Comparative animal pathology core and tissue cohort outreach

PD Dr. med. vet. Katja Steiger

Technical University of Munich
Institute of Pathology(link is external)
Core Facility Comparative Experimental Pathology(link is external)

E-Mail(link sends e-mail)

Prof. Dr. med. Wilko Weichert

Technical University of Munich
Institute of Pathology(link is external)

E-Mail(link sends e-mail)

  

Project Summary


Z01 provides an already established and fully equipped morphomolecular comparative experimental pathology platform aiming at cutting-edge animal phenotyping supplemented by a comparative human tissue cohort outreach for the assessment of the complex roles of aberrant intrinsic and extrinsic immune cell signaling in cancer. Thus, this central project will support all subprojects in the implementation of translational tissue-based morphomolecular analyses of (pre-)neoplastic cells and immune cells into their research programs, which will greatly facilitate the valid interpretation of genotype-phenotype correlations.

Publications

Bacteria and bacteriophage consortia are associated with protective intestinal metabolites in patients receiving stem cell transplantation.

Thiele Orberg, E., Meedt, E., Hiergeist, A., Xue, J., Heinrich, P., Ru, J., Ghimire, S., Miltiadous, O., Lindner, S., Tiefgraber, M., Goldel, S., Eismann, T., Schwarz, A., Gottert, S., Jarosch, S., Steiger, K., Schulz, C., Gigl, M., Fischer, J.C., Janssen, K.P., Quante, M., Heidegger, S., Herhaus, P., Verbeek, M., Ruland, J., van den Brink, M.R.M., Weber, D., Edinger, M., Wolff, D., Busch, D.H., Kleigrewe, K., Herr, W., Bassermann, F., Gessner, A., Deng, L., Holler, E., Poeck, H. (2024). Nat Cancer.

DOI:10.1038/s43018-023-00669-x

High RIPK3 expression is associated with a higher risk of early kidney transplant failure

Wahida, A., Schmaderer, C., Buttner-Herold, M., Branca, C., Donakonda, S., Haberfellner, F., Torrez, C., Schmitz, J., Schulze, T., Seibt, T., Ollinger, R., Engleitner, T., Haller, B., Steiger, K., Gunthner, R., Lorenz, G., Yabal, M., Bachmann, Q., Braunisch, M.C., Moog, P., Matevossian, E., Assfalg, V., Thorban, S., Renders, L., Spath, M.R., Muller, R.U., Stippel, D.L., Weichert, W., Slotta-Huspenina, J., von Vietinghoff, S., Viklicky, O., Green, D.R., Rad, R., Amann, K., Linkermann, A., Brasen, J.H., Heemann, U., Kemmner, S. (2023). iScience 26, 107879.

DOI:10.1016/j.isci.2023.107879

High RIPK3 expression is associated with a higher risk of early kidney transplant failure.

Wahida, A., Schmaderer, C., Buttner-Herold, M., Branca, C., Donakonda, S., Haberfellner, F., Torrez, C., Schmitz, J., Schulze, T., Seibt, T., Ollinger, R., Engleitner, T., Haller, B., Steiger, K., Gunthner, R., Lorenz, G., Yabal, M., Bachmann, Q., Braunisch, M.C., Moog, P., Matevossian, E., Assfalg, V., Thorban, S., Renders, L., Spath, M.R., Muller, R.U., Stippel, D.L., Weichert, W., Slotta-Huspenina, J., von Vietinghoff, S., Viklicky, O., Green, D.R., Rad, R., Amann, K., Linkermann, A., Brasen, J.H., Heemann, U., Kemmner, S. (2023). iScience 26, 107879.

DOI:10.1016/j.isci.2023.107879

Intestinal B cells license metabolic T-cell activation in NASH microbiota/antigen-independently and contribute to fibrosis by IgA-FcR signalling

Kotsiliti, E., Leone, V., Schuehle, S., Govaere, O., Li, H., Wolf, M. J., Horvatic, H., Bierwirth, S., Hundertmark, J., Inverso, D., Zizmare, L., Sarusi-Portuguez, A., Gupta, R., O'Connor, T., Giannou, A. D., Shiri, A. M., Schlesinger, Y., Beccaria, M. G., Rennert, C., Pfister, D., Öllinger, R., Gadjalova, I., Ramadori, P., Rahbari, M., Rahbari, N., Healy, M. E., Fernández-Vaquero, M., Yahoo, N., Janzen, J., Singh, I., Fan, C., Liu, X., Rau, M., Feuchtenberger, M., Schwaneck, E., Wallace, S. J., Cockell, S., Wilson-Kanamori, J., Ramachandran, P., Kho, C., Kendall, T. J., Leblond, A. L., Keppler, S. J., Bielecki, P., Steiger, K., Hofmann, M., Rippe, K., Zitzelsberger, H., Weber, A., Malek, N., Luedde, T., Vucur, M., Augustin, H. G., Flavell, R., Parnas, O., Rad, R., Pabst, O., Henderson, N. C., Huber, S., Macpherson, A., Knolle, P., Claassen, M., Geier, A., Trautwein, C., Unger, K., Elinav, E., Waisman, A., Abdullah, Z., Haller, D., Tacke, F., Anstee, Q. M. & Heikenwalder, M. (2023). J Hepatol, 79, 296-313.

