The Liver Pathobiology Laboratory of Gregory J. Gores, M.D., is focused on the cellular and molecular mechanisms by which dysregulation of cellular signaling events results in the development of disease. In particular, the laboratory studies the underlying mechanisms that result in liver injury and carcinogenesis.
The laboratory has developed models of cholestasis that mimic the human disease. Using these models, deleterious signaling pathways are delineated, and therapeutic targets and approaches identified. A wide variety of techniques are used, including genetic animal models, organoids and cell culture models.
State-of-the-art technologies currently used include:
- Airyscan (super-resolution) confocal microscopy for imaging
- Cytometry by time-of-flight (CyTOF) mass spectrometry for immunoprofiling
- High-pressure liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomics
- Single-cell RNA sequencing and NanoString for transcriptomics
- Spatial transcriptomics
Current studies are focused on the role of ductular reactive cells and macrophages in promoting disease pathogenesis in models of cholestasis.
Dr. Gores and his team are also examining the mechanisms by which oncogenic Hippo pathway signaling promotes carcinogenesis of the biliary tree and cancer progression. They are also exploring how the Hippo pathway via yes-associated protein (YAP) dysregulation mediates tumor resistance. These studies are designed to identify therapeutic targets for the treatment of liver cancer. A current focus of the laboratory also is immunotherapy for liver cell cancer. Individuals interested in pursuing research in the Liver Pathobiology Laboratory are encouraged to contact Dr. Gores directly.