MOSAIC team

The objective of the team is to elucidate the molecular and cellular mechanisms underlying focal epilepsies with malformations of cortical development, with a focus on somatic mutations.

The research is based on the concept that the human brain is a genetic mosaic resulting from somatic mutations acquired during neurodevelopment. Cortical malformations represent a preferred model for studying this mosaicism, allowing us to understand how mutations affecting a subset of neuronal cells can disrupt cortical architecture and generate epileptogenic foci. The team is using multidisciplinary approaches, from genetic and genomic studies on postoperative epileptic brain tissue, to in vitro functional tests using brain organoids, to in vivo approaches using mouse models.

The research program has three main objectives:

1. To elucidate the genetic etiology of epileptogenic cortical malformations (in particular focal cortical dysplasia) by identifying somatic mutations in brain tissue;
2. To understand the pathogenic and neurodevelopmental mechanisms underlying focal epilepsies by determining specific determinants of cell type in cortical organoids and mouse models;
3. Investigate novel, precision targeted therapeutics to correct molecular abnormalities associated with cortical malformations.
    

Main publications

2025

• Baldassari S, Klingler E, Gomez Teijeiro L, Doladilhe M, Raoux C, Roig Puiggros S, Bizzotto S, Sami L, Ribierre T, Aronica E, Adle-Biassette H, Chipaux M, Jabaudon J and Baulac S. Single-cell genotyping and transcriptomic profiling in focal cortical dysplasia. Nat Neurosci. 2025. doi.org/10.1038/s41593-025-01936-z.

2024

• Boßelmann, C.M., Leu, C., Brünger, T. Hoffmann L, Baldassari S, …, Baulac S, et al. Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR. Nat Commun 15, 10429 (2024).
• Ribierre T, Bacq A, Baldassari S, Maletic M, Roussel D, Donneger F, Doladilhe M, Le Roux I, Chassoux F, Devaux B, Adle-Biassette H, Ferrand-Sorbets S, Dorfmüller G, Chipaux M, Poncer JC and Baulac S. Targeting pathogenic cells reduces seizures in neurodevelopmental mTOR-related epilepsy. Nat Neurosci. 2024 Jun;27(6):1125-1136. doi: 10.1038/s41593-024-01634-2.

2023

• Okoh J, Mays J, Bacq A, Chen C, Imambeyev K, Zhou H, Jafar-Nejad P, Noebels J, Baulac S and Costa-Mattioli M. Targeted suppression of mTORC2 reduces seizures across models of epilepsy. Nat Commun. 2023 Nov 14;14(1):7364. doi: 10.1038/s41467-023-42922-y.
• Checri R, Chipaux M, Ferrand-Sorbets S, Raffo E, Bulteau C, Rosenberg SD, Doladilhe M, Dorfmüller G, Adle-Biassette H, Baldassari S, Baulac S. Detection of brain somatic mutations in focal cortical dysplasia during epilepsy presurgical workup. Brain Commun. 2023 Jun 1;5(3):fcad174. doi: 10.1093/braincomms/fcad174.
• Chung C, Yang X, Bae T , Vong K, Mittal S , Conti V, Guerrini R, Devinsky O, Wilson A. Silva Jr 18, Helio R. Machado 7, Mathern G , Abyzov A, Baldassari S, Baulac S, Focal Cortical Dysplasia Neurogenetics Consortium &, Brain Somatic Mosaicism Network  and Gleeson J. Comprehensive multiomic profiling of somatic mutations in malformations of cortical development. Nat Genet. 2023 Feb;55(2):209-220. doi: 10.1038/s41588-022-01276-9

2021

• Kim S*, Baldassari S*, Sim NS, Chipaux M, Dorfmüller G, Kim DS, Chang WS, Taly V, Lee JH and Baulac S. Detection of Brain Somatic Mutations in Cerebrospinal Fluid from Refractory Epilepsy Patients. Annals of Neurology 2021. Jun;89(6):1248-1252. doi: 10.1002/ana.26080.
• Bonduelle T, Hartlieb T, Baldassari S, Sim NS, Kim SH, Kang HC, Kobow K, Coras R, Chipaux M, Dorfmüller G, Adle-Biassette H, Aronica E, Lee JH, Blumcke I and Baulac S. Frequent SLC35A2 brain mosaicism in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). Acta Neuropathol Commun 2021 Jan 6;9(1):3. doi: 10.1186/s40478-020-01085-3 . 

2019

• Baldassari S, Ribierre T, Marsan E, Adle-Biassette H, Ferrand-Sorbets S, Bulteau C, Dorison N, Fohlen M, Polivka M, Weckhuysen S, Dorfmüller G, Chipaux M, and Baulac S. Dissecting the genetic basis of focal cortical dysplasia: a large cohort study. Acta Neuropathol 2019 Dec;138(6):885-900. doi: 10.1007/s00401-019-02061-5.

2018

• Ribierre T, Deleuze C, Bacq A, Baldassari S, Marsan E, Chipaux M, Muraca G, Roussel D, Navarro V, Leguern E, Miles R and Baulac S. Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy. Journal of Clinical Investigation 2018. Jun 1;128(6):2452-2458. doi: 10.1172/JCI99384.