A5044677661- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Genetic and Kidney Cyst Diseases
- Hedgehog Signaling Pathway Studies
- Tissue Engineering and Regenerative Medicine
- Corneal Surgery and Treatments
- RNA Research and Splicing
- Renal and related cancers
- Genetics and Neurodevelopmental Disorders
- Wound Healing and Treatments
- Circadian rhythm and melatonin
- Connective Tissue Growth Factor Research
- Cancer-related gene regulation
- Neuroscience and Neuropharmacology Research
- Autoimmune and Inflammatory Disorders Research
- interferon and immune responses
- Connective tissue disorders research
- Immune cells in cancer
- Wnt/β-catenin signaling in development and cancer
- Bone health and treatments
- Genetic Syndromes and Imprinting
- Developmental Biology and Gene Regulation
- ATP Synthase and ATPases Research
- Epigenetics and DNA Methylation
- Sphingolipid Metabolism and Signaling
Sanofi (United States)
2020-2024
Universität Innsbruck
2021-2022
Justus-Liebig-Universität Gießen
2016
Université Paris Cité
2006-2014
Délégation Paris 5
2006-2014
Centre National de la Recherche Scientifique
2006-2014
Inserm
2006-2014
Institut Pasteur
2011-2012
Gènes, synapses et cognition
2011-2012
Fondation FondaMental
2012
Autosomal dominant polycystic kidney disease (ADPKD) and other forms of PKD are associated with dysregulated cell cycle proliferation. Although no effective therapy for the treatment is currently available, possible mechanism-based approaches beginning to emerge. A therapeutic intervention targeting aberrant cilia-cell connection using CDK-inhibitor R-roscovitine showed arrest in jck cpk models that not orthologous human ADPKD. To evaluate whether CDK inhibition approach will translate into...
Abstract Methylation is a prevalent post-transcriptional modification encountered in coding and non-coding RNA. For RNA methylation, cells use methyltransferases small organic substances as methyl-group donors, such S -adenosylmethionine (SAM). SAM other nucleotide-derived cofactors are viewed evolutionary leftovers from an world, which riboswitches have regulated, ribozymes catalyzed essential metabolic reactions. Here, we disclose the thus far unrecognized direct link between present-day...
The reparative properties of amniotic membrane allografts are well-suited for a broad spectrum specialties. Further enhancement their utility can be achieved by designing to the needs each application through development novel processing techniques and tissue configurations. As such, this study evaluated material characteristics biological two PURION
Polycystic kidney diseases (PKDs) comprise a subgroup of ciliopathies characterized by the formation fluid-filled cysts and progression to end-stage renal disease. A mechanistic understanding cystogenesis is crucial for development viable therapeutic options. Here, we identify CDK5, kinase active in post mitotic cells, as new important mediator PKD progression. We show that long-lasting attenuation juvenile cystic kidneys ( jck ) mouse model nephronophthisis pharmacological inhibition CDK5...
Mutations in interleukin-1 receptor accessory protein like 1 (IL1RAPL1) gene have been associated with non-syndromic intellectual disability (ID) and autism spectrum disorder. This interacts synaptic partners PSD-95 PTPδ, regulating the formation function of excitatory synapses. The aim this work was to characterize consequences three IL1RAPL1 mutations, two novel causing deletion exon 6 (Δex6) one point mutation (C31R), identified patients ID. Using immunofluorescence electrophysiological...
Abstract Mental retardation (MR) affects approximately 2% of the population. About 10% all MR cases result from defects X‐linked genes. Mutations in most more than 20 known genes causing nonspecific form (MRX) are very rare and may account for less 0.5–1% MR. Linkage studies extended pedigrees followed by mutational analysis MRX linked interval often only way to identify a genetic cause disorder. We performed linkage several families, one family with four males we mapped disease an...
Abstract Background Intellectual disability (ID) is frequently associated with sleep disorders. Treatment melatonin demonstrated efficacy, suggesting that, at least in a subgroup of patients, the endogenous level may not be sufficient to adequately set sleep-wake cycles. Mutations ASMT gene, coding last enzyme pathway have been reported as risk factor for autism spectrum disorders (ASD), which are often comorbid ID. Thus aim study was ascertain genetic variability large cohort patients ID...
Pathological fibrosis is a significant complication of surgical procedures resulting from the accumulation excess collagen at site repair which can compromise tissue architecture and severely impede function affected tissue. Few prophylactic treatments exist to counteract this process; however, use amniotic membrane allografts has demonstrated promising clinical outcomes. This study aimed identify underlying mechanism action by utilizing relevant models that accurately represent...
Development of a disease-modifying therapy to treat autosomal dominant polycystic kidney disease (ADPKD) requires well-characterized preclinical models that accurately reflect the pathology and biochemical changes associated with disease. Using Pkd1 conditional knockout mouse, we demonstrate subtly altering timing extent deletion can have significant impact on origin severity cyst formation. postnatal day 1 or 2 results in cysts arising from both cortical medullary regions, whereas days 3–8...
