A5005713802- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Genetic factors in colorectal cancer
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- BRCA gene mutations in cancer
- Colorectal Cancer Treatments and Studies
- Cell Adhesion Molecules Research
- Erythrocyte Function and Pathophysiology
- DNA Repair Mechanisms
- Cellular transport and secretion
- Cancer Treatment and Pharmacology
- 3D Printing in Biomedical Research
- Nuclear Structure and Function
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- Cell Image Analysis Techniques
- Hippo pathway signaling and YAP/TAZ
- Chromatin Remodeling and Cancer
- Glioma Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- Renal and related cancers
- Renal cell carcinoma treatment
Institut Curie
2015-2025
Sorbonne Université
2011-2025
Centre National de la Recherche Scientifique
2017-2025
Université Paris Sciences et Lettres
2016-2025
Physique des Cellules et Cancers
2019-2022
Inserm
2011-2019
Centre de Recherche Saint-Antoine
2011
Hôpital Saint-Antoine
2011
Hotspot mutations in the spliceosome gene SF3B1 are reported ∼20% of uveal melanomas. is involved 3'-splice site (3'ss) recognition during RNA splicing; however, molecular mechanisms its mutation have remained unclear. Here we show, using RNA-Seq analyses melanoma, that SF3B1(R625/K666) results deregulated splicing at a subset junctions, mostly by use alternative 3'ss. Modelling differential junctions SF3B1(WT) and cell lines demonstrates splice pattern strictly depends on status...
CDK12 is a recurrently mutated gene in serous ovarian carcinoma, whose downregulation associated with impaired expression of DNA damage repair genes and subsequent hypersensitivity to DNA-damaging agents PARP1/2 inhibitors. In this study, we investigated the genomic landscape inactivation patients carcinoma. We show that loss was consistently particular instability pattern characterized by hundreds tandem duplications up 10 megabases (Mb) size. Tandem were bimodal (∼0.3 ∼3 Mb) size...
Genetic mutations affecting chromatin modifiers are widespread in cancers. In malignant peripheral nerve sheath tumors (MPNSTs), Polycomb repressive complex 2 (PRC2), which plays a crucial role gene silencing, is inactivated through recurrent core subunits embryonic ectoderm development (EED) and suppressor of zeste 12 homolog (SUZ12), but PRC2’s main catalytic subunit enhancer (EZH2) have never been found. This contrast to myeloid lymphoid malignancies, harbor frequent loss-of-function...
Therapeutic strategies targeting Homologous Recombination Deficiency (HRD) in breast cancer requires patient stratification. The LST (Large-scale State Transitions) genomic signature previously validated for triple-negative carcinomas (TNBC) was evaluated as biomarker of HRD luminal (hormone receptor positive) and HER2-overexpressing (HER2+) tumors. related to the number large-scale chromosomal breakpoints SNP-array tumor profile applied identify in-house TCGA sets tumors, which status...
Tunnelling nanotubes (TNTs) connect distant cells and mediate cargo transfer for intercellular communication in physiological pathological contexts. How generate these actin-mediated protrusions to span lengths beyond those attainable by canonical filopodia remains unknown. Through a combination of micropatterning, microscopy, optical tweezer-based approaches, we demonstrate that TNTs formed through the outward extension actin achieve distances greater than mean length branched...
Epidermal growth factor receptor (EGFR) and VEGF(R) signaling show extensive cross-talk, providing a rationale for joint targeting of the two pathways. However, combinations monoclonal antibodies (mAb) EGFR VEGF showed disappointing activity in patients with colorectal cancer (CRC). We speculated that inhibition surface receptors ligands might only partly prevent oncogenic whereas small-molecule tyrosine kinase inhibitors (TKI) would also influence intracellular signaling.Mice CRC xenografts...
Migrating cells present a variety of paths, from random to highly directional ones. While movement can be explained by basal intrinsic activity, persistent requires stable polarization. Here, we quantitatively address emergence migration in (hTERT)-immortalizedRPE1 (retinal pigment epithelial) over long timescales. By live cell imaging and dynamic micropatterning, demonstrate that the Nucleus-Golgi axis aligns with direction leading efficient movement. We show polarized trafficking is...
