Aberrant CXCR4 signaling in lymphoma

  

Project Summary


The CXCR4-CXCL12 pathway regulates migration and proliferation of hematopoietic stem and progenitor cells in the bone marrow niche and is essential for normal B-cell lymphopoiesis. We have established a first-in-man targeting of CXCR4 by a CXCR4-specific peptide. This proposal aims at identifying the role and mechanisms of aberrant CXCR4 activity in lymphomagenesis including novel mouse models, forward genomic screening, analysis of disturbed BCR signaling and resistance mechanisms towards BCR pathway targeting drugs. Aberrant CXCR4 expression and function is also recurrently observed in solid tumors, where it is associated with cancer cell dissemination and poor prognosis. The project will thus extend the studies to solid cancer models within this CRC.

Lewis, R., Habringer, S., Kircher, M., Hefter, M., Peuker, C. A., Werner, R., Ademaj-Kospiri, V., Gable, A., Weber, W., Wester, H. J., Buck, A., Herhaus, P., Lapa, C. & Keller, U. (2021). EJNMMI Res, 11, 77.

DOI:10.1186/s13550-021-00822-6


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)


Heider, M., Eichner, R., Stroh, J., Morath, V., Kuisl, A., Zecha, J., Lawatscheck, J., Baek, K., Garz, A. K., Rudelius, M., Deuschle, F. C., Keller, U., Lemeer, S., Verbeek, M., Gotze, K. S., Skerra, A., Weber, W. A., Buchner, J., Schulman, B. A., Kuster, B., Fernandez-Saiz, V., Bassermann, F. (2021). Mol Cell 81, 1170-1186.e10.

DOI:10.1016/j.molcel.2020.12.046(link is external)


Schneeweis, C., Hassan, Z., Schick, M., Keller, U., Schneider, G. (2021). Br J Cancer 124, 531-538.

DOI:10.1038/s41416-020-01119-6(link is external)


Wirth, M., Schick, M., Keller, U., Kronke, J. (2020). Cancers (Basel) 12, 3764.

DOI:10.3390/cancers12123764


Herhaus, P., Lipkova, J., Lammer, F., Yakushev, I., Vag, T., Slotta-Huspenina, J., Habringer, S., Lapa, C., Pukrop, T., Hellwig, D., Wiestler, B., Buck, A. K., Deckert, M., Wester, H. J., Bassermann, F., Schwaiger, M., Weber, W., Menze, B., Keller, U. (2020). Journal of Nuclear Medicine 61, 1765-1771.

DOI:10.2967/jnumed.120.241703(link is external)


Hong, Y., Singh, N., Bamopoulos, S., Gjerga, E., Schmalbrock, L. K., Balabanian, K., Schick, M., Keller, U., Wirth, M. (2020). Biomedicines 8, 590.

DOI:10.3390/biomedicines8120590(link is external


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


O'Connor, T., Zhou, X., Kosla, J., Adili, A., Garcia Beccaria, M., Kotsiliti, E., Pfister, D., Johlke, A. L., Sinha, A., Sankowski, R., Schick, M., Lewis, R., Dokalis, N., Seubert, B., Hochst, B., Inverso, D., Heide, D., Zhang, W., Weihrich, P., Manske, K., Wohlleber, D., Anton, M., Hoellein, A., Seleznik, G., Bremer, J., Bleul, S., Augustin, H. G., Scherer, F., Koedel, U., Weber, A., Protzer, U., Forster, R., Wirth, T., Aguzzi, A., Meissner, F., Prinz, M., Baumann, B., Hopken, U. E., Knolle, P. A., von Baumgarten, L., Keller, U., Heikenwalder, M. (2019). Cancer Cell 36, 250-267 e9.

DOI:10.1016/j.ccell.2019.08.001(link is external)


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)


Piraud, M., Wennmann, M., Kintzele, L., Hillengass, J., Keller, U., Langs, G., Weber, M.A., Menze, B.H. (2019). Med Image Anal 57, 214-225.

DOI: 10.1016/j.media.2019.07.001(link is external)


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)


Maurer, S., Herhaus, P., Lippenmeyer, R., Hänscheid, H., Kircher, M., Schirbel, A., Maurer, H.C., Buck, A.K., Wester, H.J., Einsele, H., Grigoleit, G.U., Keller, U., Lapa C. (2019). J Nucl Med 60, 1339-1405.

DOI: (link is external)


Nimmagadda, S.C., Frey, S., Müller, P., Wolleschak, D., Weinert, S., Keller, U., Edelmann, B., Fischer, T. (2019). Haematologica 104, e288-e292.

DOI: (link is external)