Forschungsteam Schindl

Chemoresistance in breast cancer correlates with increased expression of TRPC5. In breast cancer tumor cells, functional TRPC5 ion channels are localized in extracellular vesicles (EVs).

We investigate the release of TRPC5-containing EVs from breast cancer tumor cells and their significance for tumor progression using a vascularized in vivo embryonic chicken tumor model, the so-called CAM assay. At the same time, we will perform calcium (Ca²⁺) and fluorescence imaging of the progressing tumor in order to explain the role of TRPC5 in the development of chemoresistance.

Our goal is to track the formation and transfer of fluorescently labeled TRPC5 EVs as well as the Ca²⁺ signals associated with this process in the involved tumor cells with high spatial and temporal resolution. In addition, we will investigate Ca²⁺-dependent gene regulation programs, for example NFAT, both in individual tumor cells and in CAM tumors.

• Duration: starts 2026
  Funding: FWF
• Project Lead: Rainer Schindl

Glioblastoma is an aggressive form of brain tumor. Glioblastoma cells communicate and grow using intracellular calcium signaling pulses. These signals help the tumor survive, resist therapies, and reconnect after surgery. Our project investigates a completely new approach to controlling these calcium signals using light.

We aim to develop a new class of molecules that can switch a central calcium channel—called Orai1—on and off solely by illuminating the cells with light of different colors. By turning this channel “on” and “off” with light, we want to better understand how calcium signals propagate through networks of tumor cells and how they activate key signaling proteins that drive cancer growth.

To achieve this, we will produce light-sensitive variants of existing Orai1 blockers, test them using state-of-the-art imaging technologies, and study in real time how glioblastoma cells respond. This photopharmacological approach allows us to control cellular behavior with exceptional precision.

The project is jointly led by Bernadett Bacsa, Sanja Curcic, and Rainer Schindl together with cooperation partner Toma Glasnov for synthetic chemistry and optical control of ion channels. By pooling their expertise, new ways are opening up to understand—and possibly disrupt—the communication systems that make glioblastoma so difficult to treat.

Duration: starts 2026
Funding: FWF
Project Leads: Rainer Schindl and Bernadett Bacsa

Our research focuses on the development of contactlessly controlled chemotherapy that is administered directly at the tumor site. We investigate spatiotemporally controlled chemotherapy and its effects on the tumor microenvironment (TME), as well as its potential for clinical application.

In the laboratory, we combine implant prototypes with preclinical tumor models (pancreatic carcinomas, fibrosarcomas, and brain tumors) to enable site-specific and temporally precise release of therapeutics. In doing so, we study the pharmacokinetics and pharmacodynamics of chemotherapy, analyze the dynamic processes within the tumor microenvironment, and deliberately control them to promote tumor-suppressive effects.

Duration: ongoing

Funding: BioTechMed Graz, EIC Pathfinder

Project Lead: Linda Waldherr

Project Partners: Julia Kargl, Nassim Ghaffari, Beate Rinner, Martina Schweiger, Johannes Bintinger, Hannes Mikula, Linköping University, CEITEC Brno, Marton Bojtar

Glioblastoma is an aggressive form of brain tumor. Glioblastoma cells communicate and grow using intracellular calcium signaling pulses. These signals help the tumor survive, resist therapies, and reconnect after surgery. Our project investigates a completely new approach to controlling these calcium signals using light.

We aim to develop a new class of molecules that can switch a central calcium channel—called Orai1—on and off solely by illuminating the cells with light of different colors. By turning this channel “on” and “off” with light, we want to better understand how calcium signals propagate through networks of tumor cells and how they activate key signaling proteins that drive cancer growth.

To achieve this, we will produce light-sensitive variants of existing Orai1 blockers, test them using state-of-the-art imaging technologies, and study in real time how glioblastoma cells respond. This photopharmacological approach allows us to control cellular behavior with exceptional precision.

The project is jointly led by Bernadett Bacsa, Sanja Curcic, and Rainer Schindl together with cooperation partner Toma Glasnov for synthetic chemistry and optical control of ion channels. By pooling their expertise, new ways are opening up to understand—and possibly disrupt—the communication systems that make glioblastoma so difficult to treat.

Duration: starts 2026
Funding: FWF
Project Leads: Rainer Schindl and Bernadett Bacsa

TRPC6 channels are Ca²⁺-permeable ion channels increasingly recognized as important regulators of immune responses and are highly expressed in the lung. Our preliminary data demonstrate functional expression of TRPC6 in human eosinophils, suggesting their role in allergic airway inflammation. We investigate the (patho)physiological role of TRPC6-mediated signaling in eosinophils in the context of allergic asthma.

