lab

Molecular and cellular mechanisms underlying neurodevelopmental disorders

Lab Head: Ype-Elgersma

Lab Description

Neurodevelopmental disorders (i.e. intellectual disability, autism) affect 1% of the population, and often have a genetic basis. Our lab seeks to get insight in the molecular and cellular mechanisms underlying these disorders, with the ultimate goal to develop treatments. Our research is divided into three research lines: (1) Improving genetic diagnosis, (2) Understanding the mechanisms underlying neurodevelopmental disorders (3) Translational studies (i.e. clinical trials) to improve the quality of life of the affected individuals.

Improving diagnosis

To improve genetic diagnosis, we have developed together with van Woerden lab a functional genomics screen (PRiSM) to rapidly determine if a genetic variant is pathogenic. This screen is not only important for providing a diagnosis, but also allows us to get more insight in the genes underlying neurodevelopment.


Understanding the mechanisms underlying neurodevelopmental disorders

To get more insight in the pathophysiology of neurodevelopmental disorders, we typically make use of genetically engineered mouse models. Mouse models are analyzed at the biochemical, cellular (electrophysiological) and behavioral level. By analyzing the mouse models at all these levels we try to understand the specific function of these genes and proteins in brain development and learning and memory. Besides mouse models, we are currently also exploring the value of iPS cells to study these disorders. The genes and proteins that we specifically focus on are proteins associated with the RAS-ERK-MTOR signaling pathway and the proteasome.


Translational research  

To translate our findings to the patients, we are part of the ENCORE expertise center for neurodevelopmental disorders, for which Ype Elgersma is the scientific director.  ENCORE  has large expertise outpatient clinic for Angelman Syndrome, Neurofibromatosis (NF1), Tuberous Sclerosis (TSC), Fragile X and genetic forms of autism.

Lab Members

Ype Elgersma
Prof.Dr. Ype Elgersma (Y)
Full Professor
Lab Head
Ben Distel
Ben Distel
Associate Professor
Edwin Mientjes
Dr. Edwin Mientjes
Postdoctoral Fellow
Diana Rotaru
Diana Rotaru
Postdoctoral Fellow
Annelot van Esbroeck
Annelot van Esbroeck
Postdoctoral Fellow
Eva Niggl
Eva Niggl
Phd Student
Anouk Heuvelmans
Anouk Heuvelmans
Phd Student
Claudia Milazzo
Claudia Milazzo
Phd Student
Antonia Belecha
Antonia Belecha
Master Student
Charlotte Kraan
Charlotte Kraan
Secretary
Minetta Elgersma Hooisma
Minetta Elgersma Hooisma
Research Technician
Wallaard Ilse
Wallaard Ilse
Research Technician
Mehrnoush Aghadavoud Jolfaei
Mehrnoush Aghadavoud Jolfaei
Research Technician

Recent Publications

The effect of lamotrigine on cortical inhibition and plasticity in Neurofibromatosis type 1: Exploratory analysis of a randomized controlled trial (NF1-EXCEL).

Ottenhoff MJ, Heuvelmans A, Castricum J, Tulen JH, Rens G, Fujiyama H, Levin O, Swinnen SP, Moll HA, Wit MY, Elgersma Y
in Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 2025
DOI: 10.1016/j.clinph.2025.02.270

Genetic investigation of the ubiquitin-protein ligase E3A gene as putative target in Angelman syndrome.

Manoubi W, Mahdouani M, Hmida D, Kdissa A, Rouissi A, Turki I, Gueddiche N, Soyah N, Saad A, Bouwkamp C, Elgersma Y, Mougou-Zerelli S, Gribaa M
in World journal of clinical cases 2024
DOI: 10.12998/wjcc.v12.i3.503

A recurrent missense variant in the E3 ubiquitin ligase substrate recognition subunit FEM1B causes a rare syndromic neurodevelopmental disorder.

Lecoquierre F, Punt AM, Ebstein F, Wallaard I, Verhagen R, Studencka-Turski M, Duffourd Y, Moutton S, Tran Mau-Them F, Philippe C, Dean J, Tennant S, Brooks AS, van Slegtenhorst MA, Jurgens JA, Barry BJ, Chan WM, England EM, Martinez Ojeda M, Engle EC, Robson CD, Morrow M, Innes AM, Lamont R, Sanderson M, Krüger E, Thauvin C, Distel B, Faivre L, Elgersma Y, Vitobello A
in Genetics in medicine : official journal of the American College of Medical Genetics 2024
DOI: 10.1016/j.gim.2024.101119

Lamotrigine for cognitive deficits associated with neurofibromatosis type 1: A phase II randomized placebo-controlled trial.

