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Finkernagel Lab
Interactions in ovarian carcinoma microenvironment

High-grade serous ovarian carcinoma is the most lethal of all gynecological malignancies. It is unique among human cancers in its early and continuous spread via peritoneal cavity fluid. This fluid - which at advanced stages frequently accumulates as an effusion called ascites - is composed of cancer cells, various host cells, growth factors, cytokines and exosomes and plays a pivotal role in metastasis and immune suppression.

Our group is focused on the interaction of tumor and host cells and in ascites, spheroids and invaded tissues, with a focus on macrophages, T cells, NK cells, adipocytes, mesothelial cells and fibroblasts.

Towards this goal we apply in-depth bioinformatic methods to analyze data generated by high throughput 'omics' approaches coupled with advanced cell culture systems modeling the ovarian cancer microenvironment (See Reinartz, Finkernagel et al., Genome  Biology 2016; Adhikary et al.  BMC Genomics 2017; Worzfeld et al. Molecular and cellular proteomics, 2018).

IL-6 and IL-10 signaling in ovarian carcinoma ascites. Red: produced by tumor cells (Tu), Blue: produced by tumor associated macrophages (TAM). Asterisks: associated with a poor clinical outcome. Modified from: Reinartz, Finkernagel et al., Genome Biology 2016 under Creative Commons Attribution 4.0 International License.

For more information on ovarian carcinoma, please visit the Ovarian Cancer Research Alliance - OvaRA website.

Full publication list.

1 - Unger, Annika; Finkernagel, Florian; Hoffmann, Nathalie; Neuhaus, Felix; Joos, Barbara; Nist, Andrea; Stiewe, Thorsten; Visekruna, Alexander; Wagner, Uwe; Reinartz, Silke; Müller-Brüsselbach, Sabine; Müller, Rolf; Adhikary, Till (2018). Chromatin Binding of c-REL and p65 Is Not Limiting for Macrophage IL12B Transcription During Immediate Suppression by Ovarian Carcinoma Ascites. Frontiers in immunology 10.3389/fimmu.2018.01425

2 - Feld, Christine; Sahu, Peeyush; Frech, Miriam; Finkernagel, Florian; Nist, Andrea; Stiewe, Thorsten; Bauer, Uta-Maria; Neubauer, Andreas (2018). Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1. Nucleic acids research 10.1093/nar/gky119

3 - Stielow, Bastian; Finkernagel, Florian; Stiewe, Thorsten; Nist, Andrea; Suske, Guntram (2018). MGA, L3MBTL2 and E2F6 determine genomic binding of the non-canonical Polycomb repressive complex PRC1.6. PLOS Genetics 10.1371/journal.pgen.1007193

4 - Lieber, Sonja; Reinartz, Silke; Raifer, Hartmann; Finkernagel, Florian; Dreyer, Tobias; Bronger, Holger; Jansen, Julia M; Wagner, Uwe; Worzfeld, Thomas; Müller, Rolf; Huber, Magdalena (2018). Prognosis of ovarian cancer is associated with effector memory CD8 + T cell accumulation in ascites, CXCL9 levels and activation-triggered signal transduction in T cells. OncoImmunology 10.1080/2162402X.2018.1424672

5 - Worzfeld, Thomas; Finkernagel, Florian; Reinartz, Silke; Konzer, Anne; Adhikary, Till; Nist, Andrea; Stiewe, Thorsten; Wagner, Uwe; Looso, Mario; Graumann, Johannes; Müller, Rolf (2018). Proteotranscriptomics Reveal Signaling Networks in the Ovarian Cancer Microenvironment. Molecular & Cellular Proteomics 10.1074/mcp.RA117.000400

6 - Kovač, Kristina; Sauer, Anja; Mačinković, Igor; Awe, Stephan; Finkernagel, Florian; Hoffmeister, Helen; Fuchs, Andreas; Müller, Rolf; Rathke, Christina; Längst, Gernot; Brehm, Alexander (2018). Tumour-associated missense mutations in the dMi-2 ATPase alters nucleosome remodelling properties in a mutation-specific manner. Nature Communications 10.1038/s41467-018-04503-2

7 - Thieme, Karl G.; Gerke, Jennifer; Sasse, Christoph; Valerius, Oliver; Thieme, Sabine; Karimi, Razieh; Heinrich, Antje K.; Finkernagel, Florian; Smith, Kristina; Bode, Helge B.; Freitag, Michael; Ram, Arthur F. J.; Braus, Gerhard H. (2018). Velvet domain protein VosA represses the zinc cluster transcription factor SclB regulatory network for Aspergillus nidulans asexual development, oxidative stress response and secondary metabolism. PLOS Genetics 10.1371/journal.pgen.1007511

