Inserm
2005-2024
Sorbonne Université
2020-2024
Centre de Recherche Saint-Antoine
2020-2024
Integrated Genetic Approaches in Therapeutic Discovery for Rare Diseases
2016-2019
University at Buffalo, State University of New York
2019
Centre National de la Recherche Scientifique
2001-2013
In-Q-Tel
2007
ABSTRACT The early steps of adeno-associated virus (AAV) infection involve attachment to a variety cell surface receptors (heparan sulfate, integrins, and fibroblast growth factor receptor 1) followed by clathrin-dependent or independent internalization. Here we have studied the subsequent intracellular trafficking AAV particles from endosomal compartment nucleus. Human lines were transduced with recombinant (rAAV) carrying reporter gene (luciferase green fluorescent protein) in presence...
The molecular events by which eccentric muscle contractions induce damage and remodelling remain largely unknown. We assessed whether exercise modulates the expression of proteinases (calpains 1, 2 3, proteasome, cathepsin B+L), structural proteins (alpha-sarcoglycan desmin), heat shock Hsp27 alphaB-crystallin. Vastus lateralis biopsies from twelve healthy male volunteers were obtained before, immediately after, 1 14 days after a 30 min downhill treadmill running exercise. Eccentric induced...
Hereditary spastic paraplegia (HSP) encompasses a group of rare genetic diseases primarily affecting motor neurons. Among these, type 11 (SPG11) represents complex form HSP caused by deleterious variants in the SPG11 gene, which encodes spatacsin protein. Previous studies have described several potential roles for spatacsin, including its involvement lysosome and autophagy mechanisms, neuronal neurites development or mitochondria function. Despite these findings, precise function protein...
Calpain 3 is known as the skeletal muscle–specific member of calpains, a family intracellular nonlysosomal cysteine proteases. It was previously shown that defects in human calpain gene are responsible for limb girdle muscular dystrophy type 2A (LGMD2A), an inherited disease affecting predominantly proximal muscles. To better understand function and pathophysiological mechanisms LGMD2A also to develop adequate model therapy research, we generated capn3-deficient mice by targeting. fully...
Calpain 3 is a nonlysosomal cysteine protease whose biological functions remain unknown. We previously demonstrated that this altered in limb girdle muscular dystrophy type 2A patients. Preliminary observations suggested its gene subjected to alternative splicing. In paper, we characterize transcriptional and posttranscriptional events leading alterations involving the NS, IS1, IS2 regions and/or calcium binding domains of mouse calpain (capn3). These can be divided into three groups: (i)...
The spontaneous emergence of phenotypic heterogeneity in clonal populations mammalian cells vitro is a rule rather than an exception. We consider two simple, mutually non-exclusive models that explain the generation diverse cell types homogeneous population. In first model, switch consequence extrinsic factors. Initially identical may become different because they encounter local environments induce adaptive responses. According to second intrinsic occur even environments.We have...
Mutations in the dysferlin gene are cause of Limb-girdle Muscular Dystrophy type 2B and Miyoshi Myopathy. The protein has been implicated sarcolemmal resealing, leading to idea that pathophysiology deficiencies is due a deficit membrane repair. Here, we show using two different approaches fullfiling repair as asseyed by laser wounding assay not sufficient for alleviating deficient pathology. First, generated transgenic mouse overexpressing myoferlin test hypothesis myoferlin, which...
Abstract Objective Limb‐girdle muscular dystophy 2A ( LGMD 2A, OMIM ) is a slowly progressive myopathy caused by the deficiency in calpain 3, calcium‐dependent cysteine protease of skeletal muscle. Methods In this study, we carried out an observational study clinical manifestations and disease progression genetically confirmed patients for up to 4 years. A total 85 patients, aged 14–65 years, were recruited three centers located metropolitan France, Basque country, Reunion Island. They...
