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Prof. Dr. Jonathan Sleeman

The central aim of the Sleeman lab is to understand the process of metastasis and to use this knowledge to develop novel anti-cancer therapies. Working mainly on breast cancer and melanoma, our research currently includes studies on genetic changes and signaling pathways that promote metastasis, tumor-induced lymphangiogenesis, and dissemination via the lymphatics. Another major focus is to understand the microenvironmental regulation of metastatic spread and dormancy, including how changes in the extracellular matrix composition (in particular hyaluronan) and the induction of senescence promote metastasis. In the context of MI3, we are investigating how pro-inflammatory signaling molecules act as regulators of dissemination and metastatic outgrowth. Here, key interests focus on the role of pulmonary macrophages and neutrophils in shaping lung metastatic niches.

Role of neutrophils during the formation of lung metastases. A. Recruitment of neutrophils (red) to the vicinity of terminal bronchioles (green) during the formation of metastatic niches in the lung. B. CyTOF analysis of the mobilization of metastasis-promoting neutrophils into the blood.

Publications

Thiele W, Krishnan J, Rothley M, Weih D, Plaumann D, Kuch V, Quagliata L, Weich HA, and Sleeman JP. (2012). VEGFR-3 is expressed on megakaryocyte precursors in the murine bone marrow and plays a regulatory role in megakaryopoiesis. Blood, 120: 1899-1907.

Hansen MT, Forst B, Cremers N, Quagliata L, Ambartsumian N, Grum-Schwensen B, Klingelhöfer J, Abdul-Al A, Herrmann P, Osterland M, Stein U, Nielsen GH, Scherer PE, Lukanidin E, Sleeman JP*, Grigorian M*. (2015). A link between inflammation and metastasis: serum amyloid A1 and A3 induce metastasis, and are targets of metastasis-inducing S100A4.  Oncogene, 34: 424-35 * Equal contribution

Alishekevitz D, Gingis-Velitski S, Kaidar-Person O, Gutter-Kapon L, Scherer SD, Raviv Z, Merquiol E, Ben-Nun Y, Miller V, Rachman-Tzemah C, Timaner M, Mumblat Y, Ilan N, Loven D, Hershkovitz D, Satchi-Fainaro R, Blum G, Sleeman JP, Vlodavsky I and Shaked Y. (2016). Macrophage-induced lymphangiogenesis and metastasis following paclitaxel chemotherapy is regulated by VEGFR-3. Cell Reports 17: 1344-1356

Bauer J, Rothley M, Schmaus A, Quagliata L, Ehret M, Biskup M, Orian-Rousseau V, Jackson DG, Pettis RJ, Harvey A, Bräse S, Thiele W and Sleeman JP. (2018). TGFβ counteracts LYVE-1-mediated induction of lymphangiogenesis by small hyaluronan oligosaccharides. J Mol Med (Berl) 96: 199-209

Schreiber C, Saraswati S, Harkins S, Gruber A, Cremers N, Thiele W, Rothley M, Plaumann D, Korn C, Armant O, Augustin HG and Sleeman JP. (2019) Loss of ASAP1 in mice impairs adipogenic and osteogenic differentiation of mesenchymal progenitor cells through dysregulation of FAK/Src and AKT signaling. PLoS Genetics, 15(6): e1008216

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