By studying metabolic adaptations and vulnerabilities in inherited metabolic diseases, we gain deep insights into the relation beween different layers of regulation, enzyme kinetics, and metabolic network dynamics. Since the affected pathways are the same in different diseases, we believe that our computational models and analytical tools can be translated to different inherited or acquired diseases.
Our main field of interest is the dynamics of metabolic networks to:
Our current projects focus on accelerating diagnosis of > 1,800 inherited metabolic diseases, personalised medicine for inherited fatty-acid oxidation and glycogen storage diseases, and targeting of cancer metabolism.
To integrate the different layers of metabolic regulation, we develop computational models that can simulate and predict metabolic responses towards genetic variation, nutritional challenges, or medication. We make models patient-specific by including genetic variants and/or individual proteome profiles (the latter with Dr. Karin Wolters). For quantification of metabolite concentrations and metabolic fluxes we use mass spectrometry and stable-isotope fluxomics approaches. To bridge the large gap between patient physiology and computational models of cellular metabolism, we use in vitro (organoids) and ex vivo (precision-cut organ slices) for metabolic studies. In close collaboration with our clinical partners, we translate our findings to clinical applications, such as monitoring of treatment efficacy for inherited metabolic diseases or metabolic adjuvant therapy in cancer treatment.
Research in systems medicine is intrinsically interdisciplinary. This is reflected in the training of our PhD students. Whereas each student has a different focus, they all work in collaborations between computational, experimental, and clinical experts, among whom colleagues in the Laboratory of Paediatrics, the Beatrix Children’s Hospital UMCG, the departments of Laboratory Medicine and Oncology, and the Groningen Research Institute of Pharmacy.
The Dutch academic metabolic centers & patient organization VKS collaborate in United for Metabolic Diseases UMD, a unique, innovative and multidisciplinary collaboration with the common goal to perform innovative research in order to improve diagnosis, prevention, treatment and care for patients and families with an inherited metabolic disease. As a board member, I strongly support the ambitions and efforts of UMD. Our own systems medicine approach fits with the goals of UMD, since computational models and analytical tools developed for one disease can be applied to gain insights in other diseases.
At the European level this vision is shared and pioneered in a large consortium of computational modellers, clinical chemists, metabolic paediatricians, patient organisations, and the European reference network MetabERN in the Recon4IMD project in which we take part.
UMCG
Department of Pediatrics (HPC EA12)
Postbus 30.001
9700 RB Groningen
The Netherlands
Visiting address
UMCG
Antonius Deusinglaan 1
3226.0406
9713 AV Groningen
The Netherlands
