A5047251846- Porphyrin Metabolism and Disorders
- Neonatal Health and Biochemistry
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Lysosomal Storage Disorders Research
- Heme Oxygenase-1 and Carbon Monoxide
- Retinoids in leukemia and cellular processes
- Kidney Stones and Urolithiasis Treatments
- Glycogen Storage Diseases and Myoclonus
- Metabolism and Genetic Disorders
- Folate and B Vitamins Research
- RNA Interference and Gene Delivery
- Neurogenetic and Muscular Disorders Research
- Colorectal Cancer Screening and Detection
- Pluripotent Stem Cells Research
- Stress Responses and Cortisol
- Diet and metabolism studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Amino Acid Enzymes and Metabolism
- Adipose Tissue and Metabolism
- Reproductive biology and impacts on aquatic species
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Muscle Physiology and Disorders
Université de Bordeaux
2013-2024
Bordeaux Population Health
2006-2024
Inserm
2013-2024
Centre Hospitalier Universitaire de Bordeaux
2002-2024
Laboratory of Excellence GR-Ex
2013-2024
Hôpital Pellegrin
2013-2024
Laboratoire de Biochimie
2020-2024
Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers
2012-2022
Laboratoire de Biochimie
2022
Institut des Maladies Génétiques Imagine
2020-2021
Abstract CRISPR-Cas9 is a promising technology for genome editing. Here we use Cas9 nuclease-induced double-strand break DNA (DSB) at the UROS locus to model and correct congenital erythropoietic porphyria. We demonstrate that homology-directed repair rare compared with NHEJ pathway leading on-target indels causing unwanted dysfunctional protein. Moreover, describe unexpected chromosomal truncations resulting from only one DSB in cell lines primary cells by p53-dependent mechanism....
Abstract The CRISPR-Cas9 system has revolutionized our ability to precisely modify the genome and led gene editing in clinical applications. Comprehensive analysis of products at targeted cut-site revealed a complex spectrum outcomes. ON-target genotoxicity is underestimated with standard PCR-based methods necessitates appropriate more sensitive detection methods. Here, we present two complementary Fluorescence-Assisted Megabase-scale Rearrangements Detection (FAMReD) systems that enable...
The off-patent marketed antifungal ciclopirox improves symptoms in a mouse model of congenital erythropoietic porphyria.
Glycogen storage disease type II (GSDII) or Pompe is an autosomal recessive disorder caused by acid alpha-glucosidase (GAA) deficiency, leading to lysosomal glycogen accumulation. Affected individuals store mainly in cardiac and skeletal muscle tissues resulting fatal hypertrophic cardiomyopathy respiratory failure the most severe infantile form. Enzyme replacement therapy has already proved some efficacy, but results remain variable especially muscle. Substrate reduction was successfully...
Age-related memory decline including spatial reference is considered to begin at middle-age and coincides with reduced adult hippocampal neurogenesis. Moreover, a dysfunction of vitamin A signalling pathway has been involved in the appearance age-related deficits but also neurogenesis alterations. The present study aims testing hypothesis that mid-life supplementation would be successful strategy prevent deficits. Thus, middle-aged Wistar rats were submitted enriched diet tested 4 months...
To assess automatic computer-aided in situ recognition of the morphological features pure and mixed urinary stones using intra-operative digital endoscopic images acquired a clinical setting.In this single-centre study, urologist with 20 years' experience intra-operatively prospectively examined surface section all kidney encountered. Calcium oxalate monohydrate (COM) or Ia, calcium dihydrate (COD) IIb, uric acid (UA) IIIb criteria were collected classified to generate annotated datasets. A...
A disruption of the vitamin signaling pathway has been involved in age-related memory decline and hippocampal plasticity alterations. Using deficiency (VAD), a nutritional model leading to hyposignaling retinoid pathway, we have recently demonstrated that retinoic acid (RA), active metabolite A, is efficient reverse VAD-induced spatial deficits adult neurogenesis Besides, excess glucocorticoids (GCs) occurring with aging known strongly inhibit functions few studies report on counteracting...
