Biology subjects

Beyer, S.

Publications and source records attributed to Beyer, S..

4 recordsLinked to original sources

bioRxiv2026

Breast Cancer-derived PDGFB Remodels the CNS Vascular Niche to Promote Brain, Spinal and Leptomeningeal Metastasis

Background: Central nervous system (CNS) metastases are a major driver of breast cancer (BC) mortality. Recently, our group demonstrated that platelet-derived growth factor-B (PDGFB) and its receptor, platelet-derived growth factor receptor-beta (PDGFR{beta}), promote BC metastasis to the brain; however, the cellular/molecular mechanisms driving this process remain unclear. Here, we investigated tumor-derived PDGFB effects on the CNS vascular niche in regulating metastatic spread. Methods: Triple-negative BC cells were engineered to overexpress PDGFB and used to evaluate endothelial sprouting, blood-brain barrier (BBB) function, vascular permeability and experimental CNS metastasis. A novel retro-orbital (RO) injection model was used to study leptomeningeal/spinal experimental metastasis. Results: PDGFB enhanced human brain microvascular endothelial cell (HBMEC) sprouting, induced cell migration in BBB spheroids, increased permeability in 3D models, and disrupted tight junction proteins in HBMECs. Notably, alterations in vascular permeability were observed in both PDGFR{beta}-positive and PDGFR{beta}-negative endothelial systems, suggesting PDGFB can remodel the CNS vasculature through multiple mechanisms. In vivo, PDGFB increased CNS metastatic burden and altered tumor vasculature in xenograft and allograft models of BC. Furthermore, PDGFB promoted robust colonization of both spinal and leptomeningeal compartments, identifying a previously underappreciated role for this signaling pathway in a clinically devastating form of CNS metastasis. Analysis of patient transcriptomic datasets revealed enrichment of angiogenesis-related pathways in PDGFB-high tumors from patients who developed CNS metastases. Conclusions: Collectively, these findings identify tumor-derived PDGFB as a key regulator of CNS vascular remodeling and metastatic tropism, while introducing a new experimental framework to study spinal metastases and leptomeningeal disease in BC.

cancer biology↗

bioRxiv2026

An ER Retrieval-and-Release System Reveals Ligand-Independent Basal Signaling by Cell Surface TCRs

The T cell receptor (TCR) machinery comprises the ligand-binding TCR{beta} and the CD3 signaling dimers. Individual subunits are synthesized in the endoplasmic reticulum (ER) and only the fully assembled TCRs reach the cell surface. We engineered a system to retained CD3{varepsilon} is in the ER. This allowed only partial TCR assembly, while continuous retrieval of CD3{varepsilon} from the Golgi back to the ER enabled complete assembly. Synchronous TCR release by biotin addition caused a transient increase in surface TCR abundance that gradually returned to steady-state levels. Mathematical modeling revealed that TCR levels were controlled by feedback mechanisms. Notably, surface-localized, but not ER-localized, TCRs spontaneously generated ligand-independent basal signaling. Phosphoproteomic analyses revealed that this signal is similar, but not identical, to ligand-induced TCR activation signals, with distinct phosphorylation patterns already evident at the CD3 subunits. Our findings establish the TCR retrieval-and-release system as a tool to investigate ligand-independent basal TCR signaling.

immunology↗

bioRxiv2026

Automatic pain face analysis in mice: Applied to a varied dataset with non-standardized conditions

Biomedical research relies on scientifically validated tools to assess pain, suffering, and distress in laboratory animals to ensure their well-being. In mice, the most frequently used laboratory animals, the Mouse Grimace Scale (MGS) provides a reliable tool for the assessment of facial expression changes caused by impaired well-being. However, no automated tool can yet reliably assess all features of the MGS across different mouse strains under varying experimental or housing conditions in real-time, as the variability present in recorded image datasets poses substantial challenges for computer vision models. Despite this technical difficulty, variability across subsets in terms of mouse strain, treatments, laboratory, and image acquisition setup is essential for paving the way toward MGS assessment under non-standardized conditions in the home cage rather than standardized cage-side recording setups. Against this background, a large and diverse dataset containing five subsets is introduced and a deep learning model was trained to predict the average MGS scores ranging between 0 and 2. It achieved a root mean squared error (RMSE) of 0.26 when trained on all subsets of the dataset, outperforming the average human rater in terms of error magnitude. The correlation between human raters and automated MGS scores was very high (Pearsons r=0.85). In the cross-dataset evaluation, one subset was excluded from training and used for testing the model. This approach yielded higher errors compared to models trained and tested on the same subsets. A model restricted to the feature of orbital tightening showed lower performance than one trained on all facial features of the MGS. Overall, the most reliable model for predicting average MGS scores for a novel dataset is the one trained on the combined subsets. Performance may be further enhanced by fine-tuning the model using human-generated MGS scores for a portion of the novel subset.

animal behavior and cognition↗

bioRxiv2023

Viral modulation of type II interferon increases T cell adhesion and virus spread

During primary infection, varicella zoster virus (VZV) infects epithelial cells in the respiratory lymphoid organs and mucosa. Subsequent infection of lymphocytes, T cells in particular, causes primary viremia allowing systemic spread throughout the host, including the skin. This results in the expression of cytokines, including interferons (IFNs) which partly limit primary infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. How VZV infects lymphocytes from epithelial cells while evading the cytokine response has not been fully established. Here, we show that VZV glycoprotein C (gC) binds IFN-{gamma} and modifies its activity. Transcriptomic analysis revealed that gC in combination with IFN-{gamma} increased the expression of a small subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), as well as several chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of epithelial cells resulted in lymphocyte function-associated antigen 1 (LFA-1)-dependent T cell adhesion. This gC activity required a stable interaction with IFN-{gamma} and signalling through the IFN-{gamma} receptor. Finally, the presence of gC during infection increased VZV spread from epithelial cells to peripheral blood mononuclear cells. This constitutes the discovery of a novel strategy to modulate the activity of IFN-{gamma}, inducing the expression of a subset of ISGs, leading to enhanced T cell adhesion and virus spread.

microbiology↗