Research Topics
Genomes and Genes | Silvere M van der MaarelSummaryAffiliation: Leiden University Medical Center Country: The Netherlands Publications
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Publications
Epigenetic mechanisms in health and diseaseS M van der Maarel
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands
Ann Rheum Dis 67:iii97-100. 2008..While our understanding of these epigenetic disease mechanisms steadily increases, the challenge will be to develop new drugs that specifically deal with the epigenetic lesion...- Facioscapulohumeral muscular dystrophy: consequences of chromatin relaxationSilvere M van der Maarel
Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands
Curr Opin Neurol 25:614-20. 2012..The purpose of this review is to provide a comprehensive overview of our current understanding of the disease mechanism and to discuss the observations supporting the possibility of a developmental defect in this disorder... 
Facioscapulohumeral muscular dystrophy and DUX4: breaking the silenceSilvere M van der Maarel
Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, Netherlands
Trends Mol Med 17:252-8. 2011..FSHD is thereby the first example of a human disease caused by the inefficient repression of a retrogene in a macrosatellite repeat array...- The D4Z4 repeat-mediated pathogenesis of facioscapulohumeral muscular dystrophySilvere M van der Maarel
Leiden University Medical Center, Center for Human and Clinical Genetics, Leiden, The Netherlands
Am J Hum Genet 76:375-86. 2005 
Facioscapulohumeral muscular dystrophySilvere M van der Maarel
Leiden University Medical Center LUMC, Department of Human Genetics, Postal zone S 3 P, PO Box 9600, 2300 RC Leiden, The Netherlands
Biochim Biophys Acta 1772:186-94. 2007..Clearly, better disease models need to be developed to identify and test novel intervention strategies to eventually improve the quality of life for patients with FSHD...- Novel protein-protein interactions inferred from literature contextHerman H H B M van Haagen
Biosemantics Association, Department of Human Genetics, Leiden University Medical Center, Leiden, and Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands
PLoS ONE 4:e7894. 2009..Our framework can be used for prioritizing potential interaction partners, hitherto undiscovered, for follow-up studies and to aid the generation of accurate protein interaction maps... - Calpain 3 is a rapid-action, unidirectional proteolytic switch central to muscle remodelingAntoine de Morrée
Center for Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
PLoS ONE 5:e11940. 2010..Consequently, SUMO2 is deregulated in patient muscle tissue. Our study thus uncovers unexpected crosstalk between CAPN3 proteolysis and protein sumoylation, with strong implications for muscle remodeling... - Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscleYanchao Huang
Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
Hum Mol Genet 17:1855-66. 2008..Thus, our findings suggest interconnectivity between both diseases by revealing a novel physiological role for CAPN3 in regulating the dysferlin protein complex... - Self-regulated alternative splicing at the AHNAK locusAntoine de Morrée
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
FASEB J 26:93-103. 2012..A small 17-kDa isoform of Periaxin similarly traffics between the cytoplasm and the nucleus to regulate mRNA splicing. Thus, AHNAK constitutes a novel mechanism in post-transcriptional control of gene expression... - A unifying genetic model for facioscapulohumeral muscular dystrophyRichard J L F Lemmers
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
Science 329:1650-3. 2010..These findings suggest that FSHD arises through a toxic gain of function attributable to the stabilized distal DUX4 transcript... - Worldwide population analysis of the 4q and 10q subtelomeres identifies only four discrete interchromosomal sequence transfers in human evolutionRichard J L F Lemmers
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
Am J Hum Genet 86:364-77. 2010.... - Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHDJessica C de Greef
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
Hum Mutat 30:1449-59. 2009..In conclusion, we describe two ways to develop FSHD: (1) contraction-dependent or (2) contraction-independent D4Z4 hypomethylation on the 4qA161 subtelomere... - Generation of isogenic D4Z4 contracted and noncontracted immortal muscle cell clones from a mosaic patient: a cellular model for FSHDYvonne D Krom
Leiden University Medical Center, Leiden, The Netherlands
Am J Pathol 181:1387-401. 2012..These cell lines will facilitate pairwise comparisons to identify FSHD-specific differences and are expected to create new opportunities for high-throughput drug screens... - Epigenetic regulation of the X-chromosomal macrosatellite repeat encoding for the cancer/testis gene CT47Judit Balog
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
Eur J Hum Genet 20:185-91. 2012.... - Specific sequence variations within the 4q35 region are associated with facioscapulohumeral muscular dystrophyRichard J L F Lemmers
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
Am J Hum Genet 81:884-94. 2007..We also show that each of these haplotypes has its unique sequence signature, and we propose that specific SNPs in the disease haplotype are essential for the development of FSHD... - Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2Richard J L F Lemmers
