NeuroDevDiseaseModelling

Organization profile

Organisation Profile

The research team investigates molecular mechanisms underlying neurodevelopmental disorders, especially mechanisms causing features requiring treatment such as challenging behavioural problems in fragile X syndrome (FXS) and autism related disorders.  The ultimate goal is to develop improved treatment strategies for these disorders. The team uses patient-specific induced pluripotent stem cells (iPSCs) for disease modelling in dish. Studies explore alterations of functional responses in iPSC-derived neuronal cells in a cell type-dependent manner and explore contribution of astrocytes to impaired neuronal network function.

Previous work of the lab has functionally characterized differentiation of glutamate-responsive human and mouse neural progenitors and demonstrated aberrances during early stages of neuronal cell differentiation in FXS.  The recently published studies revealed enhanced intracellular Ca2+ responses to AMPA receptor activation in neural progenitors differentiated from human iPSCs generated from somatic cells of FXS males compared to controls. Increased Ca2+-permeable AMPA receptor (CP-AMPAR) activity associates with increased Ca2+ influx via L-type voltage-gated calcium channels and augmented responses to membrane depolarization and to NMDA and type I metabotropic glutamate receptor activation. Changes of Ca2+ dynamics affect fate determination, differentiation, and migration of FXS neural progenitors. Increased Ca2+ influx through CP-AMPARs renders neural progenitors more susceptible to excitotoxicity. Increased vulnerability may act as a selective factor during cell differentiation and interfere with establishment of neocortical circuits leading to network hyperexcitability in FXS brain.

Fields of Science

  • 3112 Neurosciences
  • 1184 Genetics, developmental biology, physiology

International and National Collaboration

Publications and projects within past five years.