Synapses are the fundamental information processing units of the brain, and their dysfunction underlies a broad spectrum of neurological and neurodevelopmental disorders. My research focuses on elucidating the molecular principles of synaptic communication and translating this knowledge into novel therapeutic strategies.
We use human patient-derived brain cells in a dish to assess synaptic dysfunction directly in patient-specific genetic backgrounds. The functional assays we use are optimised for therapeutic screening and target validation.
We study:
Presynaptic mechanisms of synaptic plasticity
We investigate synaptic transmission mechanisms by studying the function of key proteins of the synaptic vesicle release machinery (STXBP1, SV2, SYT1 o.a.) in wildtype and disease model systems (mouse and human IPSC-derived neurons). One important goal is to design rational therapeutic strategies. We have identified several kinase pathways (PKC, ERK, CDK5, PNAS 2006, Neuron 2007, JCB 2014, EMBOJ 2016) and other modifiers (Fbxo41, Sci Rep 2019, iScience 2022) that control synaptic transmission. These pathways are excellent drug targets for treatment of brain disorders.
Building on this mechanistic expertise combined with the fundamental insights in human neuronal communication in healthy and diseased IPSC-derived neurons (Hum. Mol. Genet. 2024, Neurobiol. Dis. 2025, Biol. Psy. 2023), my group maintains active collaborations with biotech and pharmaceutical companies to translate presynaptic biology into therapeutic innovation.
Secretory vesicle dynamics and release
Neuropeptides are powerful neuromodulators that regulate essential biological processes, including cognition, metabolism, and energy balance. Dysfunction of neuropeptide secretion is implicated in disorders such as intellectual disability, obesity, and diabetes. In this research line, we study the molecular principles governing neuropeptide release and its impact on synaptic communication. Using newly developed optical reporters and quantitative assays, we have identified key proteins controlling neuropeptide release (JCB 2012, eLife 2015, JCS 2017, Neuron 2019, eLife 2023, JCB 2025, eLife 2025).
We use this knowledge to study neuropeptide signaling in brain disorders such as Prader Willi Syndrome and Obesity. In addition, we exploit our in-depth knowledge on release principles to study secretion and uptake of extracellular vesicles (EVs or exosomes). We study the potential of these EVs as therapeutic delivery vehicles for brain disorders.
