RESEARCH
Our research focuses on understanding mechanisms of human brain development using stem cell–based and direct reprogramming approaches, with the long-term goal of enabling next-generation cell therapies for neurological and psychiatric disorders.
We develop advanced human cell culture models derived from stem cells and patient-specific cells and evaluate these in preclinical systems to accelerate translation toward clinical applications. A central focus of our work is human interneurons, key regulators of brain activity that are implicated in disorders such as schizophrenia, epilepsy, and Alzheimer’s disease, yet remain technically challenging to generate from human sources.
To address these challenges, we apply state-of-the-art technologies to generate and characterise human neurons from novel cell sources. We combine reprogramming approaches with advanced 2D and 3D stem cell culture systems, in vivo models, and a broad range of analytical techniques, including electrophysiology, RNA sequencing, lineage tracing, and cell-specific manipulation.
Human Glia Reprogramming for Cell Repair
Neuronal reprogramming holds strong potential for restoring neuronal populations and repairing brain circuits. While this approach has been extensively studied in rodent systems, translation to human cells has remained limited.
In our group, we apply reprogramming strategies to human glial precursor cells derived from stem cells using a unique protocol. Using this platform, we were the first to demonstrate efficient conversion of human glia into Parvalbumin (PV) interneurons across multiple systems, including in vivo mouse models, as well as 2D and 3D human cultures.
This approach is notably fast, with human glial cells acquiring neuronal properties and hallmarks of PV interneurons within weeks, substantially faster than traditional stem cell differentiation methods. Importantly, the generated neurons closely resemble primary human chandelier interneurons at the transcriptomic level, highlighting their relevance for disease modelling and therapeutic development.
Current research focuses on glia-to-interneuron reprogramming in advanced 3D human culture systems and evaluating their functional impact in in vivo disease models. This work opens new possibilities for engineering defined human neuronal subtypes and represents an important step toward future brain repair strategies.
In Vitro Modelling of Human Interneurons in Disease
GABAergic interneurons play a critical role in maintaining the balance between excitation and inhibition in the brain. Disruption of this balance is a key feature of many neurological and psychiatric disorders.
Our research aims to generate disease-relevant human interneurons using both reprogramming and stem cell differentiation strategies. We have shown that adult human fibroblasts can be directly reprogrammed into interneurons, and more recently established protocols to derive specific interneuron subtypes, such as somatostatin interneurons, from human embryonic stem cells.
These approaches can be applied to patient-derived induced pluripotent stem cells (iPSCs), enabling the study of interneuron dysfunction in disorders such as schizophrenia. Using organoid, spheroid, and assembloid systems, we investigate subtype-specific features of human interneurons, including electrophysiological properties, gene expression profiles, and morphology, and compare patient-derived cells to healthy controls.