Cell Biology and Genetics, Epilepsy
Unique contributions and highlights
In Cell Biology
We have established techniques to discover new auto-antibodies against neuronal antigens in our lab. We furthermore test patient populations with epilepsy (and comorbidities) and other diseases to further delineate the clinical spectrum of auto-antibody mediated brain diseases.
Using an animal model, we previously demonstrated a sustained impact of febrile seizures on hippocampal neurodevelopment (Swijsen et al., Epilepsia 2012;53(11):1968-1977; fig 1). In adult patients with temporal lobe epilepsy plus a history of febrile seizures, we observed epigenetic alterations in the hippocampus (De Nijs et al., Clin Epigenetics 2019;11(1):118)
Funded by a ZonMw Off-road grant and in collaboration with TU Eindhoven and Leiden University Medical Centre LUMC, we currently develop and validate an animal-free model of epilepsy to test future antiepileptic treatments. To this end, we co-culture 3D human resected brain tissue on differentiated human inducible pluripotent stem cells (fig 2).
We are studying the prevalence of autoantibodies against metabotropic glutamate receptor 1 in drug resistant epilepsy. We aim to reveal the autoantibody effector functions using a new method to track calcium concentration changes inside of cells. Additionally, we are working in the development of an autoimmune animal model to characterize the pathogenic mechanism of the autoantibodies, and novel treatment strategies.
We described our results from our own experience in using whole exome sequencing in clinical practice in the first 100 patients (Snoeijen-Schouwenaars Epilepsia 2019), abd (and???) further phenotyping studies were published for separate genes (Mulhern et al, Ann Neurol 2018; Reijnders et al, J Clin Gen 2018).
Involved staff in this crossroad:
- Govert Hoogland
- Laurence de Nijs
- Olaf Schijns
- Bert Aldenkamp
- Rob Rouhl
- Mario Losen
- Pilar Martinez
- Anita Vincke
- Shenghua Zong
- Marina Damas