A5034969903- Melanoma and MAPK Pathways
- PI3K/AKT/mTOR signaling in cancer
- Protein Tyrosine Phosphatases
- CRISPR and Genetic Engineering
- Synthesis and biological activity
- RNA and protein synthesis mechanisms
- Synthesis of Tetrazole Derivatives
- RNA modifications and cancer
- interferon and immune responses
- RNA Research and Splicing
- Colorectal Cancer Treatments and Studies
- Genetics, Bioinformatics, and Biomedical Research
- Lung Cancer Treatments and Mutations
- Ethics in Clinical Research
- Academic Publishing and Open Access
- Cancer Genomics and Diagnostics
- RNA Interference and Gene Delivery
- Molecular Biology Techniques and Applications
- Bioinformatics and Genomic Networks
- COVID-19 Clinical Research Studies
- Protein Degradation and Inhibitors
- Infectious Diseases and Mycology
- Fungal Plant Pathogen Control
- RNA regulation and disease
- Angiogenesis and VEGF in Cancer
EM Strasbourg Business School
2023
Novartis (Switzerland)
2006-2020
Novartis (United States)
2020
Novartis Institutes for BioMedical Research
2006-2020
Friedrich Miescher Institute
1997-2001
Tumors put in a vulnerable position Cancer cells often display alterations metabolism that help fuel their growth. Such metabolic “rewiring” may also work against the cancer cells, however, by creating new vulnerabilities can be exploited therapeutically. A variety of human tumors show changes methionine caused loss gene coding for 5-methylthioadenosine phosphorylase (MTAP). Mavrakis et al. and Kryukov found MTAP renders cell lines sensitive to growth inhibition compounds suppress activity...
In eukaryotes, double-stranded (ds) RNA induces sequence-specific inhibition of gene expression, referred to as interference (RNAi). invertebrates, RNAi can be triggered effectively by either long dsRNAs or 21- 23-nt-long short interfering (si) duplex RNAs, acting effectors RNAi. siRNAs recently have been shown act potent inducers in cultured mammalian cells. However, studies activated dsRNA are impeded its nonspecific effects, mediated dsRNA-dependent protein kinase PKR and RNase L. Here,...
CRISPR/Cas9 has emerged as a powerful new tool to systematically probe gene function. We compared the performance of CRISPR RNAi-based loss-of-function screens for identification cancer dependencies across multiple cell lines. dropout consistently identified more lethal genes than RNAi, implying that many cellular may require full inactivation. However, in two aneuploid models, we found all within highly amplified regions, including nonexpressed genes, scored by CRISPR, revealing an...
Abstract FTY720, a potent immunomodulator, becomes phosphorylated in vivo (FTY-P) and interacts with sphingosine-1-phosphate (S1P) receptors. Recent studies showed that FTY-P affects vascular endothelial growth factor (VEGF)–induced permeability, an important aspect of angiogenesis. We show here FTY720 has antiangiogenic activity, potently abrogating VEGF- S1P-induced angiogenesis implant corneal models. administration tended to inhibit primary significantly inhibited metastatic tumor mouse...
EphB4 and its cognitive ligand ephrinB2 play an important role in embryonic vessel development vascular remodeling. In addition, several reports suggest that this receptor pair is also involved pathologic formation adults including tumor angiogenesis. Eph/ephrin signaling a complex phenomena characterized by forward through the tyrosine kinase of ephrin reverse various protein–protein interaction domains phosphorylation motifs ligands. Therefore, interfering with EphR/ephrin means targeted...
The Hippo (Hpo) pathway is a novel signaling that controls organ size in Drosophila and mammals deregulated variety of human cancers. It consists set kinases that, through number phosphorylation events, inactivate YAP, transcriptional co-activator cellular proliferation apoptosis. We have identified PTPN14 as YAP-binding protein negatively regulates YAP activity by controlling its localization. Mechanistically, we find the interaction ectopic with can be mediated respective WW PPxY motifs....
