Sepsis is a life-threatening organ dysfunction resulting from severe systemic inflammation caused by an infection. Despite many improved therapeutic measures, the mortality rate from sepsis is still 15-25%, and for septic shock 30-50% (Hotchkiss et al., 2016). Endothelial cells, which line the inner surface of blood vessels and capillary beds, play a central role in this life-threatening condition. In the early stages of sepsis, microbial factors such as LPS, which binds to Toll-like receptors, are responsible for directly activating endothelial cells. Endogenous agonists – released by activated leukocytes, endothelial cells or damaged cells for instance – subsequently promote the endothelial dysfunction. In this project we plan to develop new, highly-standardised cell models in which the specific signalling pathways of the Toll-like receptors can be switched on or off by means of light induction. From the light-activatable cell lines obtained in this way, we will establish physiologically relevant models of sepsis which can then be used to investigate intracellular signalling pathways and expression of different sepsis-inducing factors, microvascular endothelial permeability, and potential therapeutic agents. The objective is to mimic sepsis-inducing inflammation by switching the signalling pathways on or off (in the absence of bacterial factors) optogenetically. The project is being carried out in cooperation with Danube University Krems and UK St. Pölten.
Development of powerful diagnostic procedures and new therapeutic approaches in inflammation and sepsis
Department of Science & Technology
Project Description
- Further Information
- Status: Ongoing
- Project ID : 1201
-
Sponsor
:
Land NÖ
- Project Leader
- Prof.(FH) Mag. Dr. Christoph WiesnerProfessor (FH) Institute Biotechnology
![Prof.(FH) Mag. Dr. Christoph Wiesner | Professor (FH) Institute Biotechnology - IMC Fachhochschule Krems]()
Prof.(FH) Mag. Dr. Christoph Wiesner
Professor (FH) Institute Biotechnology
Institute Biotechnology
- Cell and Molecular Biology
- Drug Screening
- Project management
- Medical and Pharmaceutical BiotechnologyBachelor of Science in Engineering / full-time
- Medical and Pharmaceutical BiotechnologyMaster of Science in Engineering / full-time
-
Optogenetische Stammzellen in heterotypische Tumorsphäroiden
Project Leader, Department of Science & Technology
-
EvoFerm
Department of Science & Technology
-
Spike-Fermentation
Department of Science & Technology
-
Entwicklung einer optogenetisch kontrollierbaren MSC-Zelllinie für die präzise Regulation immunmodulatorischer Faktoren
Project Leader, Department of Science & Technology
-
Biomarker-basierte therapeutische Prävention von Knochenmetastasen beim Mammakarzinom: die phathophysiologische Rolle der endostalen Nische
Project Leader, Department of Science & Technology
-
Entwicklung leistungsfähiger Diagnostikverfahren und neuer Therapieansätze in Inflammation und Sepsis
Project Leader, Department of Science & Technology
-
Theraferm
Department of Science & Technology
-
Nachhaltiges biologisches Recycling von umweltbedenklichen Stoffen (Rare Earth Elements) aus Elektronikabfall und Abwässern
Department of Science & Technology
-
Optogenetische Krebsmodelle
Department of Science & Technology
-
Testung von rekombinanten polyklonalen Antikörperfragmenten gegen Gluten-Peptide
Department of Science & Technology
-
Zellbasierte Testsysteme für bioaktive Substanzen
Department of Science & Technology
Stierschneider, A., Wiesner, C. (2024): Shedding light on the molecular and regulatory mechanisms of TLR4 signaling in endothelial cells under physiological and inflamed conditions. Frontiers in Immunology, 14(1264889): 1-15.
Doi: https://doi.org/10.3389/fimmu.2023.1264889Colleselli, K., Stierschneider, A., Wiesner, C. (2023): An Update on Toll-like Receptor 2, Its Function and Dimerization in Pro- and Anti-Inflammatory Processes. International Journal of Molecular Sciences.
Doi: https://doi.org/10.3390/ijms241512464Colleselli, K., Ebeyer-Masotta, M., Neuditschko, B., Stierschneider, A., Pollhammer, C., Potocnjak, M., Hundsberger, H., Herzog, F., Wiesner, C. (2023): Beyond Pattern Recognition: TLR2 Promotes Chemotaxis, Cell Adhesion, and Migration in THP-1 Cells. Cells, 12(10): 1425.
