A5023451113- Polyoxometalates: Synthesis and Applications
- X-ray Diffraction in Crystallography
- Organometallic Complex Synthesis and Catalysis
- Metal-Organic Frameworks: Synthesis and Applications
- Adipose Tissue and Metabolism
- Crystallization and Solubility Studies
- RNA and protein synthesis mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Metal complexes synthesis and properties
- Microbial Metabolic Engineering and Bioproduction
- Coordination Chemistry and Organometallics
- RNA modifications and cancer
- Magnetism in coordination complexes
- Viral Infectious Diseases and Gene Expression in Insects
- Chemical Reaction Mechanisms
- Chemical Synthesis and Reactions
- RNA Research and Splicing
- Synthesis and characterization of novel inorganic/organometallic compounds
- Crystallography and molecular interactions
- Crystal Structures and Properties
- Chemical Synthesis and Characterization
- CRISPR and Genetic Engineering
- Organometallic Compounds Synthesis and Characterization
- Metalloenzymes and iron-sulfur proteins
- Inorganic Chemistry and Materials
McGill University
2016-2025
McGill University Health Centre
2010-2021
Université de Montréal
2000-2018
Goodman (Japan)
2015
Cancer Research Center
2015
University of Wisconsin–Madison
2011
Philadelphia University
2010
University of Pennsylvania
2010
Data Management Services (United States)
2009
Target (United States)
2009
Disablement of cell death programs in cancer cells contributes to drug resistance and some cases has been associated with altered translational control. As eukaryotic translation initiation factor 4E (eIF4E) cooperates c-Myc during lymphomagenesis, induces resistance, is a genetic modifier the rapamycin response, we have investigated effect dysregulation ribosome recruitment phase on tumor progression chemosensitivity. eIF4E subunit eIF4F, complex that stimulates by delivering DEAD-box RNA...
The ability to modify the genome of any cell at a precise location has drastically improved with recent discovery and implementation CRISPR/Cas9 editing technology. However, capacity introduce specific directed changes given loci is hampered by fact that major cellular repair pathway occurs following Cas9-mediated DNA cleavage erroneous non-homologous end joining (NHEJ) pathway. Homology-directed recombination (HDR) far less efficient than NHEJ makes screening clones containing...
Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is a frequent occurrence in human cancers and major promoter chemotherapeutic resistance. Inhibition one downstream target this pathway, mTORC1, has shown potential to improve chemosensitivity. However, mechanisms genetic modifications that confer sensitivity mTORC1 inhibitors remain unclear. Here, we demonstrate loss TSC2 E μ- myc murine lymphoma model leads activation accelerated oncogenesis caused by defective...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT31P and 183W NMR Spectroscopic Evidence for Novel Peroxo Species in the "H3[PW12O40].cntdot.yH2O/H2O2" System. Synthesis X-ray Structure of Tetrabutylammonium (.mu.-Hydrogen phosphato)bis(.mu.-peroxo)bis(oxoperoxotungstate) (2-): A Catalyst Olefin Epoxidation a Biphase MediumLaurent Salles, Catherine Aubry, Rene Thouvenot, Francis Robert, Claudine Doremieux-Morin, Genevieve Chottard, Henry Ledon, Yves Jeannin, Jean Marie BregeaultCite this: Inorg....
The crystal structures of three compounds have been determined at room temperature, namely [Gd(hfa)3Cu(salen)] (1), [Y(hfa)3Cu(salen)] (2), and [Gd(hfa)3Cu(salen)(Meim)] (3), the structure a fourth compound, [La(hfa)3(H2O)Cu(salen)] (4), has −100 °C; hfa = hexafluoroacetylacetonato, salen N,N'-ethylenebis(salicylideneaminato), Meim 1-methylimidazole. [La(hfa)3Ni(salen)] (5), isomorphous with 1, also synthesized. 1 crystallizes in monoclinic system, space group P21/n, 17.292(5) Å, b 22.370(5)...
Cytoplasmic stress granules (SGs) are specialized regulatory sites of mRNA translation that form under different conditions known to inhibit initiation. The formation SG occurs via two pathways; the eukaryotic initiation factor (eIF) 2alpha phosphorylation-dependent pathway mediated by and eIF2alpha phosphorylation-independent inactivation factors eIF4A eIF4G. In this study, we investigated effects targeting steps in HeLa cells. By depleting eIF2alpha, demonstrate reduced levels...
Deregulation of cap-dependent translation is associated with cancer initiation and progression. The rate-limiting step protein synthesis the loading ribosomes onto mRNA templates stimulated by heterotrimeric complex, eukaryotic factor (eIF)4F. This represents an attractive target for anticancer drug discovery because it resides at nexus TOR signaling pathway. We have undertaken ultra-high-throughput screen to identify inhibitors that prevent assembly eIF4F complex. One identified compounds...
Abstract The Myc/Max/Mad family of transcription factors and the eukaryotic initiation factor 4F (eIF4F) complex play fundamental roles in regulating cell growth, proliferation, differentiation, oncogenic transformation. eIF4F is involved recruitment ribosomes to mRNAs thought generally be rate-limiting phase translation. Here, we show that c-Myc directly activates three subunits (eIF4E, eIF4AI, eIF4GI). These transcriptional effects are mediated through canonical E-boxes (5′CACGTG3′)...
The recruitment of ribosomes to eukaryotic cellular mRNAs requires the activity two prototypic RNA helicases, initiation factor (eIF) 4AI and eIF4AII. eIF4A isoforms are highly conserved, thought be functionally interchangeable, directed 5' m(7)GpppN cap structure during translation by virtue their assembly into eIF4F, a heterotrimeric complex that also harbors eIF4E binding protein eIF4G scaffolding unit. During course interference experiments aimed at investigating respective roles eIF4AI...