FGFR1 was recently shown to be activated as part of a compensatory response prolonged treatment with the MEK inhibitor trametinib in several KRAS-mutant lung and pancreatic cancer cell lines. We hypothesize that other receptor tyrosine kinases (RTK) are also feedback-activated this context. Herein, we profile large panel lines for contribution RTKs feedback activation phospho-MEK following inhibition, using an SHP2 (SHP099) blocks RAS mediated by multiple RTKs. find RTK-driven widely exists...
Maturation of 18S rRNA and biogenesis the 40S ribosomes in yeast requires a large number trans-acting factors, including U3 small nucleolar ribonucleoprotein (U3 snoRNP), recently characterized cyclase-like protein Rcl1p. snoRNP is key particle orchestrating early 35S cleavage events. A unique property Rcl1p that it specifically associates with snoRNP, but this association appears to occur only at level nascent not monoparticle. Here we report characterization Bms1p, multiple structures,...
Abstract In the last decade Open Science principles have been successfully advocated for and are being slowly adopted in different research communities. response to COVID-19 pandemic many publishers researchers sped up their adoption of practices, sometimes embracing them fully partially or a sub-optimal manner. this article, we express concerns about violation some its potential impact on quality output. We provide evidence misuses these at stages scientific process. call wider practices...
Article15 May 1997free access The human RNA 3′-terminal phosphate cyclase is a member of new family proteins conserved in Eucarya, Bacteria and Archaea Pascal Genschik Institut de Biologie Moléculaire des Plantes du CNRS, 12 rue Général Zimmer, 67084 Strasbourg, France Search for more papers by this author Eric Billy Friedrich Miescher-Institut, PO Box 2543, 4002 Basel, Switzerland Michal Swianiewicz Witold Filipowicz Corresponding Author Information Genschik2, Billy1, Swianiewicz1 1...
Cell autonomous cancer dependencies are now routinely identified using CRISPR loss-of-function viability screens. However, a bias exists that makes it difficult to assess the true essentiality of genes located in amplicons, since entire amplified region can exhibit lethal scores. These false-positive hits either be discarded from further analysis, which models represent significant number hits, or methods developed rescue true-positives within regions. We propose two positive regions by...
Abstract The introduction of MAPK pathway inhibitors paved the road for significant advancements in treatment BRAF-mutant (BRAFMUT) melanoma. However, even BRAF/MEK inhibitor combination therapy has failed to offer a curative option, most likely because these pathways constitute codependent signaling network. Concomitant PTEN loss function (PTENLOF) occurs approximately 40% BRAFMUT melanomas. In this study, we sought identify nodes PTEN/PI3K that would be amenable combined with...
The histone 3 lysine 79 (H3K79) methyltransferase (HMT) DOT1L is known to play a critical role for growth and survival of MLL-rearranged leukemia. Serendipitous observations during high-throughput drug screens indicated that the use inhibitors might be expandable multiple myeloma (MM). Through pharmacologic genetic experiments, we could validate essential viability subset MM cell lines, in line with recent report from another team. In vivo activity against established xenografts was observed...
Abstract Metabolic genes are increasingly recognized as targets of somatic genetic alteration in human cancer often leading to profound changes intracellular metabolite concentrations. 5-Methylthioadenosine Phosphorylase (MTAP) is a key enzyme the methionine salvage pathway that metabolizes methylthioadenosine (MTA) adenine and methionine. Its chromosomal position proximal CDKN2A results frequent collateral homozygous deletion wide range cancers. By interrogating data from large scale...
The 2',3'-cyclic phosphate termini are produced, as either intermediates or final products, during RNA cleavage by many different endoribonucleases. Likewise, ribozymes such hammerheads, hairpins, the hepatitis delta ribozyme, generate ends. Discovery of 3'-terminal cyclase has indicated that cyclic in can also be produced an entirely mechanism. 3'-phosphate converts into phosphodiester ATP-dependent reaction which involves formation covalent cyclase-AMP and RNA-N3' pp5' A intermediates....
The practice of clinical research is strictly regulated by law. During submission and review processes, compliance such with the laws enforced in country where it was conducted not always correctly filled authors or verified editors. Here we 456 studies published IHU Méditerranée Infection (Marseille, France) identify a range issues stated authorization research, ethically potentially legally. Of these, 248 were same ethics committee reference, even though subjects, samples countries...