Ottenhoff MJ, Mous SE, Castricum J, Rietman AB, Oostenbrink R, van der Vaart T, Tulen JHM, Parra A, Ramos FJ, Legius E, Moll HA, Elgersma Y, de Wit MY
in Developmental medicine and child neurology 2024
DOI: 10.1111/dmcn.16094

Joining forces to develop individualized antisense oligonucleotides for patients with brain or eye diseases: the example of the Dutch Center for RNA Therapeutics.

Aartsma-Rus A, Collin RWJ, Elgersma Y, Lauffer MC, van Roon-Mom W
in Therapeutic advances in rare disease 2024
DOI: 10.1177/26330040241273465

autoMEA: machine learning-based burst detection for multi-electrode array datasets.

Hernandes V, Heuvelmans AM, Gualtieri V, Meijer DH, van Woerden GM, Greplova E
in Frontiers in neuroscience 2024
DOI: 10.3389/fnins.2024.1446578

UBE3A expression during early postnatal brain development is required for proper dorsomedial striatal maturation.

Rotaru DC, Wallaard I, de Vries M, van der Bie J, Elgersma Y
in JCI insight 2023
DOI: 10.1172/jci.insight.166073

HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder.

Niggl E, Bouman A, Briere LC, Hoogenboezem RM, Wallaard I, Park J, Admard J, Wilke M, Harris-Mostert EDRO, Elgersma M, Bain J, Balasubramanian M, Banka S, Benke PJ, Bertrand M, Blesson AE, Clayton-Smith J, Ellingford JM, Gillentine MA, Goodloe DH, Haack TB, Jain M, Krantz I, Luu SM, McPheron M, Muss CL, Raible SE, Robin NH, Spiller M, Starling S, Sweetser DA, Thiffault I, Vetrini F, Witt D, Woods E, Zhou D, Elgersma Y, van Esbroeck ACM
in American journal of human genetics 2023
DOI: 10.1016/j.ajhg.2023.07.005

Hyperphagia, Growth, and Puberty in Children with Angelman Syndrome.

Bindels-de Heus KGCB, Hagenaar DA, Dekker I, van der Kaay DCM, Kerkhof GF, Elgersma Y, de Wit MY, Mous SE, Moll HA
in Journal of clinical medicine 2023
DOI: 10.3390/jcm12185981

Bone health in children with Angelman syndrome at the ENCORE Expertise Center.

Bindels-de Heus KGCB, Hagenaar DA, Mous SE, Dekker I, van der Kaay DCM, Kerkhof GF, Elgersma Y, Moll HA, de Wit MY
in European journal of pediatrics 2023
DOI: 10.1007/s00431-023-05231-6

Cortical Inhibition and Plasticity in Major Depressive Disorder.

Castricum J, Birkenhager TK, Kushner SA, Elgersma Y, Tulen JHM
in Frontiers in psychiatry 2022
DOI: 10.3389/fpsyt.2022.777422

A cross-species spatiotemporal proteomic analysis identifies UBE3A-dependent signaling pathways and targets.

Pandya NJ, Meier S, Tyanova S, Terrigno M, Wang C, Punt AM, Mientjes EJ, Vautheny A, Distel B, Kremer T, Elgersma Y, Jagasia R
in Molecular psychiatry 2022
DOI: 10.1038/s41380-022-01484-z

A novel automated approach for improving standardization of the marble burying test enables quantification of burying bouts and activity characteristics

Lucas Wahl, A. Mattijs Punt, Tara Arbab, Ingo Willuhn, Ype Elgersma, Aleksandra Badura
in eNeuro 2022
DOI: 10.1523/ENEURO.0446-21.2022

The MAP3K7 gene: further delineation of clinical characteristics and genotype/phenotype correlations.

van Woerden GM, Senden R, de Konink C, Trezza RA, Baban A, Bassetti JA, van Bever Y, Bird LM, van Bon BW, Brooks AS, Guan Q, Klee EW, Marcelis C, Rosado JM, Schimmenti LA, Shikany AR, Terhal PA, Nicole Weaver K, Wessels MW, van Wieringen H, Hurst AC, Gooch CF, Steindl K, Joset P, Rauch A, Tartaglia M, Niceta M, Elgersma Y, Demirdas S
in Human mutation 2022
DOI: 10.1002/humu.24425

From first report to clinical trials: a bibliometric overview and visualization of the development of Angelman syndrome research.

Zampeta FI, Distel B, Elgersma Y, Iping R
in Human genetics 2022
DOI: 10.1007/s00439-022-02460-x
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Vacancies

There are currently no vacancies on our lab.