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dr. B.P.C. Koeleman

dr. B.P.C. Koeleman

Associate Professor
  • Group Koeleman, section Genetics

Biography

Biography

Dr. Bobby Koeleman is Group Leader at the department of Genetics within the Center for Molecular Medicine at the University Medical Center Utrecht since 2001.  He is an expert in genetics, dedicated to find genetic causes of both common and rare genetic disease, and subsequently aims to translate the genetic finding to clinical relevance. He received a NWO VIDI grant in 2010, and support by various grants from the Dutch  Diabetes  Foundation,  Dutch  Hart  Foundation, Dutch  Epilepsy  Foundation,  Dutch  Arthritis  Foundation, Zon-MW  NWO,  and  EU  Fp6,  Fp7, and  ESF programs.

We focus on the genetic causes of Autoimmune diseases and epilepsy. An important aim of our studies is to translate genetic findings to clinical relevance. We perform genetic research of common epilepsy through Genome-Wide Association Studies (GWAS) and pharmacogenetic studies.  We have coordinated analysis of the first GWAS in common epilepsies that showed that SCN1A is the major susceptibility locus for both focal and generalized epilepsy. Large patients cohorts are at the hart of these studies and we are collaborating with the Epilepsy Expert center SEIN to establish the largest epilepsy cohort in The Netherlands.  

We further are dedicated to find the monogenic causes of severe childhood epilepsy. Through Next Generation Sequencing studies we have contributed to the discovery of several new epilepsy genes, including HCN1, STX1B, CHD2, and DNM1. We are particularly interested to improve diagnosis and treatment, and find new treatment modalities for these rare genetic epilepsies, through detailed geno-phenotype and functional studies.

Finally, we are performing translational studies in Type 1 Diabetes together with the LUMC in a Dutch network that is particular interested in post-translation modification as a source of novel disease determinants and biomarkers. 

Research line

Epilepsy genetics

Most recent key publications

1: Hardies K, de Kovel CG, Weckhuysen S, Asselbergh B, Geuens T, Deconinck T, Azmi A, May P, Brilstra E, Becker F, Barisic N, Craiu D, Braun KP, Lal D, Thiele H, Schubert J, Weber Y, van 't Slot R, Nürnberg P, Balling R, Timmerman V, Lerche H, Maudsley S, Helbig I, Suls A, Koeleman BPC, De Jonghe P; autosomal recessive working group of the EuroEPINOMICS RES Consortium. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. Brain. 2015;138(Pt 11):3238-50
2: Remarkable Phenytoin Sensitivity in 4 Children with SCN8A-related Epilepsy: A Molecular Neuropharmacological Approach. Boerma RS, Braun KP, van de Broek MP, van Berkestijn FM, Swinkels ME, Hagebeuk EO, Lindhout D, van Kempen M, Boon M, Nicolai J, de Kovel CG, Brilstra EH, Koeleman BPC. Neurotherapeutics. 2015 Epub
3: 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, Veggiotti 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 ;138:1198-207. (* shared last author)
4: Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies. International League Against Epilepsy Consortium on Complex Epilepsies. Lancet Neurol. 2014;13(9):893-903. A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy. Kuiper JJ, Van Setten J, Ripke S, Van 'T Slot R, Mulder F, Missotten T, Baarsma GS, Francioli LC, Pulit SL, De Kovel CG, Ten Dam-Van Loon N, Den Hollander AI, Huis in het Veld P, Hoyng CB, Cordero-Coma M, Martín J, Llorenç V, Arya B, Thomas D, Bakker SC, Ophoff RA, Rothova A, De Bakker PI, Mutis T, Koeleman BPC. Hum Mol Genet. 2014 ;23(22):6081-7.

Fellowship and Awards

1: Dutch Diabetes Research Foundation (Diabetes Fonds Nederland, DFN) Network Grant. 2015
2: EU-Fp7 program grant. “EPIPGX, Epilepsy Pharmacogenomics: delivering biomarkers for clinical use”2012
3: NWO-VIDI grant. “Genetics of common Epilepsies” 2010
4: Dutch Epilepsy Foundation (Nederlands Epilepsie Fonds). “ Next generation sequencing for epilepsy disease gene discovery and improved DNA diagnostics” 2009
5: Dutch Rheuma Research Foundation (Reumafonds Nederland). “ Unravelling the molecular pathogenesis of Rheumatoid Arthritis without antibodies against citrullinated peptides using a Genome Wide Association” 2009

Research Output (293)

Genetic and Functional Differences between Duplicated Zebrafish Genes for Human SCN1A

Weuring Wout J., Hoekman Jos W., Braun Kees P.J., Koeleman Bobby P.C. 1 Feb 2022, In: Cells. 11 , p. 1-8

CRISPRa-Mediated Upregulation of scn1laa during Early Development Causes Epileptiform Activity and dCas9-Associated Toxicity

Weuring Wout J., Dilevska Ivana, Hoekman Jos, Van De Vondervoort Joep, Koetsier Martijn, Van 'T Slot Ruben H., Braun Kees P.J., Koeleman Bobby P.C. Aug 2021, In: CRISPR Journal. 4 , p. 575-582 8 p.

Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations

Stevelink Remi, Luykx Jurjen J., Lin Bochao D., Leu Costin, Lal Dennis, Smith Alexander W., Schijven Dick, Carpay Johannes A., Rademaker Koen, Rodrigues Baldez Roiza A., Devinsky Orrin, Braun Kees P.J., Jansen Floor E., Smit Dirk J.A., Koeleman Bobby P.C., , Jul 2021, In: Epilepsia. 62 , p. 1518-1527 10 p.