The clustered regularly interspaced short palindromic repeat (CRISPR)-associated enzyme Cas9 is an RNA-guided nuclease that has been widely adapted for genome editing in eukaryotic cells. However, the vivo target specificity of poorly understood and most studies rely on silico predictions to define potential off-target spectrum. Using chromatin immunoprecipitation followed by sequencing (ChIP-seq), we delineate genome-wide binding panorama catalytically inactive directed two different single...
Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with limited treatment options. Although metabolic reprogramming hallmark of many cancers, including PDA, previous attempts to target changes therapeutically have been stymied by drug toxicity and tumour cell plasticity. Here, we show that PDA cells engage an eIF4F-dependent translation program supports redox central carbon metabolism. Inhibition the eIF4F subunit, eIF4A, using synthetic rocaglate CR-1-31-B (CR-31) reduced...
In this study, we aimed to address the current limitations of therapies for macro-metastatic triple-negative breast cancer (TNBC) and provide a therapeutic lead that overcomes high degree heterogeneity associated with disease. Specifically, focused on well-documented but clinically underexploited cancer-fueling perturbations in mRNA translation as potential vulnerability. We therefore developed an orally bioavailable rocaglate-based molecule, MG-002, which hinders ribosome recruitment...
Tuberous sclerosis complex (TSC) is an inherited multi-system neurocutaneous disorder where patients often present with neurodevelopmental manifestations such as epilepsy and TSC-associated neuropsychiatric (TAND) that includes autism spectrum (ASD). TSC caused by inactivating mutations in TSC1 or TSC2 tumor suppressor genes, encoded proteins hamartin (TSC1) tuberin (TSC2) forming a functional inhibiting mechanistic target of rapamycin 1 (mTORC1) signaling. This has led to treatment...
Melanomas display poor response rates to adjuvant therapies because of their intrinsic resistance proapoptotic stimuli. This study indicates that such can be overcome, at least partly, through the targeting eEF1A elongation factor with narciclasine, an Amaryllidaceae isocarbostyril controlling plant growth. Narciclasine displays IC50 growth inhibitory values between 30–100 nM in melanoma cell lines, irrespective levels Normal noncancerous lines are much less affected. At nontoxic doses,...
A cornerstone of the antiviral interferon response is phosphorylation eukaryotic initiation factor (eIF)2alpha. This limits availability eIF2.GTP.Met-tRNA(i)(Met) ternary complexes, reduces formation 43S preinitiation and blocks viral (and most cellular) mRNA translation. However, many viruses have developed counterstrategies that circumvent this cellular response. Herein, we characterize a novel class translation inhibitors block complex prevent assembly complexes. We find driven by HCV...
The 5' RNA cap structure (m7GpppRNA) is a key feature of eukaryotic mRNAs with important roles in stability, splicing, polyadenylation, mRNA export, and translation. Higher eukaryotes can further modify this minimal the addition methyl group on ribose 2'-O position first transcribed nucleotide (m7GpppNmpRNA) sometimes adjoining (m7GpppNmpNmpRNA). In higher eukaryotes, DXO protein was previously shown to be responsible for both decapping degradation transcripts harboring aberrant ends such as...
Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities pre-clinical cancer studies. As result, this compounds has been significantly expanded through the development efficient synthetic schemes. However, it is unknown whether all members rocaglate act similar mechanisms action. Here, we present comprehensive study comparing biological >200 rocaglates better understand how presence different...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTResolution and asymmetric synthesis of ortho-substituted (benzaldehyde)tricarbonylchromium complexesAlex Alexakis, Pierre Mangeney, Ilane Marek, Francoise Rose-Munch, Eric Rose, Assia Semra, Francis RobertCite this: J. Am. Chem. Soc. 1992, 114, 21, 8288–8290Publication Date (Print):October 1, 1992Publication History Published online1 May 2002Published inissue 1 October 1992https://doi.org/10.1021/ja00047a049RIGHTS & PERMISSIONSArticle...
We report that combining a DNA analog (2 0 F-ANA) with rigid RNA analogs [2 F-RNA and/or locked nucleic acid (LNA)] in siRNA duplexes can produce gene silencing agents enhanced potency.The favored conformations of these two are different, and them 1-1 pattern led to reduced affinity, whereas alternating short continuous regions individual modifications increased affinity relative an RNA:RNA duplex.Thus, the binding at key duplex could be tuned by changing incorporation DNA-like RNA-like...
The process of translation occurs at a nexus point downstream number signal pathways and developmental processes. Modeling activation the PTEN/AKT/mTOR pathway in Emu-Myc mouse is valuable tool to study tumor genotype/chemosensitivity relationships vivo. In this model, blocking initiation with silvestrol, an inhibitor ribosome recruitment step has been showed modulate sensitivity tumors effect standard chemotherapy. However, inhibitors elongation have tested as potential anti-cancer...
Translation is regulated predominantly at the initiation phase by several signal transduction pathways that are often usurped in human cancers, including PI3K/Akt/mTOR axis. mTOR exerts unique administration over translation regulating assembly of eukaryotic factor (eIF) 4F, a heterotrimeric complex responsible for recruiting 40S ribosomes (and associated factors) to mRNA 5′ cap structures. Hence, there much interest targeted therapies block eIF4F activity assess consequences on tumor cell...
Significance Multiple myeloma (MM) is a cancer that develops in the bone marrow and remains incurable to this day. It type shows hallmarks of deregulated protein synthesis control. To uncover new vulnerabilities disease, we performed focused RNAi screen identify components translation apparatus that, when depleted, would sensitize tumor cells dexamethasone (DEX), component frontline therapy cancer. We found suppression eukaryotic initiation factor 4F, heterotrimeric complex required for...