A5063058719- Porphyrin Metabolism and Disorders
- Neonatal Health and Biochemistry
- Heme Oxygenase-1 and Carbon Monoxide
- CRISPR and Genetic Engineering
- Diet and metabolism studies
- Pluripotent Stem Cells Research
- Cancer, Hypoxia, and Metabolism
- Digestive system and related health
- Metabolism and Genetic Disorders
- Peroxisome Proliferator-Activated Receptors
- Gut microbiota and health
- Adipose Tissue and Metabolism
- Kidney Stones and Urolithiasis Treatments
- RNA regulation and disease
- Cancer, Lipids, and Metabolism
- Clinical Nutrition and Gastroenterology
- Folate and B Vitamins Research
- Iron Metabolism and Disorders
- Inflammatory mediators and NSAID effects
- Renal and related cancers
- Fatty Acid Research and Health
- Glioma Diagnosis and Treatment
- Photodynamic Therapy Research Studies
- Lipid metabolism and biosynthesis
- Hematopoietic Stem Cell Transplantation
Inserm
2010-2024
Université de Bordeaux
2016-2024
Bordeaux Population Health
2019-2024
Laboratory of Excellence GR-Ex
2013-2024
Centre Hospitalier Universitaire de Bordeaux
2014-2024
Hôpital Pellegrin
2014-2024
Laboratoire de Biochimie
2020-2024
Biotherapy of Genetic Diseases, Inflammatory Disorders and Cancers
2013-2021
Institut des Maladies Génétiques Imagine
2020-2021
AgroParisTech
2013-2016
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....
High-protein diets are used for body weight reduction, but consequences on the large intestine ecosystem poorly known. Here, rats were fed 15 days with either a normoproteic diet (NP, 14% protein) or hyperproteic-hypoglucidic isocaloric (HP, 53% protein). Cecum and colon recovered analysis. Short- branched-chain fatty acids, as well lactate, succinate, formate, ethanol contents, markedly increased in colonic luminal contents of HP (P < 0.05 less) to lower extent cecal content. This was...
Abstract CRISPR-Cas9 is a promising technology for gene therapy. However, the ON-target genotoxicity of nuclease due to DNA double-strand breaks has received little attention and probably underestimated. Here we report that genome editing targeting globin genes induces megabase-scale losses heterozygosity (LOH) from cut-site telomere (5.2 Mb). In established lines, frequent terminal chromosome 11p truncations rare copy-neutral LOH. primary hematopoietic progenitor/stem cells, detect 1.1%...
Butyrate, a short-chain fatty acid produced by the colonic bacterial fermentation is able to induce cell growth inhibition and differentiation in colon cancer cells at least partially through its capacity inhibit histone deacetylases. Since butyrate expected impact cellular metabolic pathways cells, we hypothesize that it could exert antiproliferative properties altering metabolism. We show although Caco2 oxidized both glucose into CO(2) , they displayed higher oxidation rate with as...
OBJECTIVE—Pyruvate dehydrogenase complex (PDC) serves as the metabolic switch between glucose and fatty acid utilization. PDC activity is inhibited by kinase (PDK). shares same substrate, i.e., pyruvate, glyceroneogenesis, a pathway controlling release from white adipose tissue (WAT). Thiazolidinediones activate glyceroneogenesis. We studied regulation rosiglitazone of PDK2 PDK4 isoforms tested hypothesis that glyceroneogenesis could be controlled PDK. RESEARCH DESIGN AND...
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.
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...
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...
Lactose malabsorption is associated with rapid production of high levels osmotic compounds, such as organic acids and SCFA in the colon, suspected to contribute onset lactose intolerance. Adult rats are lactase deficient present study was conducted evaluate vivo metabolic consequences acute ingestion, including host–microbiota interactions. Rats received diets 25 % sucrose (S25 control group) or (L25 experimental group). lactic acid were quantified intestinal contents portal blood....
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...
(1) Background: Congenital erythropoietic porphyria (CEP), named Günther's disease, is a rare recessive type of porphyria, resulting from deficient uroporphyrinogen III synthase (UROS), the fourth enzyme heme biosynthesis. The phenotype ranges extremely severe perinatal onset, with life-threatening hemolytic anaemia, to mild or moderate cutaneous involvement in late-onset forms. This work reviewed CEP cases recorded France order analyse their various presentations and evolution. (2) Methods:...
Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder of the heme biosynthetic pathway that characterized by uroporphyrinogen III synthase (UROS) deficiency and accumulation non-physiological isomer I porphyrins. These phototoxic metabolites predominantly produced erythron result in ineffective erythropoiesis, chronic hemolysis splenomegaly, but they also disseminate tissues causing bullous photosensitivity to UV light skin fragility may progress scarring with photo...
Radiosensitization of glioblastoma is a major ambition to increase the survival this incurable cancer. The 5-aminolevulinic acid (5-ALA) metabolized by heme biosynthesis pathway. 5-ALA overload leads accumulation intermediate fluorescent metabolite protoporphyrin IX (PpIX) with radiosensitization potential, never tested in relevant model glioblastoma. We used patient-derived tumor cell line grafted orthotopically create brain model. evaluated growth and burden after different regimens...
CRISPR/Cas9 is a promising technology for gene correction. However, the edition often biallelic, and uncontrolled small insertions deletions (indels) concomitant to precise correction are created. Mutation-specific guide RNAs were recently tested correct dominant inherited diseases, sparing wild-type allele. We an original approach compound heterozygous recessive mutations. compared editing efficiency genotoxicity by biallelic RNA versus mutant allele-specific in iPSCs derived from...