Principal Investigator
Email: Stefanie.Geisler@uibk.ac.at
Phone: +43-(0)512 507 58844
ORCID: https://orcid.org/0000-0002-8898-0108
MAIN RESEARCH INTEREST
Voltage-gated calcium channels (CaVs) provide the primary mechanism for activity-regulated Ca2+ influx into CNS neurons and thus drive fundamental neuronal functions, including synaptic plasticity, cell excitability and gene expression. Not surprisingly, dysfunction of CaVs is associated with numerous syndromes, such as autism, epilepsy, and Parkinson's disease. The ultimate goal of my research is to make a strong contribution in resolving the role of neuronal voltage-gated calcium channels and their accessory subunits (Stac, α2δ) in normal and diseased brain function. For my studies, I am employing a multidisciplinary approach, including primary cell cultures (mouse chromaffin cells, glutamatergic cortical & GABAergic medium spiny neurons), electrophysiology (heterologous expression systems, primary cultures, brain slices) & calcium imaging, fluorescence microscopy, and behavioral analysis.
This research group investigates the role of neuronal voltage-gated calcium channels and their accessory subunits (Stac, α2δ) in both normal and diseased brain function. We aim to obtain a comprehensive understanding from the molecular to the circuit level.
We are currently focusing on the following topics:
Role of genetic CACNA1D variants in human neurons and neuroendocrine chromaffin cells
In collaboration with members of an FWF-funded research group, our lab investigates how genetic mutations in the CACNA1D gene, which encodes the CaV1.3 L-type calcium channel, contribute to neurodevelopmental and neuroendocrine disorders. One focus is on understanding how these mutations affect hormone-secreting adrenal chromaffin cells using electrophysiological recordings, hormone assays, and transgenic mouse models. A second project explores the impact of CACNA1D variants on human neuronal function by studying iPSC-derived neurons and cerebral organoids through calcium imaging, patch-clamp electrophysiology, and pharmacological modulation. Together, these approaches aim to uncover disease mechanisms and evaluate targeted therapies for CACNA1D-associated syndromes.
Physiological role of Stac2 adaptor protein in CNS neurons
Somatodendritic CaV1.2 and CaV1.3 L-type Ca2+ channels (LTCC) convey Ca2+ influx that drives fundamental neuronal functions, including synaptic plasticity and cell excitability. A negative feedback mechanism tightly regulates Ca2+ entry through LTCC, known as Ca2+-dependent inactivation (CDI). Recent studies in cultured cells revealed that overexpression of the SH3 and cysteine-rich domain protein 2 (Stac2) inhibits CDI of LTCC thereby prolonging Ca2+ influx. In this project, we aim to address the physiological role of Stac2 in healthy and potentially diseased brain neurons. Since STAC2 missense mutations have been identified in patients with schizophrenia our findings will begin to provide novel insights into how Stac2 may contribute to pathology of neuropsychiatric-related behaviors. We employ a multidisciplinary approach consisting of primary cell cultures, electrophysiology, calcium imaging, fluorescence microscopy, and behavioral analysis. Master Thesis projects available for this topic:
Role of Stac2 adaptor protein in mouse chromaffin cell function (together with theTuluc group)
Chromaffin cells (CCs) have intrinsic mechanisms that regulate their excitability. Similar to neurons, they contain a variety of ion channels that contribute to complex firing patterns and, as a result, to hormone release- a process known as excitation-secretion (ES) coupling. ES coupling in adrenal CCs requires calcium ion (Ca2+) influx through high-voltage activated calcium channels (HVCCs). These channels are multi-protein complexes that include a pore-forming α1 subunit, which is responsible for voltage sensing and ion conduction, along with auxiliary subunits that modulate Ca2+ influx. In this project, we investigate the physiological role of the Stac2 protein in modulating HVCCs, as well as its effect on electrical activity and catecholamine (CA) release of CCs.
