Research
Vanhaesebroeck has made fundamental contributions to the understanding of cell signalling and how this knowledge can be exploited therapeutically by either inhibiting or activating signalling pathways. [5]
His work focuses on lipid second messengers, particularly the PI3K family. His research has contributed to the understanding of how different PI3K isoforms function and how they regulate immune responses and cancer progression. [6] [7] To enable these studies, he developed novel genetic approaches to accurately model kinase inhibition in model organisms. [8]
In 1997, Vanhaesebroeck and collaborators identified the p110δ isoform of PI3K (PI3Kδ), which is primarily expressed in white blood cells. [9] [10] His group later demonstrated its critical role in regulating B and T cell function. He and his colleagues later discovered that inactivation of PI3Kδ paradoxically activates the immune system, [11] which is now the basis for its exploration in cancer immunotherapy for solid tumours. [12]
These findings contributed to the development of PI3Kδ inhibitors, some of which have been approved for the treatment of hematological malignancies and the activated PI3Kδ syndrome (APDS), and are under investigation for use in cancer immunotherapy. [13]
Vanhaesebroeck’s laboratory has also made major contributions to understanding the roles of the PI3Kα isoform in metabolism and insulin signalling, vascular biology, and vascular anomalies, which helped lead to the clinical approval of a PI3Kα inhibitor in the PI3K-driven overgrowth syndrome. [14]
His group has also developed small-molecule PI3K activators, expanding potential therapeutic approaches for diseases involving kinase dysregulation. [15] [16]
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