Biology subjects

Imre, G.

Publications and source records attributed to Imre, G..

3 recordsLinked to original sources

bioRxiv2026

Revamped transposon-induced hepatocellular carcinoma model reveals deep similarities of cancer-driver landscapes across mice and humans

Genome-scale cancer-driver discovery is limited by statistical uncertainty in driver calling and by experimental constraints on mutations available for selection. We developed 3xfOnc3 - a three-frame Sleeping Beauty (SB) mutagenesis system designed to broaden functional perturbations and reduce integration biases of traditional SB screens - and tested it in vivo in mouse liver. Within 12 months, 60% of mice developed heterogeneous hepatocellular tumors. Tumor-selected integrations were interpreted against an empirical reference from SB-based therapeutic gene delivery to hepatocytes, enabling correction for gene targetability. Background-aware filtering prioritized 315 driver candidates, including 243 protein-coding genes. Tumors were multiclonal, and identical integration-marked lineages expanded differently across lesions, supporting context-dependent clonal expansion. SB hits within young L1 subfamily members were selectively enriched in tumors. Human orthologues of candidate drivers were enriched for Cancer Gene Census genes and protein-altering pan-cancer mutations. Together, 3xfOnc3 reveals a background-corrected driver landscape linking driver selection to clonal tumor evolution and cross-species cancer relevance.

cancer biology↗

bioRxiv2026

A preclinical resistance framework discovers the virulence risks of antibiotics in development

Several new antibiotics target multidrug-resistant pathogens, yet resistance is still evaluated mainly by drug-susceptibility, leaving consequences for bacterial pathogenicity poorly understood. Here, we develop a framework integrating resistance evolution, genomic surveillance and host-pathogen phenotyping to classify antibiotics by resistance potential and pathogenic consequences. Applying this framework to Klebsiella pneumoniae identified functionally distinct antibiotic candidates associated with elevated virulence risk. Resistance evolution rapidly increased virulence through clinically-relevant mutations, without direct selection for pathogenicity. Despite distinct genetic routes, resistance converged on cell-envelope rewiring. A single resistance mutation increased epithelial adhesion, intracellular colonization, macrophage immune-evasion, and tissue persistence in murine infection models, transforming K. pneumoniae into a more invasive and cytotoxic pathogen. Risk-profile analysis revealed partial decoupling of resistance and pathogenicity, with some low-resistance antibiotics yielding highly-virulent populations. These findings establish resistance-driven virulence as an underappreciated translational hazard and call for incorporating host-pathogen interactions into resistance surveillance and preclinical antibiotic development.

microbiology↗

bioRxiv2026

Intrahepatic reporter assay reveals leaky somatic blockade of L1 retrotransposition in mice

Long interspersed element-1 (LINE-1, L1) retrotransposition has long been proposed to occur in somatic tissues, yet direct experimental evidence distinguishing adult somatic events from early embryonic insertions has remained limited. Here we establish an intrahepatic L1 reporter assay that enables immunohistochemical detection and quantitative analysis of L1 retrotransposition in vivo. Using autonomous and non-autonomous L1 reporter variants, we demonstrate clearly detectable somatic L1 activity in the mouse liver. Comparative analysis of L1 activity in liver tissue and tumor-derived cell culture reveals that tumor cells preferentially restrict L1 at early regulatory stages, consistent with epigenetic control, whereas downstream defence mechanisms are comparatively permissive. In contrast, normal liver tissue shows stronger restriction at later stages of the L1 life cycle. Together, our results provide direct experimental evidence for somatic L1 retrotransposition in vivo in adult liver and reveal distinct regulatory strategies that shape L1 activity in tumor versus normal somatic cells. TeaserGenome destabilizing L1 retrotransposon activity is present in somatic tissues, where it likely contributes to cancer development.

genetics↗