DOI:10.1016/j.jhep.2023.04.037

The fusion oncogene VAV1-MYO1F triggers aberrant T-cell receptor signaling in vivo and drives peripheral T-cell lymphoma in mice.

Morrish, E., Wartewig, T., Kratzert, A., Rosenbaum, M., Steiger, K. & Ruland, J. (2022). Eur J Immunol, e2250147.

DOI:10.1002/eji.202250147

Vascular Remodeling Is a Crucial Event in the Early Phase of Hepatocarcinogenesis in Rodent Models for Liver Tumorigenesis

Tulessin, M., Sarker, R.S.J., Griger, J., Leibing, T., Geraud, C., Weichert, W., Steiger, K., Mogler, C. (2022). Cells 11.

DOI:10.3390/cells11142129

pT3 colorectal cancer revisited: a multicentric study on the histological depth of invasion in more than 1000 pT3 carcinomas-proposal for a new pT3a/pT3b subclassification

Foersch, S., Lang-Schwarz, C., Eckstein, M., Geppert, C., Schmitt, M., Konukiewitz, B., Groll, T., Schicktanz, F., Engel, J., Gleitsmann, M., Westhoff, C.C., Frickel, N., Litmeyer, A.S., Grass, A., Jank, P., Lange, S., Tschurtschenthaler, M., Wilhelm, D., Roth, W., Vieth, M., Denkert, C., Nagtegaal, I., Weichert, W., Jesinghaus, M. (2022). Br J Cancer.

DOI:10.1038/s41416-022-01889-1

Aquaporin-4 prevents exaggerated astrocytosis and structural damage in retinal inflammation

Maisam Afzali, A., Stuve, L., Pfaller, M., Aly, L., Steiger, K., Knier, B., Korn, T. (2022). J Mol Med (Berl).

DOI:10.1007/s00109-022-02202-6

Comparative Study of the Role of Interepithelial Mucosal Mast Cells in the Context of Intestinal Adenoma-Carcinoma Progression

Groll, T., Silva, M., Sarker, R.S.J., Tschurtschenthaler, M., Schnalzger, T., Mogler, C., Denk, D., Scholch, S., Schraml, B.U., Ruland, J., Rad, R., Saur, D., Weichert, W., Jesinghaus, M., Matiasek, K., Steiger, K. (2022). Cancers (Basel) 14.

DOI:10.3390/cancers14092248

CXCL9 inhibits tumour growth and drives anti-PD-L1 therapy in ovarian cancer

Seitz, S., Dreyer, T.F., Stange, C., Steiger, K., Brauer, R., Scheutz, L., Multhoff, G., Weichert, W., Kiechle, M., Magdolen, V., Bronger, H. (2022). Br J Cancer.

DOI:10.1038/s41416-022-01763-0

Circulating Tumor DNA Profiling of a Diffuse Large B Cell Lymphoma Patient with Secondary Acute Myeloid Leukemia

Kerle, I.A., Jägerhuber, L., Secci, R., Pfarr, N., Blüm, P., Roesch, R., Götze, K.S., Weichert, W., Bassermann, F., Ruland, J., Winter, C. (2022). Cancers 14.

DOI:10.3390/cancers14061371

Molecular Genetic Investigation of Digital Melanoma in Dogs

Conrad, D., Kehl, A., Beitzinger, C., Metzler, T., Steiger, K., Pfarr, N., Fischer, K., Klopfleisch, R., Aupperle-Lellbach, H. (2022). Vet Sci 9.

DOI:10.3390/vetsci9020056

The BCL-2 family member BOK promotes KRAS-driven lung cancer progression in a p53-dependent manner

Meinhardt, A.L., Munkhbaatar, E., Hockendorf, U., Dietzen, M., Dechant, M., Anton, M., Jacob, A., Steiger, K., Weichert, W., Brcic, L., McGranahan, N., Branca, C., Kaufmann, T., Dengler, M.A., Jost, P.J. (2022). Oncogene

DOI:10.1038/s41388-021-02161-1

Elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in gastric cancer: a distinct microsatellite instability type with potential clinical impact?