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
Nat Genet 44:1370-4. 2012..Our study identifies SMCHD1 as an epigenetic modifier of the D4Z4 metastable epiallele and as a causal genetic determinant of FSHD2 and possibly other human diseases subject to epigenetic regulation... - In vivo detection of amyloid-β deposits using heavy chain antibody fragments in a transgenic mouse model for Alzheimer's diseaseRob J A Nabuurs
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
PLoS ONE 7:e38284. 2012.... - Interspecies translation of disease networks increases robustness and predictive accuracySeyed Yahya Anvar
Center for Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
PLoS Comput Biol 7:e1002258. 2011..This study presents a state-of-the-art strategy in constructing interspecies disease networks that provide crucial information on regulatory relationships among genes, leading to better understanding of the disease molecular mechanisms... - Epigenetic mechanisms of facioscapulohumeral muscular dystrophyJessica C de Greef
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
Mutat Res 647:94-102. 2008..In this review, we discuss the genetic and epigenetic changes observed in patients with FSHD and the possible disease mechanisms that may be associated with FSHD pathogenesis... - Pathogenic IgG4 subclass autoantibodies in MuSK myasthenia gravisJaap J Plomp
Department of Neurology, Medical Genetics Center, Leiden University Medical Center, Leiden, The Netherlands
Ann N Y Acad Sci 1275:114-22. 2012.... - Modeling oculopharyngeal muscular dystrophy in myotube cultures reveals reduced accumulation of soluble mutant PABPN1 proteinVered Raz
Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
Am J Pathol 179:1988-2000. 2011..We suggest that this difference can contribute to muscle weakness in OPMD... - Contractions of D4Z4 on 4qB subtelomeres do not cause facioscapulohumeral muscular dystrophyRichard J F L Lemmers
Leiden University Medical Center, Center for Human and Clinical Genetics, Department of Human Genetics, Leiden, The Netherlands
Am J Hum Genet 75:1124-30. 2004..Thus, in addition to a contraction of D4Z4, additional cis-acting elements on 4qA may be required for the development of FSHD. Alternatively, 4qB subtelomeres may contain elements that prevent FSHD pathogenesis... - Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2Jessica C de Greef
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Am J Hum Genet 88:796-804. 2011.... - Protein studies in dysferlinopathy patients using llama-derived antibody fragments selected by phage displayYanchao Huang
1Leiden University Medical Center, Center for Human and Clinical Genetics, Leiden, The Netherlands
Eur J Hum Genet 13:721-30. 2005..Using these antibody fragments, we found that calpain 3, which shows a secondary reduction in the dysferlinopathies, interacts with dysferlin... - Selection of VHH antibody fragments that recognize different Aβ depositions using complex immune librariesRinse Klooster
Department of Human and Clinical Genetics, Medical Genetics Center, Leiden University Medical Center, Leiden, The Netherlands
Methods Mol Biol 911:241-53. 2012..We show that this can result in binders that preferentially recognize the target of interest when present in specific structures depending on the antigen source... - Poly(A) binding protein nuclear 1 levels affect alternative polyadenylationEleonora de Klerk
Center for Human and Clinical Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
Nucleic Acids Res 40:9089-101. 2012.... - Reversible aggregation of PABPN1 pre-inclusion structuresVered Raz
Department of Human Genetics, Leiden University Medical Centre, The Netherlands
Nucleus 2:208-18. 2011..Together our results demonstrate that the aggregation process of WT- and expPABPN1 differs in steps preceding inclusion formation, suggesting that pre-aggregated protein species could represent the cytotoxic structures... - Clinical Dutch-English Lambert-Eaton Myasthenic syndrome (LEMS) tumor association prediction score accurately predicts small-cell lung cancer in the LEMSMaarten J Titulaer
Leiden University Medical Center, Leiden, The Netherlands
J Clin Oncol 29:902-8. 2011..In view of its profound impact on therapy and survival, we developed and validated a score to identify the presence of SCLC early in the course of LEMS... - SOX antibodies in small-cell lung cancer and Lambert-Eaton myasthenic syndrome: frequency and relation with survivalMaarten J Titulaer
Department of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
J Clin Oncol 27:4260-7. 2009..Clinical outcome with respect to SOX antibodies was evaluated, as the SOX-related antitumor immune response might help to control the tumor growth... - Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patientsSeyed Yahya Anvar
Center for Human and Clinical Genetics, Leiden University Medical Center, P, O, Box 9600, 2300 RC Leiden, The Netherlands
Skelet Muscle 1:15. 2011..We suggest that the natural decrease in proteasome expression and its activity during muscle aging contributes to the onset of the disease... - Genome-wide analysis of macrosatellite repeat copy number variation in worldwide populations: evidence for differences and commonalities in size distributions and size restrictionsMireille Schaap
