Article
Multidisciplinary Sciences
Khashayar Roohollahi, Yvonne de Jong, Govind Pai, Mohamad Amr Zaini, Klaas de Lint, Daoud Sie, Martin A. Rooimans, Davy Rockx, Elizabeth E. Hoskins, Najim Ameziane, Rob Wolthuis, Hans Joenje, Susanne Wells, Josephine Dorsman
Summary: Head-and-neck squamous cell carcinomas (HNSCCs) are common in patients with Fanconi anemia (FA), and standard chemo-radiation therapy is not well tolerated in these patients. This study aimed to find alternative treatment options for FA-HNSCC by identifying genomic and transcriptomic events associated with the disease. The researchers used sequencing techniques to identify copy-number alterations in FA-HNSCC and found that amplification of 11q22.2 was a prevalent event. They also discovered that a small molecule inhibitor of BIRC2-3 could selectively kill FA tumor cells that overexpressed these genes. The findings suggest that inhibition of BIRC2-3 may be a potential therapeutic approach for FA-HNSCC.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Sara Carvalhal, Ingrid Bader, Martin A. Rooimans, Anneke B. Oostra, Jesper A. Balk, Rene G. Feichtinger, Christine Beichler, Michael R. Speicher, Johanna M. van Hagen, Quinten Waisfisz, Mieke van Haelst, Martijn Bruijn, Alexandra Tavares, Johannes A. Mayr, Rob M. F. Wolthuis, Raquel A. Oliveira, Job de Lange
Summary: BUB1 mutations cause neurodevelopmental disorder with cellular phenotypes similar to other syndromes.
Editorial Material
Biochemical Research Methods
Jeroen A. A. Demmers
JOURNAL OF PROTEOMICS
(2022)
Article
Biochemical Research Methods
Lennart van der Wal, Karel Bezstarosti, Jeroen A. A. Demmers
Summary: This study investigated the specificities and functional roles of proteasome associated DUBs using quantitative ubiquitinomics. The results showed distinct effects on the global ubiquitinome upon removal of USP14 or UCH37, suggesting less functional redundancy than previously anticipated. The study also questioned the alleged specificity of the small molecule inhibitor b-AP15 due to its broad and severe off-target effects.
JOURNAL OF PROTEOMICS
(2022)
Article
Biochemistry & Molecular Biology
Marvin van Toorn, Yasemin Turkyilmaz, Sueji Han, Di Zhou, Hyun-Suk Kim, Irene Salas-Armenteros, Mihyun Kim, Masaki Akita, Franziska Wienholz, Anja Raams, Eunjin Ryu, Sukhyun Kang, Arjan F. Theil, Karel Bezstarosti, Maria Tresini, Giuseppina Giglia-Mari, Jeroen A. Demmers, Orlando D. Scha, Jun-Hyuk Choi, Wim Vermeulen, Jurgen A. Marteijn
Summary: Nucleotide excision repair (NER) is a mechanism that removes DNA damage through a cut-and-patch reaction, which helps prevent cancer and aging. HLTF is an important factor in NER that actively evicts DNA damage to coordinate the transition between excision and DNA synthesis steps, thereby safeguarding genome integrity.