Doi: https://doi.org/10.3390/cells12101425Stierschneider, A., Neuditschko, B., Colleselli, K., Hundsberger, H., Herzog, F., & Wiesner, C. (2023): Comparative and Temporal Characterization of LPS and Blue-Light-Induced TLR4 Signal Transduction and Gene Expression in Optogenetically Manipulated Endothelial Cells. Cells, 12(697).
Doi: https://doi.org/10.3390/cells12050697Weitzenböck, HP., Gschwendtner, A., Wiesner, C., Depke, M., Schmidt, F., Trautinger, F., Hengstschläger, M., Hundsberger, H., Mikula, M. (2022): Proteome analysis of NRF2 inhibition in melanoma reveals CD44 up-regulation and increased apoptosis resistance upon vemurafenib treatment. Cancer Medicine, 11(4): 956-967.
Doi: https://doi.org/10.1002/cam4.4506Stierschneider, A., Grünstäudl, P., Colleselli, K., Atzler, J., Klein, C., Hundsberger, H., Wiesner, C. (2021): Light-Inducible Spatio-Temporal Control of TLR4 and NF-κB-Gluc Reporter in Human Pancreatic Cell Line. International Journal of Molecular Sciences, 22(17): 9232.
Doi: https://doi.org/10.3390/ijms22179232Pretsch, A., Nagl, M., Wiesner, C., Hollaus, R., Genov, M. (2021): Polyguanidine polymers and methods of use thereof (US11013760B2). United States Patent Office.
Hundsberger, H., Stierschneider, A., Sarne, V., Ripper, D., Schimon, J., Weitzenböck, H. P., Schild, D., Jacobi, N., Eger, A., Atzler, J., Klein, C. T., & Wiesner, C. (2021): Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models. Molecules (Basel, Switzerland), 26(3): 717.
Doi: https://doi.org/10.3390/molecules26030717Sarne, V., Huter, S., Braunmueller, S., Rakob, L., Jacobi, N., Kitzwögerer, M., Wiesner, C., Obrist, P., & Seeboeck, R. (2020): Promoter Methylation of Selected Genes in Non-Small-Cell Lung Cancer Patients and Cell Lines. International journal of molecular sciences, 21(13): 4595.
Doi: https://doi.org/10.3390/ijms21134595Pretsch, A., Nagl, M., Wiesner, C., Hollaus, R., Genov, M. (2019): Method for producing polyguanidines (US10335431B2). United States Patent Office.
Jacobi, N., Seeboeck, R., Hofmann, E., Schweiger, H., Smolinska, V., Mohr, T., Boyer, A., Sommergruber, W., Lechner, P., Pichler-Huebschmann, C., Önder, K., Hundsberger, H., Wiesner, C., & Eger, A. (2017): Organotypic three-dimensional cancer cell cultures mirror drug responses in vivo: lessons learned from the inhibition of EGFR signaling. Oncotarget, 8(64): 107423–107440.
Doi: https://doi.org/10.18632/oncotarget.22475Jacobi, N., Smolinska, V., Seeboeck, R., Stierschneider, A., Klein, C., Hofmann, E., Wiesner, C., Mohr, T., Oender, K., Lechner, P., Kaiser, H., Hundsberger, H., Eger, A. (2017): 3D Anti-Cancer drug discovery models: A promising approach for precision medicine. In IMC Fachhochschule Krems GmbH (Hrsg.), Online-Tagungsband FHK Forschungsforum 2017. Krems: FFH.
Hundsberger, H., Koppensteiner, A., Hofmann, E., Ripper, D., Pflüger, M., Stadlmann, V., Klein, C. T., Kreiseder, B., Katzlinger, M., Eger, A., Forster, F., Missbichler, A., & Wiesner, C. (2017): A Screening Approach for Identifying Gliadin Neutralizing Antibodies on Epithelial Intestinal Caco-2 Cells. SLAS discovery : advancing life sciences R & D, 22(8): 1035–1043.
Doi: https://doi.org/10.1177/2472555217697435Pretsch, A., Nagl, M., Wiesner, C., Burgmann, H. (2017): Bioactive polymers (US9567294B2). United States Patent Office.
