Thijs Lefever

The phenotype is not simply a direct manifestation of the genome, nor are protein functions static. Biological resilience, especially in Eukaryotes, is maintained by complex, higher-level molecular networks that involve dynamic interactions between proteins and metabolites. At ProGenTomics, we developed a novel multi-omics mass spectrometry-based approach that provides a direct view into this functional entanglement by sequentially isolating the metabolome, the proteome and the histone epigenome from the same cell pellet. This unique combination allows us to define a so-called 'energy-information' axis: histone post-translational modifications (hPTMs) serve as signal integrators, regulating gene transcription/translation based on the cell's metabolic state. In cancer biology, this feedback loop is vital, where altered metabolism drives hPTM dysregulation, contributing directly to malignancy. As the only lab worldwide integrating untargeted histone PTM mapping with proteomics and metabolomics, our initial proof-of-principle focused on AML cell lines to map these fundamental biomolecular connections. 
My research is the next step within this ambitious vision by focusing on tracking the kinetics of 13C-labeled metabolite incorporation into the histone layer through time-lapse designs in both cell lines and primary patient samples. The use of 13C-labeled metabolites is key, as it provides a concrete visualization of metabolic flux, which we call “the arrow of time”. This extra factor allows the multi-omics network to go from descriptive to mechanistic, making it more information-rich and usable in clinical situations. In parallel, I am optimizing and automating our sample preparation methods to achieve the best analytical resolution and coverage of histone PTMs. 
 

After completing my Master's degree in Drug Development at Ghent University in 2025, I transitioned into a PhD research at the Laboratory of Pharmaceutical Biotechnology under the guidance of Prof. Dr. M. Dhaenens. In 2024, I completed my Master's thesis at TUM University in Munich, where my research centered on mycotoxin analysis using mass spectrometry. Currently, I’m involved in setting up the new European initiative called Mass-Spectrometry-based Histone Epigenetics (MSHE), where we bring together researchers who focus on understanding the role of histone(PTM)s in disease. 
 

• Lab address: Campus Heymans (FFW), Ottergemsesteenweg 460, Building A, B-9000 Gent
• ProGenTomics (UGent core facility for proteomics)
• Thijs Lefever is interested to receive invitations for presentations or talks