A5015059989- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Genetics and Neurodevelopmental Disorders
- Pancreatic function and diabetes
- Genomics and Chromatin Dynamics
- Carcinogens and Genotoxicity Assessment
- Renal and related cancers
- Metabolism, Diabetes, and Cancer
- Prenatal Screening and Diagnostics
- Genomics and Rare Diseases
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Genomic variations and chromosomal abnormalities
- Adrenal and Paraganglionic Tumors
- Vascular Anomalies and Treatments
- Biochemical and Molecular Research
- Pituitary Gland Disorders and Treatments
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Pluripotent Stem Cells Research
- Renal cell carcinoma treatment
- Protein Kinase Regulation and GTPase Signaling
- Diabetes and associated disorders
University Hospital of Geneva
2016-2024
University of Geneva
1989-2024
Génétique Médicale & Génomique Fonctionelle
2023
Geneva College
2020-2021
University of Sheffield
2006-2013
Institute of Cancer Research
2011
Stanford University
2000-2006
McLean Hospital
2004
Case Western Reserve University
2004
Alzforum
2004
In normal human cells, damage due to ultraviolet light is preferentially removed from active genes by nucleotide excision repair (NER) in a transcription-coupled (TCR) process that requires the gene products defective Cockayne syndrome (CS). Oxidative damage, including thymine glycols, shown be TCR cells individuals and xeroderma pigmentosum (XP)-A, XP-F, XP-G patients who have NER defects but not severe CS. Thus, of oxidative an XPG function distinct its endonuclease activity. These results...
Primary cultures of rat hepatocytes were used to investigate the regulation glucokinase gene expression by insulin and glucagon. Insulin added in physiological concentrations culture medium causes de novo induction mRNA. The induced plateau is reached 4 8 h after addition, mRNA level remains high as long present. Comparison potencies insulin, proinsulin, insulin-like growth factor I this system indicates that mediated via receptor. magnitude effect independent extracellular glucose...
Glucokinase, a key regulatory enzyme of glucose metabolism in mammals, provides an interesting model tissue-specific gene expression. The single-copy is expressed principally liver, where it gives rise to 2.4-kilobase mRNA. islets Langerhans the pancreas also contain glucokinase. Using cDNA complementary rat liver glucokinase mRNA, we show that normal pancreatic and tumoral islet cells mRNA species approximately 400 nucleotides longer than hepatic Hybridization with synthetic...
We present the results of our technical validation process in establishing analysis circulating tumor DNA (ctDNA) as a diagnostic tool. Like most cells body, shed blood flow. Analysis ctDNA mutational content can provide invaluable information on genetic makeup tumor, and assist oncologists deciding therapy, or following residual disease. However, low absolute amounts fraction constitute formidable analytical challenges. A key step is to avoid contamination with genomic from cell lysis....
Repair of UV-induced DNA lesions in terminally differentiated human hNT neurons was compared to that their repair-proficient precursor NT2 cells.Global genome repair (6-4)pyrimidine-pyrimidone photoproducts significantly slower than the cells, and cyclobutane pyrimidine dimers (CPDs) not detected neurons.This deficiency global did appear be due denser chromatin structure neurons.By contrast, CPDs were removed efficiently from both strands transcribed genes neurons, with nontranscribed strand...
Immuno-oncology is an ever growing field that has seen important progress across the spectrum of cancers. Responses can be deep and durable. However, as only a minority patients respond to checkpoint inhibition, predictive biomarkers are needed. Cancer genetic disease arising from accumulation somatic mutations in DNA affected cells. Tumor mutational burden (TMB), represents number tumor form neoantigens, responsible for immunogenicity tumors. Randomized controlled trials have so far failed...
Nucleotide excision repair (NER), which is arguably the most versatile DNA system, strongly attenuated in human cells of monocytic lineage when they differentiate into macrophages. Within active genes, however, both strands continue to be proficiently repaired. The proficient nontranscribed strand cannot explained by dedicated subpathway transcription-coupled (TCR), targeted transcribed expressed genes. We now report that previously termed differentiation-associated (DAR) depends upon...
Human embryonic stem cells (hESCs) tend to lose genomic integrity during long periods of culture in vitro and acquire a cancer-like phenotype. In this study, we aim at understanding the contribution point mutations adaptation process providing mechanistic explanation for their accumulation. We observed that, due absence p21/Waf1/Cip1, cultured hESCs lack proper cell cycle checkpoints are vulnerable kind DNA damage usually repaired by highly versatile nucleotide excision repair (NER) pathway....
The human XPG (ERCC5) gene encodes a large acidic protein that corrects the ultraviolet light sensitivity of cells from both xeroderma pigmentosum complementation group G and rodent ERCC 5. Here we characterize five sequence alterations minor splicing defect in XP-G patient XP125LO. Three these changes are polymorphic variants whereas remaining two, one each allele, inactivate vivo. These single point mutations provide formal proof defects give rise to form pigmentosum, their locations...
In cultured rat hepatocytes, transcription of the glucokinase‐gene is turned on by insulin and off glucagon/cAMP, latter being dominant effector system. It thus possible that in absence hormones gene maintained a repressed state basal level cAMP turns relieving repression, for instance via activation cyclic‐nucleotide phosphodiesterase. Three inhibitors this class enzymes were tested their effect insulin‐dependent induction glucokinase hepatocytes. Isobutyl methylxanthine, prototype...
Global nucleotide excision repair is greatly attenuated in terminally differentiated mammalian cells. We observed this phenomenon human neurons and macrophages, noting that the transcription-coupled pathway remains functional there no significant reduction levels of enzymes. have discovered ubiquitin-activating enzyme E1 complements deficiency macrophage extracts, although concentration upon differentiation, our results indicate a phosphorylation E1. In preliminary studies, we identified...
Bi-allelic loss-of-function variants of OTOA are a well-known cause moderate-to-severe hearing loss. Whereas non-allelic homologous recombination-mediated deletions the gene well known, conversions to pseudogene OTOAP1 have been reported in literature but never fully described nor their pathogenicity assessed. Here, we report two unrelated patients with moderate hearing-loss, who were compound heterozygotes for converted allele and deletion OTOA. The initially detected through sequencing...