Cells need to adjust their metabolism to fulfill changing needs for building blocks, energy and protection from stress. We search for vulnerabilities in known or newly discovered metabolic pathways that might be targeted in future therapies for variety of diseases ranging from cancer to Parkinson's disease.

The local ‘success’ of a cancer cell is measured by its ability to proliferate and survive better with the available nutrients than its neighboring cells. Like any other cell, a cancer cell needs to maintain cellular integrity and fulfill baseline housekeeping functions. All cell types need to synthesize ATP by breaking down nutrients in pathways such as glycolysis, citric acid cycle and mitochondrial oxidative phosphorylation. In addition, proliferating cells in general and cancer cells in particular need to generate bio-mass, composed of amino acids, nucleotides and lipids. Synthesis of these components starts with precursors that are intermediary products in the same pathways that are used to synthesize cellular ATP. Several adjustments of the flux through these pathways are needed to reconcile cellular demand for biosynthetic building blocks and for ATP synthesis.

 

We are investigating the role of a series of enzymes, for which we have reason to believe that they might be involved in the synthesis of regulatory molecules. In these studies, we use a combination of state-of-the-art metabolomics (GC-MS and LC-MS) and genetic manipulation of cell lines to understand the cellular effects of novel regulatory molecules. Classical enzymological studies (in collaboration with the laboratory of Emile Van Schaftingen & Maria Veiga-Da-Cunha) on purified proteins are then used to understand the molecular basis of the observed effects. Eventually, we hope that our work will reveal novel therapeutic targets in cancer. Currently, we are particularly interested in several phosphatases that might serve to eliminate metabolic side-products or metabolic regulators.

 

While we strive to understand processes involved in cancer biology, we remain very much open to surprising discoveries. As such, we have recently discovered a novel post-translational modification of α-dystroglycan by ribitolphosphorylation. Furthermore, we are following-up on observations that suggest that so far unknown biochemical changes may contribute to the development of Parkinson’s disease.

 

Complete list on PubMed
Guido Bommer
Institut de Duve
Avenue Hippocrate 75 - B1.75.08
B-1200 Bruxelles
Tel:
+32 2 764 75 68
Fax:
+32 2 764 75 98
Secretary:
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