Jean-Baptiste Demoulin

Major achievements

• Discovery of PDGFRB mutations as leading cause of pediatric myofibroma and myofibromatosis.
• Mechanisms whereby PDGF receptor alterations lead to leukemia, primary familial brain calcification, Penttinen and Kosaki syndromes.
• Validation of tyrosine kinase inhibitors as treatment of several diseases linked to PDGF receptors.

Question

How do growth factor receptors contribute to human diseases and how can we target them for therapy?

Research focus

PDGF receptors are key cell surface sensors that regulate the growth and migration of mesenchymal cells in all organs. Alterations of PDGF receptor genes (PDGFRA and PDGFRB) have been associated to a variety of human pathologies, including cancer, leukemia, brain calcification, aneurysms and congenital disorders such as Penttinen and Kosaki syndromes. Understanding how mutations of these two genes can lead to such an array of different diseases in not only a fascinating fundamental quest but also the key to finding cures for these debilitating pathological conditions.

The Demoulin laboratory is the reference center for testing PDGF receptor variants. Gene alterations are identified using next generation sequencing technologies. The team has developed multiple assays to assess the impact of PDGFRA and PDGFRB mutations in cell culture. The sensitivity to tyrosine kinase inhibitors is also tested in vitro. The team benefits from a network of collaborations with clinicians, pathologists and geneticists.

PDGF receptors signal by phosphorylating intracellular proteins on tyrosines. This leads to the activation of signaling enzymes (e.g. phosphatidylinositol-3 kinase, phospholipase Cγ, AKT, ERK…) and transcription factors (e.g. STAT1, STAT3, STAT5, SRF, SREBP1). This process is studied using phospho-proteomics and RNA sequencing. Receptor mutations associated with distinct diseases can lead to either a gain or a loss specific signaling pathways.

Jean-Baptiste Demoulin has always been passionate about receptor signaling. He obtained a degree in Pharmacy from UCLouvain (Belgium) in 1994. He joined the lab of Prof. Jean-Christophe Renauld at the Ludwig Institute for Cancer Research (Brussels branch), where he obtained his PhD in pharmaceutical sciences in 1999, working on interleukin-9 receptor signal transduction. He then moved to Uppsala University (Sweden) in the lab of Prof. Carl-Henrik Heldin, as FNRS post-doctoral fellow. He obtained a Marie-Sklodowska-Curie fellowship to pursue his research on PDGF receptor in the same laboratory. He became associate professor at UCLouvain in 2003 and joined the de Duve institute as a group leader. He started to teach molecular and cellular biology at the faculty of medicine in 2004. He was promoted to a full professor position in 2016. He published more than one hundred scientific papers in international journals and obtained grants from FNRS, Opération Télévie, the Belgian Foundation against Cancer, Biowin and the King Baudouin Foundation.

Honors

Jean-Baptiste Demoulin received several awards for his work on receptor signaling, including two prizes from the Royal Academy of Medicine of Belgium.

Affiliations

• Group Leader, de Duve Institute
• Full Professor, UCLouvain