Herz, A.L., Wisser, S., Kohlruss, M., Slotta-Huspenina, J., Jesinghaus, M., Grosser, B., Steiger, K., Novotny, A., Hapfelmeier, A., Schmidt, T., Gaida, M.M., Weichert, W., Keller, G. (2022). J Pathol Clin Res.

DOI:10.1002/cjp2.257

Genetic alterations of the SUMO isopeptidase SENP6 drive lymphomagenesis and genetic instability in diffuse large B-cell lymphoma

Schick, M., Zhang, L., Maurer, S., Maurer, H.C., Isaakaidis, K., Schneider, L., Patra, U., Schunck, K., Rohleder, E., Hofstetter, J., Baluapuri, A., Scherger, A.K., Slotta-Huspenina, J., Hettler, F., Weber, J., Engleitner, T., Maresch, R., Slawska, J., Lewis, R., Istvanffy, R., Habringer, S., Steiger, K., Baiker, A., Oostendorp, R.A.J., Miething, C., Lenhof, H.P., Bassermann, F., Chapuy, B., Wirth, M., Wolf, E., Rad, R., Muller, S., Keller, U. (2022). Nat Commun 13, 281.

DOI:10.1038/s41467-021-27704-8

Keratinocyte-intrinsic BCL10/MALT1 activity initiates and amplifies psoriasiform skin inflammation

Kurgyis, Z., Vornholz, L., Pechloff, K., Kemeny, L.V., Wartewig, T., Muschaweckh, A., Joshi, A., Kranen, K., Hartjes, L., Mockel, S., Steiger, K., Hameister, E., Volz, T., Mellett, M., French, L.E., Biedermann, T., Korn, T., Ruland, J. (2021). Sci Immunol 6, eabi4425.

DOI:10.1126/sciimmunol.abi4425

Neuroendocrine Differentiation in Conventional Colorectal Adenocarcinomas: Incidental Finding or Prognostic Biomarker?

Konukiewitz, B., Kasajima, A., Schmitt, M., Schwamborn, K., Groll, T., Schicktanz, F., Delbridge, C., Schutze, L.M., Wilhelm, D., Lang, C., Lange, S., Foersch, S., Jank, P., Steiger, K., Werder, A.V., Denkert, C., Weichert, W., Kloppel, G., Jesinghaus, M. (2021). Cancers (Basel) 13.

DOI:10.3390/cancers13205111

Loss of satb2 occurs more frequently than cdx2 loss in colorectal carcinoma and identifies particularly aggressive cancers in high‐risk subgroups

Schmitt, M., Silva, M., Konukiewitz, B., Lang, C., Steiger, K., Halfter, K., Engel, J., Jank, P., Pfarr, N., Wilhelm, D., Foersch, S., Denkert, C., Tschurtschenthaler, M., Weichert, W., Jesinghaus, M. (2021). Cancers 13.

DOI:10.3390/cancers13246177

XIAP restrains TNF-driven intestinal inflammation and dysbiosis by promoting innate immune responses of Paneth and dendritic cells

Wahida, A., Muller, M., Hiergeist, A., Popper, B., Steiger, K., Branca, C., Tschurtschenthaler, M., Engleitner, T., Donakonda, S., De Coninck, J., Ollinger, R., Pfautsch, M.K., Muller, N., Silva, M., Usluer, S., Thiele Orberg, E., Bottcher, J.P., Pfarr, N., Anton, M., Slotta-Huspenina, J.B., Nerlich, A.G., Madl, T., Basic, M., Bleich, A., Berx, G., Ruland, J., Knolle, P.A., Rad, R., Adolph, T.E., Vandenabeele, P., Kanegane, H., Gessner, A., Jost, P.J., Yabal, M. (2021). Sci Immunol 6, eabf7235.

DOI:10.1126/sciimmunol.abf7235

Loss of CDX2 in colorectal cancer is associated with histopathologic subtypes and microsatellite instability but is prognostically inferior to hematoxylin-eosin-based morphologic parameters from the WHO classification

Konukiewitz, B., Schmitt, M., Silva, M., Pohl, J., Lang, C., Steiger, K., Halfter, K., Engel, J., Schlitter, A.M., Boxberg, M., Pfarr, N., Wilhelm, D., Foersch, S., Tschurtschenthaler, M., Weichert, W., Jesinghaus, M. (2021). Br J Cancer.