Genov, M., Kreiseder, B., Nagl, M., Wiesner, C. et al. (2016): Tetrahydroanthraquinone Derivative (±)-4-Deoxyaustrocortilutein Induces Cell Cycle Arrest and Apoptosis in Melanoma Cells via Upregulation of p21 and p53 and Downregulation of NF-kappaB. Journal of Cancer, 7(5): 555.
Doi: https://doi:10.7150/jca.13614Preisitsch, M., Niedermeyer, T., Heiden, SE., Neidhardt, I., Kumpfmueller, J., Wurster, M., Harmrolfs, K., Wiesner, C., Enke, H., Mueller, R., Mundt, S. (2016): Cylindrofridins A–C, Linear Cylindrocyclophane-Related Alkylresorcinols from the Cyanobacterium Cylindrospermum stagnale. Journal of natural products, 79(1): 106-115.
Doi: https://doi.org/10.1021/acs.jnatprod.5b00768Preisitsch, M., Heiden, SE., Beerbaum, M., Niedermeyer, T., Schneefeld, M., Herrmann, J., Kumpfmueller, J., Thuermer, A., Neidhardt, I., Wiesner, C., Daniel, R., Mueller, R., Bange, FC., Schmieder, P., Schweder, T., Mundt, S. (2016): Effects of halide ions on the carbamidocyclophane biosynthesis in Nostoc sp. CAVN2. Marine drugs, 14(1): 21.
Doi: https://doi.org/10.3390/md14010021Preisitsch, M., Harmrolfs, K., Pham, HT., Heidern, SE., Fuessl, A., Wiesner, C., Pretsch, A., Switecka-Hagenbruch, M., Niedermeyer, TH., Mueller, R., Mundt, S. (2015): Anti-MRSA-acting carbamidocyclophanes H-L from the Vietnamese cyanobacterium Nostoc sp. CAVN2. The Journal of antibiotics, 68(9): 600-600.
Doi: https://doi.org/10.1038/ja.2015.79Kreiseder, B., Holper-Schichl, Y. M., Muellauer, B., Jacobi, N., Pretsch, A., Schmid, J. A., de Martin, R., Hundsberger, H., Eger, A., & Wiesner, C. (2015): Alpha-catulin contributes to drug-resistance of melanoma by activating NF-κB and AP-1. PloS one, 10(3): e0119402.
Doi: https://doi.org/10.1371/journal.pone.0119402Preisitsch, M., Harmrolfs, K., Pham, H., Heiden, SE., Fuessel, A., Wiesner, C., Pretsch, A., et al. (2015): Anti-MRSA-acting carbamidocyclophanes H–L from the Vietnamese cyanobacterium Nostoc sp. CAVN2. The Journal of antibiotics, 68(3): 165-177.
Doi: https://doi.org/10.1038/ja.2014.118Pretsch, A., Nagl, M., Schwendinger, K., Kreiseder, B., Wiederstein, M., Pretsch, D., Genov, M., Hollaus, R., Zinssmeister, D., Debbab, A., Hundsberger, H., Eger, A., Proksch, P., & Wiesner, C. (2014): Antimicrobial and anti-inflammatory activities of endophytic fungi Talaromyces wortmannii extracts against acne-inducing bacteria. PloS one, 9(6): e97929.
Doi: https://doi.org/10.1371/journal.pone.0097929Kreiseder, B., Orel, L., Bujnow, C., Buschek, S., Pflueger, M., Schuett, W., Hundsberger, H., de Martin, R., Wiesner, C. (2013): α‐Catulin downregulates E‐cadherin and promotes melanoma progression and invasion. International journal of cancer, 132(3): 521-530.
Doi: https://doi.org/10.1002/ijc.27698Pflüger, M., Kapuscik, A., Lucas, R., Koppensteiner, A., Katzlinger, M., Jokela, J., Eger, A., Jacobi, N., Wiesner, C., Hofmann, E., Onder, K., Kopecky, J., Schütt, W., Hundsberger, H. (2013): A combined impedance and AlphaLISA-based approach to identify anti-inflammatory and barrier-protective compounds in human endothelium. Journal of biomolecular screening, 18(1): 67-74.
