Small intestinal organoid stained with Cdh1 (E-Cadherin) and Ctnnb1 (Active beta-Catenin). Mikuda et al., J Pathol 2020

Signal Transduction in the GI tract in Health and Disease

Intestinal epithelium absorbs nutrients, serves as a barrier to harmful substances, and mediates crosstalk with the immune system by responding to cytokines and bacterial components. Breakdown of the crosstalk prevents return to homeostasis and leads to disease.

We aim to decipher this crosstalk and to understand the molecular mechanisms involved in intestinal homeostasis, inflammation, and resolution of inflammation with a focus on NF-κB.

Signal Transduction in the GI tract in Health and Disease

Transcription factor NF-κB plays a key role in immune mediated diseases by regulating expression of cytokines, growth factors, as well as of anti-apoptotic mediators. How its activation in epithelial cells versus in immune cells mediates return to homeostasis is poorly understood.

We are using single cell datasets, organoids, and transgenic mouse models, and techniques in biochemistry to determine how NF-κB regulates cell fate decisions, including differentiation, senescence, and cell death.

Our aim is to shed light on the contribution of NF-κB and its divergent transcriptomes to development and progression of immune mediated diseases of the gut.

Scientific questions:

Which signalling pathways in intestinal epithelium contribute to inflammation versus resolution?
Where and how does NF-κB direct anti- versus pro-inflammatory responses in the gut?
Which signalling pathways and mediators can be used as relevant targets for disease treatment?

Funding:

Charité 3^R (Adding 3R value to biomedical research): "Refining analgesia through combined and measurable score systems for inflammation, pain, and inflammatory signalling"
DFG (KO 6390/1-1)
Fritz Thyssen Foundation
Re-Thinking Health