Biology subjects

Soro-Barrio, P.

Publications and source records attributed to Soro-Barrio, P..

3 recordsLinked to original sources

bioRxiv2025

Multimodal profiling unveils a reversible basal-like breast cancer cell state resistant to AKT inhibition

The PI3K/AKT/mTOR pathway is central to cell metabolism and growth. However, pharmacological inhibition of the pathway is not uniformly effective across cancer types, or even within a single cancer model. In this study, we leverage oblique plane microscopy of triple negative breast cancer organoids, as well as lineage tracing to uncover a source of heterogeneity. Non-genetic resistance to AKT inhibition is associated with basal cell features of normal breast epithelium and the master transcription factor of basal cell state, {Delta}Np63, is sufficient to confer resistance. Cells can transition between states within four weeks and therefore, AKT inhibition only delays tumour growth, with tumours rich in KRT14+ cells resulting. Thus, under selection, triple negative breast cancer exploits a repertoire of cell states inherent to the breast.

cancer biology↗

bioRxiv2024

Dominant RDH12-retinitis pigmentosa impairs photoreceptor development and cone function in retinal organoids

Retinal dehydrogenase 12 (RDH12) is a photoreceptor NADPH-dependent retinal reductase enzyme, converting all-trans-retinal to all-trans-retinol. Heterozygous variants in RDH12 cause a rare autosomal dominant (AD) retinitis pigmentosa. As no disease models exist, we generated human induced pluripotent stem cell derived retinal organoids (RO) from a RDH12-AD patient (with pathogenic c.759del p.(Phe254Leufs*24) variant), alongside a healthy control (WT). RDH12-AD RO exhibited correct localisation of RDH12 to the photoreceptor inner segments up to week 44; transmission electron microscopy at week 37 showed photoreceptors were less abundant and shorter in length compared to WT. Visual cone function, retinol biosynthesis and the vitamin A pathway were also highly disrupted at week 44. Our study is the first to describe a RDH12-AD disease model with pathology at later stages of photoreceptor differentiation, in keeping with the milder disease course seen in humans. It provides insights into the aetiology and possible targets for future therapeutic development.

pathology↗

bioRxiv2021

Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria

Recent initiatives to improve translation of findings from animal models to human disease have focussed on reproducibility but quantifying the relevance of animal models remains a challenge. Here we use comparative transcriptomics of blood to evaluate the systemic host response and its concordance between humans with different clinical manifestations of malaria and five commonly used mouse models. Plasmodium yoelii 17XL infection of mice most closely reproduces the profile of gene expression changes seen in the major human severe malaria syndromes, accompanied by high parasite biomass, severe anemia, hyperlactatemia, and cerebral microvascular pathology. However, there is also considerable discordance of changes in gene expression between species and across all models, indicating that the relevance of biological mechanisms of interest in each model should be assessed before conducting experiments. Our data will aid selection of appropriate models for translational malaria research, and the approach is generalizable to other disease models.

genomics↗