0000000000520537

AUTHOR

Marta Futema

showing 3 related works from this author

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.

2016

Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub…

Proteomics0301 basic medicineSystems AnalysisDNA Mutational Analysislnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]General Physics and AstronomyDatasets as Topicmethods [Chromatography Affinity]ProteomicsSensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]Chromatography AffinityMass SpectrometryProtein Interaction Mappingtherapy [Ciliopathies]genetics [Ciliopathies]methods [Molecular Targeted Therapy]Molecular Targeted TherapyProtein Interaction MapsMultidisciplinaryCiliumChemistry (all)Qabnormalities [Spine]pathology [Ciliopathies]genetics [Muscle Hypotonia]therapy [Muscle Hypotonia]Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]metabolism [Proteins]isolation & purification [Proteins]physiology [Biological Transport]3. Good healthCell biologyVesicular transport proteinpathology [Dwarfism]metabolism [Cilia]Muscle Hypotoniaddc:500pathology [Muscle Hypotonia]pathology [Spine]genetics [Dwarfism]Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]ScienceDwarfismExocystBiologyArticleGeneral Biochemistry Genetics and Molecular BiologyPhysics and Astronomy (all)03 medical and health sciencesIntraflagellar transportCiliogenesisOrganelleHumansCiliaBiochemistry Genetics and Molecular Biology (all)ProteinsBiological TransportGeneral Chemistrytherapy [Dwarfism]Fibroblastsgenetics [Proteins]CiliopathiesSpinemethods [Protein Interaction Mapping]Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]030104 developmental biologyProteostasisHEK293 Cellsmethods [Proteomics]
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RNA sequencing-based transcriptome profiling of cardiac tissue Implicados novela putative disease mechanisms in FLNC-associated arrhythmogenic cardio…

2020

Arrhythmogenic cardiomyopathy (ACM) encompasses a group of inherited cardiomyopathies including arrhythmogenic right ventricular cardiomyopathy (ARVC) whose molecular disease mechanism is associated with dysregulation of the canonical WNT signalling pathway. Recent evidence indicates that ARVC and ACM caused by pathogenic variants in the FLNC gene encoding filamin C, a major cardiac structural protein, may have different molecular mechanisms of pathogenesis. We sought to identify dysregulated biological pathways in FLNC-associated ACM. RNA was extracted from seven paraffin-embedded left ventricular tissue samples from deceased ACM patients carrying FLNC variants and sequenced. Transcript le…

FilaminsDNA Mutational Analysis030204 cardiovascular system & hematologyGene mutationFilaminArticleTranscriptome03 medical and health sciences0302 clinical medicineHumansMedicineGenetic Predisposition to Disease030212 general & internal medicineJAM2FLNCGeneArrhythmogenic Right Ventricular Dysplasiabusiness.industryGene Expression ProfilingDNAArrhythmogenic cardiomyopathy Filamin C Focal adhesion pathway Integrin linked kinase pathway RNA sequencingActin cytoskeletonPatologiaCell biologyPhenotypeMutationCardiology and Cardiovascular MedicinebusinessMYL7
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Filamin C variants are associated with a distinctive clinical and immunohistochemical arrhythmogenic cardiomyopathy phenotype.

2020

Background: Pathogenic variants in the filamin C (FLNC) gene are associated with inherited cardiomyopathies including dilated cardiomyopathy with an arrhythmogenic phenotype. We evaluated FLNC variants in arrhythmogenic cardiomyopathy (ACM) and investigated the disease mechanism at a molecular level. Methods: 120 gene-elusive ACM patients who fulfilled diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) were screened by whole exome sequencing. Fixed cardiac tissue from FLNC variant carriers who had died suddenly was investigated by histology and immunohistochemistry. Results: Novel or rare FLNC variants, four null and five variants of unknown significance, were id…

medicine.medical_specialtyFilaminsCardiomyopathyContrast MediaGadolinium030204 cardiovascular system & hematologyVentricular tachycardiaSudden deathRight ventricular cardiomyopathy03 medical and health sciences0302 clinical medicineCardiac magnetic resonance imagingInternal medicinemedicineHumansCor030212 general & internal medicineFLNCcardiovascular diseasesArrhythmogenic Right Ventricular DysplasiaExome sequencingmedicine.diagnostic_testbusiness.industryDilated cardiomyopathymedicine.diseasePatologiaPhenotypeMutationCardiologyCardiomyopathiesCardiology and Cardiovascular Medicinebusiness
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