Biology subjects

Hauer, C.

Publications and source records attributed to Hauer, C..

4 recordsLinked to original sources

bioRxiv2026

Tumor control of lysosomal acidification promotes lipoprotein assimilationand ferroptosis resistance

Lysosomes are acidic organelles that fuel cancer progression by facilitating nutrient acquisition and metabolic adaptation, yet the determinants through which cancer cells sustain specialized lysosomal functions are not fully delineated. Notably, assimilation of dietary antioxidants within lipoproteins, a lysosome-dependent process, protects tumors from ferroptosis, an oxidative form of cell death, raising the possibility that tumors evolve mechanisms to enhance this process. Here, we applied genetic screens to identify regulators of lysosome-dependent lipoprotein assimilation and ferroptosis resistance and identified ZNF217, a frequently amplified transcriptional regulator in human cancers, as a driver of tumor lysosomal function and ferroptosis resistance. ZNF217 promoted lipoprotein assimilation through transcriptional maintenance of RAB11FIP4, an endolysosomal protein. Loss of either ZNF217 or RAB11FIP4 impaired lysosomal acidification across multiple cancer types, leading to defective lipoprotein assimilation, increased lipid peroxidation, ferroptosis sensitivity, and impaired tumor growth. Mechanistically, RAB11FIP4 boosts lysosomal acidity through maintenance of RAB7A activity. Finally, disruption of ZNF217 in breast cancer cell lines and patient-derived organoids, a tumor context linked to ZNF217 expression, reduced lysosomal acidity and impaired cancer growth through increased ferroptosis sensitivity. Together, we identify transcriptional regulation of lysosomal acidification as a key metabolic adaptation that enables extracellular antioxidant acquisition and tumor progression.

cancer biology↗

bioRxiv2026

BatSpot: a retrainable neural network for automatic detection and classification of bat echolocation and detection of buzzes and social calls

O_LIBats are a diverse taxonomic group that display a wide range of interesting behaviours. Many bats are keystone species for their ecosystem, are IUCN Red-listed as vulnerable to critically endangered, and subject to human-wildlife conflicts arising from anthropogenic expansion. Yet bats remain understudied both with respect to behaviour, population ecology and conservation status. One of the major challenges when studying bats is obtaining data. Their nocturnal lifestyle and use of ultrasonic echolocation makes them difficult to track and record using traditional methods. Recent advances in passive acoustic monitoring have allowed researchers to record large amounts of data, but the detection and classification of vocalisations remain a challenge. Most available tools are either for profit or are limited to a narrow geographic range, and mostly focus on echolocation search phase calls. C_LIO_LIHere we present BatSpot, a convolutional neural network trained to detect search phase calls, buzzes and social calls. It also offers the option to classify the search phase calls to species(-complex) level. We provide a GUI that allows researchers to retrain or transfer-train the models for their specific needs and validate the performance. C_LIO_LIWe test the performance of all models and show that they perform better than both commercial and open-source solutions (search phase file level F1: 0.97 vs 0.96, buzz detector F1: 0.95 vs 0.11). We furthermore show that retraining the search phase call detector for a new country with examples from just 59 recordings massively improves the performance (F1: 0.48 to 0.79). C_LIO_LIBatSpot will enable bat researchers globally to automate detection and classification with minimal effort and includes novel options for social call and buzz detection, typically not featured in other automated tools for bat monitoring. C_LI

ecology↗

bioRxiv2024

Hydrogel-embedded precision-cut lung slices support ex vivo culture of in vivo-induced premalignant lung lesions

Lung cancer is the leading cause of global cancer death and prevention strategies are key to reducing mortality. Medical prevention may have a larger impact than treatment on mortality by targeting high-risk populations and reducing their lung cancer risk. Premalignant lesions (PMLs) that can be intercepted by prevention agents are difficult to study in humans but easily accessible in murine preclinical carcinogenesis studies. Precision-cut lung slices (PCLS) are underutilized as an ex vivo model for lung cancer studies due to limited culture time. Embedding PCLS within bioengineered hydrogels extends PCLS viability and functionality for up to six weeks. Here, we embedded PCLS generated from urethane-induced murine PMLs in cell-degradable and non-degradable hydrogels to study viability and activity of the tissues over six weeks. PMLs in hydrogel-embedded PCLS maintained viability, gene expression, and proliferation. Treatment of hydrogel-embedded PCLS containing urethane-induced PMLs with iloprost, a known lung cancer prevention agent, recapitulated in vivo gene expression and activity. These studies also showed that iloprost reduced proliferation and PML size in hydrogel-embedded PCLS, with some differences based on hydrogel formulation and suggested that hydrogel-embedded PCLS models may support long-term culture of in vivo generated PMLs to improve preclinical studies of lung cancer and prevention agents.

cancer biology↗

bioRxiv2023

Tissue-engineered models of lung cancer premalignancy

Lung cancer is the leading global cause of cancer-related deaths. Although smoking cessation is the best preventive action, nearly 50% of all lung cancer diagnoses occur in people who have already quit smoking. Research into treatment options for these high-risk patients has been constrained to rodent models of chemical carcinogenesis, which are time-consuming, expensive, and require large numbers of animals. Here we show that embedding precision-cut lung slices within an engineered hydrogel and exposing this tissue to a carcinogen from cigarette smoke creates an in vitro model of lung cancer premalignancy. Hydrogel formulations were selected to promote early lung cancer cellular phenotypes and extend PCLS viability up to six weeks. In this study, hydrogel-embedded lung slices were exposed to the cigarette smoke derived carcinogen vinyl carbamate, which induces adenocarcinoma in mice. At six weeks, analysis of proliferation, gene expression, histology, tissue stiffness, and cellular content revealed that vinyl carbamate induced the formation of premalignant lesions with a mixed adenoma/squamous phenotype. Two putative chemoprevention agents were able to freely diffuse through the hydrogel and induce tissue-level changes. The design parameters selected using murine tissue were validated with hydrogel-embedded human PCLS and results showed increased proliferation and premalignant lesion gene expression patterns. This tissue-engineered model of human lung cancer premalignancy is the starting point for more sophisticated ex vivo models and a foundation for the study of carcinogenesis and chemoprevention strategies.

bioengineering↗