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
BMC Genomics 14:143. 2013..Copy number variation, stability and genetic heterogeneity of the autosomal macrosatellite repeats RS447 (chromosome 4p), MSR5p (5p), FLJ40296 (13q), RNU2 (17q) and D4Z4 (4q and 10q) and X chromosomal DXZ4 and CT47 were investigated... - Intrinsic Epigenetic Regulation of the D4Z4 Macrosatellite Repeat in a Transgenic Mouse Model for FSHDYvonne D Krom
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
PLoS Genet 9:e1003415. 2013..These transgenic mice therefore represent a valuable animal model for FSHD and will be a useful resource to study the molecular mechanisms underlying FSHD and to test new therapeutic intervention strategies... - A genome-wide signature of glucocorticoid receptor binding in neuronal PC12 cellsJ Annelies E Polman
Division of Medical Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden University Medical Center, Leiden, 2333 CC, The Netherlands
BMC Neurosci 13:118. 2012..The objective of the present study was to identify genome-wide glucocorticoid receptor binding sites in neuronal PC12 cells using Chromatin ImmunoPrecipitation combined with next generation sequencing (ChIP-Seq)... - Therapeutic exon skipping for dysferlinopathies?Annemieke Aartsma-Rus
Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
Eur J Hum Genet 18:889-94. 2010..We also show that DYSF exon skipping seems to be as straightforward as DMD exon skipping, as AONs to induce efficient skipping of four DYSF exons were readily identified... - FRG1P-mediated aggregation of proteins involved in pre-mRNA processingSilvana van Koningsbruggen
Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands
Chromosoma 116:53-64. 2007..Intriguingly, among FRG1P-associated proteins are SMN and PABPN1, both being involved in neuromuscular disorders, possibly through RNA biogenesis-related processes... - AHNAK, a novel component of the dysferlin protein complex, redistributes to the cytoplasm with dysferlin during skeletal muscle regenerationYanchao Huang
Center for Human and Clinical Genetics, Leiden Univesity Medical Center, Leiden, The Netherlands
FASEB J 21:732-42. 2007..It may also have significant implications for understanding the biology of AHNAK-containing exocytotic vesicles, "enlargosomes," in plasma membrane remodeling and repair... - Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in miceRinse Klooster
Department of Human Genetics, Medical Genetics Centre, Leiden University Medical Centre, Leiden, The Netherlands
Brain 135:1081-101. 2012.... - Proteomic analysis of the dysferlin protein complex unveils its importance for sarcolemmal maintenance and integrityAntoine de Morrée
Center for Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
PLoS ONE 5:e13854. 2010..Together our analyses show that dysferlin is not only a membrane repair protein but also important for muscle membrane maintenance and integrity... - Structural basis for a PABPN1 aggregation-preventing antibody fragment in OPMDAntonietta Impagliazzo
Leiden University Medical Center, Center for Human and Clinical Genetics, Leiden, The Netherlands
FEBS Lett 584:1558-64. 2010..These results may increase our understanding of the PABPN1 aggregation mechanism and the therapeutic potential of 3F5... - Differential recognition of vascular and parenchymal beta amyloid depositionKim S Rutgers
Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands
Neurobiol Aging 32:1774-83. 2011..Continued use and characterization of these reagents will be necessary to fully understand the performance of these immunoreagents... - Equal proportions of affected cells in muscle and blood of a mosaic carrier of facioscapulohumeral muscular dystrophyMaria Manuela O Tonini
Departamento de Biologia, Human Genome Research Center, , , , CEP: 05508-090, , SP, Brazil
Hum Genet 119:23-8. 2006..This finding supports the hypothesis that a mitotic contraction of D4Z4 is an early embryonic event and indicates that the degree of mosaicism in PBL is representative for that of muscle... - Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiationSara T Winokur
Department of Biological Chemistry, 202 Sprague Hall, University of California, Irvine, CA 92697, USA
Hum Mol Genet 12:2895-907. 2003..Improper nuclear localization of 4qter is discussed as an alternative model for FSHD gene regulation and pathogenesis... - Localization of 4q35.2 to the nuclear periphery: is FSHD a nuclear envelope disease?Peter S Masny
Department of Biological Chemistry, University of California, Irvine 92697, USA
Hum Mol Genet 13:1857-71. 2004..Interestingly, it is not D4Z4 itself that mediates interaction with the envelope, as sequences proximal to D4Z4 (i.e. D4S139) localize closer to the nuclear periphery, perhaps accounting for the chromosome 4 specificity of the disease...
Research Grants
- Llama-derived phage display antibody arrays for FSHDSilvere van der Maarel; Fiscal Year: 2003..Evidently, these antibodies can also be used individually for specific immunohistochemical and immunocytochemical studies. ..
- FSHD as a Disorder of Impaired RNA BiogenesisSilvere van der Maarel; Fiscal Year: 2007..Moreover, on the long term, we expect that uniform myogenic cell models with well-defined disease parameters for FSHD will be of importance for pharmaceutical intervention studies. ..