http://bura.brunel.ac.uk/handle/2438/8611 Thu, 26 Mar 2026 06:48:06 GMT 2026-03-26T06:48:06Z http://bura.brunel.ac.uk/handle/2438/33035 Title: Men Talk Less Than Women During Multitasking Authors: Szameitat, A; Szameitat, D Abstract: ... Description: ... Thu, 01 Jan 2026 00:00:00 GMT http://bura.brunel.ac.uk/handle/2438/33035 2026-01-01T00:00:00Z http://bura.brunel.ac.uk/handle/2438/33013 Title: A CDCA2–MYC positive feedback loop controls cancer cells survival Authors: Stamatiou, K; Ligammari, L; Bothota, M; Tsavou, A; Gokhan E; Cicirò, Y; Zacarias, M; Soucek, L; Sala, A; Vagnarelli, P Abstract: Cellular myelocytomatosis oncogene (MYC) transcription factors are encoded by a family of genes that include the prototype member MYC, MYCN and MYCL, and most human cancers display expression alterations of MYC genes. MYC is regulated at multiple levels, and its stability and activity are modulated by protein phosphorylation. Although there is a reasonable knowledge of the kinases required for MYC modifications, the counteracting phosphatases have been understudied. Here, we have investigated the role of the chromatin-associated protein phosphatase 1 (PP1) regulatory subunit CDCA2, also known as Repo-Man, in the regulation of MYC proteins in cancer cells. Using RNA interference and degron-mediated degradation of CDCA2, we have demonstrated that the PP1 subunit is required for cMYC and MYCN stabilization and viability of triple-negative breast cancer, neuroblastoma and colon cancer cells. Proximity ligation assays indicate that both cMYC and MYCN are in close proximity to CDCA2 in vivo. Furthermore, we have shown that CDC2A is a bona fide MYC target gene in cancer cells, revealing a reciprocal regulatory loop that could be exploited for therapeutic purposes. Description: Data accessibility: The data underpinning the publication will be shared by the corresponding author upon request. Electronic supplementary material is available online [56]. Stamatiou Ket al. 2026 Supplementary material from: A CDCA2 - MYC positive feedback loop controls cancer cells survival. Figshare. (doi:10.6084/m9.figshare.c.8295614). Wed, 11 Mar 2026 00:00:00 GMT http://bura.brunel.ac.uk/handle/2438/33013 2026-03-11T00:00:00Z http://bura.brunel.ac.uk/handle/2438/32999 Title: Multi-omic analyses reveal a differential contribution of chromatin-associated PP1 holoenzymes to mitotic exit and G1 re-establishment Authors: Stamatiou, K; Huguet, F; Budzinska, M; de las Heras, JI; Ragusa, D; de Castro, I; Spanos, C; Rappsilberg, J; Vagnarelli, P Abstract: Mitotic exit is an important part of the cell cycle, requiring the coordination of many chromatin and cytoskeleton remodeling events to successfully complete cell division and maintain cell identity. Protein dephosphorylation is a key step in directing mitotic exit, and protein phosphatase 1 (PP1) is essential to this process; however, the specific contribution of its numerous targeting subunits is still unknown. Here, we have investigated the function of three chromatin-associated PP1-targeting subunits in mitosis exit: Repo-Man, Ki-67, and protein phosphatase 1 nuclear targeting subunit (PNUTS). We generated endogenously tagged, auxin-degradable alleles for each subunit in the human cell line HCT116 and used a multi-omic approach to address their specific contributions toward transcription resumption, chromatin accessibility, and protein dephosphorylation at the transition from mitosis to G1. This approach identified their distinct role in mitotic exit, provided datasets for the cell-cycle community, and highlighted functions for Ki-67 and Repo-Man in genome stability and organization. Description: Highlights: • Multi-omic profiling uncovers divergent PP1-holoenzyme functions at the M-to-G1 transition • Repo-Man loss accelerates mitotic exit by weakening SAC signaling • Ki-67 depletion disrupts centromere compaction and CENP-B/C loading • PNUTS degradation increases RNA Pol II-S5 phosphorylation, R-loops, and DNA damage; Resource availability: Lead contact: Requests for further information and resources should be directed to and will be fulfilled by the lead contact, Paola Vagnarelli (paola.vagnarelli@brunel.ac.uk). Materials availability: All unique/stable reagents generated in this study are available from the lead contact with a completed materials transfer agreement. Data and code availability: • ATAC-seq, RNA-seq, and ChIP-seq data have been deposited at ArrayExpress as