8 - Kreher, Judith; Kovač, Kristina; Bouazoune, Karim; Mačinković, Igor; Ernst, Anna Luise; Engelen, Erik; Pahl, Roman; Finkernagel, Florian; Murawska, Magdalena; Ullah, Ikram; Brehm, Alexander (2017). EcR recruits dMi-2 and increases efficiency of dMi-2-mediated remodelling to constrain transcription of hormone-regulated genes. Nature Communications 10.1038/ncomms14806

9 - Schütz, C; Inselmann, S; Sausslele, S; Dietz, C T; Müller, M C; Eigendorff, E; Brendel, C A; Metzelder, S K; Brümmendorf, T H; Waller, C; Dengler, J; Goebeler, M E; Herbst, R; Freunek, G; Hanzel, S; Illmer, T; Wang, Y; Lange, T; Finkernagel, F; Hehlmann, R; Huber, M; Neubauer, A; Hochhaus, A; Guilhot, J; Xavier Mahon, F; Pfirrmann, M; Burchert, A (2017). Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML. Leukemia 10.1038/leu.2017.9

10 - Adhikary, Till; Wortmann, Annika; Finkernagel, Florian; Lieber, Sonja; Nist, Andrea; Stiewe, Thorsten; Wagner, Uwe; Müller-Brüsselbach, Sabine; Reinartz, Silke; Müller, Rolf (2017). Interferon signaling in ascites-associated macrophages is linked to a favorable clinical outcome in a subgroup of ovarian carcinoma patients. BMC Genomics 10.1186/s12864-017-3630-9

11 - Gossmann, Jennifer; Stolte, Manfred; Lohoff, Michael; Yu, Philipp; Moll, Roland; Finkernagel, Florian; Garn, Holger; Brendel, Cornelia; Bittner, Alwina; Neubauer, Andreas; Huynh, Minh Q (2016). A Gain-Of-Function Mutation in the Plcg2 Gene Protects Mice from Helicobacter felis-Induced Gastric MALT Lymphoma. PloS one 10.1371/journal.pone.0150411

12 - Reinartz, Silke; Finkernagel, Florian; Adhikary, Till; Rohnalter, Verena; Schumann, Tim; Schober, Yvonne; Nockher, W Andreas; Nist, Andrea; Stiewe, Thorsten; Jansen, Julia M; Wagner, Uwe; Müller-Brüsselbach, Sabine; Müller, Rolf (2016). A transcriptome-based global map of signaling pathways in the ovarian cancer microenvironment associated with clinical outcome. Genome biology 10.1186/s13059-016-0956-6

13 - Finkernagel, Florian; Reinartz, Silke; Lieber, Sonja; Adhikary, Till; Wortmann, Annika; Hoffmann, Nathalie; Bieringer, Tim; Nist, Andrea; Stiewe, Thorsten; Jansen, Julia M.; Wagner, Uwe; Müller-Brüsselbach, Sabine; Müller, Rolf (2016). The transcriptional signature of human ovarian carcinoma macrophages is associated with extracellular matrix reorganization. Oncotarget 10.18632/oncotarget.12180

14 - Hampel, Martin; Jakobi, Mareike; Schmitz, Lara; Meyer, Ute; Finkernagel, Florian; Doehlemann, Gunther; Heimel, Kai (2016). Unfolded Protein Response (UPR) Regulator Cib1 Controls Expression of Genes Encoding Secreted Virulence Factors in Ustilago maydis. PLOS ONE 10.1371/journal.pone.0153861

15 - Rohnalter, Verena; Roth, Katrin; Finkernagel, Florian; Adhikary, Till; Obert, Julia; Dorzweiler, Kristina; Bensberg, Maike; Müller-Brüsselbach, Sabine; Müller, Rolf (2015). A multi-stage process including transient polyploidization and EMT precedes the emergence of chemoresistent ovarian carcinoma cells with a dedifferentiated and pro-inflammatory secretory phenotype. Oncotarget 10.18632/oncotarget.5552

16 - Kemmerer, Marina; Finkernagel, Florian; Cavalcante, Marcela Frota; Abdalla, Dulcineia Saes Parra; Müller, Rolf; Brüne, Bernhard; Namgaladze, Dmitry (2015). AMP-activated protein kinase interacts with the peroxisome proliferator-activated receptor delta to induce genes affecting fatty acid oxidation in human macrophages. PLoS ONE 10.1371/journal.pone.0130893

17 - Schumann, Tim; Adhikary, Till; Wortmann, Annika; Finkernagel, Florian; Lieber, Sonja; Schnitzer, Evelyn; Legrand, Nathalie; Schober, Yvonne; Nockher, W. Andreas; Toth, Philipp M.; Diederich, Wibke E.; Nist, Andrea; Stiewe, Thorsten; Wagner, Uwe; Reinartz, Silke; Müller-Brüsselbach, Sabine; Müller, Rolf (2015). Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment. Oncotarget 10.18632/oncotarget.3826