Doi: https://doi.org/10.1177/1087057112458316Amatschek, S., Lucas, R., Eger, A., Pflueger, M., Hundsberger, H., Knoll, C., Grosse-Kracht, S., Schuett, W., Koszik, F., Maurer, D., Wiesner, C. (2011): CXCL9 induces chemotaxis, chemorepulsion and endothelial barrier disruption through CXCR3-mediated activation of melanoma cells. British journal of cancer, 104(3): 469-479.
Doi: https://doi.org/10.1038/sj.bjc.6606056Hundsberger, H., Verin, A., Wiesner, C., Pflüger, M., Dulebo, A., Schütt, W., Lasters, I., Männel, D., Wendel, A., Lucas, R. (2008): TNF: a moonlighting protein at the interface between cancer and infection. Frontiers in Bioscience, 13: 5374-86.
Doi: https://doi.org/10.2741/3087Hundsberger, H., Verin, A., Wiesner, C., Pflüger, M., Dulebo, A., Schütt, W., Lasters, I., Männel, D. N., Wendel, A., & Lucas, R. (2008): TNF: a moonlighting protein at the interface between cancer and infection. Frontiers in bioscience : a journal and virtual library, 13: 5374–5386.
Doi: https://doi.org/10.2741/3087Wiesner, C., Pflueger, M., Kopecky, J., Stys, D., Entler, B., Lucas, R., Hundsberger, H., Schuett, W. (2008): Implementation of ECIS technology for the characterization of potential therapeutic drugs that promote wound-healing. GMS Krankenhaushygiene interdisziplinar, 3(1).
Wiesner, C., Pflüger, M., Kopecky, J., Stys, D., Entler, B., Lucas, R., Hundsberger, H., Schütt, W. (2008): Implementation of ECIS technology for the characterization of potential therapeutic drugs that promote wound-healing. GMS Krankenhaushygiene Interdisziplinär, 3(1): Doc05.
Wiesner, C., Winsauer, G., Resch, U. et al. (2008): α-Catulin, a Rho signalling component, can regulate NF-κB through binding to IKK-β, and confers resistance to apoptosis. Oncogene , 27: 2159–2169.
Doi: https://doi.org/10.1038/sj.onc.1210863Wiesner, C., Lucas, R., Pflueger, M., Kleber, C., Kopecky, J., Stys, D., Entler, B., Hundsberger, H., Atzler, J., Hrouzek, P., Lukesova, A., Schuett, W., (2007): Endothelial Cell-Based Methods for the Detection of Cyanobacterial Anti- Inflammatory and Wound-Healing Promoting Metabolites. Drug Metabolism Letters, 1(4): 254-260.
Doi: https://doi.org/10.2174/187231207783221385Winter, D., Moser, J., Kriehuber, E., Wiesner, C., Knobler, R., Trautinger, F., Bombosi, P., Stingl, G., Petzelbauer, P., Rot, A., & Maurer, D. (2007): Down-modulation of CXCR3 surface expression and function in CD8+ T cells from cutaneous T cell lymphoma patients. Journal of immunology, 179(6): 4272-4282.
Doi: https://doi.org/10.4049/jimmunol.179.6.4272Lucas, R., Hundsberger, H., Pflueger, M., Fischer, B., Morel, D., Braun, C., Wendel, A., Chakraborty, T., Schuett, W., Wiesner, C., Hamacher, J. (2007): The Tumor Necrosis Factor-Derived TIP Peptide: A Potential Anti-Edema Drug. Letters in Drug Design & Discovery, 4(5): 336-340.
Doi: https://doi.org/10.2174%2F157018007780867816Hofer-Warbinek, R., Schmid, J.A., Mayer, H., Winsauer, G., Orel, L., Mueller, B., Wiesner, C., Binder, B.R., de Martin, R. (2004): A highly conserved proapoptotic gene, IKIP, located next to the APAF1 gene locus, is regulated by p53. Cell Death & Differentiation, 11(12): 1317 - 1325.
Doi: https://doi.org/10.1038%2Fsj.cdd.4401502Wiesner, C., Hoeth, M., De Martin, R. (2003): Functional screening for transcription factors (US20030059858A1). United States Patent Office.
Wiesner, C., Hoeth, M., Binder, B.R., de Martin, R. (2002): A functional screening assay for the isolation of transcription factors. Nucleic Acids Research, 30(16): e80.
Doi: https://doi.org/10.1093/nar/gnf079
