Graduate School GRK 2573 "The inflammatory tumor secretome – from understanding to novel therapies", project RP5
Project RP5: "The role of CDK - NF-κB crosstalk in shaping de novo protein synthesis, shedding and secretion of inflammatory mediators"
Short summary:
Researchers at the Universities Marburg and Giessen with a track record in tumor biology initiated this proposal for a research training group (RTG) with focus on the role of the inflammation-driven tumor secretome for tumor progression and therapy resistance. The aim is to establish an internationally competitive research center for the training of outstanding PhD/MD students in this emerging field and to integrate scientific and medical students as early as possible into research projects. The tumor secretome definition includes secretory factors released by cancer cells and by host cells within the tumor microenvironment (TME). Recently, the tumor secretome has emerged as a key player in tumorigenesis and therapy resistance and holds great promise as a source for novel cancer biomarkers and drug targets. However, its composition and impact on the reciprocal cross-talk of tumor cells and host cells remain to be investigated in detail. The RTG focuses specifically on the molecular dissection and functional analysis of secreted factors in ovarian cancer, pancreatic cancer and leukemia as diseases that are critically dependent on the TME. One focus of the research program is the role of the inflammatory NF-κB-dependent and the p53-regulated secretome components (proteins) including extracellular vesicles (EVs), which modulate the plasticity of tumor-associated immune cells, cancer cell invasion, metastasis, and therapy response. Moreover, we will analyze the consequences of chemotherapy and DNA damage on the secretome and its role for the anti-tumor response. The distinguishing feature of the RTG is the focus on primary patient-derived samples and in vitro models together with the integrated education of basic and clinical students. Coordinated 7 theoretical as well as practical courses and an internship/fellowship program will be provided within a structured curriculum. State of the art methods covering omics technologies, bioinformatics, imaging methods, in vitro cell culture models and mouse tumor models are allocated by established core facilities and by the participating research groups with outstanding expertise in the specific topic. The program aims to allow the investigation of the cellular communication within the TME focusing on the secretome on an internationally high professional level. Altogether, these measures will educate a generation of scientists engaged in tumor biology in general and tumor secretome research, in particular, addressing both, basic scientific questions and clinical cancer research. This will open career possibilities in academic research and beyond, such as industry, academic management, or society.