Article
Biochemistry & Molecular Biology
Enrico Ne, Raquel Crespo, Ray Izquierdo-Lara, Shringar Rao, Selin Kocer, Alicja Gorska, Thomas van Staveren, Tsung Wai Kan, David van de Vijver, Dick Dekkers, Casper Rokx, Panagiotis Moulos, Pantelis Hatzis, Robert-Jan Palstra, Jeroen Demmers, Tokameh Mahmoudi
Summary: This study identifies new proteins associated with latent HIV-1 and discovers novel latency-reversing agents. It demonstrates the potential of these compounds to reverse HIV-1 latency in infected cells and synergize with other known latency-reversing agents.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Endocrinology & Metabolism
Rodrigo Canibano-Fraile, Laurike Harlaar, Carlos A. dos Santos, Marianne Hoogeveen-Westerveld, Jeroen A. A. Demmers, Tim Snijders, Philip Lijnzaad, Robert M. Verdijk, Nadine A. M. E. van der Beek, Pieter A. van Doorn, Ans T. van der Ploeg, Esther Brusse, W. W. M. Pim Pijnappel, Gerben J. Schaaf
Summary: Pompe disease is an inherited metabolic myopathy characterized by lysosomal glycogen accumulation caused by deficiency of acid alpha-glucosidase (GAA). This study found elevated protein levels of enzymes involved in glucose uptake and cytoplasmic glycogen synthesis in skeletal muscle of Pompe disease mice and patients. These metabolic changes occur before muscle wasting and may aggravate the disease phenotype.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Genetics & Heredity
Daphne J. Smits, Jordy Dekker, Rachel Schot, Brahim Tabarki, Amal Alhashem, Jeroen A. A. Demmers, Dick H. W. Dekkers, Antonio Romito, Peter J. van der Spek, Tjakko J. van Ham, Aida M. Bertoli-Avella, Grazia M. S. Mancini
Summary: CLEC16A is a membrane-associated C-type lectin protein that regulates autophagy and mitophagy. It is associated with various auto-immune and neurological disorders and has a role in neurodevelopment. In this study, CLEC16A truncating variants were identified in patients with severe neurodevelopmental disorder. The truncated CLEC16A lost its localization and interaction with other proteins, leading to disrupted vesicle sorting and dysregulated mitophagy. This study highlights the importance of CLEC16A in endosomal sorting and its role in neurodegeneration and brain development.
Article
Biochemistry & Molecular Biology
Elliot Sollis, Joery den Hoed, Marti Quevedo, Sara B. Estruch, Arianna Vino, Dick H. W. Dekkers, Jeroen A. A. Demmers, Raymond Poot, Pelagia Deriziotis, Simon E. Fisher
Summary: TBR1 is a neuron-specific transcription factor involved in brain development and associated with neurodevelopmental disorders such as autism spectrum disorder, intellectual disability, and speech delay. Through affinity purification coupled to mass spectrometry, approximately 250 putative TBR1-interaction partners have been identified, including transcription factors, chromatin modifiers, and proteins related to autism and intellectual disability.
HUMAN MOLECULAR GENETICS
(2023)
Article
Oncology
Gilles S. van Tienderen, Marije E. A. van Beek, Ivo J. Schurink, Oskar Rosmark, Henk P. Roest, Jantine Tieleman, Jeroen Demmers, Iain Muntz, James Conboy, Gunilla Westergren-Thorsson, Gijsje Koenderink, Luc J. W. van der Laan, Monique M. A. Verstegen
Summary: Cholangiocarcinoma (CCA) is an aggressive type of liver cancer that often metastasizes to the lungs and lymph nodes, resulting in poor patient outcomes. However, the mechanisms behind CCA metastasis are not well understood. In order to study the interactions between CCA tumor cells and the extracellular matrix (ECM) of metastatic sites, researchers created an in vitro model using patient-derived CCA organoids (CCAOs) combined with decellularized human lung and lymph node tissues. This model allowed for the investigation of how the ECM influences metastatic processes and provides new insights into cancer metastasis.
FRONTIERS IN ONCOLOGY
(2023)
Article
Materials Science, Biomaterials
Gilles S. van Tienderen, James Conboy, Iain Muntz, Jorke Willemse, Jantine Tieleman, Kathryn Monfils, Ivo J. Schurink, Jeroen A. A. Demmers, Michail Doukas, Gijsje H. Koenderink, Luc J. W. Van der Laan, Monique M. A. Verstegen
Summary: Tumor initiation and progression depend on the interaction between cancer cells and their microenvironment, including the extracellular matrix (ECM). This study extensively characterized the ECM of liver cancer tumors, identifying distinct malignancy-related ECM signatures and divergent mechanical properties. The findings contribute to a better understanding of the alterations to the tumor ECM during liver cancer development.