Individual cells take lineage commitment decisions in a way that is not necessarily uniform. We address this issue by characterising transcriptional changes cord blood-derived CD34+ at the single-cell level and integrating data with cell division history morphological determined time-lapse microscopy. show major leading to multilineage-primed gene expression state occur very rapidly during first cycle. One of 2 stable lineage-primed patterns emerges gradually each variable timing. Some reach...
The insecticidal efficacy towards Helicoverpa armigera lepidopteran larvae of recombinant Autographa californica M nucleopolyhedroviruses, expressing depressant and excitatory scorpion anti‐insect selective toxins, was investigated. ET 50 (effective paralysis time 50%) values obtained with the viruses toxin, LqhIT2, LqhIT1, were 59 h 66 h, respectively, whereas value wild‐type virus longer, 87 post infection. effects when using two distinct temporally regulated viral promoters revealed...
Despite the stochastic noise that characterizes all cellular processes cells are able to maintain and transmit their daughter stable level of gene expression. In order better understand this phenomenon, we investigated temporal dynamics expression variation using a double reporter model. We compared cell clones with transgenes coding for highly mRNA fluorescent proteins expressing destabilized mRNA-s proteins. Both types displayed strong heterogeneity levels. However, products produced...
Abstract Patients with head and neck squamous cell carcinomas (HNSCC) often have poor outcomes due to suboptimal risk management treatment strategies; yet integrating novel prognostic biomarkers into clinical practice is challenging. Here, we report the presence of multinucleated giant cells (MGC)—a type macrophages—in tumors from patients HNSCC, which are associated a favorable prognosis in treatment-naive preoperative chemotherapy–treated patients. Importantly, MGC density increased...
Duchenne Muscular Dystrophy (DMD), a muscle degenerative disease affecting young boys, arises from the loss of dystrophin. Current gene therapy approaches aim to restore shortened form dystrophin (microdystrophin) via Adeno-Associated Vector (AAV) delivery, but clinical studies show limited efficacy, emphasizing need for improved strategies such as combined therapies. In this study, we identified lysosomal perturbations in myofibers DMD patients and animal models, an overlooked mechanism...
Wolman disease (WD) is a severe lysosomal storage disorder characterized by fatal lipid accumulation caused the deficiency of metabolic enzyme, Lysosomal Acid Lipase (LAL), involved in hydrolysis cholesterols and triglycerides. Due to imbalance lipids homeostasis, WD patients suffer from hepatosplenomegaly, hepatic failure adrenal calcification resulting premature infant death within first year age. In this work, we explored multiple imaging analyses fully characterize phenotype LAL...
Patients with mutations in the Artemis gene display a complete absence of T- and B lymphocytes, together increased cellular radiosensitivity; this leads to radiosensitive severe combined immunodeficiency (RS-SCID). Allogenic hematopoietic stem-cell (HSC) transplantation is only partially successful an human leukocyte antigen-genoidentical donor, has prompted search for alternative therapeutic approaches such as therapy. In study, self-inactivated lentiviral vector expressing was used...
Abstract Background The complexity of the skeletal muscle and identification numerous human disease-causing mutations in its constitutive proteins make it an interesting tissue for proteomic studies aimed at understanding functional relationships interacting both health diseases. Method We undertook a large-scale study using two-hybrid screens skeletal-muscle cDNA library to establish proteome-scale map protein-protein interactions centered on involved limb-girdle muscular dystrophies...
When human cord blood–derived CD34+ cells are induced to differentiate, they undergo rapid and dynamic morphological molecular transformations that critical for fate commitment. In particular, the pass through a transitory phase known as “multilineage-primed” state. These characterized by mixed gene expression profile, different in each cell, with coexpression of many genes characteristic concurrent cell lineages. The aim our study is understand mechanisms establishment exit from this We...
Despite the essential role of plasma cells in health and disease, cellular mechanisms controlling their survival secretory capacity are still poorly understood. Here, we identified soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Sec22b as a unique critical regulator cell maintenance function. In absence Sec22b, were hardly detectable serum antibody titers dramatically reduced. Accordingly, Sec22b-deficient mice fail to mount protective immune response. At...