Our laboratory has laid the foundation for an proper determination of the endogenous AHR ligand 6-formylindolo[3,2-b]carbazole (FICZ), which is a photoproduct of the amino acid tryptophan, and its role in the physiological AHR signaling. We will analyze the endogenous AHR pathways and the FICZ-AHR-cytochrome P4501A1 (CYP1A1) feedback regulatory loop and how environmental pollutants and other drugs or xenobiotics interfere with this signaling. The long-term goal is to determine how common FICZ is in biological matrices and define which cellular pathways FICZ and its metabolites participate in and thereby be able to predict type and degree of interference with xenobiotics. We will (1) develop specific analytical tools to trap FICZ and FICZ binding proteins (2) identify light-independent pathways that also could result in FICZ formation (3) identify FIZC regulated AHR-independent pathways.