A5024756534- Amino Acid Enzymes and Metabolism
- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Biotin and Related Studies
- Parkinson's Disease Mechanisms and Treatments
- Advanced biosensing and bioanalysis techniques
- Plant responses to water stress
- Metabolism and Genetic Disorders
- Cell Adhesion Molecules Research
- Medical Imaging and Pathology Studies
- Polyamine Metabolism and Applications
- Amyotrophic Lateral Sclerosis Research
- Genomics and Rare Diseases
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Muscle metabolism and nutrition
- Toxoplasma gondii Research Studies
- Enzyme Structure and Function
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Metabolomics and Mass Spectrometry Studies
- Lipid metabolism and biosynthesis
- Nanoplatforms for cancer theranostics
University of Oslo
2019-2023
Institut de Recherche sur le Cancer et le Vieillissement de Nice
2016-2018
Inserm
2016-2018
Institute for Research in Biomedicine
2016-2017
Centre National de la Recherche Scientifique
2016
Universitat de Barcelona
2007-2016
Centre for Biomedical Network Research on Rare Diseases
2007-2016
University of Liège
2004
The matrix metalloproteinases (MMPs) play a key role in normal and pathological angiogenesis by mediating extracellular degradation and/or controlling the biological activity of growth factors, chemokines, cytokines. Specific functions individual MMPs as anti- or proangiogenic mediators remain to be elucidated. In present study, we assessed impact single combined MMP deficiencies vivo vitro models (malignant keratinocyte transplantation aortic ring assay, respectively). MMP-9 was...
The CD98/LAT1 complex is overexpressed in aggressive human cancers and thereby described as a potential therapeutic target. This promotes tumorigenesis with CD98 (4F2hc) engaging β-integrin signaling while LAT1 (SLC7A5) imports essential amino acids (EAA) mTORC1 activity. However, it unclear to which member of the heterodimer carries most prevalent protumoral action. To answer this question, we explored tumoral each by gene disruption CD98, LAT1, or both inhibition selective inhibitor...
The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remains elusive. Here, we have screened for regulators PRKN-independent using an siRNA library targeting 197 proteins containing lipid interacting domains. We identify Cyclin G-associated kinase (GAK) and Protein Kinase C Delta (PRKCD) as mitophagy, with both being dispensable PRKN-dependent starvation-induced autophagy. demonstrate that the activity GAK PRKCD are required efficient vitro, is present...
Cells use noncanonical autophagy, also called conjugation of ATG8 to single membranes (CASM), label damaged intracellular compartments with ubiquitin-like family proteins in order signal danger caused by pathogens or toxic compounds. CASM relies on E3 complexes sense membrane damage, but so far, only the mechanism activate ATG16L1-containing complexes, associated proton gradient loss, has been described. Here, we show that TECPR1-containing are key mediators cells treated a variety...
4F2hc (CD98hc) is a multifunctional type II membrane glycoprotein involved in amino acid transport and cell fusion, adhesion, transformation. The structure of the ectodomain human has been solved using monoclinic (Protein Data Bank code 2DH2) orthorhombic 2DH3) crystal forms at 2.1 2.8 A, respectively. It composed (betaalpha)(8) barrel an antiparallel beta(8) sandwich related to bacterial alpha-glycosidases, although lacking key catalytic residues consequently activity. 2DH3 dimer with...
The centrosome is the master orchestrator of mitotic spindle formation and chromosome segregation in animal cells. Centrosome abnormalities are frequently observed cancer, but little known their origin about pathways affecting homeostasis. Here we show that autophagy preserves organization stability through selective turnover centriolar satellite components, a process termed doryphagy. Autophagy targets organizer PCM1 by interacting with GABARAPs via C-terminal LIR motif. Accordingly,...
CD98hc functions as an amino acid (AA) transporter (together with another subunit) and integrin signaling enhancer. It is overexpressed in highly proliferative cells both physiological pathological conditions. deletion induces strong impairment of cell proliferation vivo vitro. Here, we investigate CD98hc-associated AA transport survival proliferation. By using chimeric versions CD98hc, the two protein can be uncoupled. Although recovering capacity restores vitro CD98hc-null cells,...
The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical early-onset forms (T2D). Focused studies were also tissues ob/ob db/db mice. We document that T2D, both early late onset, characterized by reduced muscle expression genes involved branched-chain amino acids (BCAA) metabolism. Weighted Co-expression Networks...
