The core research idea and goal of this RTG is to investigate various clinically relevant inflammatory cues as trigger of early pancreatic carcinogenesis. Through the joint use of core in vitro and in vivo platforms and state-of-the-art technologies, this RTG offers an excellent opportunity to comprehensively elucidate the role of a variety of inflammation-related inputs during early pancreatic carcinogenesis in order to improve the chances of early diagnosis and detect novel treatment avenues for this dismal disease.
The RTG involves a close collaboration of clinical scientists with broad expertise in pancreatic research ranging from pancreatic genetics, fibrosis, metabolism and malignant transformation, and comprising different clinical specialties such as gastroenterology, visceral surgery and oncology. The clinical scientists are closely interacting with basic preclinical researchers with expert knowledge in a broad spectrum of relevant in vitro and in vivo models in molecular and cellular biology, anatomy, pharmacology, protein mass spectrometry as well as cutting-edge technologies including functional genomics, epigenetics, imaging, bioinformatics and molecular pathology. This allows for innovative combinations of various strategies ranging from comparative analysis of different inflammation-driven mouse models to cutting-edge CRISPR/Cas technologies that decipher the underlying molecular networks. The joint collaborative effort offers a unique setting to elucidate the complex mechanisms of inflammation-induced early pancreatic carcinogenesis.
The importance of inflammatory triggers and early diagnosis of malignancies in general and the dismal prognosis and raising incidence of PDAC in particular will lead to a great need for scientists qualified in these fields in the near future, both in academic research and biotech companies. Therefore, our innovative qualification program which combines basic, translational and clinical research aspects offers a unique opportunity for students and early career scientists. Due to the close interaction between clinical and basic research groups, the qualification program for PhD and MD students as well as for clinical scientists will be closely interlinked and will benefit from the already established MD graduate school (HaPKoM ) and Clinical scientist program of the Medical Faculty as well as the Unibund mentoring program.
Projects A1 - A3 focus on the comparative characterization of three different in vivo mouse models recapitulating genetically-, obesity-, and exogenously-induced chronic inflammation and their impact on early K-Ras-dependent carcinogenesis.
Projects B1 - B6 utilize various in vitro modelling approaches based on the murine models in A1-A3 aiming to decipher the impact of different stromal components including macrophages, NK cells, fibroblasts, platelets and T cells on malignant transformation. This includes direct and indirect co-culture techniques to characterize the functional effects and molecular mechanisms of the stromal crosstalk with preinvasive pancreatic cells.
Projects C1 - C4 focus on the functional characterization of candidates differentially regulated during inflammation-induced early pancreatic carcinogenesis in order to identify relevant novel diagnostic and/or therapeutic targets. While projects C1 and C2 aim to identify and characterize protein signatures and post- translational modifications as well as deregulated control mechanisms of gene expression by RBPs, projects C3 and C4 focus on transcriptional modulators including lncRNAs and exploit innovative functional genetics approaches to identify relevant novel therapeutic targets.