Biography
Our primary research interest centers around the genetic causes of human diseases, with a specific emphasis on neurodevelopmental disorders (NDD) and epilepsy. Central to our work are the invaluable patient collections we have established, as well as our pivotal role in a national network dedicated to collecting samples from individuals with epilepsy for genetic research. Moreover, our close association with the genetic diagnostic and clinical genetics department provides critical support to over 600 individuals dealing with NDD and epilepsy.
In recent years, our investigations have focused on the identification of biomarkers and clinical factors that influence the clinical outcomes in Dravet syndrome. We have meticulously characterized mutations in epilepsy-related genes, conducted genetic association studies on common forms of epilepsy, leading to the pioneering large-scale GWAS on epilepsy. Our research has also explored the intricate connections between epilepsy and other brain-related disorders. Additionally, we have dedicated efforts to exploring monogenic causes of epilepsy and chromosomal abnormalities.
Our recent focus has shifted towards translating our genetic findings into clinical applications. We are actively researching the impact of genetics on epilepsy surgery and treatment outcomes, while also exploring the therapeutic implications of having an epilepsy-related genetic mutation. In addition, we are at the forefront of developing innovative gene therapies for NDD, encompassing gene modulation and editing techniques, and RNA therapy.
Research line
Epilepsy genetics
Most recent key publications
- Increased prime edit rates in KCNQ2 and SCN1A via single nicking all-in-one plasmids. Dirkx N, Weuring WJ, De Vriendt E, Smal N, van de Vondervoort J, van 't Slot R, Koetsier M, Zonnekein N, De Pooter T, Weckhuysen S, Koeleman BPC. BMC Biol. 2023 ;21(1):156.
- CRISPRa-mediated upregulation of scn1Laa during early development causes epileptiform activity and dCas9-associated toxicity. Weuring WJ, Dilevska I, Hoekman J, van de Vondervoort J, Koetsier M, van ’t Slot RH, Braun KPJ, Koeleman BPC. CRISPR Journal. 2021. 4(4):575-582.
- NaV1.1 and NaV1.6 selective compounds reduce the behavior phenotype and epileptiform activity in a novel zebrafish model for Dravet Syndrome. Weuring WJ, Singh S, Volkers L, Rook MB, van 't Slot RH, Bosma M, Inserra M, Vetter I, Verhoeven-Duif NM, Braun KPJ, Rivara M, Koeleman BPC. PLoS One. 2020;15(3):e0219106.
- Neurodevelopmental Disorders Caused by De Novo Variants in KCNB1 Genotypes and Phenotypes. de Kovel CGF, Syrbe S, Brilstra EH, Verbeek N, Kerr B, Dubbs H, Bayat A, Desai S, Naidu S, Srivastava S, Cagaylan H, Yis U, Saunders C, Rook M, Plugge S, Muhle H, Afawi Z, Klein KM, Jayaraman V, Rajagopalan R, Goldberg E, Marsh E, Kessler S, Bergqvist C, Conlin LK, Krok BL, Thiffault I, Pendziwiat M, Helbig I, Polster T, Borggraefe I, Lemke JR, van den Boogaardt MJ, Møller RS, Koeleman BPC. JAMA Neurol. 2017;74(10):1228-1236.
- CHD2 variants are a risk factor for photosensitivity in epilepsy. Galizia EC, Myers CT, Leu C, de Kovel CG, Afrikanova T, Cordero-Maldonado ML, Martins TG, Jacmin M, Drury S, Krishna Chinthapalli V, Muhle H, Pendziwiat M, Sander T, Ruppert AK, Møller RS, Thiele H, Krause R, Schubert J, Lehesjoki AE, Nürnberg P, Lerche H; EuroEPINOMICS CoGIE Consortium, Palotie A, Coppola A, Striano S, Gaudio LD, Boustred C, Schneider AL, Lench N, Jocic-Jakubi B, Covanis A, Capovilla G, Veggotti P, Piccioli M, Parisi P, Cantonetti L, Sadleir LG, Mullen SA, Berkovic SF, Stephani U, Helbig I, Crawford AD, Esguerra CV, Kasteleijn-Nolst Trenité DG, Koeleman BPC, Mefford HC, Scheffer IE, Sisodiya SM. Brain. 2015.
- GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture. International League Against Epilepsy Consortium on Complex Epilepsies. Nat Genet. 2023;55(9):1471-1482.
