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
Annelot van Esbroeck
Annelot van Esbroeck
Postdoctoral Fellow
Edwin Mientjes
Dr. Edwin Mientjes
Postdoctoral Fellow
Diana Rotaru
Diana Rotaru
Postdoctoral Fellow
Isabella Zampeta
Isabella Zampeta
Phd Student
Myrthe Ottenhoff
Myrthe Ottenhoff
Phd Student
Claudia Milazzo
Claudia Milazzo
Phd Student
Mattijs Punt
Mattijs Punt
Phd Student
Eva Niggl
Eva Niggl
Phd Student
Jesminne Castricum
Jesminne Castricum
Phd Student
Anouk Heuvelmans
Anouk Heuvelmans
Phd Student
Minke de Kwant
Minke de Kwant
Master Student
Jelle Stringer
Jelle Stringer
Master Student
Dana Vervloet
Dana Vervloet
Master Student
Charlotte Kraan
Charlotte Kraan
Secretary
Mehrnoush Aghadavoud Jolfaei
Mehrnoush Aghadavoud Jolfaei
Research Technician
Ilse Wallaard
Ilse Wallaard
Research Technician
Minetta Elgersma Hooisma
Minetta Elgersma Hooisma
Research Technician

Recent Publications

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

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

Molecular and behavioral consequences of Ube3a gene overdosage in mice.

Punt AM, Judson MC, Sidorov MS, Williams BN, Johnson NS, Belder S, den Hertog D, Davis CR, Feygin MS, Lang PF, Jolfaei MA, Curran PJ, van IJcken WF, Elgersma Y, Philpot BD
in JCI insight 2022
DOI: 10.1172/jci.insight.158953

Adult gene reinstatement restores the learning and plasticity deficits of knockout mice.

Rigter PMF, Wallaard I, Aghadavoud Jolfaei M, Kingma J, Post L, Elgersma M, Elgersma Y, van Woerden GM
in iScience 2022
DOI: 10.1016/j.isci.2022.105303

Multidimensional analysis of behavior predicts genotype with high accuracy in a mouse model of Angelman syndrome.

Tanas JK, Kerr DD, Wang L, Rai A, Wallaard I, Elgersma Y, Sidorov MS
in Translational psychiatry 2022
DOI: 10.1038/s41398-022-02206-3

The Hippocampal Response to Acute Corticosterone Elevation Is Altered in a Mouse Model for Angelman Syndrome.

Viho EMG, Punt AM, Distel B, Houtman R, Kroon J, Elgersma Y, Meijer OC
in International journal of molecular sciences 2022
DOI: 10.3390/ijms24010303

Unlike dietary restriction, rapamycin fails to extend lifespan and reduce transcription stress in progeroid DNA repair-deficient mice.

Birkisdóttir MB, Jaarsma D, Brandt RMC, Barnhoorn S, van Vliet N, Imholz S, van Oostrom CT, Nagarajah B, Portilla Fernández E, Roks AJM, Elgersma Y, van Steeg H, Ferreira JA, Pennings JLA, Hoeijmakers JHJ, Vermeij WP, Dollé MET
in Aging cell 2021
DOI: 10.1111/acel.13302

Loss of nuclear UBE3A activity is the predominant cause of Angelman syndrome in individuals carrying UBE3A missense mutations.

Bossuyt SNV, Punt AM, de Graaf IJ, van den Burg J, Williams MG, Heussler H, Elgersma Y, Distel B
in Human molecular genetics 2021
DOI: 10.1093/hmg/ddab050

TAOK1 is associated with neurodevelopmental disorder and essential for neuronal maturation and cortical development.

van Woerden GM, Bos M, de Konink C, Distel B, Trezza RA, Shur NE, Barañano K, Mahida S, Chassevent A, Schreiber A, Erwin AL, Gripp KW, Rehman F, Brulleman S, Mc Cormack R, de Geus G, Kalsner L, Sorlin A, Bruel AL, Koolen DA, Gabriel MK, Rossi M, Fitzpatrick DR, Wilkie AOM, Calpena E, Johnson D, Brooks A, van Slegtenhorst M, Fleischer J, Groepper D, Lindstrom K, Micheil Innes A, Goodwin A, Humberson J, Noyes A, Langley KG, Telegrafi A, Blevins A, Hoffman J, Guillen Sacoto MJ, Juusola J, Monaghan KG, Punj S, Simon M, Pfundt R, Elgersma Y, Kleefstra T
in Human mutation 2021
DOI: 10.1002/humu.24176

UBE3A reinstatement as a disease-modifying therapy for Angelman syndrome.

Elgersma Y, Sonzogni M
in Developmental medicine and child neurology 2021
DOI: 10.1111/dmcn.14831

Mono-ubiquitination of Rabphilin 3A by UBE3A serves a non-degradative function.

Avagliano Trezza R, Punt AM, Mientjes E, van den Berg M, Zampeta FI, de Graaf IJ, van der Weegen Y, Demmers JAA, Elgersma Y, Distel B
in Scientific reports 2021
DOI: 10.1038/s41598-021-82319-9
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Vacancies

There are currently no vacancies on our lab.