Biology subjects

Hoefer, S.

Publications and source records attributed to Hoefer, S..

3 recordsLinked to original sources

bioRxiv2026

Prospective pan-cancer phosphoproteomics at clinical scale extends therapeutic options in precision oncology

Genomics-guided precision oncology has improved survival in cancer entities with actionable mutations but cannot capture oncogenic signaling that manifests at the protein level. Here, we report a prospective, real-world pan-cancer study profiling proteomes and phosphoproteomes of 1,998 tumor samples from adults and children with rare or advanced cancers enrolled in the German precision oncology programs DKFZ/NCT/DKTK MASTER, CATCH and INFORM and their molecular tumor boards (MTBs). We developed tumor proteome activity status (TOPAS) scores for 46 clinically relevant kinases, an immune activity score capturing antigen presentation and T-cell activation and identified therapeutically targetable cell-surface proteins for 94% of patients. These readouts enhance MTB recommendations by exposing actionable non-genomic kinase activity, refining interpretation of oncogenic genome alterations, and highlighting cell-surface treatment options. Three proof-of-concept analyses indicate clinical utility including kinase activity-stratified pazopanib response in sarcoma, immune activity score-tracked checkpoint-inhibitor outcomes pan-cancer, and a phosphoproteomic biomarker distinguishing EGFR-inhibitor response in chordoma.

cancer biology↗

bioRxiv2025

Quantitative modelling of biological response dynamics reveals novel patterns in plant volatile signalling

Biological responses to environmental stimuli are inherently dynamic. Recent technological advances enable detailed time-resolved measurements of such responses. However, a standard for quantitative characterisation of dynamics is lacking, thus limiting biological insights and comparisons. We developed an unbiased mathematical model structure that allows for the quantification of biological response curve dynamics without a priori knowledge of underlying biochemical mechanisms. Using the model to quantify the dynamics of stress-induced plant volatiles, we uncover a range of novel patterns in volatile signalling, including i) a strong light-independent impact of the time of day of wounding on the onset, duration and shape of the volatile induction responses, ii) an accentuation of volatile-specific induction curve shapes by herbivory-associated molecular patterns (HAMPs) and iii) independent regulation of the strength and duration of volatile induction across genotypes. The model performs well across biochemically diverse responses, suggesting broad applicability to inducible responses. The model is also robust to partial response curves, low resolution data and complex multi-modal responses arising from overlapping stimuli, enabling identification of priming events from otherwise convoluted curves. As all responses measured conform to a common model structure, yet parameter values diverge markedly, we conclude that biologically meaningful information is ignored when dynamics are not quantified. The presented approach will pave the way to identifying new biological response patterns, and their function, across the tree of life.

plant biology↗

bioRxiv2025

Volatile-suppressed peptide signaling enhances volatile responses in plant-plant interactions

Plant volatiles shape plant-plant interactions by acting as defense regulators and response factors. While plant volatile biosynthesis is well understood, how their emission is regulated remains largely elusive. Here, we show that small peptide signaling regulates induced volatile release in maize. Following herbivore attack, green leaf volatiles such as (Z)-3-hexenyl acetate (HAC) are released and induce terpene and indole emissions from neighboring plants. This process is accompanied by reduced expression of the ZmCLE1E9 gene and the ZmBAM1A, ZmBAM1B and ZmBAM3C receptor genes in HAC-exposed plants. Exogenous ZmCLE1E9 peptide inhibits HAC-triggered volatile release by limiting stomatal aperture. This inhibition disappears in the Zmbam1a/Zmbam1b/Zmbam3c triple mutant. Molecular docking supports ZmCLE1E9 and ZmBAMs as ligand-receptor pairs. Furthermore, Zmcle1e9 and Zmbams triple mutants show increased volatile emissions upon HAC exposure. In summary, we show that upon HAC perception, maize plants enhance their capacity to release terpenes and indole via the suppression of CLE1E9 signaling. This behavior allows maize plants to rapidly deploy volatile cues in response to stress volatiles and thus shape the infochemical dynamics of multitrophic environments.

plant biology↗