Denis Jabaudon, Thomas Blauwblomme and Rima Nabbout

At Institut Imagine, the Brain Development and Epilepsy Hub brings together complementary expertise to better understand and treat pediatric epilepsies. By combining fundamental science with translational research, and working in close collaboration with the Necker-Enfants Malades Hospital and the CRéER reference center, where every patient acts as a driving force behind research, we aim to advance diagnosis, treatments, and future prospects for affected children.

The hub’s research is centered around three major axes led by Denis Jabaudon, Thomas Blauwblomme, and Rima Nabbout. Together, we aim to decode the construction of the human cortex, understand how developmental disruptions lead to epilepsy and neurodevelopmental disorders, and identify the levers needed to intervene earlier and in a more targeted manner.

Denis Jabaudon leads work in developmental neurobiology, revealing how genes orchestrate the birth, migration, and organization of neurons into networks. His research also highlights how specific genetic or environmental alterations can disrupt this delicate balance and promote the onset of seizures.

In parallel, Thomas Blauwblomme explores epileptogenic cortical dysplasias, specifically those linked to mutations in the mTOR pathway. He has identified an impairment in the KCC2 transporter, a sign of abnormal neuronal excitability from the earliest stages of development, offering new benchmarks to guide surgical and therapeutic decisions.

Finally, Rima Nabbout’s translational program on developmental and epileptic encephalopathies—particularly those associated with ion channel defects—integrates clinical and neuropsychological data with molecular analyses and in silico and in vivo models. Her goal is to identify diagnostic and prognostic markers, predict treatment responses, tailor interventions to each child at the right time, and develop therapies that target both the underlying mechanisms and what matters most to the patient.

To understand these mechanisms, we analyze human fetal and surgical tissue. We complement this with approaches such as single-cell sequencing, spatial transcriptomics, and electrophysiological recordings to precisely map cortical cells, their interactions, their electrical activity, and their connectivity.

We also replicate these alterations in organotypic and animal models, including cortical organoids, mice, and zebrafish, to track their evolution and test new therapeutic strategies. This integrated approach establishes a direct link between clinical observations, developmental biology, and therapeutic innovation.

By uniting this expertise with strong collaborations within Imagine and with local, national, and international partners, our hub offers an environment of excellence. Our mission is to understand the mechanisms of developmental epilepsies and pave the way for innovative, personalized solutions for our young patients.

Selection of publications (full list DJ TB RN):

• Klingler et al. (2021); Science https://doi.org/10.1126/science.aba4517
• Bakouh et al. (2025); Brain 148:549-563. https://doi.org/10.1093/brain/awae262