NEXMIF encephalopathy:an X-linked disorder with male and female phenotypic patterns

Stamberger Hannah, Hammer Trine B, Gardella Elena, Vlaskamp Danique R M, Bertelsen Birgitte, Mandelstam Simone, de Lange Iris, Zhang Jing, Myers Candace T, Fenger Christina, Afawi Zaid, Almanza Fuerte Edith P, Andrade Danielle M, Balcik Yunus, Ben Zeev Bruria, Bennett Mark F, Berkovic Samuel F, Isidor Bertrand, Bouman Arjan, Brilstra Eva, Busk Øyvind L, Cairns Anita, Caumes Roseline, Chatron Nicolas, Dale Russell C, de Geus Christa, Edery Patrick, Gill Deepak, Granild-Jensen Jacob Bie, Gunderson Lauren, Gunning Boudewijn, Heimer Gali, Helle Johan R, Hildebrand Michael S, Hollingsworth Georgie, Kharytonov Volodymyr, Klee Eric W, Koeleman Bobby P C, Koolen David A, Korff Christian, Küry Sébastien, Lesca Gaetan, Lev Dorit, Leventer Richard J, Mackay Mark T, Macke Erica L, McEntagart Meriel, Mohammad Shekeeb S, Monin Pauline, Verbeek Nienke, Feb 2021, In: Genetics in medicine : official journal of the American College of Medical Genetics. 23 , p. 363-373 11 p.

GATOR1-related focal cortical dysplasia in epilepsy surgery patients and their families:A possible gradient in severity?

Benova Barbora, Sanders Maurits W.C.B., Uhrova-Meszarosova Anna, Belohlavkova Anezka, Hermanovska Barbora, Novak Vilem, Stanek David, Vlckova Marketa, Zamecnik Josef, Aronica Eleonora, Braun Kees P.J., Koeleman Bobby P.C., Jansen Floor E., Krsek Pavel Jan 2021, In: European Journal of Paediatric Neurology. 30 , p. 88-96 9 p.

Damaging de novo missense variants in EEF1A2 lead to a developmental and degenerative epileptic-dyskinetic encephalopathy

Carvill Gemma L, Helbig Katherine L, Myers Candace T, Scala Marcello, Huether Robert, Lewis Sara, Kruer Tyler N, Guida Brandon S, Bakhtiari Somayeh, Sebe Joy, Tang Sha, Stickney Heather, Oktay Sehribani Ulusoy, Bhandiwad Ashwin A, Ramsey Keri, Narayanan Vinodh, Feyma Timothy, Rohena Luis O, Accogli Andrea, Severino Mariasavina, Hollingsworth Georgina, Gill Deepak, Depienne Christel, Nava Caroline, Sadleir Lynette G, Caruso Paul A, Lin Angela E, Jansen Floor E, Koeleman Bobby, Brilstra Eva, Willemsen Marjolein H, Kleefstra Tjitske, Sa Joaquim, Mathieu Marie-Laure, Perrin Laurine, Lesca Gaetan, Striano Pasquale, Casari Giorgio, Scheffer Ingrid E, Raible David, Sattlegger Evelyn, Capra Valeria, Padilla-Lopez Sergio, Mefford Heather C, Kruer Michael C Jul 2020, In: Human mutation. 41 , p. 1263-1279 17 p.

De novo variants of NR4A2 are associated with neurodevelopmental disorder and epilepsy

Singh Sakshi, Gupta Aditi, Zech Michael, Sigafoos Ashley N, Clark Karl J, Dincer Yasemin, Wagner Matias, Humberson Jennifer B, Green Sarah, van Gassen Koen, Brandt Tracy, Schnur Rhonda E, Millan Francisca, Si Yue, Mall Volker, Winkelmann Juliane, Gavrilova Ralitza H, Klee Eric W, Engleman Kendra, Safina Nicole P, Slaugh Rachel, Bryant Emily M, Tan Wen-Hann, Granadillo Jorge, Misra Sunita N, Schaefer G Bradley, Towner Shelley, Brilstra Eva H, Koeleman Bobby P C 5 May 2020, In: Genetics in medicine : official journal of the American College of Medical Genetics. 22 , p. 1413-1417 5 p.

Modifier genes in SCN1A-related epilepsy syndromes

de Lange Iris M, Mulder Flip, van 't Slot Ruben, Sonsma Anja C M, van Kempen Marjan J A, Nijman Isaac J, Ernst Robert F, Knoers Nine V A M, Brilstra Eva H, Koeleman Bobby P C 1 Apr 2020, In: Molecular Genetics & Genomic Medicine. 8

NaV1.1 and NaV1.6 selective compounds reduce the behavior phenotype and epileptiform activity in a novel zebrafish model for Dravet syndrome

Weuring Wout J., Singh Sakshi, Volkers Linda, Rook Martin B., Van't Slot Ruben H., Bosma Marjolein, Inserra Marco, Vetter Irina, Verhoeven-Duif Nanda M., Braun Kees P.J., Rivara Mirko, Koeleman Bobby P.C. 1 Jan 2020, In: PLoS ONE. 15 , p. 1-17

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Schijven Dick, Stevelink Remi, McCormack Mark, van Rheenen Wouter, Luykx Jurjen J., Koeleman Bobby P.C., Veldink Jan H., , , Kenna Kevin 1 Jan 2020, In: Neurobiology of Aging. 92 , p. 153.e1-153.e5

All research output

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