Core research areas
In order to elucidate the impact and mechanisms of different chronic inflammatory stimuli on early pancreatic carcinogenesis, the RTG is structured in three different research areas A, B and C:
![[Translate to English:] Figure 2: RTG structure and contribution of the projects to the three research areas.](/fileadmin/Einrichtungsordner/Kliniken_und_Departments/DepartmentFuerInnereMedizin/KIMI/GRK-Antrag/figure02.jpg)
| NO. | PROJECT TITLE | PROJECT LEADER |
| A1 | Impact of genetically induced inflammation on early pancreatic carcinogenesis in the context of obesity | Rosendahl, Jonas, W2-Prof., MD Laumen, Helmut, PhD |
| A2 | Effect of intermittent fasting on obesity-induced early pancreatic carcinogenesis | Gericke, Martin, W2-Prof., MD |
| A3 | Influence of intestinal microbiota on inflammation- induced early pancreatic carcinogenesis | Michl, Patrick, W3-Prof., MD |
| B1 | Impact of macrophages on inflammation-induced early pancreatic carcinogenesis | Krug, Sebastian, MD* Kessler, Sonja, W3-Prof., PhD |
| B2 | Impact of NK cells on inflammation-induced early pancreatic carcinogenesis | Kielstein, Heike, W3-Prof., MD; Bazwinsky-Wutschke, PhD |
| B3 | Impact of fibroblast activation in early pancreatic carcinogenesis | Kleeff, Jörg, W3-Prof., MD Markus Glaß, PhD* |
| B4 | Mesenchymal stromal cells as immune modulators during carcinogenesis | Müller, Lutz, apl.-Prof., MD |
| B5 | Contribution of platelets to early pancreatic carcinogenesis | Hämmerle, Monika, W1-Prof., MD/PhD* |
| B6 | Impact of T cells during early pancreatic carcinogenesis | Bley, Nadine, PhD* |
| C1 | Proteomic signatures of inflammation-induced carcinogenesis | Sinz, Andrea, W3-Prof., PhD Göllner, Stefanie, PhD* |
| C2 | RNA binding proteins (RBPs) in inflammatory-driven early pancreatic carcinogenesis | Hüttelmaier, Stefan, W3-Prof., PhD |
| C3 | Role of lincRNAs in early and inflammation-driven pancreatic carcinogenesis | Gutschner, Tony, W1-Prof., PhD* |
| C4 | Functional reconstruction of genetic interaction networks in early pancreatic carcinogenesis | Böttcher, Michael, W1-Prof., PhD* |
Individual projects and participants' preliminary work related to the project
Supervisor: Jonas Rosendahl, Helmut Laumen
PhD student: NN
Specific aims:
In this project, we will analyze the novel pancreatitis mouse model CPA1-p.N256K (Cpa1 mice) and the novel pancreas cancer mouse model KC-Cpa1, in which we combined Cpa1 mice with the pancreas-specific K-RasG12D/+ genotype (KC mice: KrasG12D/wt; p48Cre+/-) to elucidate early pathomechanisms of pancreatic cancer in the context of spontaneous intrapancreatic inflammation and obesity.
Supervisor: Martin Gericke
PhD student: NN
Specific aims:
This project is designed to unravel the effects of intermittent fasting on obesity-associated pancreatic carcinogenesis and evaluate the role of M2 macrophages in this process.
A3 Michl: Influence of intestinal microbiota on inflammation-induced early pancreatic carcinogenesis
Supervisor: Patrick Michl
PhD student: NN
Specific aims:
This project aims to elucidate the influence of inflammatory cues induced by various pharmacological, genetic and metabolic triggers on the composition of intestinal and intrapancreatic microbiota and their interaction with local and systemic immune response and (pre)invasive pancreatic lesions.
Supervisor: Sebastian Krug, Sonja M. Kessler
PhD student: NN
Specific aims:
In this project, we aim to decipher the contribution of myeloid cells to inflammation-induced early carcinogenesis and the potential for therapeutic modulation.
Supervisor: Heike Kielstein, Ivonne Bazwinsky-Wutschke
PhD student: NN
Specific aim:
In this project we will unravel the impact of NK cells during early inflammation-induced pancreatic carcinogenesis by deciphering effects on both pre-invasive cells and other components of the tumor microenvironment including the endocrine compartment. In addition, we will explore pharmacological options of NK cell modulation during early carcinogenesis.
Supervisor: Jörg Kleef, Markus Glaß
PhD student: NN
Specific aims:
In project B3, we aim to identify and characterize the impact of PSCs during inflammation-driven early pancreatic carcinogenesis.
Supervisor: Lutz Müller
PhD student: NN
Specific aims:
We aim to characterize native pancreatic mesenchymal stroma cells (MSC) during stages of pancreatic carcinogenesis and to define MSC-specific immunomodulatory effects contributing to inflammation-driven PDAC development.
Supervisor: Monika Hämmerle
PhD student: NN
Specific aims:
In this project, we will investigate the specific role of platelets in the regulation of tumor initiation and progression in early pancreatic carcinogenesis with a specific focus on the regulation of PanIN- and cancer-associated immune cells in vitro and in vivo.
Supervisor: Nadine Bley neé Stöhr
PhD student: NN
Specific aims:
In project B6, we aim to characterize and compare the T cell landscape in three different inflammation-driven models of early pancreatic carcinogenesis and describe its impact on cancer progression.
Supervisor: Andrea Sinz, Stefanie Göllner
PhD student: NN
Specific aims:The aim of project C1 is to identify and functionally characterize novel protein signatures/complexes indicating early inflammation-induced pancreatic carcinogenesis with particular focus on posttranslational modifications.
Supervisor: Stefan Hüttelmaier
PhD student: NN
Specific aims:
In project C2, we aim to identify and characterize the impact of RBPs (RNA binding proteins) during inflammation-driven pancreatic carcinogenesis.
Supervisor: Tony Gutschner
PhD student: NN
Specific aims:
Our project aims to characterize the role of lincRNAs during the early steps of carcinogenesis as well as their contribution to inflammatory processes and signaling networks.
Supervisor: Michael Böttcher
PhD student: NN
Specific aims:
We will employ our dual CRISPR gene perturbation approach to systematically identify genes and genetic interactions that regulate NF-kB activation in murine KrasG12D preinvasive PanIN cells (KC cells).
