Over the course of the project, EPICAMENTE combined chromatin proteomics, quantitative mass spectrometry, metabolomics, imaging, and functional genomics to systematically investigate nuclear metabolism.
A major achievement of the project was the generation of the first comprehensive chromatome-scale analyses across human tissues and cancer models, revealing that hundreds of metabolic enzymes localise to chromatin in a context-dependent manner . This finding transformed the understanding of nuclear metabolism from an isolated phenomenon into a widespread and organised feature of genome biology.
Beyond mapping, the project provided mechanistic evidence that chromatin-associated metabolic enzymes actively regulate key nuclear processes, including transcriptional control, DNA repair, genome stability, and cell cycle progression. Several studies demonstrated that local metabolic activities on chromatin sustain epigenetic states and gene expression programs essential for cancer cell proliferation.
Importantly, EPICAMENTE showed that the spatial redistribution of metabolic enzymes can create specific cellular vulnerabilities and modulate therapeutic response independently of genetic background. These findings establish nuclear metabolism as a novel axis for cancer stratification and intervention.
The project also delivered significant technological innovation, including chromatome profiling workflows and proteoform-resolved mass spectrometry approaches, enabling systematic and reproducible analysis of chromatin-associated metabolism. These tools, together with the datasets generated, have been disseminated through high-impact publications, open-access resources, and international collaborations, ensuring broad uptake by the scientific community.
In terms of exploitation, the discoveries have led to the identification of clinically relevant metabolic vulnerabilities and supported the development of intellectual property and translational strategies aimed at improving cancer treatment.
