REpiNet - Remodelling of Epileptogenic Networks

Hyperexcitable networks arise from a variety of developmental and acquired brain pathologies. However, the mechanisms underlying the formation and maintenance of epileptic networks are not yet fully understood. Growing evidence suggests that aberrant molecular and functional network programming during epileptogenesis extends beyond the primary pathology and involves dynamic interactions between neuronal and glial elements as well as the surrounding tissue.

Our research group investigates these processes in lesion-associated epilepsies, including gangliogliomas and focal cortical dysplasia (FCD), as well as in acquired epilepsies such as temporal lobe epilepsy (TLE). Our research focuses on how pathological lesions alter adjacent brain tissue through neuronal, glial, and molecular mechanisms, and whether these changes contribute to drug resistance and persistent epileptic activity.

To address these questions, we combine studies of human surgical tissue, mouse models, and organotypic brain slice cultures with electrophysiological, histopathological, and molecular analyses. Our aim is to identify both shared and disease-specific mechanisms of epileptogenesis and pharmacoresistance and to develop novel disease-modifying therapeutic strategies.

Lab members:

• Lea Baudouin, cand. med.
• Naran Suvarnpradip, M. Sc.
• Berk Can, B. Sc
• Kittitach Sri-ngern-ngam, M. Sc. 

Current publications (selected):

• Pol E, Delhaye C, Cases-Cunillera S, Russeau M, Blachier S, Bouchet A, Piesse C, Pallud J, Huberfeld G, Pietrancosta N, Lévi S. NKCC1 as a signaling hub regulating KCC2 stability, chloride homeostasis, and seizure susceptibility. Brain. Accepted for publication. 2026.

• Cases-Cunillera S, Deboeuf L, Pyrzowski J, Nieto-Sánchez JF, Smirnov K, Iollo M, Díaz-Fernández B, Becker AJ, Le Van Quyen M, Dossi E, Huberfeld G. SpikeSpector software for MultiElectrode Arrays: Field potential analysis and spatial integration of electrophysiological and histological data. J Neurosci Methods. 2026 Jan;425:110615. doi: 10.1016/j.jneumeth.2025.110615. Epub 2025 Oct 30.

• Cases-Cunillera S, Müller P, van Waardenberg AJ, Schoch S, Huberfeld G, Höllig A, Delev D, Hamed M, Becker AJ, van Loo KMJ. Single-nucleus RNA sequencing: immature excitatory neurons and transformed glia build human BRAFV600E-negative gangliogliomas. Brain Commun. 2025 Oct 1. doi: 10.1093/braincomms/fcaf372. eCollection 2025.

• Díaz-Fernández B, Henao-Herreno D, Nieto J, Evstratova A, Cases-Cunillera S, Deboeuf L, Roux A, Dezamis E, Zanello M, Mathon B, Karachi C, Carpentier A, Varlet P, Pallud J, Capelle L, Alvarado-Rojas C, Le Van Quyen M, Huberfeld G. Differentiation of Tumor vs. Peritumoral Cortex in Gliomas by Intraoperative Electrocorticography. Neuro Oncol. 2025 Mar 24. doi: 10.1093/neuonc/noaf082.

• Cases-Cunillera S, Quatraccioni A, Rossini L, Ruffolo G, Ono T, Baulac S, Auvin S, O'Brien TJ, Henshall DC, Akman Ö, Sankar R, Galanopoulou AS. WONOEP appraisal: The role of glial cells in focal malformations associated with early onset epilepsies. Epilepsia. 2024 Oct 14. doi: 10.1111/epi.18126. Epub 2024 Oct 14.

• Cases-Cunillera S, Friker LL, Müller P, Becker AJ, Gielen GH. From bedside to bench: New insights in epilepsy-associated tumors based on recent classification updates and animal models on brain tumor networks. Mol Oncol. 2024 Jun 20. doi: 10.1002/1878-0261.13680. Epub 2024 Jun 20.

