Genetics and pathophysiology of epilepsy

The objective of the team is to elucidate the molecular and cellular mechanisms underlying focal epilepsies with malformations of cortical development, developmental and epileptic encephalopathies, and generalized genetic epilepsies.

His research builds on the recently recognized concept that the human brain is a genetic mosaic resulting from somatic mutations during neurodevelopment. 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. elucidate the genetic etiology of epileptogenic cortical malformations (in particular focal cortical dysplasia);
2. to unravel the pathogenic mechanisms and neurodevelopmental events underlying focal epilepsies by determining specific determinants of cell type in cortical organoids and mouse models;
3. study new targeted therapeutics that are innovative and ultra-precise.

Main publications

• 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. (2023) Comprehensive multiomic profiling of somatic mutations in malformations of cortical development.Nat Genet. 2023 Feb;55(2):209-220.
• Bacq A, Roussel D, Bonduelle T, Zagaglia S, Maletic M, Ribierre T, Adle-Biassette H, Marchal C, Jennesson M, An I, Picard F, Navarro V, Sisodiya S and Baulac. (2022) Cardiac investigations in sudden unexpected death in DEPDC5-related epilepsy.Annals of Neurology 2022 Jan;91(1):101-116.
• Lee WS, Baldassari S, Stephenson S, Lockhart P, Baulac S * and Leventer RJ*. (2022) Cortical dysplasia and the mTOR pathway: how the study of human brain tissue has led to insights into epileptogenesis.International Journal of Molecular Sciences 2022 Jan 25;23(3):1344 doi: 10.3390/ijms23031344.
• Baldassari S and Baulac S. (2022). Genetics of FCD: an emerging scenario; Book Chapter in « Focal Cortical Dysplasias: New Advances for Curing Epilepsy”, edited by Francine Chassoux and Andres Luis Fernandes Palmini (2022). John Libbey edition.
• Blümcke I, Budday S, Poduri A, Lal D, Kobow K and Baulac S. (2021) Neocortical development and epilepsy: insights from focal cortical dysplasia and brain tumours.Lancet Neurology 2021 Nov;20(11):943-955.
• Kim S*, Baldassari S*, Sim NS, Chipaux M, Dorfmüller G, Kim DS, Chang WS, Taly V, Lee JH and Baulac S. (2021) Detection of Brain Somatic Mutations in Cerebrospinal Fluid from Refractory Epilepsy Patients.Annals of Neurology Jun;89(6):1248-1252.
• De Fusco A, Cerullo MS, Marte A, Michetti C, Romei A, Castroflorio E, Baulac S, Benfenati F (2020). Acute knockdown of Depdc5 leads to synaptic defects in mTOR-related epileptogenesis.Neurobiol of Disease. 2020;104822. doi: 10.1016/j.nbd.2020.104822.
• 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. (2019) Dissecting the genetic basis of focal cortical dysplasia: a large cohort study.Acta Neuropathol 2019 Dec;138(6):885-900.
• 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 (2018). Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy.Journal of Clinical Investigation, Jun 1;128(6):2452-2458.
• Baulac S, Ishida S, Marsan E, Miquel C, Biraben A, Nguyen DK, Nordli D, Cossette P, Nguyen S, Lambrecq V, Vlaicu M, Daniau M, Bielle F, Andermann E, Andermann F, Leguern E, Chassoux F, Picard F (2015). Familial focal epilepsy with focal cortical dysplasia due to DEPDC5 mutations.Ann Neurol. Apr; 77(4): 675-83. Highlighted as Best Advances of 2015 by the Neurology Today Editorial Advisory Board.
• Nava C, Dalle C, Rastetter A, Striano P, de Kovel CG, Nabbout R, Cancès C, Ville D, Brilstra EH, Gobbi G, Raffo E, Bouteiller D, Marie Y, Trouillard O, Robbiano A, Keren B, Agher D, Roze E, Lesage S, Nicolas A, Brice A, Baulac M, Vogt C, El Hajj N, Schneider E, Suls A, Weckhuysen S, Gormley P, Lehesjoki AE, De Jonghe P, Helbig I, Baulac S, Zara F, Koeleman BP; EuroEPINOMICS RES Consortium, Haaf T, Leguern E, Depienne C (2014). De novo mutations in HCN1 cause early infantile epileptic encephalopathy. Nat Genet, 2014 Jun; 46(6): 640-5.
• Ishida S, Picard F, Rudolf G, Noé E, Achaz G, Thomas P, Genton P, Mundwiller E, Wolff M, Marescaux C, Miles R, Baulac M, Hirsch E, Leguern E and Baulac S (2013). Mutations of DEPDC5 cause autosomal dominant focal epilepsies. Nat Genet,Apr 26; 45(5): 552-5.