Project 4 - Liver Chip
Professor Lans Taylor is the Co-PI of Project 4 "Organotypic Liver Model for Predictive Human Toxicology and Metabolism" and the director of the University of Pittsburgh Drug Discovery Institute.
His lab usually concentrates on drug discovery and development, specifically integrated programs that apply quantitative systems pharmacology, ligand- or target-centric discovery in many therapeutic areas, and translational technology development.
Background: Even the best constructed single tissue organoid may fail to account for all injury types. For instance, the injury to the organ may not be the result of a direct contact between toxicant and organ but a combination of upstream biotransformation of the compound coupled with local interactions at the site of the injury. In order to fully elucidate toxicity of an organ by 3D in vitro methodology, a reasonable approach might be to include testing the target organ in media containing drug metabolites produced by the liver.
First Results: Our liver OCM is a liver sinusoidal unit that has demonstrated normal liver functions including drug metabolism for up to 3 weeks in culture. A key feature is the inclusion of hepatocytes, endothelial cells, macrophages and stellate cells – all genetically encoded with fluorescence-based biosensors for High Content Imaging of key pathways and mechanisms of toxicity (oxidative stress, mitochondrial dysfunction, apoptosis, immune and fibrosis response).
|Aim 1:||Transfer current 3D liver organoid to a commercial microfluidics device.|
|Aim 2:||Validate existing biosensors; Develop and validate additional biosensors for the liver, reproductive and developmental organoids.|
|Aim 3:||Adapt the University of Pittsburgh Microphysiology Database (UPMDb) to manage data, conduct analysis, QC and transfer the data to the EPA.|
Here is a link to our publicly accessible, annual report of Research Project Results.
Project 4 Team at the University of Pittsburgh (left to right): Larry Vernetti, Celeste Reese, Richard DeBiasio, JuanFang Wu, Bert Gough,
David Zaidins, Luke Bergenthal, Felipe Lee-Montiel, and Lans Taylor (PI).