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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 (287)

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 mei 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., , 1 jan 2020, In: Neurobiology of Aging. 92 , p. 153.e1-153.e5

Assessing the genetic association between vitamin B6 metabolism and genetic generalized epilepsy

Stevelink Remi, Pangilinan Faith, Jansen Floor E., Braun Kees P.J., Molloy Anne M., Brody Lawrence C., Koeleman Bobby P.C., 1 dec 2019, In: Molecular Genetics and Metabolism Reports. 21

GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways

López-Isac Elena, Acosta-Herrera Marialbert, Kerick Martin, Assassi Shervin, Satpathy Ansuman T., Granja Jeffrey, Mumbach Maxwell R., Beretta Lorenzo, Simeón Carmen P., Carreira Patricia, Ortego-Centeno Norberto, Castellvi Ivan, Bossini-Castillo Lara, Carmona F. David, Orozco Gisela, Hunzelmann Nicolas, Distler Jörg H.W., Franke Andre, Lunardi Claudio, Moroncini Gianluca, Gabrielli Armando, de Vries-Bouwstra Jeska, Wijmenga Cisca, Koeleman Bobby P.C., Nordin Annika, Padyukov Leonid, Hoffmann-Vold Anna Maria, Lie Benedicte, Ríos R., Callejas J. L., Vargas-Hitos J. A., García-Portales R., Camps M. T., Fernández-Nebro A., González-Escribano M. F., García-Hernández F. J., Castillo M. J., Aguirre M. A., Gómez-Gracia I., Fernández-Gutiérrez B., Rodríguez-Rodríguez L., García de la Peña P., Vicente E., Andreu J. L., Fernández de Castro M., López-Longo F. J., Martínez L., Fonollosa , Vonk M. C., Radstake Timothy R.D.J., , 1 dec 2019, In: Nature Communications. 10

Genomic and clinical predictors of lacosamide response in refractory epilepsies

Heavin Sinéad B., McCormack Mark, Wolking Stefan, Slattery Lisa, Walley Nicole, Avbersek Andreja, Novy Jan, Sinha Saurabh R., Radtke Rod, Doherty Colin, Auce Pauls, Craig John, Johnson Michael R., Koeleman Bobby P.C., Krause Roland, Kunz Wolfram S., Marson Anthony G., O'Brien Terence J., Sander Josemir W., Sills Graeme J., Stefansson Hreinn, Striano Pasquale, Zara Federico, Depondt Chantal, Sisodiya Sanjay, Goldstein David, Lerche Holger, Cavalleri Gianpiero L., Delanty Norman, , 1 dec 2019, In: Epilepsia Open. 4 , p. 563-571 9 p.

Implications of genetic diagnostics in epilepsy surgery candidates:A single-center cohort study

Sanders Maurits W.C.B., Lemmens Cynthia M.C., Jansen Floor E., Brilstra Eva H., Koeleman Bobby P.C., Braun Kees P.J., dec 2019, In: Epilepsia Open. 4 , p. 609-617 9 p.

Polygenic burden in focal and generalized epilepsies

Leu Costin, Stevelink Remi, Smith Alexander W., Goleva Slavina B., Kanai Masahiro, Ferguson Lisa, Campbell Ciaran, Kamatani Yoichiro, Okada Yukinori, Sisodiya Sanjay M., Cavalleri Gianpiero L., Koeleman Bobby P.C., Lerche Holger, Jehi Lara, Davis Lea K., Najm Imad M., Palotie Aarno, Daly Mark J., Busch Robyn M., Lal Dennis, 1 nov 2019, In: Brain : a journal of neurology. 142 , p. 3473-3481 9 p.

All research output

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