Group Krebs

Chronic inflammation of microbial etiology has been suggested as the underlying cause of several debilitating conditions, particularly in patients afflicted with inflammatory bowel disease (IBD) or certain types of malignancies. Our group uses mouse models and specimens from human patients to study the role of specific genes or molecular pathways for inflammation-triggered immunopathology or tumor development. We aim at a better understanding of the mechanisms underlying these pathways to possibly reveal novel therapeutic targets.

Keywords:

  • Cross-talk innate / adaptive immunity
  • Role of inflammation for cancer development
  • Immunopathology

Current research projects

Role of cytokine signaling for tumor development

Group Krebs Inflammation is a driver of cancer. We have shown that IL-33 signaling is important for the development of myeloproliferative neoplasms (MPN), a type of blood cancer, and for promoting colorectal cancer (CRC) (Mager et al., J Clin Invest, 2015; Mertz et al., OncoImmunology, 2015). We currently investigate the contribution of IL-33 to MPN progression and to the cellular and molecular mechanisms underlying IL-33-dependent CRC. For these studies, we use patient-derived samples and mouse models.

 

 

Increased levels of IL-33 protein in bone marrow of MPN patients. IL-33: brown; CD34 (endothelial cells): red

mRNA splicing and epithelial integrity

Group Krebs The intestinal barrier is often disrupted during intestinal diseases, causing gut leakiness. We have recently shown that the protein ESRP1, a regulator of mRNA splicing in epithelial cells, has a critical function to maintain the integrity of the intestinal barrier (Mager et al., eLife, 2017). In this project, we further investigate how loss or reduction of ESRP1 leads to intestinal pathogenesis, including colorectal cancer.

 

 

 

Bacteria (white arrows) penetrate the leaky intestinal barrier of Esrp1 mutant mice. Scale bars: 100 μm (from Mager et al., eLife, 2017)

Cross-talk between innate and adaptive immunity

Group Krebs The vertebrate immune system comprises the innate immune system, providing the first line of defense, and the adaptive immune system, which is triggered at a later stage and that is responsible for memory. In this project, we use different murine models to better understand how innate immune cells modulate adaptive immune responses in dependence on the inflammatory environment, in infectious (e.g. after infection with a pathogen) or sterile (e.g. for tumor surveillance) situations.

 

 

Plasmacytoid dendritic cells (pDCs) interact with natural killer (NK) cells to modulate the later-coming (CD8+ T cell) adaptive immune response