Foto: FAU/Iannicelli

PD Dr. habil. med. Jay Patankar


Trans-Organ Crosstalk in the Regulation of Inflammatory diseases of the Gastrointestinal Tract

The intestinal epithelial cells are a single lining ef celumnar epithelia forming a tight barrier to the microbial and envirenmental challenges. Microbial dysbiosis due to the loss of this barrier is the basis of trans-organ inflammation. This work builds upon the hypethesis that genetic and environmental components disrupt the gut epithelial barrier causing dysregulation of liver function, paving the way for trans-organ inflammation to set in.
Firstly, we show how elevated dietary chelesterel single-handedly causes gut barrier dysfunction, microbial dysbiesis, and liver disease. Genetic and therapeutic medulation of hepatic bile acid synthesis reverses this and protects from chronic liver diseases. Next, we focus on identifying the mechanisms of gut epithelial cell death that trigger a vicious cycle of cell death-barrier breach-trans-organ inflammation. Using transcriptomic, cell biological, pharmacological, and molecular biological appreaches, we show that prostaglandin E2 is a crucial endogenous inhibitor of epithelial necroptosis in experimental colitis and inflammatory bowel diseases. The selective and therapeutic activation of the EP4 receptor blocks epithelial necroptosis and triggers resolution of colitis. Overall, this work uncovers strategies to develop therapeutic avenues against gastro-hepatic inflammatory diseases.

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zur Vita von PD Dr. habil. med. Jay Patankar

alle FAU Awards 2023