E-MTAB-13826, E-MTAB-13827, and E-MTAB-15533 and are publicly available as of the date of publication. Mass spectrometry data have been deposited at PRIDE as PXD049319 and are publicly available as of the date of publication. • This paper analyzes existing, publicly available data, accessible at GEO: GSE186206 (Ki-67), GEO: GSE54170 (Repo-Man and PNUTS), GEO: GSE84035 (in vitro binding sequencing data for Repo-Man), GEO: GSM8413578 (PNUTS ChIP dataset), GEO: GSE86667 (H3K9me3), and GEO: GSM5640483 (LMNB1). • This paper does not report original code. • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request. Tue, 17 Mar 2026 00:00:00 GMT http://bura.brunel.ac.uk/handle/2438/32999 2026-03-17T00:00:00Z http://bura.brunel.ac.uk/handle/2438/32962 Title: Epigenomic subtypes of late-onset Alzheimer’s disease reveal distinct microglial signatures Authors: Laroche, VT; Cavill, R; Kouhsar, M; Müller, J; Reijnders, RA; Harvey, J; Smith, AR; Imm, J; Koetsier, J; Weymouth, L; MacBean, L; Pegoraro, G; Eijssen, L; Creese, B; Kenis, G; Tijms, BM; van den Hove, D; Lunnon, K; Pishva, E Abstract: Growing evidence suggests that clinical, pathological, and genetic heterogeneity in late-onset Alzheimer’s disease (LOAD) contributes to variable therapeutic outcomes, potentially explaining many trial failures. Advances in molecular subtyping through proteomic and transcriptomic profiling reveal distinct patient subgroups, highlighting disease complexity beyond amyloid-beta plaques and tau tangles. This underscores the need to expand subtyping across new molecular layers, to identify novel drug targets for different patient subgroups. In this study, we analyzed genome-wide DNA methylation (DNAm) data from three independent postmortem brain cohorts (𝑁 = 826) to identify epigenetic subtypes of LOAD. We used unsupervised clustering to define subtype-specific DNAm patterns and validated them across cohorts. We then mapped subtype signatures to brain cell types using purified-cell DNAm profiles and integrated bulk and single-nucleus RNA-seq to assess each subtype’s impact on gene expression. Finally, we examined clinical and neuropathological correlates to evaluate biological and clinical significance. We identified two distinct epigenomic subtypes of LOAD, consistently observed across three cohorts. Both subtypes exhibit significant yet distinct microglial methylation enrichment. Bulk transcriptomic analyses highlighted distinct biological mechanisms underlying these subtypes: subtype 1 was enriched for immune-related processes, while subtype 2 was characterized by neuronal and synaptic pathways. Single-nucleus transcriptional profiling of microglia indicated that both subtypes share AD-associated innate-immune remodeling, with subtype differences emerging primarily as state-dependent transcriptional shifts rather than large changes in state abundance. Overall, subtype 1 showed a relative weighting toward more inflammatory microglial programs, whereas subtype 2 showed stronger transcriptional remodeling in specific microglial states alongside relatively greater engagement of regulatory and clearance-associated features. These findings reveal distinct epigenetic and functional microglial states underlying LOAD subtypes, advancing our understanding of disease heterogeneity. This work lays the groundwork for targeted therapeutic strategies tailored to specific molecular and cellular disease profiles. Description: Data availability: The PITT-ADRC datasets used in this study are available on Synapse (https://www.synapse.org/) under Synapse ID: syn23538600. Access requires creating a Synapse user account and submitting a data access request. The UKBBN dataset is accessible via GEO under accession number GSE284764. ROSMAP datasets are also deposited on Synapse (Synapse IDs: syn7357283, syn23650893, syn3157325, syn25006903). Microglial snRNA sequencing data and markers of microglial states were obtained from https://compbio.mit.edu/microglia_states/. The ROSMAP mQTL dataset is accessible at https://mostafavilab.stat.ubc.ca/xqtl/. All codes used for DNA methylation and bulk transcriptomic analyses, clustering, replication, and cross-cohort validations are available at https://github.com/Dementia-Systems-Biology/LOAD_subtyping.; Supplementary Information is available online at: https://link.springer.com/article/10.1007/s00401-026-02990-y#Sec30 . Tue, 24 Feb 2026 00:00:00 GMT http://bura.brunel.ac.uk/handle/2438/32962 2026-02-24T00:00:00Z