Abstract The ability of cells to move and migrate is required during development, but also in the adult processes such as wound healing immune responses. In addition, cancer exploit cells’ invade spread into nearby tissue eventually metastasize. majority deaths are caused by metastasis process cell migration therefore intensively studied. A common way study observe through an optical microscope record their movements over time. However, segmenting tracking moving phase contrast time-lapse...
Semiconducting polymer nanoparticles (SPNs) are explored for applications in cancer theranostics because of their high absorption coefficients, photostability, and biocompatibility. However, SPNs susceptible to aggregation protein fouling physiological conditions, which can be detrimental vivo applications. Here, a method achieving colloidally stable low-fouling is described by grafting poly(ethylene glycol) (PEG) onto the backbone fluorescent semiconducting polymer,...
Abstract CD98 heavy chain (CD98hc) forms heteromeric amino acid (AA) transporters by interacting with different light chains. Cancer cells overexpress CD98hc-transporters in order to meet their increased nutritional and antioxidant demands, since they provide branched-chain AA (BCAA) aromatic (AAA) availability while protecting from oxidative stress. Here we show that BCAA AAA shortage phenocopies the inhibition of mTORC1 signalling, protein synthesis cell proliferation caused CD98hc...
Abstract Mechanical and metabolic cues independently contribute to the regulation of cell tissue homeostasis. However, how they cross-regulate each other during this process remains largely unknown. Here, we show that cellular metabolism can regulate integrin rigidity-sensing via sphingolipid pathway controlled by amino acid transporter coreceptor CD98hc (SLC3A2). Genetic invalidation in dermal cells impairs rigidity sensing mechanical signaling downstream integrins, including RhoA...
The removal of mitochondria in a programmed or stress-induced manner is essential for maintaining cellular homeostasis. To date, much research has focused upon mitophagy that largely regulated by the E3 ligase PRKN, with limited insight into mechanisms regulating basal "housekeeping" levels different model organisms. Using iron chelation as an inducer PRKN-independent mitophagy, we recently screened siRNA library lipid-binding proteins and determined two kinases, GAK PRKCD, act positive...
Mitophagy, the selective degradation of mitochondria by autophagy, involved in important physiological processes and defects pathways has been reported pathological conditions, such as neurodegeneration. Thus, mitophagy is an interesting target for drug discovery programs. In this investigation, we used robust phenotypic assay to screen a set 50 small heterocyclic compounds identify inducers mitophagy. We identified two compounds, VP07 JAR1.39, that induce Parkin-dependent Based on...
Mitophagy is the selective degradation of mitochondria by autophagy. It promotes turnover and prevents accumulation dysfunctional mitochondria, which can lead to cellular degeneration. known be altered in several pathological conditions, especially neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We recently demonstrated an increase autophagy flux lymphoblasts from ALS patients bearing a mutation SOD1. Thus, identification mitophagy inhibitors may therapeutic option...
Cell migration is a complex process underlying physiological and pathological processes such as brain development cancer metastasis. The autophagy-linked FYVE protein (ALFY; also known WDFY3), an autophagy adaptor to promote clearance of aggregates, has been implicated in neural during cerebral cortical neurogenesis mice. However, specific role ALFY cell motility extracellular matrix adhesion not investigated. Here, we reveal novel for the endocytic pathway migration. We show that localizes...
Abstract Mitophagy is the selective degradation of mitochondria by autophagy. It promotes turnover and prevents accumulation dysfunctional mitochondria, which can lead to cellular degeneration. known be altered in several pathological conditions, especially neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We have recently demonstrated an increase autophagy flux lymphoblasts from ALS patients bearing a mutation SOD1. Thus, identification mitophagy inhibitors may...
ABSTRACT The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy response to different stimuli remains elusive. Here, we have screened for regulators PRKN-independent using an siRNA library targeting 197 proteins containing lipid interacting domains. We identify Cyclin G-associated kinase (GAK) and Protein Kinase C Delta (PRKCD) as novel mitophagy, with both being dispensable PRKN-dependent starvation-induced autophagy. demonstrate that the activity GAK...
<div>Abstract<p>The CD98/LAT1 complex is overexpressed in aggressive human cancers and thereby described as a potential therapeutic target. This promotes tumorigenesis with CD98 (4F2hc) engaging β-integrin signaling while LAT1 (SLC7A5) imports essential amino acids (EAA) mTORC1 activity. However, it unclear to which member of the heterodimer carries most prevalent protumoral action. To answer this question, we explored tumoral each by gene disruption CD98, LAT1, or both...
<p>Table S2: Analysis of the mutations generated by ZFN in each LS174T-derived cell line used.</p>