My research focuses on cellular plasticity in pre-neoplastic lesions and mucosal injury of the stomach. My previous work showed that Notch signaling is downstream of epidermal growth factor receptor (EGFR) signaling in gastric premalignant condition Ménétrier’s disease (MD) and Notch signaling inhibition rescues biochemical and histological features of this disorder in a mouse model of MD. Preliminary data shows that parietal cells (acid secreting cells in stomach) can transdifferentiate into other cell types in MD and gastric mucosal injury mouse models. The goal of the laboratory is to investigate signaling networks that regulate cellular plasticity in pathologic conditions and normal homeostasis in the stomach. The results will form the basis for developing therapeutics.
An additional research direction is on the sexual difference of EGFR in liver. I have found that male mice express two- to three-fold higher EGFR protein in their livers compared to female mice. Notably, this sex difference in hepatic EGFR levels extends to humans. In mice, I have shown that EGFR levels in the liver are regulated by testosterone. My laboratory will investigate whether testosterone also regulates EGFR expression in human liver, the mechanism how testosterone regulates EGFR, and the effects of sex differential expression of hepatic EGFR on the male predominance of fatty liver disease and hepatocellular carcinoma (HCC).
Cell Differentiation; Liver; Metaplasia; Stem Cells; Stomach; Stomach Neoplasms; Cell Dedifferentiation; EGF Family of Proteins; Cell Plasticity