DOI:10.1038/s41416-021-01553-0

CD64-expressing phagocyte subset mediates protection against toxic kidney injury and failure

Salei, N., Ji, X., Pakalniskyte, D., Kuentzel, V., Rambichler, S., Li, N., Moser, M., Steiger, K., Buch, T., Anders, H.J., Schraml, B.U. (2021). Proc Natl Acad Sci U S A 118.

DOI:10.1073/pnas.2022311118

CXCR4 hyperactivation cooperates with TCL1 in CLL development and aggressiveness

Lewis, R., Maurer, H. C., Singh, N., Gonzalez-Menendez, I., Wirth, M., Schick, M., Zhang, L., Isaakidis, K., Scherger, A. K., Schulze, V., Lu, J., Zenz, T., Steiger, K., Rad, R., Quintanilla-Martinez, L., Espeli, M., Balabanian, K., Keller, U., Habringer, S. (2021). Leukemia.

DOI:10.1038/s41375-021-01376-1(link is external)

Morphology Matters: A Critical Reappraisal of the Clinical Relevance of Morphologic Criteria From the 2019 WHO Classification in a Large Colorectal Cancer Cohort Comprising 1004 Cases

Jesinghaus, M., Schmitt, M., Lang, C., Reiser, M., Scheiter, A., Konukiewitz, B., Steiger, K., Silva, M., Tschurtschenthaler, M., Lange, S., Foersch, S., Becker, K. F., Saur, D., Friess, H., Halfter, K., Engel, J., Boxberg, M., Pfarr, N., Wilhelm, D., Weichert, W. (2021). Am J Surg Pathol 45, 969-978.

DOI:10.1097/PAS.0000000000001692(link is external)

The Chemokine CX3CL1 Improves Trastuzumab Efficacy in HER2 Low-Expressing Cancer In Vitro and In Vivo

Dreyer, T. F., Kuhn, S., Stange, C., Heithorst, N., Schilling, D., Jelsma, J., Sievert, W., Seitz, S., Stangl, S., Hapfelmeier, A., Noske, A., Wege, A. K., Weichert, W., Ruland, J., Schmitt, M., Dorn, J., Kiechle, M., Reuning, U., Magdolen, V., Multhoff, G., Bronger, H. (2021). Cancer Immunol Res 9, 779-789.

DOI:10.1158/2326-6066.CIR-20-0327(link is external)

Targeted PI3K/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia

Ecker, V., Stumpf, M., Brandmeier, L., Neumayer, T., Pfeuffer, L., Engleitner, T., Ringshausen, I., Nelson, N., Jucker, M., Wanninger, S., Zenz, T., Wendtner, C., Manske, K., Steiger, K., Rad, R., Muschen, M., Ruland, J., Buchner, M. (2021). Nat Commun 12, 3526.

DOI:10.1038/s41467-021-23752-2(link is external)

Pathological RANK signaling in B cells drives autoimmunity and chronic lymphocytic leukemia

Alankus, B., Ecker, V., Vahl, N., Braun, M., Weichert, W., Macher-Goppinger, S., Gehring, T., Neumayer, T., Zenz, T., Buchner, M., Ruland, J. (2021). J Exp Med 218.

DOI:10.1084/jem.20200517(link is external)

MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically

Munkhbaatar, E., Dietzen, M., Agrawal, D., Anton, M., Jesinghaus, M., Boxberg, M., Pfarr, N., Bidola, P., Uhrig, S., Hockendorf, U., Meinhardt, A. L., Wahida, A., Heid, I., Braren, R., Mishra, R., Warth, A., Muley, T., Poh, P. S. P., Wang, X., Frohling, S., Steiger, K., Slotta-Huspenina, J., van Griensven, M., Pfeiffer, F., Lange, S., Rad, R., Spella, M., Stathopoulos, G. T., Ruland, J., Bassermann, F., Weichert, W., Strasser, A., Branca, C., Heikenwalder, M., Swanton, C., McGranahan, N., Jost, P. J. (2020). Nat Commun 11, 4527.

DOI:10.1038/s41467-020-18372-1

Genetically Engineered Mouse Models of Liver Tumorigenesis Reveal a Wide Histological Spectrum of Neoplastic and Non-Neoplastic Liver Lesions

Steiger, K., Gross, N., Widholz, S. A., Rad, R., Weichert, W., Mogler, C. (2020). Cancers (Basel) 12.

