P11 - Identification of the cells of origin of squamous cell lung carcinoma
Lung adenocarcinoma (LUAD) is the deadliest cancer worldwide and is mainly caused by tobacco smoke. The cell lineages of origin, the mode of mutation accumulation, and the molecular and immune-mediated pathways that lead to LUAD have not been prospectively defined, since widely used genetic mouse models do not recapitulate the complex mutation spectrum of human LUAD. We employ mouse models of LUAD triggered by stochastic mutagenesis induced by tobacco chemicals in mice. These human-faithful models provide sequential inflammatory, hyperplastic, preneoplastic, and malignant lesions in the lungs, allowing for timed observations of tumor evolution. We combine this approach with lung-restricted lineage tracing, and bulk and single-cell RNA sequencing analyses, in order to define tumor evolution. In addition to cancer cells, LUAD-infiltrating immune cells also change over time in human and mouse LUAD. In this GRK2338-P11 project, we seek to focus on the evolution of LUAD-infiltrating host cell populations in terms of cell type, gene expression patterns, but also mutation burden, if any. Using cutting edge models and analytical approaches, we seek to characterize tumor-shaping inflammation over time in LUAD.
Prof. Dr. med. Amanda Tufman, MD, B.Sc.Department of Pneumology University Hospital of Munich Ziemssenstr. 1/5 80336 München +49 89 4400 5 2590 |