Biology subjects

van Hoesel, M.

Publications and source records attributed to van Hoesel, M..

3 recordsLinked to original sources

bioRxiv2026

Long-term experimental evolution of seasonal influenza A/H3N2 virus reveals diverse evolutionary potential

The repeatability of evolutionary outcomes is a fundamental question with implications for predicting the evolution pathogens like influenza viruses. Here, we tested whether seasonal A/H3N2 influenza virus evolution follows reproducible paths in a simplified setting where the natural cellular environment is maintained but adaptive immune selection is removed. We serially passaged replicate populations of an A/H3N2 virus for 1,200 generations across 12 independent differentiated human airway epithelium culture lines (three replicates of four donors) and performed deep sequencing to reconstruct the evolutionary dynamics. Rates of variant accumulation differed significantly among lines but not among donors, and parallel evolution was minimal. Populations generated polymorphisms not observed in the global human population, reversions to historical sequences, and changes at positions held near-invariant globally since 1968. These findings suggest A/H3N2 evolutionary trajectories are shaped less by intrinsic functional constraint than by selective context and help explain why predicting influenza virus evolution remains difficult.

evolutionary biology↗

bioRxiv2025

Cell surface proteomics of patient-derived malignant rhabdoid tumor organoids identifies ROBO1 as potential CAR T cell target for pediatric solid tumors.

Malignant rhabdoid tumors are highly aggressive pediatric malignancies with limited treatment options and poor outcomes. To expand therapeutic options, we employed mass spectrometry-based cell surface proteomics on malignant rhabdoid tumor and patient-matched normal kidney organoids to identify potential CAR T cell targets. Integrating these findings with transcriptomics and protein expression data, we revealed ROBO1 as a promising target, showing strong and uniform expression across malignant rhabdoid and other pediatric tumors. ROBO1-targeted CAR T cells displayed potent anti-tumor activity in vitro, effectively eliminating tumor cells in co-cultures with organoids from malignant rhabdoid tumors, rhabdomyosarcoma, and neuroblastoma. In vivo, ROBO1 CAR T cells infiltrated tumors, induced potent tumor regression and significantly increased survival in malignant rhabdoid tumor-bearing mice. These findings establish ROBO1 as a compelling therapeutic target for CAR T cell therapy and offer a promising approach to address the critical need for effective treatments in high-risk pediatric solid tumors. Statement of significanceThis study identifies ROBO1 as a promising CAR T cell target for pediatric solid tumors. Using patient-derived tumor organoids and tissues, we demonstrate strong ROBO1 expression across several tumor entities and robust anti-tumor efficacy of ROBO1-targeted CAR T cells in vitro and in vivo, underscoring its potential for clinical translation.

cancer biology↗

bioRxiv2023

Chemotherapy-induced intestinal injury promotes Galectin-9-driven modulation of T cell function

The intestine is vulnerable to chemotherapy-induced toxicity due to its high epithelial proliferative rate, making gut toxicity an off-target effect in several cancer treatments, including conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT). In allo-HCT, intestinal damage is an important factor in the development of Graft-versus-Host Disease (GVHD), an immune complication in which donor immune cells attack the recipients tissues. Here, we developed a novel human intestinal organoid-based 3D model system to study the direct effect of chemotherapy-induced intestinal epithelial damage on T cell behavior. Chemotherapy treatment using busulfan, fludarabine, and clofarabine led to damage responses in organoids resulting in increased T cell migration, activation, and proliferation in ex-vivo co-culture assays. We identified galectin-9 (Gal-9), a beta-galactoside-binding lectin released by damaged organoids, as a key molecule mediating T cell responses to damage. Increased levels of Gal-9 were also found in the plasma of allo-HCT patients who later developed acute GVHD, supporting the predictive value of the model system in the clinical setting. This study highlights the potential contribution of chemotherapy-induced epithelial damage to the pathogenesis of intestinal GVHD through direct effects on T cell activation and trafficking promoted by galectin-9.

immunology↗