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SFB 1039

SIGNALLING BY FATTY ACID DERIVATIVES AND
SPHINGOLIPIDS IN HEALTH AND DISEASE

B03 - Sphingolipids in the pathogenesis and therapy of colitis and colitis -associated carcinogenesis

Selective variation of the sphingolipid rheostat in colon and immune cells is decisive for chronic inflammatory processes, albeit affecting carcinogenesis and cancer microenvironment differentially. In DSS/AOM colitis S1P accumulation in hematopoietic compartments caused delayed carcinogenesis, whereas selective S1P elevation in intestinal tissue led to a loss of function and a rapid carcinogenesis with a tumorpromoting milieu. Our future investigations, in addition to S1P effects in cytotoxicity assays with tumor spheroids, will encompass determination of the molecular targets of sphingolipid modulation e.g. by genomic DNA and microRNA analysis. In 3D colon organoids we focus on colon stem cell development and fibrotic remodeling.

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Principal Investigator

Prof. Dr. Heinfried H Radeke
Institute of General Pharmacology and Toxicology
Faculty of Medicine
Goethe-University Frankfurt
Theodor Stern Kai 7
60590 Frankfurt am Main