dr. B.P.C. (Bobby) Koeleman
dr. B.P.C. (Bobby) Koeleman
- Group Koeleman, section Genetics
Biography
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.
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 (296)
Nijboer Tanja C W, Hessel Ellen V S, van Haaften Gijs W, van Zandvoort Martine J, van der Spek Peter J, Troelstra Christine, de Kovel Carolien G F, Koeleman Bobby P C, van der Zwaag Bert, Brilstra Eva H, Burbach J Peter H Sep 2023, In: PLoS ONE. 18 17 p.
de Winter Josine M, Bouman Karlijn, Strom Joshua, Methawasin Mei, Jongbloed Jan D H, van der Roest Wilma, Wijngaarden Jan van, Timmermans Janneke, Nijveldt Robin, van den Heuvel Frederik, Kamsteeg Erik-Jan, van Engelen Baziel G, Galli Ricardo, Bogaards Sylvia J P, Boon Reinier A, van der Pijl Robbert J, Granzier Henk, Koeleman Bobby, Amin Ahmad S, van der Velden Jolanda, van Tintelen J Peter, van den Berg Maarten P, van Spaendonck-Zwarts Karin Y, Voermans Nicol C, Ottenheijm Coen A C 6 Nov 2022, In: Human mutation. 43 , p. 1860-1865 6 p.
Stevelink Remi, Al-Toma Dania, Jansen Floor E., Lamberink Herm J., Asadi-Pooya Ali A., Farazdaghi Mohsen, Cação Gonçalo, Jayalakshmi Sita, Patil Anuja, Özkara Çiğdem, Aydın Şenay, Gesche Joanna, Beier Christoph P., Stephen Linda J., Brodie Martin J., Unnithan Gopeekrishnan, Radhakrishnan Ashalatha, Höfler Julia, Trinka Eugen, Krause Roland, Irelli Emanuele Cerulli, Di Bonaventura Carlo, Szaflarski Jerzy P., Hernández-Vanegas Laura E., Moya-Alfaro Monica L., Zhang Yingying, Zhou Dong, Pietrafusa Nicola, Specchio Nicola, Japaridze Giorgi, Beniczky Sándor, Janmohamed Mubeen, Kwan Patrick, Syvertsen Marte, Selmer Kaja K., Vorderwülbecke Bernd J., Holtkamp Martin, Viswanathan Lakshminarayanapuram G., Sinha Sanjib, Baykan Betül, Altindag Ebru, von Podewils Felix, Schulz Juliane, Seneviratne Udaya, Viloria-Alebesque Alejandro, Karakis Ioannis, D'Souza Wendyl J., Koeleman Bobby P.C., Otte Willem M., Braun Kees P.J., Nov 2022, In: EClinicalMedicine. 53
Weuring Wout J., Hoekman Jos W., Braun Kees P.J., Koeleman Bobby P.C. 1 Feb 2022, In: Cells. 11 , p. 1-8
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.
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.
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.
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.
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.
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.