Frédéric Lemaigre

Major achievements

• Discovery of the ONECUT gene family, which is essential for liver, pancreas and nervous system development
• Characterisation of bile duct development and discovery of molecular signals driving liver morphogenesis
• Elected member of the Belgian Royal Academy of Medicine

Question

How do genes control liver morphogenesis and hepatic cell differentiation, and how does dysfunction of these genes promote liver cancer development?

Research focus

The acquisition of organ-specific properties of cells is called cell differentiation, and this process mainly occurs during embryonic development and tissue regeneration. Using transgenic mouse models, mouse embryo-derived organoids and state-of-the-art molecular and cell biology technology, Frédéric Lemaigre and his group determine how genes control differentiation of progenitor cells to mature liver cells, namely hepatocytes, biliary cells and mesenchymal cells. Using 3D imaging and spatial transcriptomics, the lab also investigates how the developing liver cells organise in three dimensions to form the organ. The data collected by the team are shared with experts in tissular engineering and regenerative therapy who attempt to construct liver tissue by recapitulating embryonic processes in vitro.

With help of European clinical centers who share pathological expertise, Frédéric Lemaigre's team also builds on its experience in cell differentiation to further study how liver cancer develops from non-malignant precursor lesions. This process is frequently characterised by loss of differentiation and partial reactivation of embryonic processes; its understanding is required for early diagnosis of liver cancer which too often manifests itself at a late stage of the disease.

Work in the team is performed in close collaboration with the group of Patrick Jacquemin who investigates pancreatic cancer development. The two groups share space, equipment and expertise.

Projects

• Cholangiocarcinoma tumour development
• Hepatic cell differentiation
• Bile duct morphogenesis

Frédéric Lemaigre studied medicine at the UCLouvain (Brussels, Belgium) and graduated in 1986. He then started a career in fundamental research under supervision of Prof. Guy Rousseau, at the de Duve Institute, to study tissue-specific regulation of mammalian gene transcription. After a stay (1991-1992) in the group of Prof. Michael Green at the University of Massachusetts Medical School (USA), to work on structure-function relationships in transcription factors, Frédéric Lemaigre obtained a permanent position at the F.R.S.-F.N.R.S. (1994) and built his team at the de Duve Institute to investigate how gene regulatory networks control cell differentiation, tissue morphogenesis, and tumour development, with focus on liver and pancreas. In 2002, he was appointed Professor at the UCLouvain Medical School where he teaches molecular biology and biochemistry, while pursuing his research at the de Duve institute.

Honors

• Alvarenga de Piauhy prize
• Eugène de Somer prize
• AstraZeneca/Biothera prize
• Elected member of the Belgian Royal Academy of Medicine

Affiliations

• Group leader, de Duve Institute
• Full Professor, UCLouvain
• Head of Liver and Pancreas Differentiation pole, UCLouvain