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Selected Publications

  1. Universitätsklinik für Dermatologie
  2. Wissenschaft & Forschung
  3. Übersicht
  4. Research groups
  5. Farlik - Innate Immune Activation Lab (INIMAC)
  6. Selected Publications

Key-Publications

* equal contribution

Rindler K, Jonak C, Alkon N, Thaler FM, Kurz H, Shaw LE, Stingl G, Weninger W, Halbritter F, Bauer WM, Farlik, M.* & Brunner, P.* (2021). Single-cell RNA sequencing reveals markers of disease progression in primary cutaneous T-cell lymphoma. Molecular Cancer, Sep 28;20(1):124.

  • We have explored the progression of cutaneous T-cell lymphoma in a unique way. By teaming up with clinicians at the MUV, Department of Dermatology, we characterized the molecular change in phenotype on single-cell level, identifying new pathways of communication between myeloid cell and T cell lymphoma cells in the skin.

Jonak, C.*, Alkon, N.*, Rindler, K., Rojahn, T., Shaw, L., Porkert, S., Weninger, W., Trautinger, F., Stingl, G., Tschandl, P., Cerroni, L., Farlik, M.* & Brunner, P.* (2021). Single-cell RNAseq profiling in a patient with discordant primary cutaneous B and T cell lymphoma reveals micromilieu-driven immune skewing. Br  J Dermatol.

  • Here, we discovered that B cell lymphomas and T cell lymphomas manipulate the tissue microenvironment in unique ways. We isolated both tumors at the same time from the same patient and performed single cell RNA-seq profiling, which revealed that both tumor cell types influence myeloid cells and fibroblasts the most and in very different ways. This finding prompted us to test fibroblasts alongside macrophages and discovered that also in CRC fibroblasts are important communication partners and shape the TES.

Rindler, K.*, Bauer, W. M.*, Jonak, C., Wielscher, M., Shaw, L. E., Rojahn, T. B., Thaler, F. M., Porkert, S., Simonitsch-Klupp, I., Weninger, W., Mayerhoefer, M. E., Farlik, M.*, & Brunner, P. M.* (2021). Single-Cell RNA Sequencing Reveals Tissue Compartment-Specific Plasticity of Mycosis Fungoides Tumor Cells. Frontiers in Immunology, 12, 666935.

  • Here we discovered that tissue compartments have a huge impact on the fate of tumor cells. Proliferative capacity in CTCL is mainly apparent in the skin when the tumor cells are in contact with the skin TES but no proliferation is detected in lymph-nodes or in peripheral blood.

Stary V., Vinay Pandey, R., Strobl J., Kleissl L., Starlinger P., Pereyra D., Weninger W., Fischer G.F., Bock C., Farlik M.* & Stary G.* (2020) A discrete subset of epigenetically primed human NK cells mediates antigen-specific immune responses. Science Immunology 5 (52).

  • In this publication we discovered an antigen-specific sub-population of NK cells that originates from the human liver and contributes to allergic reactions in the skin. This manuscript is important as it unites key methodologies – the generation, processing and integrative analysis of bulk RNA-seq and ATAC-seq samples as well as single cell RNA-seq.

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. & Hutter, C. (2019). Epigenomics and Single-Cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis. Cancer Discovery; doi: 10.1158/2159-8290.CD-19-0138.

  • Here we discovered, in collaboration with clinicians of the St. Anna Children’s Hospital, a developmental trajectory in lesions of Langerhans cell histiocytosis, which is highly depending on external signals mainly driven by cytokines, including the JAK-STAT pathway and NFkB. This trajectory results in tissue disruptive phenotypes explaining the progressive and metastatic behavior of LCH in some patients.

Farlik, M. #, Halbritter, F. #, Müller, F. #, Choudry, F. A., Ebert, P., Klughammer J., Farrow S., Santoro A., Ciaurro V., Mathur A., Uppal R., Stunnenberg H.G., Ouwehand W. H., Laurenti E., Lengauer T., Frontini M.# & Bock C#. (2016). DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation. Cell Stem Cell, 19(6), 808–822.

  • As part of the BLUEPRINT/IHEC consortium we characterized hematopoietic precursor cells from the BM and peripheral blood at the level of DNA methylation using our own low input and single cell workflow, which we developed in 2015 (previously published in Cell Reports – see below). The comparison of hematopoietic stem cells in the peripheral blood and BM revealed striking differences in the DNA methylation patterns priming ideas for in depth study of the BM structure and its role in health and disease.

Mass, E*, Ballesteros, I*, Farlik, M*, Halbritter, F*, Gunther, P*, Crozet, L, Jacome-Galarz, C.E., Händler C., Klughammer J., Kobayashi Y., Gomez-Perdiguero E., Schultze J.L., Beyer M.#, Bock C.# & Geissmann F.# (2016). Specification of tissue-resident macrophages during organogenesis. Science, 10.1126/science.aaf4238.

  • Using a combination of low input, Smart-seq2 based, RNA-seq we were able to follow macrophage development from the early embryo to post-natal days in mice. We used the RNA-seq data to derive patterns specific to distinct developmental stages of the macrophages in several different organs which went into a “score-card” matrix of expression states throughout development.

Li, J#, Klughammer, J#, Farlik, M#, Penz, T#, Spittler, A, Barbieux, C, Berishvili, E, Bock, C# & Kubicek, S# (2016). Single-cell transcriptomics reveals unique features of human pancreatic islet cell subtypes. EMBO Reports, 10.15252/embr.201540946.

  • With this paper we published the first single-cell transcriptome of the human pancreatic islets. This enabled us to describe several cell types in an unbiased way and find new markers for cell type identification. Moreover, through staining and confocal imaging of the human pancreatic islets with newly derived markers we could visualize crucial differences in the structure and orientation of pancreatic alpha and beta cells of human and mouse.

Farlik, M.#, Sheffield, N. C#., Nuzzo, A., Datlinger, P., Schönegger, A., Klughammer, J., & Bock, C. (2015). Single-Cell DNA Methylome Sequencing and Bioinformatic Inference of Epigenomic Cell-State Dynamics. Cell Reports; 10.1016/j.celrep.2015.02.001.

  • We developed one of the first protocols for single-cell DNA methylation detection on a whole genome scale. Apart from protocol development on the wet-lab side, we developed bioinformatic tools to overcome the sparse signals emanating from genomic single-cell approaches in order to assign biologically relevant meaning to the data. The herein developed software tools also assisted us in interpreting signals from transcriptomic data and are thus widely applicable in the field of single-cell analysis and beyond.