We combine functional analyses of human eosinophils with expression profiling in human and murine lung tissue. Translational relevance will be addressed using a mouse model of allergen-induced airway inflammation and state-of-the-art pharmacological and imaging approaches to define TRPC6-dependent signaling pathways.

Duration: starts 2026

Funding: FWF

Project Lead: Bernadett Bacsa

Project Partners: Eva Böhm, Thomas Bärnthaler

Sepsis is a life-threatening consequence of bacterial infection driven by dysregulated systemic inflammation and remains a major cause of mortality. Macrophages are key regulators of this response, with imbalanced pro- and anti-inflammatory polarization leading to cytokine storm and organ failure. TRPC channels are Ca²⁺-permeable ion channels that critically modulate macrophage polarization and inflammatory signaling. This project investigates the (patho)physiological relevance of TRPC-dependent signaling in macrophages during bacterial infection.

We integrate in vitro and in vivo infection models with advanced single-cell and biochemical approaches to identify TRPC channels as host-targeted therapeutic targets for pneumonia and sepsis using Burkholderia pseudomallei.

Duration: ongoing

Funding: City of Graz

Project Lead: Bernadett Bacsa

Project Partner: Sabine Wagner-Lichtenegger

We investigate the structure of the TRPC3 protein using cryo-EM, employing a novel strategy based on photoswitchable ligands to capture the previously unresolved open conformation. In our laboratory, we perform protein production and purification from cell suspensions, followed by biochemical characterization to ensure structural integrity prior to cryo-EM analysis in collaboration with Dr. Christine Ziegler at the University of Regensburg.

We utilize advanced membrane-mimetic extraction systems, including DIBMA-based nanodiscs provided by Dr. Sandrine Keller at the University of Graz. Our structural studies focus on TRPC3 in complex with two photoswitchable ligands— the lipid-mimicking OptoDArG and the non-lipid OptoBI-1 — to stabilize and visualize distinct functional states.

By resolving these structures, we aim to elucidate potential TRPC3 ion-selectivity mechanisms, ultimately enabling the rational design of targeted pharmacological agents for future therapeutic applications.

Duration: ongoing
Funding:  FWF

Project partners: Jasmin Baron, Christine Ziegler, Rainer Schindl, Sandro Keller, Gerd Leitinger, Anita Emmerstorfer-Augustin, Klaus Groschner

We have identified that TRPC1 modulates phosphorylation-dependent protein expression and cholesterol metabolism in hippocampal neurons of aged mice. Both processes are critically involved in the development and potential prevention of Alzheimer’s disease (AD). Building on these findings, this project aims to elucidate the role of TRPC1 in AD pathogenesis using dissociated hippocampal neurons exposed to amyloid-β, combined with biochemical, electrophysiological, and fluorescence imaging approaches.

This work will help establish TRPC1 as a potential contributor to AD-related mechanisms and provide a foundation for future investigations into the involvement of TRPC1 in neurodegenerative disorders.

Duration: ongoing
Funding: MEFOgraz GESUNDHEIT3000

Project partners: Julia Skerjanz, Jasmin Baron

Recent cryo-EM studies have captured TRPC6 only in closed conformations, providing limited insight into its gating dynamics even in the presence of activators. Electrophysiological data indicate that TRPC6 exhibits a short-lived open state, suggesting that its intrinsic gating behavior hampers structural characterization of the active channel.

To overcome this limitation, we employ high-speed atomic force microscopy (HS-AFM) in collaboration with Dr. Johannes Preiner, a state-of-the-art technique capable of generating high-resolution, time-resolved topographic images of membrane proteins. We aim to resolve TRPC6 gating dynamics in response to distinct agonists. Through this approach, we seek to advance the mechanistic understanding of TRPC6 function in native-like environments and establish a framework for future pharmacological modulation.

Duration: ongoing
Funding:  Austrian Academy of Science, ÖAW

Project partners: Jasmin Baron, Johannes Preiner, Rainer Schindl, Gerd Leitinger, Matthias Gsell

Dysfunction of Ca²⁺ channels is a major contributing factor in the etiology of neurodevelopmental disorders (NDDs). With this project, we aim to uncover a potential mechanistic link between Ca²⁺-permeable TRPC3 channels and NDD pathology. We have identified patient-derived TRPC3 mutations associated with NDD-like symptoms, providing a unique opportunity to explore how altered TRPC3 function may disrupt neuronal development and network formation.

