Biology subjects

Tomczak, A.

Publications and source records attributed to Tomczak, A..

4 recordsLinked to original sources

bioRxiv2026

EBV reprograms autoreactive B cells as antigen presenting cells in multiple sclerosis

Summary paragraphMultiple sclerosis (MS) is a chronic autoimmune disease targeting the central nervous system (CNS). MS develops almost exclusively in individuals previously infected with Epstein-Barr virus (EBV)1, yet the mechanisms linking EBV infection to MS pathogenesis remain incompletely defined. Here we characterized EBV-infected B cells in MS and demonstrated that EBV directly infects autoreactive anti-CNS antigen B cells and reprograms them into pro-inflammatory antigen-presenting cells (APCs). EBV B cells in MS were enriched within the CD27CD21low memory B-cell subset and exhibited upregulated B cell activation and APC transcriptional programs. Recombinant antibodies derived from MS blood and cerebrospinal fluid (CSF) EBV B cells bound brain tissue, and several cross-bound both MS-associated autoantigens and Epstein-Barr virus nuclear antigen-1 (EBNA1). In vitro, EBV B cells functioned as APCs that stimulated T peripheral helper cells, with associated activation of EBV- anti-CNS antigen B cells. Collectively, these findings support a mechanistic framework in which EBV infects and transcriptionally reprograms autoreactive anti-CNS antigen B cells into APCs that drive pathogenic anti-CNS antigen T cell and EBV- B cell responses in MS.

immunology↗

bioRxiv2024

Heat shock alters the distribution and in vivo interaction of major nuclear structural proteins, lamin and DNA topoisomerase II, with nucleic acids

Lamins and topoisomerases play a critical role in the structural support of cell nuclei, in the regulation of chromatin structure, chromatin distribution, topology of DNA, gene expression, transcription, splicing and transport. Here, we report the role of lamins and Top2 during transition from normal conditions (N), in heat shock (HS) and recovery (R) in Drosophila since the fly genome contains a single gene for B-type lamin (lamin Dm), for A-type lamin (lamin C) and Top2. Heat shock increases transient phosphorylation of lamin Dm on S25, induces changes in solubility of lamin Dm, Top2, HSF, HDAC1 and HP1 proteins, especially in S2 cells and relocates Top2 and chromatin closer to the nuclear lamina with induction of granular staining for Top2 in Kc, S2 and embryonic cells. Lamin Dm interacts with Top2 protein and HS increases the interaction. In vivo photocrosslinking and immunoprecipitation revealed a significant increase in binding to chromatin and nucleic acids upon HS induction for Top2 and lamin Dm. All the detected changes in the properties and location of proteins returned to "normal" after recovery from heat shock. This suggests an important role for lamin Dm, Top2 and their complexes in nuclear functions during HS and recovery. We propose a model in which relocation of Top2 chromatin complexes closer to the nuclear lamina and lamin Dm may help to rearrange the gene expression pattern by tethering HS inactivated genes to nuclear lamina and NPCs which might also help to bind nuclear fraction of non-HS-related transcripts at the nuclear lamina/NPCs area.

cell biology↗

bioRxiv2017

Interpretation of biological experiments changes with evolution of Gene Ontology and its annotations

Gene Ontology (GO) enrichment analysis is ubiquitously used for interpreting high throughput molecular data and generating hypotheses about underlying biological phenomena of experiments. However, the two building blocks of this analysis -- the ontology and the annotations -- evolve rapidly. We used gene signatures derived from 104 disease analyses to systematically evaluate how enrichment analysis results were affected by evolution of the GO over a decade. We found low consistency between enrichment analyses results obtained with early and more recent GO versions. Furthermore, there continues to be strong annotation bias in the GO annotations where 58% of the annotations are for 16% of the human genes. Our analysis suggests that GO evolution may have affected the interpretation and possibly reproducibility of experiments over time. Hence, researchers must exercise caution when interpreting GO enrichment analyses and should reexamine previous analyses with the most recent GO version.

bioinformatics↗

bioRxiv2017

Gene annotation bias impedes biomedical research

1We found tremendous inequality across gene and protein annotation resources. We observe that this bias leads biomedical researchers to focus on richly annotated genes instead of those with the strongest molecular data. We advocate for researchers to reduce these biases by pursuing data-driven hypotheses.

bioinformatics↗