BIOMATERIALS ADVANCES
(2023)
Article
Biochemical Research Methods
Zeliha Yalcin, Danielle Koot, Karel Bezstarosti, Daniel Salas-Lloret, Onno B. Bleijerveld, Vera Boersma, Mattia Falcone, Roman Gonzalez-Prieto, Maarten Altelaar, Jeroen A. A. Demmers, Jacqueline J. L. Jacobs
Summary: Ubiquitination plays a crucial role in cellular processes, but dysregulation of ubiquitin machinery enzymes can lead to pathogenesis. Defining in vivo substrates of individual ubiquitin-conjugating enzymes is challenging. In this study, we used proteomics methods to identify in vivo targets of UBE2D3, an E2 enzyme with unclear roles. UBE2D3 depletion affected the global proteome and the ubiquitinome, especially molecular pathways related to mRNA translation. Our findings show that UBE2D3 is involved in ribosome-associated protein quality control and autophagic protein quality control.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Cell Biology
Hoyee Tsui, Sebastiaan Johannes van Kampen, Su Ji Han, Viviana Meraviglia, Willem B. van Ham, Simona Casini, Petra van der Kraak, Aryan Vink, Xiaoke Yin, Manuel Mayr, Alexandre Bossu, Gerard A. Marchal, Jantine Monshouwer-Kloots, Joep Eding, Danielle Versteeg, Hesther de Ruiter, Karel Bezstarosti, Judith Groeneweg, Sjoerd J. Klaasen, Linda W. Van Laake, Jeroen A. A. Demmers, Geert J. P. L. Kops, Christine L. Mummery, Toon A. B. Van Veen, Carol Ann Remme, Milena Bellin, Eva van Rooij
Summary: Arrhythmogenic cardiomyopathy (ACM) is a progressive cardiac disease caused by inherited mutations, such as plakophilin-2 (PKP2), which lead to decreased expression of desmosomal and adherens junction (AJ) proteins. In vitro and in vivo experiments demonstrated impaired contractility, cardiac dysfunction, and fibrosis associated with PKP2 mutations. Proteomics analysis revealed the involvement of the ubiquitin-proteasome system (UPS) in ACM pathogenesis, and inhibition of UPS improved cardiomyocyte function. The study highlights the potential therapeutic strategy of targeting protein degradation and improving desmosomal protein stability for ACM treatment.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Vincent Gaggioli, Calvin S. Y. Lo, Nazaret Reveron-Gomez, Zuzana Jasencakova, Heura Domenech, Hong Nguyen, Simone Sidoli, Andrey Tvardovskiy, Sidrit Uruci, Johan A. Slotman, Yi Chai, Joao G. S. C. Souto Goncalves, Eleni Maria Manolika, Ole N. Jensen, David Wheeler, Sriram Sridharan, Sanjiban Chakrabarty, Jeroen Demmers, Roland Kanaar, Anja Groth, Nitika Taneja
Summary: Chromatin signalling cascade, regulated by a checkpoint, activates the histone methyltransferase EHMT2/G9a to assemble heterochromatin at stressed replication forks. G9a, together with SUV39h1, induces chromatin compaction through accumulating repressive modifications, H3K9me1/me2/me3, at stressed replication forks. Untimely heterochromatin disassembly by demethylase KDM3A exposes forks to PRIMPOL-mediated genome instability, leading to chemotherapeutic drug sensitivity.
NATURE CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Carlota Davo-Martinez, Angela Helfricht, Cristina Ribeiro-Silva, Anja Raams, Maria Tresini, Sidrit Uruci, Wiggert A. van Cappellen, Nitika Taneja, Jeroen A. A. Demmers, Alex Pines, Arjan F. Theil, Wim Vermeulen, Hannes Lans
Summary: The SWI/SNF family of ATP-dependent chromatin remodeling complexes is frequently mutated in cancer and is involved in multiple DNA damage response mechanisms. Different subunits of the BAF, PBAF and ncBAF complexes are recruited to double-strand breaks (DSBs) in a transcription-dependent manner and promote homologous recombination. PBAF and ncBAF complexes facilitate RNA polymerase II eviction and initiate transcriptional silencing near DNA damage, while BAF complex helps to maintain this silencing. ARID1A-containing BAF complexes aid in R-loop resolution and DNA repair by promoting the recruitment of RNaseH1 and RAD52.
NUCLEIC ACIDS RESEARCH
(2023)