Sørensen Lab
My group has expertise in studying the molecular and cellular mechanisms of neurotransmitter release in chemical synapses and in neuroendocrine cells.
Information processing in the brain requires fusion of transmitter-laden synaptic vesicles within the up to a quadrillion (1015) synaptic connections between neurons, leading to activation of postsynaptic receptors. This is one of the most fascinating processes in our body and understanding how the synapse works and can transmit information within a fraction of a millisecond is a rewarding endeavor.
My group investigates the molecular machinery for neurotransmitter release, the postsynaptic receptors and the defects that lead to disease. We do electrophysiological and optical measurements on living cells (either mouse neurons, or neurons differentiated from human stem cells, iPSCs) and combine this with genetic and molecular biology methods (mouse knockouts, CRISPR, viral expression). We work with presynaptic proteins, which are directly linked to exocytosis, i.e. SNARE-proteins, synaptotagmins, etc, but also with the postsynaptic receptors (e.g. GABAA-receptors, the major inhibitory receptors in the brain). We denoted the term SNAREopathies for diseases caused by mutation in the SNARE-proteins (Verhage and Sørensen, 2020, Neuron 107, 22-37) and we are currently investigating diseases caused by mutation in STXBP1, SNAP25 and several GABAA receptor subunits.
- To identify the mechanisms by which variants in the synaptic machinery lead to disease. Our work is concerned with developmental and epileptic encephalopathy, which are devastating conditions, usually diagnosed in children within the first year of life. Typical symptoms are multiple neurodevelopmental delays, motor problems, intellectual disability, epilepsy and autism. We use a combination of methods, including differentiation of neurons from variant-expressing human iPSCs, microscopy and electrophysiological measurements of synaptic transmission. It is our goal to be able to develop new treatments, based on solid knowledge of the disease mechanism. To reach this goal, we work together with clinicians. Recently, we have established medium-throughput methods that allow semi-automated activity measurements from 2D cultures of human neurons, which might be used in drug screening. We are part of a Lundbeck Collaborative project, in collaboration with The Danish Epilepsy Hospital, and University of Sydney, Australia. We are also part of an EU-wide project funded by ERDERA (European Rare Diseases Research Alliance) and the Innovation Foundation with 7 other partners, where we will test drugs for the SNAREopathies.
Example papers:
Vold VA, Yang J, Østergaard M, Lassen AS, Kádková A, Kumar A, Walter AM, Zhang Y.*, Sørensen JB* (2026). SNAP-25 disease variants affect synaptic transmission by destabilizing SNARE complexxes within a multimeric SNARE ring. Cell Reports 45(2):116870.*Corresponding authors.
Østergaard M, Barbagallo P, Frederiksen HRS, Chung WK, Møller RS, Larsen MR, Freude K, Verhage M, Sørensen JB. (2025). SNAP25 disease variant I67N: synaptic phenotypes, drug response, and proteome changes in human neurons. Brain 148(9):3300-3313.
Kádková A., Murach J., Østergaard M., Malsam A., Malsam J., Söllner T.H., Sørensen J.B. (2024). SNAP25 disease mutations change the energy landscape for synaptic exocytosis due to aberrant protein-protein interactions. Elife 12, RP88619.
Verhage M., Sørensen J.B. (2020). SNAREopathies: Diversity in Mechanisms and Symptoms. Neuron. 107(1):22-37.
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identifying the detailed mode-of-action of the machinery for neurotransmitter release. This part of our work is concerned with how the synapse works in its basal state, and it forms the basis for our work on disease. Among the questions we are concerned with is how membrane fusion is triggered by Ca2+, what the role is of different synaptotagmin isoforms (e.g. synaptotagmin-7 vs synaptotagmin-1), how they collaborate with other proteins of the release machinery, the role of membrane-shaping BAR-domain proteins etc. We are also currently interested in short-term synaptic plasticity (the ability of synapses to change their output) and how synaptic plasticity plays a role for working memory.
Example papers:
Radecke J., Seeger R., Kádková A., Laugks U., Khosrozadeh A., Goldie K.N., Lucic V, Sørensen J.B.*, Zuber B* (2023). Morphofunctional changes at the active zone during synaptic vesicle exocytosis. * Corresponding authors. EMBO Rep. 24(5):e55719.
Tawfik B., Martins J.S., Houy S., Imig C., Pinheiro P.S., Wojcik S.M., Brose N., Cooper B.H., Sørensen J.B. (2021). Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming. Elife 10, e64527.
Gowrisankaran S., Houy S., Peña del Castillo J.G., Steubler V., Gelker M., Kroll J., Pinheiro P.S., Schwitters, D., Halbsgut N., Pechstein A., van Weering J., Maritzen, T., Haucke V., Raimundo N., Sørensen J.B.*, Milosevic I.* (2020). Endophilin-A controls recruitment, priming and fusion of neurosecretory vesicles.* Corresponding authors. Nature Comm. 11:1-18.
