Group Bock

Group Bock

research group

Dissecting cell type-specific chromatin dynamics driven by oncogenic JAK-STAT signaling

Network Contribution

JAK-STAT signaling is vital for the development, survival and response of immune cells. Intriguingly, members of the JAK-STAT pathway are frequently mutated in cancer and are known to drive several haematopoietic malignancies. Based on our observation that key regulatory regions of myeloid development are specifically hypermethylated in the lymphoid lineage, we hypothesize that oncogenic transformation by aberrant STAT activity is dependent on a permissive epigenome. To identify cell type-specific differences in the response to JAK-STAT signaling, we will isolate specific lymphoid and myeloid cell populations from wild-type and STAT-deficient mice and analyse their epigenome and transcriptome response upon treatment with STAT-activating cytokines. The cross-talk between JAK-STAT signaling and the epigenome will be investigated using in vivo transplants of retrovirally transformed bone marrow harbouring known STAT3 and STAT5 mutations, which will provide a basis for dissecting the epigenome dynamics of oncogenic transformation. The ensuing insights into STAT-induced oncogenic reprogramming of the epigenome could potentially contribute to the development of precision therapies for STAT-driven leukaemia.

Team

photo of Christoph Bock

Christoph Bock

Team Leader

Christoph Bock

Christoph Bock studied computer science and business information systems at the University of Mannheim, DE. After completing his PhD thesis in bioinformatics at the Max Planck Institute for Informatics in Saarbrücken, DE, he joined the Broad Institute and the Harvard Department for Stem Cell and Regenerative Biology as a postdoctoral fellow working on human epigenome mapping. He joined CeMM as a principal investigator in 2012 and coordinates the NGS activities of CeMM and MUV. His research focuses on the role of the epigenome in cancer.

Thomas Krausgruber

Team Member

Mustapha Jaiteh

Team Member

Publications

SFB-F61 / F28 related publications - Group Bock
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Kollmann, K., Heller, G., Schneckenleitner, C., Warsch, W., Scheicher, R., Ott, R.G., Schäfer, M., Fajmann, S., Schlederer, M., Schiefer, A.-I., Reichart, U., Mayerhofer, M., Hoeller, C., Zöchbauer-Mueller, S., Kerjaschki, D., Bock, C., LKenner, L., Hoefler, G., Freissmuth, M., Green, A.R., Moriggl, R., Busslinger, M., Malumbres, M., and Sexl, V. (2013).
A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.
Cancer Cell 24: 167-181. doi: dx.doi.org/10.1016/j.ccr.2013.07.012
Milosevic Feenstra, J.D., Nivarthi, H., Gisslinger, H., Leroy, E., Rumi, E., Chachoua, I., Bagienski, K., Kubesova, B., Pietra, D., Gisslinger, B., Milanesi, C., Jager, R., Chen, D., Berg, T., Schalling, M., Schuster, M., Bock, C., Constantinescu, S.N., Cazzola, M., and Kralovics, R. (2016).
Whole exome sequencing identifies novel MPL and JAK2 mutations in triple negative myeloproliferative neoplasms.
Blood 127, 325-332
Pham, H.T.T., Maurer, B., Prchal-Murphy, M., Grausenburger, R., Grundschober, E., Javaheri, T., Nivarthi, H., Boersma, A., Kolbe, T., Elabd, M., Halbritter, F., Pencik, J., Kazemi, Z., Grebien, F., Hengstschlager, M., Kenner, L., Kubicek, S., Farlik, M., Bock, C., Valent, P., Muller, M., Rulicke, T., Sexl, V., and Moriggl, R. (2018).
STAT5BN642H is a driver mutation for T cell neoplasia.
J Clin Invest 128, 387-401
Baumgartner, C., Toifl, S., Farlik, M., Halbritter, F., Scheicher, R., Fischer, I., Sexl, V., Bock, C. and Baccarini, M. (2018)
An ERK-Dependent Feedback Mechanism Prevents Hematopoietic Stem Cell Exhaustion
Cell Stem Cell. 2018 May 17. pii: S1934-5909(18)30221-2. doi: 10.1016/j.stem.2018.05.003
Simonovic, N., Witalisz-Siepracka, A., Meissl, K., Lassnig, C., Reichart, U., Kolbe, T., Farlik, M., Bock, C., Sexl, V., Mueller, M. and Strobl, B.
NK Cells Require Cell-Extrinsic and -Intrinsic TYK2 for Full Functionality in Tumor Surveillance and Antibacterial Immunity
J Immunol. 2019 Feb 4. pii: jimmunol.1701649. doi: 10.4049/jimmunol.1701649
Halbritter, F., Farlik, M., Schwentner, R., Jug, G., Fortelny, N., Schnoller, T., Pisa, H., Schuster, L. C., Reinprecht, A., Czech, T., Gojo, J., Holter, W., Minkov, M., Bauer, W. M., Simonitsch-Klupp, I., Bock, C. and Hutter, C.
Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis
Journal: Cancer Discov