We characterize these mutations using a multidisciplinary approach that integrates electrophysiology, fluorescence imaging, biochemical assays, and transgenic mouse models. Through this strategy, we investigate how TRPC3 variants influence channel gating, calcium signaling, neuronal morphology, and synaptic integration during critical periods of brain development.

With this project, we aim to define TRPC3 as a previously unrecognized molecular player in NDDs, establish causal relationships between TRPC3 dysfunction and neurodevelopmental phenotypes, and generate a mechanistic framework that may guide future therapeutic strategies targeting TRPC3-mediated signaling in neurodevelopmental disorders.

Duration: ongoing
Funding:  FWF

Project partners: Julia Skerjanz, Stephanie Efthymiou, Gerald Obermair, Thomas Stockner, Klaus Groschner, Pedro Sanchez Murcia

TRPC3 and TRPC6 are Ca²⁺‑permeable ion channels increasingly recognized as regulators of immune cell function. Psoriasis is a chronic inflammatory skin disease driven by dysregulated innate and adaptive immunity. Altered TRPC6 expression has been observed in psoriatic lesions, but the role of TRPC3/6‑mediated signaling in immune regulation during psoriatic inflammation remains unclear.

We investigate whether TRPC3/6‑dependent Ca²⁺ signaling shapes immune cell activation and contributes to psoriatic disease development. Our goal is to identify the immune cell subsets most affected by TRPC3/6 modulation and assess the therapeutic potential of targeting these channels.

Duration: starts 2026

Funding: Medical University of Graz

Project Lead: Sanja Curcic

Project Partners: Peter Wolf, Nicole Golob-Schwarzl, Theresa Benezeder, Klaus Groschner

Mechanical stress has recently been recognized as an important driver of skin inflammation, and the mechanosensitive ion channel PIEZO1 has emerged as a promising therapeutic target in keratinocytes and fibroblasts. Our preliminary data show that PIEZO1 activation promotes the release of inflammatory cytokines, while its basal activity is essential for inflammation‑induced cytokine production.

We investigate whether inhibition or modulation of PIEZO1 can reduce keratinocyte‑driven inflammation in chronic skin disease. Our goal is to identify the key signaling pathways underlying PIEZO1‑mediated immune functions and to determine whether manipulating this channel could offer a new strategy for controlling cutaneous inflammation.

Duration: ongoing 

Funding: Kulturamt der Stadt Graz

Project Lead: Sanja Curcic

Project Partners: Birgit Lohberger, Klaus Groschner, Thomas Bärnthaler, Michael Dengler

Coordinated calcium signalling within the tumour cell network is the basis for the progression of glioblastoma (GBM), the most aggressive primary brain tumour. The newly discovered, physiologically active pseudosynaptic connections between neurons and GBM cells that regulate calcium signals reveal the potential for repurposing standard neurostimulation methods for the treatment of brain tumours.

In this project, we are investigating the function of calcium ion channels and their role in signal transduction within the GBM network, specifically how they regulate  further gene expression and growth of tumour cells. To this end, we use alternating electric fields in vitro and ex ovo to suppress GBM progression and focus on the molecular effects on cellular and intercellular calcium signals in GBM. In the laboratory, we combine live-cell techniques such as electrophysiology and fluorescence microscopy in cell experiments and in the 3R tumour model on the chorioallantoic membrane of chicken embryos. Using fluorescence-based reporters for calcium and gene regulation, we aim to resolve the effects of electrical stimulation on tumour growth in terms of time and location. 

Duration: ongoing

Funded by: Land Steiermark, FWF

Project leader: Marta Nowakowska-Desplantes

Project partners: Rainer Schindl, Linda Waldherr, Zhanat Koshenov, CEITEC Brno, KU Leuven

The PHOENIX project develops a new class of light-activatable chemotherapeutics using so-called “photocages” to minimize the systemic toxicity of conventional cancer treatments through precise, controllable, and localized drug release. These xanthenium-based photocages are activated by light (orange to red spectrum) and enable oxygen-independent drug release, making them particularly effective for treating therapy-resistant, hypoxic tumors. Compared to existing technologies, photocages are characterized by improved photochemical efficiency and high stability under physiological conditions. The platform allows for both local application and tumor-specific targeting through conjugation with antibodies and hydrogels.

Duration: starting in 2026

Funded by: Young Pilot Call, Medical University of Graz

Project leader: Verena Handl

Project partners: Linda Waldherr, Nassim Ghaffari Tabrizi-Wizsy, Márton Bojtár