Research in Prof. Lisa Sevenich's "Experimental Neuroonco-Immunology" lab is focused on tumor immunology in brain cancer in particular brain metastasis.
You can read more about her research focus below.
Lisa Sevenich's mission is to provide scientific rationale for novel therapeutic strategies against brain metastasis.
Research in my laboratory is focused on tumor immunology in brain cancer in particular brain metastasis. We identified different disease-associated roles of brain metastasis-associated myeloid and lymphoid populations using multiomics and image-based approaches.
Based on this mechanistic insight, we seek to develop novel immune-targeted therapies for preclinical testing in ex vivo and in vivo models. We put a particular emphasis on strategies that overcome inherent or adaptive resistance mechanisms by modulating immune cell activation states and targeting metabolic pathways in brain metastasis. Such approaches comprise strategies for local immune modulation within the brain metastatic microenvironment as well as systemic approaches e.g. by targeted modification of the microbiome for immune stimulation.
Moreover, we seek to gain mechanistic insight into tumor cell characteristics that allow tumor cells to adopt to the unique tissue environment in the central nervous system. A focus is put on the acquisition of neuronal-like characteristics in brain metastatic cells as a core program of metastatic niche cooption with regard to metabolic and immunological processes.
Our mission is to provide scientific rationale for novel therapeutic strategies against brain metastasis.
Selected publications
Klemm F, Möckl A, Salamero-Boix A, Alekseeva T, Schäffer A, Schulz M, Niesel K, Maas RR, Groth M, Elie BT, Bowman RL, Hegi ME, Daniel RT, Zeiner PS, Zinke J, Harter PN, Plate KH, Joyce JA and Sevenich L: Compensatory CSF2-driven macrophage activation promotes adaptive resistance to CSF1R inhibition in breast-to-brain metastasis. (2021) Nat Cancer 2, 1086-1101
Niesel K, Schulz M, Alekseeva T, Anthes J, Salamero-Boix A, Möckl A., Oberwahren-brock T, Lolies M, Stein S, Rödel F, Sevenich L: The immune suppressive microenvironment affects efficacy of radio-immunotherapy in brain metastasis. (2021) EMBO Mol Med e13421
Schulz M, Michels B, Niesel K, Stein S, Farin H, Rödel F, Sevenich L: Cellular and molecular changes in the myeloid cell compartment during disease progression and therapeutic response in lung-to-brain metastasis. (2020) iScience Jun26;23(6):101178
Chae WH, Niesel K, Schulz M, Klemm F, Joyce JA, Prümmer M, Brill B, Bergs J, Rödel F, Pilatus U, Sevenich L: Evaluating magnetic resonance spectroscopy as a tool for monitoring therapeutic response of whole brain radiotherapy in a mouse model for breast-to-brain metastasis. (2019) Front Oncol. 27(9):1324
Sevenich L, Bowman RL, Mason SD, Quail DF, Rapaport F, Elie BT, Brogi E, Brastianos PK, Hahn WC, Holsinger LJ, Massague J, Leslie CS, Joyce JA: Analysis of tumour- and stroma-supplied proteolytic networks reveals a brain metastasis-promoting role for cathepsin S. (2014). Nat Cell Biol. 16(9):876-888
Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF, Olson OC, Quick M, Huse J, Teijeiro V, Setty M, Leslie C, Oei Y, Pedraza A, Zhang J, Brennan CW, Sutton JC, Holland EC, Daniel D, Joyce JA: CSF-1R inhibition alters macrophage polarization and blocks glioma progression. (2013) Nat Med. 19(10):1264-72
Sevenich L, Werner F, Gajda M, Schurigt U, Sieber C, Müller S, Follo M, Peters C, Reinheckel T: Transgenic expression of human cathepsin B promotes progression and metastasis of Polyoma Middle T induced breast cancer in mice (2011). Oncogene 30(1):54-64.
Sevenich L, Schurigt U, Sachse K, Gajda M, Werner F, Müller S, Vasiljeva O, Schwinde A, Klemm N, Deussing J, Peters C, Reinheckel T: Synergistic anti-tumor effects of cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice (2010). PNAS 107(6):2497-50
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