18 - Dhanyamraju, Pavan Kumar; Holz, Philipp Simon; Finkernagel, Florian; Fendrich, Volker; Lauth, Matthias (2015). Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway. Molecular cancer therapeutics 10.1158/1535-7163.MCT-14-0481

19 - Lieber, Sonja; Scheer, Frithjof; Finkernagel, Florian; Meissner, Wolfgang; Giehl, Gavin; Brendel, Cornelia; Diederich, Wibke E.; Müller-Brüsselbach, Sabine; Müller, Rolf; Muller-Brusselbach, Sabine; Muller, Rolf (2015). The inverse agonist DG172 triggers a PPAR\$\beta\$/\$\delta\$-independent myeloid lineage shift and promotes GM-CSF/IL-4-induced dendritic cell differentiation. Molecular pharmacology 10.1124/mol.114.094672

20 - Adhikary, Till; Wortmann, Annika; Schumann, Tim; Finkernagel, Florian; Lieber, Sonja; Roth, Katrin; Toth, Philipp M; Diederich, Wibke E; Nist, Andrea; Stiewe, Thorsten; Kleinesudeik, Lara; Reinartz, Silke; Müller-Brüsselbach, Sabine; Müller, Rolf (2015). The transcriptional PPARβ/δ network in human macrophages defines a unique agonist-induced activation state. Nucleic acids research 10.1093/nar/gkv331

21 - Völkel, Sara; Stielow, Bastian; Finkernagel, Florian; Stiewe, Thorsten; Nist, Andrea; Suske, Guntram; Voelkel, Sara; Stielow, Bastian; Finkernagel, Florian; Stiewe, Thorsten; Nist, Andrea; Suske, Guntram (2015). Zinc finger independent genome-wide binding of Sp2 potentiates recruitment of histone-fold protein Nf-y distinguishing it from Sp1 and Sp3. PLoS genetics 10.1371/journal.pgen.1005102

22 - Jansen, J M; Reinartz, S; Müller, R; Müller-Brüsselbach, S; Schumann, T; Finkernagel, Florian; Wortmann, A; Meissner, W; Krause, M; Wagner, U (2014). Der Zusammenhang zwischem dem Polarisationsphänotyp von Tumor-assoziierten Makrophagen (TAM), Zytokinspiegeln und dem progressionsfreien Überleben bei Ovarialkarzinompatientinnen. Geburtshilfe und Frauenheilkunde 10.1055/s-0034-1388410

23 - Kumari, Geeta; Ulrich, Tanja; Krause, Michael; Finkernagel, Florian; Gaubatz, Stefan (2014). Induction of p21CIP1 protein and cell cycle arrest after inhibition of Aurora B kinase is attributed to aneuploidy and reactive oxygen species. Journal of Biological Chemistry 10.1074/jbc.M114.555060

24 - Reinartz, Silke; Schumann, Tim; Finkernagel, Florian; Wortmann, Annika; Jansen, Julia M.; Meissner, Wolfgang; Krause, Michael; Schwörer, Anne-Marie Marie; Wagner, Uwe; Müller-Brüsselbach, Sabine; Müller, Rolf (2014). Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: Correlation of CD163 expression, cytokine levels and early relapse. International Journal of Cancer 10.1002/ijc.28335

25 - Preußner, Marco; Wilhelmi, Ilka; Schultz, Astrid-Solveig; Finkernagel, Florian; Michel, Monika; Möröy, Tarik; Heyd, Florian (2014). Rhythmic U2af26 alternative splicing controls PERIOD1 stability and the circadian clock in mice. Molecular cell 10.1016/j.molcel.2014.04.015

26 - Kellner, Nikola; Heimel, Kai; Obhof, Theresa; Finkernagel, Florian; Kämper, Jörg (2014). The SPF27 Homologue Num1 Connects Splicing and Kinesin 1-Dependent Cytoplasmic Trafficking in Ustilago maydis. PLoS Genetics 10.1371/journal.pgen.1004046

27 - Schlereth, Katharina; Heyl, Charlotte; Krampitz, Anna Maria; Mernberger, Marco; Finkernagel, Florian; Scharfe, Maren; Jarek, Michael; Leich, Ellen; Rosenwald, Andreas; Stiewe, Thorsten (2013). Characterization of the p53 Cistrome - DNA Binding Cooperativity Dissects p53's Tumor Suppressor Functions. PLoS Genetics 10.1371/journal.pgen.1003726

28 - Adhikary, T; Brandt, D T; Kaddatz, K; Stockert, J; Naruhn, S; Meissner, W; Finkernagel, Florian; Obert, J; Lieber, S; Scharfe, M; Jarek, M; Toth, P M; Scheer, F; Diederich, W E; Reinartz, S; Grosse, R; Müller-Brüsselbach, S; Müller, R (2013). Inverse PPARβ/δ agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion. Oncogene 10.1038/onc.2012.549