RESEARCHERS GEISLER GROUP
ALUMNI
TECHNICAL SUPPORT
Open Master projects for Pharmacy & Biology students:
- Project 1: Role of Stac2 in cultured neurons
- Project 2: qPCR and WB analysis of Stac2 KO mice
CURRENT RESEARCH FUNDING
- Tiroler Wissenschaftsförderung: “Role of genetic CACNA1D variants in chromaffin cells”. PI
- FWF FG 3500:“Multisystem study of pathogenic CACNA1D variants”. Project Geisler: “Effect of Cav1.3 variants on human neuron function”. PI
- NFB: “Novel model systems for studying the role of calcium channel subunits in brain disorders”. Co-PI with Gerald J. OBERMAIR (KL Krems) & Ryuichi SHIGEMOTO (ISTA)
RESEARCH NETWORK
Gerald J. OBERMAIR group
SHORT CURRICULUM
FELLOWSHIPS & THIRD-PARTY FUNDING
RESEARCH ACHIEVEMENTS (Invited talks, Symposia & Awards, selected)
- Upcoming: Accepted symposium (Co-Organizer & Talk) at the Austrian Neuroscience Association Meeting 2025, 8-10 September 2025, Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria; Symposium Title: Calcium channelopathies: beyond the ion-conducting pore
- Upcoming: Invited talk as a Daniel T. O’Connor awardee at the International Symposium on Chromaffin Cell Biology (ISCCB), 13-17 July 2025, Detroit, USA. Title: Genetic deletion of Stac2 affects electrical activity of chromaffin cells and mouse behavior
- Chair: 5th European Calcium Channel Conference (ECCC), 26-30 May 2025, Alpbach, Austria; Research flashes Session C
- Talk: The 5th European Calcium Channel Conference (ECCC), 26-30 May 2025, Alpbach, Austria. Title: Genetic deletion of Stac2 affects electrical activity of chromaffin cells and mouse behavior
- Price by the Principality of Liechtenstein for scientific research at the University of Innsbruck - Awarded annually to recognize outstanding scientific research
- Talk: Neuroday24, 16 October 2024, Lans, Austria. Title: Genetic deletion of Stac2 affects electrical activity of chromaffin cells & mouse behavior
- Talk: Center for Molecular Biosciences Innsbruck (CMBI) Meeting, 27 September 2024, Innsbruck, Austria. Title: Genetic deletion of Stac2 affects electrical activity of chromaffin cells & mouse behavior
- Talk: Austrian Pharmacological Society (APHAR) Meeting, 24 September 2024, Innsbruck, Austria. Title: Genetic deletion of Stac2 affects electrical activity of chromaffin cells & mouse behavior
- Talk: Department of Pharmacology and Toxicology Seminar Series, 14 June 2024, Innsbruck, Austria. Title: Cav channel proteomics
- Talk: The Calcium Channel Network, 25 February 1 March 2024, Boracay, Philippines. Title: Genetic deletion of Stac2 adaptor protein alters electrical activity of mouse chromaffin cells
- Poster presentation: Biophysics Austria Meeting, 8-10 July, Salzburg, Austria
- Travel Award & Poster presentation: Biophysical Society 67th Annual Meeting, 18-22 February 2023, San Diego, USA. Title: Genetic deletion of stac2 adaptor protein alters electrical activity of mouse chromaffin cells
- Poster presentation: Neuroday23, 21 November 2023, Innsbruck, Austria. Title: Genetic deletion of stac2 adaptor protein alters electrical activity of mouse chromaffin cells
- Travel Award & Poster presentation: International Symposium on Chromaffin Cell Biology (ISCCB), Hamburg, Germany. Title: Genetic deletion of stac2 adaptor protein alters electrical activity of mouse chromaffin cells
- Research flash talk & Poster presentation: 4th European Calcium Channel Conference, 24-28 May 2022, Alpbach, Austria. Title: Genetic deletion of Stac2 adaptor protein alters electrical activity of mouse chromaffin cells
- Chair: 4th European Calcium Channel Conference, 24-28 May 2022, Alpbach, Austria. Research flashes Session B
- Krems Cooperation Research Award 2021 for the PhD thesis “Redundant and specific functions of neuronal calcium channel α2d isoforms in mutant mouse models and cultured neurons”
- Talk (invited): CavX PhD Retreat, Innsbruck, Austria. Title: The α2δ-1 calcium channel subunit regulates cell excitability and exocytosis of chromaffin cells
- Poster presentation: FENS 2020 Virtual Forum, 11-15 July 2020. Title: The presynaptic calcium channel subunit α2δ-2 regulates postsynaptic GABAA-receptor abundance and axonal wiring by a trans-synaptic mechanism
- Austrian Neuroscience Association (ANA) PhD thesis award 2019 for the PhD thesis “Redundant and specific functions of neuronal calcium channel α2d isoforms in mutant mouse models and cultured neurons”
- Talk: The Calcium Channel Network, 31 March - 5 April 2019, Penang, Malaysia. Title: Presynaptic α2δ subunits of voltage-gated calcium channels regulate synaptic connectivity.
- Talk: Satellite Meeting for the International Calcium Channel Conference, Singapore. Title: Presynaptic α2δ subunits of voltage-gated calcium channels regulate synaptic connectivity.
