The Liver Pathobiology Laboratory focuses on the underlying mechanisms that result in liver cell apoptosis by studying a variety of pathways and diseases.
Cholestatic liver injury
The overall objective of this proposal is to examine the hypothesis that ductular reactive cells induce macrophage TNF-related apoptosis-inducing ligand (TRAIL) expression as a counter-regulatory process to limit their expression and are primed for cell death, which can be exploited therapeutically to attenuate cholestatic liver injury.
The specific aims of this project are to test these hypotheses:
- Does TRAIL or TRAIL receptor signaling limit the expansion of the death receptor (DR) cell population in cholestasis?
- Do DR cells promote TRAIL expression by macrophages?
- Are DR cells primed for cell death?
Hepatobiliary cancer SPORE project
The lab is testing the hypothesis that receptor tyrosine kinases mediate yes-associated protein (YAP) tyrosine phosphorylation by Src family kinases.
Specific aims to test this hypothesis are:
- How does fibroblast growth factor receptor (FGFR2) signaling lead to YAP nuclear translocation (activation) and subsequent FGFR expression?
- Can a specific threshold be defined for the percentage and intensity of YAP nuclear staining that would serve as a biomarker for response to FGFR-directed therapy?
- Is targeted FGFR inhibition effective in patients who lack receptor fusions but have activation of YAP?
Focusing on signaling to develop targeted therapies, the lab is identifying how pathological activation of the Hippo pathway effector yes-associated protein (YAP) drives cholangiocarcinoma growth and chemotherapy resistance, and using preclinical models to test novel therapeutic strategies for this deadly disease.
A group in Dr. Gore's lab is studying the mechanisms that govern the development of nonalcoholic steatohepatitis (NASH), specifically, how cell-to-cell communication influences disease progression.