Aberrant Cathepsin S activity in follicular lymphoma
Prof. Dr. med. Oliver Weigert
University Hospital of the Ludwig-Maximilians-Universität München
Medical Department III(link is external)
Laboratory for Experimental Leukemia and Lymphoma Research (ELLF)(link is external)
Project Summary
We identified novel and recurrent hotspot mutations in Cathepsin S (CTSS) as a previously unrecognized link between aberrant intracellular immune signaling and the immune microenvironment in follicular lymphoma (FL). CTSS is a cysteine protease that is highly expressed in immune cells and plays critical roles in antigen presentation and Toll-like receptor (TLR) signaling. Our previous data show that these mutations are gain-of-function and activate tumor-promoting pathways, including deregulation of TLR and MHC-II signaling. Our project will utilize in vitro and in vivo models to define the underlying molecular mechanisms, as well as the functional and clinical implications of aberrant CTSS activity in FL.
The Else Kröner Excellence Fellowships grant clinicians at senior consultant level a two-year leave of absence for an intensive research phase.
Khatamzas, E., Antwerpen, M. H., Rehn, A., Graf, A., Hellmuth, J. C., Hollaus, A., Mohr, A. W., Gaitzsch, E., Weiglein, T., Georgi, E., Scherer, C., Stecher, S. S., Gruetzner, S., Blum, H., Krebs, S., Reischer, A., Leutbecher, A., Subklewe, M., Dick, A., Zange, S., Girl, P., Müller, K., Weigert, O., Hopfner, K. P., Stemmler, H. J., von Bergwelt-Baildon, M., Keppler, O. T., Wölfel, R., Muenchhoff, M., Moosmann, A. (2022). Nat Commun 13, 5586.
DOI:10.1038/s41467-022-32772-5
Haebe, S., Keay, W., Alig, S., Mohr, A.W., Martin, L.K., Heide, M., Secci, R., Krebs, S., Blum, H., Moosmann, A., Louissaint, A., Jr., Weinstock, D.M., Thoene, S., von Bergwelt-Baildon, M., Ruland, J., Bararia, D., Weigert, O. (2021). Br J Haematol.
Gaitzsch, E., Passerini, V., Khatamzas, E., Strobl, C.D., Muenchhoff, M., Scherer, C., Osterman, A., Heide, M., Reischer, A., Subklewe, M., Leutbecher, A., Tast, B., Ruhle, A., Weiglein, T., Stecher, S.S., Stemmler, H.J., Dreyling, M., Girl, P., Georgi, E., Wolfel, R., Mateyka, L., D'Ippolito, E., Schober, K., Busch, D.H., Kager, J., Spinner, C.D., Treiber, M., Rasch, S., Lahmer, T., Iakoubov, R., Schneider, J., Protzer, U., Winter, C., Ruland, J., Quante, M., Keppler, O.T., von Bergwelt-Baildon, M., Hellmuth, J., Weigert, O. (2021). Hemasphere 5, e603.
DOI:10.1097/HS9.0000000000000603(link is external)
Bararia, D., Hildebrand, J. A., Stolz, S., Haebe, S., Alig, S., Trevisani, C. P., Osorio-Barrios, F., Bartoschek, M. D., Mentz, M., Pastore, A., Gaitzsch, E., Heide, M., Jurinovic, V., Rautter, K., Gunawardana, J., Sabdia, M. B., Szczepanowski, M., Richter, J., Klapper, W., Louissaint, A., Jr., Ludwig, C., Bultmann, S., Leonhardt, H., Eustermann, S., Hopfner, K. P., Hiddemann, W., von Bergwelt-Baildon, M., Steidl, C., Kridel, R., Tobin, J. W. D., Gandhi, M. K., Weinstock, D. M., Schmidt-Supprian, M., Sarosi, M. B., Rudelius, M., Passerini, V., Mautner, J., Weigert, O. (2020). Cell Rep 31, 107522.
DOI:10.1016/j.celrep.2020.107522(link is external)