DOI:10.3390/cancers12082265(link is external)

SUMO pathway inhibition targets an aggressive pancreatic cancer subtype

Biederstadt, A., Hassan, Z., Schneeweis, C., Schick, M., Schneider, L., Muckenhuber, A., Hong, Y., Siegers, G., Nilsson, L., Wirth, M., Dantes, Z., Steiger, K., Schunck, K., Langston, S., Lenhof, H. P., Coluccio, A., Orben, F., Slawska, J., Scherger, A., Saur, D., Muller, S., Rad, R., Weichert, W., Nilsson, J., Reichert, M., Schneider, G., Keller, U. (2020). Gut 69, 1472-1482.

DOI:10.1136/gutjnl-2018-317856

RIG-I activation is critical for responsiveness to checkpoint blockade

Heidegger, S., Wintges, A., Stritzke, F., Bek, S., Steiger, K., Koenig, P. A., Gottert, S., Engleitner, T., Ollinger, R., Nedelko, T., Fischer, J. C., Makarov, V., Winter, C., Rad, R., van den Brink, M. R. M., Ruland, J., Bassermann, F., Chan, T. A., Haas, T., Poeck, H. (2019). Sci Immunol 4.

DOI:10.1126/sciimmunol.aau8943(link is external)

Radiation-Induced Amplification of TGFB1-Induced Mesenchymal Stem Cell-Mediated Sodium Iodide Symporter (NIS) Gene I-131 Therapy

Schug, C., Kitzberger, C., Sievert, W., Spellerberg, R., Tutter, M., Schmohl, K. A., Eberlein, B., Biedermann, T., Steiger, K., Zach, C., Schwaiger, M., Multhoff, G., Wagner, E., Nelson, P. J., Spitzweg, C. (2019). Clin Cancer Res 25, 5997-6008.

DOI:10.1158/1078-0432.Ccr-18-4092(link is external)

Activated gp130 signaling selectively targets B cell differentiation to induce mature lymphoma and plasmacytoma

Scherger, A.K., Al-Maarri, M., Maurer, H.C., Schick, M., Maurer, S., Ollinger, R., Gonzalez-Menendez, I., Martella, M., Thaler, M., Pechloff, K., Steiger, K., Sander, S., Ruland, J., Rad, R., Quintanilla-Martinez, L., Wunderlich, F.T., Rose-John, S., Keller, U. (2019). JCI Insight 4.

DOI: 10.1172/jci.insight.128435(link is external)

TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection

Alfei, F., Kanev, K., Hofmann, M., Wu, M., Ghoneim, H.E., Roelli, P., Utzschneider, D.T., von Hoesslin, M., Cullen, J.G., Fan, Y., Eisenberg, V., Wohlleber, D., Steiger, K., Merkler, D., Delorenzi, M., Knolle, P.A., Cohen, C.J., Thimme, R., Youngblood, B., Zehn, D. (2019). Nature 571, 265-269.

DOI: 10.1038/s41586-019-1326-9(link is external)

Bcl10-controlled Malt1 paracaspase activity is key for the immune suppressive function of regulatory T cells

Rosenbaum, M., Gewies, A., Pechloff, K., Heuser, C., Engleitner, T., Gehring, T., Hartjes, L., Krebs, S., Krappmann, D., Kriegsmann, M., Weichert, W., Rad, R., Kurts, C., Ruland, J. (2019). Nat Commun 10, 2352.

DOI: 10.1038/s41467-019-10203-2(link is external)

Gene editing enables T-cell engineering to redirect antigen specificity for potent tumor rejection

Albers, J.J., Ammon, T., Gosmann, D., Audehm, S., Thoene, S., Winter, C., Secci, R., Wolf, A., Stelzl, A., Steiger, K., Ruland, J., Bassermann, F., Kupatt, C., Anton, M., Krackhardt, A.M. (2019). Life Sci Alliance 2.

DOI: 10.26508/lsa.201900367(link is external)

PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice

Weber, J., de la Rosa, J., Grove, C.S., Schick, M., Rad, L., Baranov, O., Strong, A., Pfaus, A., Friedrich, M.J., Engleitner, T., Lersch, R., Ollinger, R., Grau, M., Menendez, I.G., Martella, M., Kohlhofer, U., Banerjee, R., Turchaninova, M.A., Scherger, A., Hoffman, G.J., Hess, J., Kuhn, L.B., Ammon, T., Kim, J., Schneider, G., Unger, K., Zimber-Strobl, U., Heikenwalder, M., Schmidt-Supprian, M., Yang, F., Saur, D., Liu, P., Steiger, K., Chudakov, D.M., Lenz, G., Quintanilla-Martinez, L., Keller, U., Vassiliou, G.S., Cadinanos, J., Bradley, A., Rad, R. (2019). Nat Commun 10, 1415.

DOI: 10.1038/s41467-019-09180-3(link is external)