Cancer Discov. 2019 Jul 25. pii: 2159-8290.CD-19-0138. doi: 10.1158/2159-8290.CD-19-0138
Romanov, R.A., Tretiakov, E.O., Kastriti, M.E., Zupancic, M., Häring, M., Korchynska, S., Popadin, K., Benevento, M., Rebernik, P., Lallemend, F., Nishimori, K., Clotman, F., Andrews, W.D., Parnavelas, J.G., Farlik, M., Bock, C., Adameyko, I., Hökfelt, T., Keimpema, E., and Harkany, T.
Molecular design of hypothalamus development
Nature 582, 246-252. Doi: 10.1038/s41586-020-2266-0
Stary, V., Pandey, R.V., Strobl, J., Kleissl, L., Starlinger, P., Pereyra, D., Weninger, W., Fischer, G.F., Bock, C., Farlik, M., and Stary, G.
A discrete subset of epigenetically primed human NK cells mediates antigen-specific immune responses
Sci Immunol 5, eaba6232. Doi: 10.1126/sciimmunol.aba6232
Marquina-Sanchez, B., Fortelny, N., Farlik, M., Vieira, A., Collombat, P., Bock, C., and Kubicek, S.
Single-cell RNA-seq with spike-in cells enables accurate quantification of cell-specific drug effects in pancreatic islets
Genome Biol 21, 106. Doi: 10.1186/s13059-020-02006-2
Krausgruber, T., Fortelny, N., Fife-Gernedl, V., Senekowitsch, M., Schuster, L.C., Lercher, A., Nemc, A., Schmidl, C., Rendeiro, A.F., Bergthaler, A., and Bock, C.
Structural cells are key regulators of organ-specific immune responses
Nature 583, 296-302. Doi: 10.1038/s41586-020-2424-4
Fortelny, N., and Bock, C.
Knowledge-primed neural networks enable biologically interpretable deep learning on single-cell sequencing data
Genome Biol 21, 190. Doi: 10.1186/s13059-020-02100-5
Swoboda, A., Soukup, R., Eckel, O., Kinslechner, K., Wingelhofer, B., Schörghofer, D., Sternberg, C., Pham, H.T.T., Vallianou, M., Horvath, J., Stoiber, D., Kenner, L., Larue, L., Poli, V., Beermann, F., Yokota, T., Kubicek, S., Krausgruber, T., Rendeiro, A.F., Bock, C., Zenz, R., Kovacic, B., Aberger, F., Hengstschläger, M., Petzelbauer, P., Mikula, M., and Moriggl, R.
STAT3 promotes melanoma metastasis by CEBP-induced repression of the MITF pathway
Oncogene 40, 1091-1105. Doi: 10.1038/s41388-020-01584-6
Datlinger, P., Rendeiro, A.F., Boenke, T., Senekowitsch, M., Krausgruber, T., Barreca, D., and Bock, C
Ultra-high-throughput single-cell RNA sequencing and perturbation screening with combinatorial fluidic indexing
Nat Methods 18, 635-642. Doi: 10.1038/s41592-021-01153-z
Boccuni, L., Podgorschek, E., Schmiedeberg, M., Platanitis, E., Traxler, P., Fischer, P., Schirripa, A., Novoszel, P., Nebreda, A.R., Arthur, J.S.C., Fortelny, N., Farlik, M., Sexl, V., Bock, C., Sibilia, M., Kovarik, P., Mueller, M., and Decker, T.
Stress signaling boosts interferon-induced gene transcription in macrophages.
DOI 10.1126/scisignal.abq5389
Krausgruber, T., Redl, A., Barreca, D., Doberer, K., Romanovskaia, D., Dobnikar, L., Guarini, M., Unterluggauer, L., Kleissl, L., Atzmüller, D., Mayerhofer, C., Kopf, A., Saluzzo, S., Lim, C.X., Rexie, P., Weichhart, T., Bock, C., and Stary, G.
Single-cell and spatial transcriptomics reveal aberrant lymphoid developmental programs driving granuloma formation.
DOI 10.1016/j.immuni.2023.01.014.
Moorlag, S., Folkman, L., Ter Horst, R., Krausgruber, T., Barreca, D., Schuster, L.C., Fife, V., Matzaraki, V., Li, W., Reichl, S., Mourits, V.P., Koeken, V., de Bree, L.C.J., Dijkstra, H., Lemmers, H., van Cranenbroek, B., van Rijssen, E., Koenen, H., Joosten, I., Xu, C.J., Li, Y., Joosten, L.A.B., van Crevel, R., Netea, M.G., and Bock, C.
Multi-omics analysis of innate and adaptive responses to BCG vaccination reveals epigenetic cell states that predict trained immunity.
DOI 10.1016/j.immuni.2023.12.005.
Redl, A., Doberer, K., Unterluggauer, L., Kleissl, L., Krall, C., Mayerhofer, C., Reininger, B., Stary, V., Zila, N., Weninger, W., Weichhart, T., Bock, C., Krausgruber, T., and Stary, G.
Efficacy and safety of mTOR inhibition in cutaneous sarcoidosis: a single-centre trial.
DOI 10.1016/S2665-9913(23)00302-8