CIBSS Launchpad Funds Recipients 2024

Dr. Silvia Fessner geb. Groiss

Dr. Silvia Fessner geb. Groiss

Contact

Dr. Silvia Fessner geb. Groiss
Department of Medicine IV & IMITATE
University Medical Center Freiburg

T +49 761 270 63047
silvia.groiss(at)uniklinik-freiburg.de

Further Information

WWW

Selected publications:

2024

Groiss, S., Viertler, C., Kap, M., Bernhardt, G., Mischinger, H.-J., Sieuwerts, A., Verhoef, C., Riegman, P., Kruhøffer, M., Svec, D., Sjoback, R., Becker, K.-F., Zatloukal, K. Inter-patient heterogeneity in the hepatic ischemia-reperfusion injury transcriptome: Implications for research and diagnostics. New Biotechnology 79 (2024) 20-29. doi: 10.1016/j.nbt.2023.12.001.

2023

Hetmann, M., Langner, C., Durmaz, V., Cespugli, Köchl, M., K., Krassnigg, A., Blaschitz, K., Groiss, S., Loibner, M., Ruau, D., Zatloukal, K., Gruber, K., Steinkellner, G., Gruber, C., C. Identification and validation of fusidic acid and flufenamic acid as inhibitors of SARS-CoV-2 replication using DrugSolver CavitomiX. Sci Rep 13, 11783 (2023). doi: 10.1038/s41598-023-39071-z

Groiss, S., Somvilla, I., Daxböck, C., Stückler, M., Pritz, E., Brislinger, D. Bei Mu Gua Lou San facilitates mucus expectoration by increasing surface area and hydration levels of airway mucus in an air-liquid-interface cell culture model of the respiratory epitheliumBMC Complement Med Ther 23, 414 (2023). doi: 10.1186/s12906-023-04251-x

2022

Loibner, M., Barach, P., Wolfgruber, S., Langner, C., Stangl, V., Rieger, J., Föderl-Höbenreich, E., Hardt, M., Kicker, E., Groiss, S., Zacharias, M., Wurm, P., Gorkiewicz, G., Regitnig, P., Zatloukal, K. Resilience and protection of health care and research laboratory workers during the SARS-CoV-2 Pandemic: Analysis and case study from an Austrian high security laboratory. Front. Psychol. 13:901244. doi: 10.3389/fpsyg.2022.901244.

2021

Groiss, S., Somvilla, I., Daxböck, C., Fuchs, J., Lang-Olip, I., Stiegler, P., Leber, B., Liegl-Atzwanger, B., & Brislinger, D. Quantification of increased MUC5AC expression in airway mucus of smoker using an automated image-based approach. Microsc. Res. Tech. 2022;85(1):5-18. doi: 10.1002/jemt.23879. Epub 2021 Jul 20.

Groiss, S., Lammegger, R. & Brislinger, D. Anti-Oxidative and Immune Regulatory Responses of THP-1 and PBMC to Pulsed EMF Are Field-Strength DependentInt. J. Environ. Res. Public Health 2021, 18, 9519. doi: 10.3390/ijerph18189519

Groiss, S., Pabst, D., Faber, C., Meier, A., Bogdoll, A., Unger, C., Nilges, B., Strauss, S., Foederl-Hoebenreich, E., Hardt, M., Geipel, A., Reinecke, F., Korfhage, C., & Zatloukal, K., Highly resolved spatial transcriptomics for detection of rare events in cells. bioRxiv 2021.10.11.463936; doi: 10.1101/2021.10.11.463936

Fuchs, J., Nonn, O., Daxboeck, C., Groiss, S., Moser, G., Gauster, M., Lang-Olip I., & Brislinger, D. (2021). Automated Quantitative Image Evaluation of Antigen Retrieval Methods for 17 Antibodies in Placentation and Implantation Diagnostic and ResearchMicroscopy and Microanalysis, 1-12. doi:10.1017/S1431927621012630

2018

Rengachari, S; Groiss, S; Devos, J; Caron, E; Grandvaux, N; Panne, D. Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function. PNAS, 2018. doi: 10.1073/pnas.1718426115

2016

Groiss, S; Selvaraj, R; Varadavenkatesan, T; Vinayagam, R. Structural characterization, antibacterial and catalytic effect of iron oxide nanoparticles synthesized using the leaf extract of Cynometra ramiflora. Journal of Molecular Structure, 2016. doi: 10.1016/j.molstruc.2016.09.031

 

Molecular mechanisms underlying Proton-pump-inhibitor associated airway disease

Proton-pump inhibitors (PPIs) are used worldwide to treat gastroesophageal reflux disease. However, prolonged administration of PPIs has been linked to increased airway infections. PPIs target P2-type gastric (ATP4) and to a lesser degree non-gastric (ATP12) H+/K+ATPase (J.M. Shin, 2006). H+/K+ATPases regulate various cellular processes including intracellular pH and are required for Wnt-dependent left-right axis, mucociliary epidermis and brain development (M. Ritter, 1998; P. Walentek, 2012; 2015a; 2015b).

Activation of Wnt signaling is required for basal cell proliferation and maintenance and has been shown to be pH- and charge-dependent (M. Simons, 2009). Changes in pH caused by inhibition of H+ pumps such as ATP4 might therefore distort Wnt signaling by blocking Dsh localization to the membrane. This leads to massive differentiation of basal cells into epithelial cell types and depletion of stem cells during development (M. Haas, 2019; P. Walentek, 2022). Differentiation of mucociliary cell types increases Notch ligands (esp. Dll1) which causes shedding, apoptosis or transdifferentiation of multiciliated cells (MCC) thereby interfering with mucociliary clearance and removal of pathogens from the respiratory tract.

In this project, I will use the Xenopus embryonic epidermis model as well as human air-liquid-interface cell culture systems to dissect the mechanistic link between PPI administration, Wnt downregulation and Notch-mediated basal cell depletion including MCC shedding or transdifferentiation.

Aim 1 to characterize the effects of PPIs on intracellular pH and Wnt signaling activity

Aim 2 to monitor effects of PPIs on mucociliary cell behavior, Notch ligand expression and loss of MCCs

Aim 3 to target PPI effects on gene expression and tissue remodeling including long-term loss of basal cells and assess fluid flow deficits following MCC loss

Overall, these findings will verify the interference of PPIs with key signaling pathways in mucociliary development and clarify long-term effects of PPI on human basal cells with focus on the loss of MCCs and the resulting interference with mucociliary clearance.