Metabolic crosstalk and epigenomic reprogramming of macrophages and colon cancer
In this sub-project, we aim to study epigenetic reprogramming of tumor associated macrophages based on metabolic factors derived from the tumor microenvironment. We will employ innovative 3D organoid co-culture models generated from human and mouse colorectal tissues and explore the metabolic crosstalk of macrophages with normal and cancer tissues in these models. In collaboration with other project partners, we will associate specific metabolic states of the organoids, reflecting the normal or malignant colon environment, with epigenetic alterations in macrophages based on the metabolic analysis of organoid/macrophage co-cultures (T. Weichhart, E. Pohl, A. Haschemi). Further, we will study epigenetic regulation in macrophages using LOF experiments in transgenic mouse models and organoid cultures in vitro. This will allow us to identify epigenetic pathways that might affect immunometabolism and macrophage phenotypes in the tumor setting and serve as potential therapeutic targets (M. Schweiger, C. Moissl-Eichinger, G. Schabbauer, T. Weichhart).
Gerda Egger
Medical University of Vienna
Department of Pathology
Ludwig Boltzmann Institute
of Applied Diagnostics
Währinger Gürtel 18-20
1090 Vienna
gerda.egger@meduniwien.ac.at
Egger Lab
Project Members
Janette Pfneissl
PhD student
SFB Member
Kristina Draganic
PhD student
SFB Member
Loan Tran
PhD student
SFB Member
Research Publications
A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine. Kalla J, Pfneissl J, Mair T, Tran L, Egger G. Cell Oncol (Dordr). 2024 May 28. doi: 10.1007/s13402-024-00960-8. https://doi.org/10.1007/s13402-024-00960-8.
JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression. Redmer T, Raigel M, Sternberg C, Ziegler R, Probst C, Lindner D, Aufinger A, Limberger T, Trachtova K, Kodajova P, Högler S, Schlederer M, Stoiber S, Oberhuber M, Bolis M, Neubauer HA, Miranda S, Tomberger M, Harbusch NS, Garces de Los Fayos Alonso I, Sternberg F, Moriggl R, Theurillat JP, Tichy B, Bystry V, Persson JL, Mathas S, Aberger F, Strobl B, Pospisilova S, Merkel O, Egger G, Lagger S, Kenner L. Mol Cancer. 2024 May 29;23(1):114. https://doi.org/10.1186/s12943-024-02022-x.
Metabolic support by macrophages sustains colonic epithelial homeostasis. Fritsch SD, Sukhbaatar N, Gonzales K, Sahu A, Tran L, Vogel A, Mazic M, Wilson JL, Forisch S, Mayr H, Oberle R, Weiszmann J, Brenner M, Vanhoutte R, Hofmann M, Pirnes-Karhu S, Magnes C, Kühnast T, Weckwerth W, Bock C, Klavins K, Hengstschläger M, Moissl-Eichinger C, Schabbauer G, Egger G, Pirinen E, Verhelst SHL, Weichhart T. Cell Metab. 2023 Nov 7;35(11):1931-1943.e8. https://doi.org/10.1016/j.cmet.2023.09.010.
Mimicking Tumor Cell Heterogeneity of Colorectal Cancer in a Patient-derived Organoid-Fibroblast Model. Atanasova VS, de Jesus Cardona C, Hejret V, Tiefenbacher A, Mair T, Tran L, Pfneissl J, Draganić K, Binder C, Kabiljo J, Clement J, Woeran K, Neudert B, Wohlhaupter S, Haase A, Domazet S, Hengstschläger M, Mitterhauser M, Müllauer L, Tichý B, Bergmann M, Schweikert G, Hartl M, Dolznig H, Egger G. Cell Mol Gastroenterol Hepatol. 2023;15(6):1391-1419. https://doi.org/10.1016/j.jcmgh.2023.02.014.