• Müller P, Dietrich D, Schoch S, Pitsch J, Becker AJ, Cases-Cunillera S. Ganglioglioma cells potentiate neuronal network synchronicity and elicit burst discharges via released factors. Neurobiol Dis. 2024 Jan;190:106364. doi: 10.1016/j.nbd.2023.106364. Epub 2023 Nov 24.

• Vana NS, van Loo KMJ, van Waardenberg AJ, Tießen M, Cases-Cunillera S, Sun W, Quatraccioni A, Schoch S, Dietrich D. Early cortical oligodendrocyte precursor cells are transcriptionally distinct and lack synaptic connections. Glia. 2023 May 25. doi: 10.1002/glia.24388.

• Antoniou A, Auderset L, Kaurani L, Sebastian E, Zeng Y, Allahham M, Cases-Cunillera S, Schoch S, Gruendemann J, Fischer A, Schneider A. Neuronal extracellular vesicles and associated microRNAs induce circuit connectivity downstream BDNF. Cell Rep. 2023 Feb 28;42(2):112063. doi: 10.1016/j.celrep.2023.112063. Epub 2023 Feb 6.

• Kyriazi M, Müller P, Pitsch J, van Loo KMJ, Quatraccioni A, Opitz T, Schoch S, Becker AJ, Cases-Cunillera S. Neurochemical profile of BRAFV600E/AktT308D/S473D mouse gangliogliomas reveals impaired GABAergic system inhibition. Dev Neurosci. 2022 Dec 20. doi: 10.1159/000528587.

• Pohlentz MS, Müller P, Cases-Cunillera S, Opitz T, Surges R, Hamed M, Vatter H, Schoch S, Becker AJ, Pitsch J. Characterisation of NLRP3 pathway-related neuroinflammation in temporal lobe epilepsy. PLoS One. 2022 Aug 16;17(8):e0271995. doi: 10.1371/journal.pone.0271995. eCollection 2022.

• Cases-Cunillera S, van Loo KMJ, Pitsch J, Quatraccioni A, Sivalingam S, Salomoni P, Borger V, Dietrich D, Schoch S, Becker AJ. Heterogeneity and excitability of BRAFV600E-induced tumors is determined by Akt/mTOR-signaling state and Trp53-loss. Neuro Oncol. 2022 May 4;24(5):741-754. doi: 10.1093/neuonc/noab268.

• Schoch S, Quatraccioni A, Robens BK, Maresch R, van Loo KMJ, Cases-Cunillera S, Kelly T, Opitz T, Borger V, Dietrich D, Pitsch J, Beck H, Becker AJ. Ste20-like Kinase Is Critical for Inhibitory Synapse Maintenance and Its Deficiency Confers a Developmental Dendritopathy. J Neurosci. 2021 Sep 29;41(39):8111-8125. doi: 10.1523/JNEUROSCI.0352-21.2021. Epub 2021 Aug 16.

• Laaniste L, Srivastava PK, Stylianou J, Syed N, Cases-Cunillera S, Shkura K, Zeng Q, Rackham OJL, Langley SR, Delahaye-Duriez A, O'Neill K, Williams M, Becker A, Roncaroli F, Petretto E, Johnson MR. Integrated systems-genetic analyses reveal a network target for delaying glioma progression. Ann Clin Transl Neurol. 2019 Sep;6(9):1616-1638. doi: 10.1002/acn3.50850. Epub 2019 Aug 17.

Current funding/grants:

• BONFOR Forschungsförderprogramm - Medizinische Fakultät
• Herbert-Reeck-Foundation-Preis

Collaborative Research Consortia/ Scientific Co-operations:

• DFG-Graduiertenkolleg (GRK3151)
• Prof. Dr. med. Albert Becker, Institut für Zelluläre Neurowissenschaften II, Universitätsklinikum Bonn
• Dr. Valentina Zschernack, Institut für Neuropathologie, Universitätsklinikum Bonn
• Dr. Karen van Loo, Sektion Epileptologie der Uniklinik RWTH Aachen
• Prof. Dr. med. Gilles Huberfeld, Institut de Psychiatrie et Neurosciences de Paris - INSERM U1266