The JMY protein is an important regulator of the actin cytoskeleton, involved in cell migration and morphogenesis. Expressed in the developing brain, it is associated with several key processes of neurogenesis, including neurite formation, dendritogenesis, myelination, and neuronal migration. However, its specific role in human brain development remains poorly characterized.
In parallel, our work demonstrates that JMY plays a central role in the pathophysiology of glioblastoma, a highly aggressive brain tumor. Following irradiation, glioblastoma stem cells increase their migratory and invasive capacities through a pathway involving HIF1a and JMY. This activation promotes the formation of actin-rich structures known as tumor microtubes, which are associated with therapeutic resistance.
This project aims to investigate JMY as a common regulator of neurodevelopment and tumor plasticity.
In a first axis, we will analyze the impact of JMY deficiency in human brain organoids derived from iPS cells, in order to assess its effects on proliferation, differentiation, neurogenesis, and cortical organization.
In a second axis, a high-throughput pharmacological screening will be conducted to identify inhibitors capable of blocking radiation-induced migration of glioblastoma tumor stem cells.
The expected results will improve our understanding of JMY’s role in the human brain and support the development of new strategies aimed at limiting glioblastoma recurrence after radiotherapy.