29 - Esterlechner, Jasmina; Reichert, Nina; Iltzsche, Fabian; Krause, Michael; Finkernagel, Florian; Gaubatz, Stefan (2013). LIN9, a Subunit of the DREAM Complex, Regulates Mitotic Gene Expression and Proliferation of Embryonic Stem Cells. PLoS ONE 10.1371/journal.pone.0062882

30 - Stockert, Josefine; Wolf, Alexander; Kaddatz, Kerstin; Schnitzer, Evelyn; Finkernagel, Florian; Meissner, Wolfgang; M??ller-Br??sselbach, Sabine; Kracht, Michael; M??ller, Rolf (2013). Regulation of TAK1/TAB1-Mediated IL-1?? Signaling by Cytoplasmic PPAR??/??. PLoS ONE 10.1371/journal.pone.0063011

31 - Stielow, Christina; Stielow, Bastian; Finkernagel, Florian; Scharfe, Maren; Jarek, Michael; Suske, Guntram (2013). SUMOylation of the polycomb group protein L3MBTL2 facilitates repression of its target genes. Nucleic acids research 10.1093/nar/gkt1317

32 - Terrados, Gloria; Finkernagel, Florian; Stielow, Bastian; Sadic, Dennis; Neubert, Juliane; Herdt, Olga; Krause, Michael; Scharfe, Maren; Jarek, Michael; Suske, Guntram (2012). Genome-wide localization and expression profiling establish Sp2 as a sequence-specific transcription factor regulating vitally important genes. Nucleic Acids Research 10.1093/nar/gks544

33 - Meier, Karin; Mathieu, Eve Lyne; Finkernagel, Florian; Reuter, L Maximilian; Scharfe, Maren; Doehlemann, Gunther; Jarek, Michael; Brehm, Alexander (2012). LINT, a novel dL(3)mbt-containing complex, represses malignant brain tumour signature genes. PLoS Genetics 10.1371/journal.pgen.1002676

34 - Mathieu, Eve Lyne; Finkernagel, Florian; Murawska, Magdalena; Scharfe, Maren; Jarek, Michael; Brehm, Alexander (2012). Recruitment of the ATP-dependent chromatin remodeler dMi-2 to the transcribed region of active heat shock genes. Nucleic Acids Research 10.1093/nar/gks178

35 - Adhikary, Till; Kaddatz, Kerstin; Finkernagel, Florian; Schönbauer, Anne; Meissner, Wolfgang; Scharfe, Maren; Jarek, Michael; Blöcker, Helmut; Müller-Brüsselbach, Sabine; Müller, Rolf (2011). Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor-β/δ (PPARβ/δ). PLoS ONE 10.1371/journal.pone.0016344

36 - Stockert, Josefine; Adhikary, Till; Kaddatz, Kerstin; Finkernagel, Florian; Meissner, Wolfgang; Müller-Brüsselbach, Sabine; Müller, Rolf (2011). Reverse crosstalk of TGFβ and PPARβ/δ signaling identified by transcriptional profiling. Nucleic Acids Research 10.1093/nar/gkq773

37 - Stielow, Bastian; Krüger, Imme; Diezko, Rolf; Finkernagel, Florian; Gillemans, Nynke; Kong-a-San, John; Philipsen, Sjaak; Suske, Guntram (2010). Epigenetic silencing of spermatocyte-specific and neuronal genes by SUMO modification of the transcription factor Sp3. PLoS genetics 10.1371/journal.pgen.1001203

38 - Herkert, Barbara; Dwertmann, Anne; Herold, Steffi; Abed, Mona; Naud, Jean-Francois; Finkernagel, Florian; Harms, Gregory S.; Orian, Amir; Wanzel, Michael; Eilers, Martin (2010). The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis. The Journal of Cell Biology 10.1083/jcb.200908103

39 - Heimel, Kai; Scherer, Mario; Vranes, Miroslav; Wahl, Ramon; Pothiratana, Chetsada; Schuler, David; Vincon, Volker; Finkernagel, Florian; Flor-Parra, Ignacio; Kämper, Jörg (2010). The transcription factor rbf1 is the master regulator for b-mating type controlled pathogenic development in Ustilago maydis. PLoS Pathogens 10.1371/journal.ppat.1001035

40 - Kaddatz, Kerstin; Adhikary, Till; Finkernagel, Florian; Meissner, Wolfgang; Müller-Brüsselbach, Sabine; Müller, Rolf (2010). Transcriptional profiling identifies functional interactions of TGFβ and PPARβ/δ signaling: synergistic induction of ANGPTL4 transcription. The Journal of biological chemistry 10.1074/jbc.M110.142018