prof. Maarten Dhaenens (PhD)

The phenotype is not simply a direct manifestation of the genome (Philip Ball, 2023). In fact, attributing functions, traits or diseases solely on the basis of genetic aberrations has proven to be an oversimplification. Even protein function alters drastically as a function of the complex interactions with neighbouring proteins and metabolites, which together lead to higher-level molecular networks, i.e. macroscales, that boost biological resilience, most notably in Eukaryotes. 

At ProGenTomics, we have developed a novel multi-omics mass spectrometry-based approach that accesses these macroscales, providing answers to more emergent questions on cancer and stemness. The power of the approach lies in the unique combination of the three functionally entangled omics layers, i.e. the histone epigenome, the metabolome and the proteome that are sequentially isolated from the same sample. With an adequately complex experimental design this allows building a biomolecular network that directly probes the interplay between metabolic state, epigenetic read-out and the expressed protein pool. We provide a novel biomolecular perspective, wherein epigenetic changes in histones lead to newly expressed proteins that convert other metabolites, which are projected back onto the histones in the form of hPTMs, completing a feedback loop—an 'energy-information' axis—where histones serve as the signal integrators, regulating gene activity based on the metabolic state of the cell. This view goes back to the first Eukaryote merger, where the Archaeal contributor provided the histones, allowing genome expansion and better control of gene activity by reading out the energy state of the bacterial endosymbiont that became the mitochondrion. In cancer biology, the altered metabolism is not merely a byproduct of tumorigenesis but rather a requirement for tumor initiation and progression. In this new view, hPTMs become dysregulated due to metabolic changes, contributing to uncontrolled cell proliferation, impaired differentiation, and other hallmarks of malignancy through altered protein expression.  

Only a few groups worldwide are currently dedicated to this MS-based study of the histone language and ProGenTomics is the only lab integrating untargeted histone PTM mapping with metabolomics and proteomics. Therefore, in collaborations, we provide robustly pre-processed data in different browsable and interactive formats that enable others to easily find novel associations and develop follow-up mechanistic studies. Our first proof of principle focused exclusively on AML cell lines to specifically surface fundamental biological connections in the biomolecular network and for the first time defining the concept of “functional entanglement”. 
 

A biologist by education, I started working with mass spectrometry in proteomics in 2004, during my MaNaMa in Medical Biotechnology. I have been working at the lab for Pharmaceutical Biotechnology ever since, focusing on the fine art of mass spectrometry in proteomics on a plethora of different subjects, the first one of which rheumatology, the most exotic one being archaeology (palaeoproteomics). Since the serendipitous discovery of a histone clipping event in leukemia cells in 2008, the research of the lab has increasingly shifted towards histone research. 
The ProGenTomics service lab was founded in 2016 and became the UGent Proteomics core facility in 2023. It has since created a new perspective on service and the potential of mass spectrometry for the future of molecular biology and other fields.
As former president of the Belgian Proteomics Association and current executive committee member of the European Proteomics association (EuPA) as founding chair of the Industry Committee, I am trying to help shape the future of proteomics in Europe.
 

• Amélie De Maesschalck - doctoral fellow
• Thijs Lefever - doctoral fellow
• dr. Simon Daled (PhD) - postdoc and core facility manager
   

• "Profiling histone post-translational modifications to identify signatures of epigenetic drug response in T-cell acute lymphoblastic leukemia". 2025.
• "Mass Spectrometry-based Profiling of Single-cell Histone Post-translational Modifications to Dissect Chromatin Heterogeneity". 2024.
• "Histone clipping: the punctuation in the histone code". EMBO Reports, 22(8), e53440. 2021.
• "Integrative Proteomic Profiling Reveals PRC2-Dependent Epigenetic Crosstalk Maintains Ground-State Pluripotency". Cell Stem Cell, 24(1), 123-137.e8. 2019.  
• "A large scale mass spectrometry-based histone screening for assessing epigenetic developmental toxicity. Scientific Reports, 12(1). 2022.  
• "Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction". Nature Cell Biology 2022 24:6, 24(6), 858–871. 2022.
• "Histone proteolysis: A proposal for categorization into clipping and degradation". BIOESSAYS 2015 (PMID: 25350939)
• "Quantitative proteomics to characterize specific histone H2A proteolysis in chronic lymphocytic leukemia and the myeloid THP-1 cell line" INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 2014 (PMID: 24871368)
• "Laser microdissection for the assessment of the clonal relationship between chronic lymphocytic leukemia/small lymphocytic lymphoma and proliferating B cells within lymph node pseudofollicles" LEUKEMIA 2011 (PMID: 21321570)
   

• member of BIG-N2N
• ProGenTomics
• address: Ottergemsesteenweg 460, B-9000 Gent
• dr. Dhaenens is interested to receive invitations for presentations or talks