Significance The genetic disease congenital erythropoietic porphyria (CEP) results from the accumulation of toxic porphyrins owing to an enzymatic uroporphyrinogen III synthase (UROS) defect. We have already shown that UROS C73R and P248Q mutants, usually associated with a severe phenotype, conserve partial intrinsic activity but suffer kinetic instability premature degradation by proteasome pathway. now demonstrate treatment clinically approved inhibitor could rescue mutant expression in...
Successful treatment of blood disorders by gene therapy has several complications, one which is the frequent lack selective advantage genetically corrected cells. Erythropoietic protoporphyria (EPP), caused a ferrochelatase deficiency, good model hematological genetic with spontaneous in vivo selection. This disease characterized accumulation protoporphyrin red cells, bone marrow, and other organs, resulting severe skin photosensitivity. Here we develop self-inactivating lentiviral vector...
Glycogen storage disease type II (GSDII) or Pompe is an autosomal recessive disorder caused by defects in the acid α-glucosidase gene, which leads to lysosomal glycogen accumulation and enlargement of lysosomes mainly cardiac muscle tissues, resulting fatal hypertrophic cardiomyopathy respiratory failure most severely affected patients. Enzyme replacement therapy has already proven be beneficial this disease, but correction pathology skeletal still remains a challenge. As substrate...
Abstract Background Glycogen storage disease type II (GSDII) or Pompe is an inherited of glycogen metabolism caused by a lack functional lysosomal acid α‐glucosidase (GAA). Affected individuals store in lysosomes resulting fatal hypertrophic cardiomyopathy and respiratory failure the most severe form. Even if enzyme replacement therapy (ERT) has already proven some efficacy, its results remain heterogeneous skeletal muscle, especially cross reactive immunological material (CRIM)‐negative...
Chronic myeloid leukemia disease (CML) found effective therapy by treating patients with tyrosine kinase inhibitors (TKI), which suppress the BCR-ABL1 oncogene activity. However, majority of achieving remission TKI still have molecular evidences persistence. Various mechanisms been proposed to explain persistence and recurrence. One hypotheses is that primitive leukemic stem cells (LSCs) can survive in presence TKI. Understanding leading resistance LSCs CML a critical issue but limited...
Congenital erythropoietic porphyria (CEP) is an inborn error of heme biosynthesis characterized by uroporphyrinogen III synthase (UROS) deficiency resulting in deleterious porphyrin accumulation blood cells responsible for hemolytic anemia and cutaneous photosensitivity. We analyzed here the molecular basis UROS impairment associated with twenty nine missense mutations actually described CEP patients. Using a computational biophysical joint approach we predicted that most disease-causing...
Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder of the liver metabolism due to functional deficiency peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). AGT results in overproduction oxalate which complexes with calcium form insoluble calcium-oxalate salts urinary tracts, ultimately leading end-stage renal disease. Currently, only curative treatment for PH1 combined liver-kidney transplantation, limited by donor organ shortage and lifelong requirement...
We report the case of a 78-year-old patient with late diagnosis hyperoxaluria type III (PH3). He developed renal failure after nephrectomy for clear cell papillary carcinoma and complained recurrent urolithiasis some 30 years, whose aetiology was never identified. Biochemical laboratory investigations urine composition revealed marked but normal concentrations urinary glyceric glycolic acid as well stones idiopathic calcium-oxalate appearance. Furthermore, dietary survey showed excessive...
The biggest abiotic threat to banana (Musa spp.) production is water deficit, but physiological indicators in plantations are lacking. Canopy Cover (CC) seems be a relevant parameter, so far not used fields. Field experiments were conducted determine the effect of optimal irrigation (FI) versus rainfed (RF) on CC and Leaf Area Indices (LAI) two with different cultivars (Mchare 'Huti Green' [HG, AA] Cavendish 'Grand Naine'[GN, AAA]) (n = 3 for HG, n 4 GN) until harvest cycle 1 (C1), studying...
Studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic (DHA), and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding nuclear receptors such as retinoid X (RXRs) retinoic (RARs). Moreover, EPA/DHA retinoids activate notably kinase signaling pathways AKT or MAPK, which includes ERK1/2. This suggests these may modulate function a similar way. Therefore, we investigated middle-aged rats behavioral molecular...