Research in the Berkers group focusses on metabolomics: studying the small molecule metabolite profile of cells using mass spectrometry. My group employs a mechanistic metabolomics strategy. By performing metabolic tracer studies using a variety of stable-isotope nutrients and combining such studies with targeted metabolism-oriented proteomics studies, we aim to gain mechanistic insight into cellular metabolism. We apply our metabolomics tools to two biomedical frameworks: metabolism-mediated drug resistance and immuno-metabolism.

Metabolism-mediated drug resistance
Metabolic rewiring is increasingly acknowledged to play a role in the sensitivity of cancer cells to anti-cancer therapies. We use metabolomics to find targetable metabolic changes in drug-resistant cells, to study the metabolic mode of action of drugs, or to obtain insight into adverse drug effects. In particular, we investigate proteasome inhibitors, which hold great promise for the treatment of cancer, but are associated with adverse effects and the occurrence of resistance. By characterizing the pathways that cells use to adapt to the action of proteasome inhibitors, we aim to reveal novel therapeutic targets for combination treatment and open up possibilities to treat resistant patients.

Immuno-metabolism
Immune responses depend on the balance between two types of T cells: conventional T cells (Tconv), that kill infected or tumor cells, and regulatory T cells (Treg), that inhibit the response of conventional T cells to self- and foreign antigens and are thereby critical to inhibit autoimmunity. Treg and Tconv share many features, including co-stimulatory and cytokine receptors, but differ significantly in their metabolic features. In an Institute for Chemical Immunology project we develop metabolomics strategies to map metabolic differences between these different T cells. Ultimately, we aim to identify metabolic targets that can be exploited to selectively modulate T-cell activity.