To process information the brain is constantly changing the strength of the individual contacts (synapses) between nerve cells. Strict control of synaptic plasticity is important, as dysregulation is often associated with neurological disorders.
My lab studies the mechanisms that support synaptic plasticity and their dysfunction in disorders such as Alzheimer’s, epilepsy, schizophrenia and autism to provide novel treatment options and therapeutic targets.
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, 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. In addition, thanks to our expert knowledge on synaptic proteins we collaborate with several biotech/pharma companies to develop novel anti-epileptic therapies, cognition enhancers, gene therapeutics for rare brain disorders, and therapeutic delivery options.
Secretory vesicle dynamics and release
Neuropeptides are neuromodulatory molecules that control vital biological processes. Dysregulation of neuropeptide secretion is associated with cognitive disorders, obesity and diabetes. We study neuropeptide release mechanisms and the effect of secreted neuropeptides on synaptic transmission in several disease models. Using novel optical assays, we have identified the major proteins controlling neuropeptide vesicle release (JCB 2012, eLife 2015, JCS 2017, Neuron 2019). We use this knowledge to study neuropeptide signaling in brain disorders such as Prader Willi Syndrome and Obesities. 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.
