Nicolas H. Thomä

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Nicolas H. Thomä is a German biochemist and structural biologist who is a full professor at EPFL’s School of Life Sciences and directs the Paternot Chair for Cancer Research in Lausanne, Switzerland. He studies how genome stability, gene expression, and DNA repair work, using biochemistry, cryo-EM, genomics, imaging, and chemical biology.

Education and career: He earned his PhD at the University of Cambridge, working with Peter Leadlay and Phil Evans. He then did a postdoc with Roger Goody at the Max Planck Institute for Molecular Physiology, focusing on protein–ligand interactions. In 2001 he trained in X‑ray crystallography in Nikola Pavletich’s lab at Memorial Sloan Kettering Cancer Center. He joined the Friedrich Miescher Institute for Biomedical Research in 2006 as a junior group leader and was promoted to senior group leader in 2012. He became a full professor at EPFL in 2023.

Research focus: Thomä’s lab studies large molecular machines that control genome stability, transcription, and DNA repair. They work in two main areas: (1) how DNA‑binding proteins, especially transcription factors, operate when DNA is wrapped in chromatin; (2) how chromatin is linked to ubiquitin ligases, enzymes that tag proteins for destruction. The team has determined cryo‑EM structures of pioneer transcription factors bound to DNA motifs within nucleosomes, showing how these factors function in chromatin. They have also shed light on how cells recognize UV‑induced DNA damage and how Cullin–RING E3 ubiquitin ligases assemble and are regulated by the COP9 signalosome, explaining how these ligases drive protein degradation and influence DNA repair, signaling, cell division, and differentiation. This work helps explain diseases that arise when these pathways go wrong and highlights druggable targets.

Drug discovery notes: A key goal is to develop small molecules that induce targeted protein degradation, often called molecular glues. These molecules bring a ubiquitin ligase together with a target protein to trigger its destruction. The research on thalidomide and related compounds explains how such drugs work at the molecular level and why thalidomide derivatives are highly successful in treating multiple myeloma and other blood cancers. The lab also shows that other compounds can promote protein–protein interactions that lead to degradation, suggesting new strategies for drug design.