Projects
p53 and its novel targets in healthy neurodevelopment and microcephaly, studied in mice. KU Leuven
The tumor suppressor P53 (also named TP53) in humans ((T)p53 in mice) is of pivotal importance for the maintenance of genome stability. About 50% of cancers involve P53 gene mutation, making P53 one of the most extensively investigated genes/proteins. p53 is a transcription factor that can (de)activate genes (“p53 targets”) by binding to specific regulatory DNA sequences. p53 activates genes involved in cell cycle arrest, DNA repair and ...
Identification and functional characterization of novel genes causing syndromic microcephaly. KU Leuven
Microcephalie (MC) in humans is a condition characterized by abnormal small head circumference for the respective age and sex. It can occur as isolated feature (non-syndromic forms) or in combination with other characteristics (syndromic forms). MC is genetically heterogeneous, but some of the non-syndromic forms were explained by mutations in genes implicated in cell division and cell cycle progression, including structural genes involved in ...
Building relevant Zika virus infection models to study neuroinvasiveness and vertical/sexual transmission and to assess the potential of novel antiviral strategies KU Leuven
Arboviruses are viruses that are transmitted among vertebrate hosts by arthropods, typically ticks and mosquitoes. Among this group of viruses are important human pathogens that can cause severe and long-term complications. These pathogens include chikungunya virus (CHIKV) and Zika virus (ZIKV), whose re-emergence has been recognized as a global health challenge. Acute CHIKV infections are characterized by fever, myalgia and polyarthritis, ...
Integrated, multimodal phenotypic analysis of Ppp2r1a knockin mice: new in vivo models of syndromic PP2A-related (neuro)developmental disorders. KU Leuven
De novo, recurrent mutations in PPP2R1A, encoding the scaffolding Aα subunit of Protein Phosphatase 2A (PP2A), were recently identified among the new genetic causes of intellectual disability (ID) and (neuro)developmental delay (NDD). Two biochemically and clinically distinguishable subgroups were determined. One group of variants (exemplified by M180T) caused a milder phenotype (moderate ID, no seizures, macrocephaly tendency, absent in ...
SymBioSys: from variome to phenome. KU Leuven
Metabolic and epigenetic interplay in neural progenitor cells: investigating neurodevelopmental disorders associated with impaired neural progenitor cell expansion (MEPIcephaly). KU Leuven
Neurodevelopmental disorders (NDD) result in variable neurological and psychological impairments. Here, we focus on microcephaly-associated NDDs that are characterized by a critical decrease in brain size, primarily caused by impaired neural stem and progenitor cell (NPC) expansion in the fetal neocortex. Previously, gene mutations associated with abnormal cell cycle progression, centrosome formation and DNA repair have been identified, yet a ...
Radiation effects on human brain development, modeled in human brain organoids Ghent University
A functional human genome project: integrated research of human congenital disorders. KU Leuven
Unveiling the role of FOXG1 in neurodevelopment and disease: a comprehensive analysis using neural organoids, imaging and Single Cell Sequencing Ghent University
This study aims to investigate the role of FOXG1 in neurodevelopment and disease. The forkhead box G1 protein, encoded by FOXG1, acts as a transcriptional repressor primarily expressed within the brain. It is essential for the development of the forebrain and forebrain derived structures. Furthermore, fine-tuned FOXG1 levels are essential for balancing excitatory and inhibitory neuron populations. Loss-of-function (LoF) of FOXG1 is associated ...