- Talk: Joint Meeting of Austrian Neuroscience Excellence Network, 7-9 May 2018, Alpbach, Austria. Talk title: The presynaptic calcium channel subunit α2δ-2 regulates axonal wiring and postsynaptic GABAA-receptor abundance
- Poster presentation: 3rd European Calcium Channel Conference, 9-12 May 2018, Alpbach, Austria. Title: The presynaptic calcium channel subunit α2δ-2 regulates axonal wiring and postsynaptic GABAA-receptor abundance
- Travel award & talk: 15th Meeting of the Austrian Neuroscience Association (ANA), 24-26 September 2017, Klosterneuburg, Austria. Talk title: The presynaptic calcium channel subunit α2δ-2 regulates axonal wiring and postsynaptic GABAA-receptor abundance
- Talk: Life Science PhD Meeting, 18-19 April 2017, Innsbruck, Austria. Talk title: The presynaptic calcium channel subunit α2δ-2 regulates axonal wiring and postsynaptic GABAA-receptor abundance
PEER REVIEW ACTIVITIES
THIRD MISSION / PUBLIC OUTREACH
SEMINAR/MEETING ORGANIZATION
TRAININGS
PRESS REPORTS
MEMBERSHIPS
PUBLICATIONS
- Del Rivero Morfin, P. J., Chavez, D. S., Jayaraman, S., Yang, L., Geisler, S. M., Kochiss, A. L., Tuluc, P., Colecraft, H. M., Marx, S. O., Liu, X. S., Rajadhyaksha, A. M., & Ben-Johny, M. (2024). A genetically encoded actuator boosts L-type calcium channel function in diverse physiological settings. Science advances, 10(44), eadq3374. https://doi.org/10.1126/sciadv.adq3374
- Geisler, S. M.*, Ottaviani, M. M.*, Jacobo-Piqueras, N., Theiner, T., Mastrolia, V., Guarina, L., Ebner, K., Obermair, G. J., Carbone, E., & Tuluc, P. (2024). Deletion of the α2δ-1 calcium channel subunit increases excitability of mouse chromaffin cells. The Journal of physiology, 602(15), 3793–3814. https://doi.org/10.1113/JP285681, *shared
- Jacobo-Piqueras, N., Theiner, T., Geisler, S. M., & Tuluc, P. (2024). Molecular mechanism responsible for sex differences in electrical activity of mouse pancreatic β cells. JCI insight, 9(6), e171609. https://doi.org/10.1172/jci.insight.171609
- Ablinger, C., Eibl, C., Geisler, S. M., Campiglio, M., Stephens, G. J., Missler, M., & Obermair, G. J. (2022). α2δ-4 and Cachd1 Proteins Are Regulators of Presynaptic Functions. International journal of molecular sciences, 23(17), 9885. https://doi.org/10.3390/ijms23179885
- Tuluc, P., Theiner, T., Jacobo-Piqueras, N., & Geisler, S. M. (2021). Role of High Voltage-Gated Ca2+ Channel Subunits in Pancreatic β-Cell Insulin Release. From Structure to Function. Cells, 10(8), 2004. https://doi.org/10.3390/cells10082004
- El Ghaleb, Y., Schneeberger, P. E., Fernández-Quintero, M. L., Geisler, S. M., Pelizzari, S., Polstra, A. M., van Hagen, J. M., Denecke, J., Campiglio, M., Liedl, K. R., Stevens, C. A., Person, R. E., Rentas, S., Marsh, E. D., Conlin, L. K., Tuluc, P., Kutsche, K., & Flucher, B. E. (2021). CACNA1I gain-of-function mutations differentially affect channel gating and cause neurodevelopmental disorders. Brain: a journal of neurology, 144(7), 2092–2106. https://doi.org/10.1093/brain/awab101
- Schöpf, C. L., Ablinger, C.*, Geisler, S. M.*, Stanika, R. I.*, Campiglio, M., Kaufmann, W. A., Nimmervoll, B., Schlick, B., Brockhaus, J., Missler, M., Shigemoto, R., & Obermair, G. J. (2021). Presynaptic α2δ subunits are key organizers of glutamatergic synapses. Proceedings of the National Academy of Sciences of the United States of America, 118(14), e1920827118. https://doi.org/10.1073/pnas.1920827118, *shared
- Geisler, S. M., Benedetti, A., Schöpf, C. L., Schwarzer, C., Stefanova, N., Schwartz, A., & Obermair, G. J. (2021). Phenotypic Characterization and Brain Structure Analysis of Calcium Channel Subunit α2δ-2 Mutant (Ducky) and α2δ Double Knockout Mice. Frontiers in synaptic neuroscience, 13, 634412. https://doi.org/10.3389/fnsyn.2021.634412
- Geisler, S., Schöpf, C. L., Stanika, R., Kalb, M., Campiglio, M., Repetto, D., Traxler, L., Missler, M., & Obermair, G. J. (2019). Presynaptic α2δ-2 Calcium Channel Subunits Regulate Postsynaptic GABAA Receptor Abundance and Axonal Wiring. The Journal of neuroscience : the official journal of the Society for Neuroscience, 39(14), 2581–2605. https://doi.org/10.1523/JNEUROSCI.2234-18.2019
- Geisler, S.*, Schöpf, C. L.*, & Obermair, G. J. (2015). Emerging evidence for specific neuronal functions of auxiliary calcium channel α₂δ subunits. General physiology and biophysics, 34(2), 105–118. https://doi.org/10.4149/gpb_2014037, *shared
Zooming into the mouse brain- From cytoarchitecture to synaptic connections: Triple immunofluorescence labelings of mouse brain sagittal sections with neuronal markers Ctip2 (red) and Tbr1 (green) and Hoechst to counterstain nuclei (blue). The inset depicts pre- and postsynaptic contacts between cultured hippocampal neurons transfected with mCherry or eGFP (pseudocolored in yellow and magenta).
Cover image The Journal of Neuroscience (Geisler et al., 2019, J Neurosci. 39:2581-2605).