Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; CRISPR-Cas Systems; Genes, Tumor Suppressor; Immune Evasion; Immunotherapy; Inflammation; Lung; Mice, Knockout; Oncogenes
In the focus of our research are tumor intrinsic and extrinsic events during the development of lung tumors driven by mutations in KRAS or EGFR. We aim to understand how alterations in the tumor affect the stroma and vice versa. A particular emphasis lies on the inflammatory aspect of lung tumorigenesis, as well as to identify novel therapeutic strategies to treat patients suffering from this devastating disease. To study lung tumorigenesis, we have developed and established several in vitro and in vivo models in our laboratory.
Techniques, methods & infrastructure
We use conditional mouse models for autochthonous lung tumors driven by KRAS or EGFR mutations, orthotopic transplantation models into syngeneic immunocompetent mice and/or immunodeficient mice. Furthermore we developed T cell dependent mouse models of lung tumorigenesis via overexpression of the ovalbumin antigen.
Moreover, CRISPR/Cas9 technology is well established in our laboratory to tailor human and mouse lung tumor cell lines.
- Breitenecker, K. et al., 2021. Down-regulation of A20 promotes immune escape of lung adenocarcinomas. Science Translational Medicine, 13(601), p.eabc3911. Available at: http://dx.doi.org/10.1126/scitranslmed.abc3911.
- Moll, H.P. et al., 2018. Afatinib restrains K-RAS–driven lung tumorigenesis. Science Translational Medicine, 10(446), p.eaao2301. Available at: http://dx.doi.org/10.1126/scitranslmed.aao2301.
- Caratti, B. et al. (2022) ‘The glucocorticoid receptor associates with RAS complexes to inhibit cell proliferation and tumor growth’, Science Signaling, 15(726). Available at: http://dx.doi.org/10.1126/scisignal.abm4452.
- Mohrherr, J. et al. (2019) ‘JAK–STAT inhibition impairs K‐RAS‐driven lung adenocarcinoma progression’, International Journal of Cancer, 145(12), pp. 3376–3388. Available at: http://dx.doi.org/10.1002/ijc.32624.
- Sdelci, S. et al. (2019) ‘MTHFD1 interaction with BRD4 links folate metabolism to transcriptional regulation’, Nature Genetics, 51(6), pp. 990–998. Available at: http://dx.doi.org/10.1038/s41588-019-0413-z.