Gary Peltz (Anesthesia)
Jeffrey Glenn (Medicine)
Sara Michie (Pathology)

This project will determine if analyses performed in mice with humanized livers could better predict drug-induced liver toxicity in human subjects.

Project Description and Impact: Because of inter-species differences in drug metabolism and in their physiology, in vivo animal toxicology testing has not always accurately predicted whether drug-induced liver injury (DILI) will occur in humans. Because of this, un-expected DILI has become the most common reason for regulatory actions after drug approval. This application will determine whether a novel TK-NOG chimeric mouse with a highly humanized liver can more accurately predict whether DILI will occur in humans. This program will enable a 21st century experimental system to improve the safety of 21st century drug development.  These pioneering toxicology studies performed in humanized mice represent collaboration between a systems biologist who developed this advanced platform (G.P.), a hepatologist interested in HCV (J.G.), and an anatomic pathologist (SAM).