Chromosome conformation in mammals is closely related to gene regulation. Within topologically associating domains, where genomic contacts are enriched, genes tend show correlated expression across tissues and conditions, suggesting domain-wide mechanisms coregulating multiple genes, such as enhancer sharing or local histone mark spreading. At the single-cell level, transcription occurs sporadic bursts, transcriptional coordination has been observed between proximal but how folding of...
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a major renal pathology provoked by the deletion of PKD1 or PKD2 genes leading to local tubule dilation followed formation numerous cysts, ending up with failure in adulthood. In vivo , tubules are tightly packed, so that dilating and expanding cysts may have mechanical influence on adjacent tubules. To decipher role this coupling between tubules, we developed kidney-on-chip reproducing parallel networks packed tubes. This original...
Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations European ancestry. A genome-wide association study 259 uveal melanoma patients compared to 401 controls all ancestry revealed candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43-2.05). This was replicated an independent set 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression
Abstract Transformed isolated cells are usually extruded from normal epithelia and subsequently eliminated. However, multicellular tumors outcompete healthy cells, highlighting the importance of collective effects. Here, we investigate this situation in vitro by controlling space time activity Src oncoprotein within a Madin–Darby Canine Kidney (MDCK) epithelial cell monolayer. Using an optogenetics approach with expressing synthetic light-sensitive version (optoSrc), reversibly trigger...
Oxalis features: independent control of p O 2 , pH and the liquid flowrate. equilibration time in medium: 3 minutes. accuracy: mmHg. Flowrate as low 1 μL min −1 to avoid shear stress.
The evolutionary emergence of the primitive gut in Metazoa is one decisive events that conditioned major transition, leading to origin animal development. It thought have been induced by specification endomesoderm (EM) into multicellular tissue and its invagination (i.e., gastrulation). However, biochemical signals underlying EM gastrulation remain unknown. Herein, we find hydrodynamic mechanical strains, reminiscent soft marine flow, trigger active invagination/gastrulation or curvature...
Abstract Tunneling nanotubes (TNTs) connect distant cells and mediate cargo transfer for intercellular communication in physiological pathological contexts. How generate these actin-mediated protrusions to span lengths beyond those attainable by canonical filopodia remains unknown. Through a combination of micropatterning, microscopy optical tweezer-based approaches, we demonstrate that TNTs forming through the outward extension actin (not cellular dislodgement) achieve distances greater...
BRCA2 is the major high-penetrance predisposition gene for luminal (estrogen receptor [ER] positive) breast cancers. However, many mutant carriers lack family history of breast/ovarian cancers and do not benefit from genetic testing. Specific genomic features associated with inactivation in tumors could help identify patients whom a test may be proposed. A series ER-positive invasive ductal carcinomas (IDCs) including 30 mutations 215 control cases was studied by single-nucleotide...
Numerous anticancer agents and environmental mutagens target DNA. Although all such compounds interfere with the progression of replication fork inhibit DNA synthesis, there are marked differences in DNA-damage response pathways they trigger, relative impact proximal or distal signal transducers on cell survival is mainly lesion-specific. Accordingly, checkpoint kinase inhibitors current clinical development show synergistic activity some DNA-targeting agents, but not others. In present...
Abstract Cell division drives multicellular growth and its dysregulation can cause disease. While approximately 44 divisions are needed to produce without death all 10 13 cells in the human body, current methods limited count cell vivo across diverse mammalian types. Here we introduce DivisionCounter, a method over large ranges (∼70 divisions) using an easy fluorescence readout. We demonstrate that DivisionCounter accurately measures average of both vitro . Its use revealed leukemia tumor...
SUMMARY The mechanisms by which cells exert forces on their nuclei to migrate through openings smaller than the nuclear diameter remain unclear. In microfluidic devices, hourglass shape of nucleus and its strain patterns as it translocates narrow constrictions suggest pulling forces. We use CRISPR/Cas9 fluorescently label nesprin-2 giant, a protein that links cytoskeleton interior nucleus. demonstrate giant accumulates at front during deformation constrictions, independently lamina. find...
The mechanisms by which cells exert forces on their nuclei to migrate through openings smaller than the nuclear diameter remain unclear. In microfluidic devices, hourglass shape of nucleus and its strain patterns as it translocates narrow constrictions suggest pulling forces. We use CRISPR/Cas9 label nesprin-2 giant, a protein that links cytoskeleton interior nucleus. demonstrate giant accumulates at front during deformation constrictions, independently lamina. find nesprins are more mobile...