Identification of Biomarkers and Trajectories of Prostate Cancer Progression: A Bioinformatics Fusion of Weighted Correlation Network Analysis and Machine Learning. Raheleh Sheibani-Tezerji, Carlos Uziel Pérez Malla, Gabriel Wasinger, Katarina Misura, Astrid Haase, Anna Malzer, Jessica Kalla, Loan Tran, Gerda Egger. bioRxiv 2023.03.02.530740; https://doi.org/10.1101/2023.03.02.530740.
STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway. Pencik J, Philippe C, Schlederer M, Atas E, Pecoraro M, Grund-Gröschke S, Li WJ, Tracz A, Heidegger I, Lagger S, Trachtová K, Oberhuber M, Heitzer E, Aksoy O, Neubauer HA, Wingelhofer B, Orlova A, Witzeneder N, Dillinger T, Redl E, Greiner G, D'Andrea D, Östman JR, Tangermann S, Hermanova I, Schäfer G, Sternberg F, Pohl EE, Sternberg C, Varady A, Horvath J, Stoiber D, Malcolm TI, Turner SD, Parkes EE, Hantusch B, Egger G, Rose-John S, Poli V, Jain S, Armstrong CWD, Hoermann G, Goffin V, Aberger F, Moriggl R, Carracedo A, McKinney C, Kennedy RD, Klocker H, Speicher MR, Tang DG, Moazzami AA, Heery DM, Hacker M, Kenner L. Mol Cancer. 2023 Aug 12;22(1):133. https://doi.org/10.1186/s12943-023-01825-8.
Zrimšek M, Kuchaříková H, Draganić K, Dobrovolná P, Heiss Spornberger V, Winkelmayer L, Hassler MR, Lochmanová G, Zdráhal Z, Egger G. Quantitative Acetylomics Uncover Acetylation-Mediated Pathway Changes Following Histone Deacetylase Inhibition in Anaplastic Large Cell Lymphoma. Cells. 2022 Aug 2;11(15):2380. https://doi.org/10.3390/cells11152380.
Dillinger T, Sheibani-Tezerji R, Pulverer W, Stelzer I, Hassler MR, Scheibelreiter J, Pérez Malla CU, Kuroll M, Domazet S, Redl E, Ely S, Brezina S, Tiefenbacher A, Rebhan K, Hübner N, Grubmüller B, Mitterhauser M, Hacker M, Weinhaeusel A, Simon J, Zeitlinger M, Gsur A, Kramer G, Shariat SF, Kenner L, Egger G. Identification of tumor tissue-derived DNA methylation biomarkers for the detection and therapy response evaluation of metastatic castration resistant prostate cancer in liquid biopsies. Mol Cancer. 2022 Jan 3;21(1):7. doi: 10.1186/s12943-021-01445-0. https://doi.org/10.1186/s12943-021-01445-0.
KMT2C methyltransferase domain regulated INK4A expression suppresses prostate cancer metastasis. Limberger T, Schlederer M, Trachtová K, Garces de Los Fayos Alonso I, Yang J, Högler S, Sternberg C, Bystry V, Oppelt J, Tichý B, Schmeidl M, Kodajova P, Jäger A, Neubauer HA, Oberhuber M, Schmalzbauer BS, Pospisilova S, Dolznig H, Wadsak W, Culig Z, Turner SD, Egger G, Lagger S, Kenner L. Mol Cancer. 2022 Mar 30;21(1):89. doi: 10.1186/s12943-022-01542-8. https://doi.org/10.1186/s12943-022-01542-8.
DNA hypomethylation leads to cGAS-induced autoinflammation in the epidermis. Beck MA, Fischer H, Grabner LM, Groffics T, Winter M, Tangermann S, Meischel T, Zaussinger-Haas B, Wagner P, Fischer C, Folie C, Arand J, Schöfer C, Ramsahoye B, Lagger S, Machat G, Eisenwort G, Schneider S, Podhornik A, Kothmayer M, Reichart U, Glösmann M, Tamir I, Mildner M, Sheibani-Tezerji R, Kenner L, Petzelbauer P, Egger G, Sibilia M, Ablasser A, Seiser C. EMBO J. 2021 Nov 15;40(22):e108234. https://doi.org/10.15252/embj.2021108234.