Ruiter M., Kádková A, Scheutzow A, Malsam J. Söllner TH and Sørensen J.B. (2019). An electrostatic energy barrier for SNARE-dependent spontaneous and evoked synaptic transmission. Cell Reports 26: 2340-2352.
- Kovačević J, Houy S, Pires J, Kádková A, Li Z, Lammertse HCA, Martins JS, Öttl M, Wierda K, Wortel J Sørensen JB*, Verhage M* (2026). Phenotypic diversity is caused by non-linear genetic interactions between two SNAREopathy genes. Psychiatry 31(7): 3929-3944. *Equal contribution.
- Vold VA, Yang J, Østergaard M, Lassen AS, Kádková A, Kumar A, Walter AM, Zhang Y.*, Sørensen JB (2026). SNAP-25 disease variants affect synaptic transmission by destabilizing SNARE complexes within a multimeric SNARE ring. Cell Reports 45(2):116870.
- Østergaard M, Barbagallo P, Frederiksen HRS, Chung WK, Møller RS, Larsen MR, Freude K, Verhage M, Sørensen JB. (2025). SNAP25 disease variant I67N: synaptic phenotypes, drug response, and proteome changes in human neurons. Brain 148(9):3300-3313.
- Kádková A., Murach J., Østergaard M., Malsam A., Malsam J., Söllner T.H., Sørensen J.B. (2024). SNAP25 disease mutations change the energy landscape for synaptic exocytosis due to aberrant protein-protein interactions. Elife 12, RP88619.
- Dos Santos A.B., Larsen SD, Guo L, Barbagallo P., Montalant A., Verhage M., Sørensen J.B., Perrier J.-F. (2023). Microcircuit failure in STXBP1 encephalopathy leads to hyperexcitability. Cell Reports Med. 4(12):101308.
- Radecke J., Seeger R., Kádková A., Laugks U., Khosrozadeh A., Goldie K.N., Lucic V, Sørensen J.B.*, Zuber B* (2023). Morphofunctional changes at the active zone during synaptic vesicle exocytosis. EMBO Rep. 24(5):e55719. * Corresponding authors.
- Tawfik B., Martins J.S., Houy S., Imig C., Pinheiro P.S., Wojcik S.M., Brose N., Cooper B.H., Sørensen J.B. (2021). Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming. Elife 10:e64527.
- Verhage M., Sørensen J.B. (2020). SNAREopathies: Diversity in Mechanisms and Symptoms. Neuron 107(1):22-37.
- Gowrisankaran S., Houy S., Peña del Castillo J.G., Steubler V., Gelker M., Kroll J., Pinheiro P.S., Schwitters, D., Halbsgut N., Pechstein A., van Weering J., Maritzen, T., Haucke V., Raimundo N., Sørensen J.B.*, Milosevic I.* (2020). Endophilin-A controls recruitment, priming and fusion of neurosecretory vesicles. Nature Comm. 11:1-18. * Corresponding authors
- Kobbersmed JRL, Grasskamp AT, Meida J, Böhme MA, Ditlevsen S, Sørensen JB*, Walter AM*. (2020). Rapid regulation of vesicle priming explains synaptic facilitation despite heterogeneous vesicle:Ca2+ channel distances Elife pii: e51032. * Corresponding authors.
- Ruiter M., Kádková A, Scheutzow A, Malsam J. Söllner TH and Sørensen J.B. (2019). An electrostatic energy barrier for SNARE-dependent spontaneous and evoked synaptic transmission. Cell Reports 26: 2340-2352.
- Kádková A., Radecke J., and Sørensen J.B. (2018). The SNAP-25 protein family. Neuroscience 420:50-71. (Invited review)
- Mohrmann R., De Wit H., Verhage M., Neher E., and Sørensen J.B. (2010). Fast vesicle fusion in living cells requires at least three SNARE-complexes. Science 330, 502-505.
Patch-clamp electrophysiology in vitro and in brain slices
Cell culture (incl. human neurons differentiated from iPSCs, self-innervating (autaptic) neurons on astrocyte islands)
Life fluorescence imaging, incl. Ca2+ imaging for activity measurements in a 96-well format
Immunohistochemistry and confocal microscopy, superresolution imaging (STORM, SIM)
Viral vectors (Semliki Forest virus, lentivirus – we do our own packaging of viruses)
DNA methods (CRISPR, plasmid preparation, mutagenesis, subcloning, sequencing, etc.)
Western blot
Ca2+-uncaging, lipid uncaging (optical uncaging)
Amperometry (chrono-voltammetry)
Course leader for master and PhD-course Neuronal Signaling / Basic neuroscience
Teaching for Medical students (Nervesystemet), Molecular Biomedicine students (Kursus i Cellulær neurofysiologi, Cellular Neuroscience), Odontology students (Kursus i Cellulær neurofysiologi), Human biology students (Course in Advanced Cell Biology, Neuronal Signaling: course leader) and Neuroscience students (Neuroscience I: module leader for synaptic transmission).
Lab members
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