Thiopurines are in widespread clinical use for the treatment of immunological disorders and certain cancers. However, failure due to resistance or adverse drug reactions common, asking new therapeutic strategies. We investigated potential 6-thioguanosine monophosphate (6sGMP) prodrugs overcome 6-thioguanine. successfully developed synthetic routes toward diverse 6sGMP prodrugs, tested their proliferation inhibitory different cell lines, examined mode action. Our results show that...
Abstract Objective Results of genome scans in rheumatoid arthritis (RA) have suggested that the tumor necrosis factor receptor I (TNFRI) and TNFRII loci ( TNFR1 TNFR2 ) are susceptibility loci. A polymorphism was found to be associated with familial RA. is mutated TNFR‐associated periodic syndrome (TRAPS). We undertook this study test exonic closest TRAPS mutations site (+36 A/G) for association Methods DNA samples were available from two groups French Caucasian population: 1) 100 families 1...
The colonic surface epithelium produces acetylcholine, released after the binding of propionate to GPCRs for this short-chain fatty acid (SCFA). This epithelial acetylcholine then induces anion secretion via stimulation receptors. key enzyme responsible synthesis, choline acetyltransferase, is known be unselective as regards used esterification choline. As permanently exposed high concentrations different SCFAs produced by bacterial fermentation, we investigated whether esters other than...
Abstract Tendon injuries are among the most common ailments of musculoskeletal system. Prolonged inflammation and persistent vasculature complications associated with poor healing. Damaged tendon, replaced scar tissue, never completely regains native structural or biomechanical properties. This study evaluated effects micronized dehydrated human amnion/chorion membrane (μdHACM) on inflammatory environment hypervascularity tendinopathy. Stimulation tenocytes interleukin‐1 beta (IL1β) induced...
Sevelamer hydrochloride, a noncalcium phosphate binder, has been shown to reduce coronary artery and aortic calcification, improve trabecular bone mineral density in hemodialysis patients with chronic kidney disease. Here, we examined whether sevelamer given orally for 12 wk normal food could restore volume (BV) strength aged ovariectomized (OVX) rats starting at 4 after OVX. Dual-energy x-ray absorptiometry, microcomputerized tomography, histomorphometry analyses showed that OVX animals...
Abstract Bardet–Biedl syndrome (BBS) is a pleiotropic autosomal recessive ciliopathy affecting multiple organs. The development of potential disease-modifying therapy for BBS will require concurrent targeting multi-systemic manifestations. Here, we show the first time that monosialodihexosylganglioside accumulates in Bbs2−/− cilia, indicating impairment glycosphingolipid (GSL) metabolism BBS. Consequently, tested whether pathology mice can be reversed by underlying ciliary defect via...
One-step conversion chemistry makes RNA with internal site-specific 2′-azido modifications readily accessible from 2′-amino RNA; it is significantly more efficient compared to thus far used phosphotriester generate such RNA.
AbstractRecent advances in understanding the molecular pathogenesis of polycystic kidney diseases (PKD) are being translated into promising treatments. Currently, a response to therapy preclinical animal models PKD can only be evaluated after several weeks treatment. The availability biomarkers for rapid efficacy assessment would greatly facilitate drug development process. Here we applied SELDI-TOF technology establish serum and urinary biomarker signatures associated with therapeutic...
A naturally occurring riboswitch can utilize 7-aminomethyl- O 6 -methyl-7-deazaguanine (m preQ 1 ) as cofactor for methyl group transfer resulting in cytosine methylation. This recently discovered riboswitch-ribozyme activity opens new avenues the development of RNA labeling tools based on tailored -alkylated derivatives. Here, we report a robust synthesis this class pyrrolo[2,3- d ]pyrimidines starting from readily accessible N 2 -pivaloyl-protected 6-chloro-7-cyano-7-deazaguanine....
Canonical Wnt signaling is a major pathway known to regulate diverse physiological processes in multicellular organisms. Signaling tightly regulated by feedback mechanisms; however, persistent dysregulation of this implicated the progression multiple disease states. In study, proteomic analysis identified endogenous antagonists micronized dehydrated human amnion/chorion membrane (μdHACM); thereby, prompting study further characterize intrinsic properties μdHACM as it relates activity, vitro....
The growing interest in 3-methylcytidine (m3C) originates from the recent discoveries of m3C modified tRNAs humans as well its intensively debated occurrence mRNA. Moreover, formation can be catalyzed by RNA without assistance proteins has been demonstrated for a naturally occurring riboswitch fold using methylated form cognate ligand cofactor. Additionally, new sequencing methods have developed to detect this modification transcriptome-wide manner. For all these reasons, an increasing...
Metabolic labeling has emerged as a powerful tool to endow RNA with reactive handles allowing for subsequent chemical derivatization and processing. Recently, thiolated nucleosides, such 4-thiouridine (4sU), have attracted great interest in metabolic labeling-based sequencing approaches (TUC-seq, SLAM-seq, TimeLapse-seq) study cellular expression decay dynamics. For these other applications (e.g. PAR-CLIP), thus far only the naked nucleoside 4sU been applied. Here we examined concept of...