Liver Injury Research
The Gandhi laboratory is investigating mechanisms of liver injury with specific focus on hepatic stellate cells (HSCs). HSCs (8-10% of liver cell population) are the major cell type to cause liver fibrosis, but they also have a unique ability to induce acute liver injury directly by producing numerous cytokines and chemokines, and also by modulating characteristics of resident and infiltrating immune and inflammatory cells. The current focus of this program is to delineate precise mechanisms by which HSCs orchestrate inflammatory and immunological responses in the liver using a novel mouse model of HSC depletion (developed in our laboratory) and co-culture techniques.
The other research program investigates the mechanisms of steatohepatitis and its sequel (fibrosis, cirrhosis and cancer) due to hepatocyte-specific deficiency of a protein named Augmenter of Liver Regeneration (ALR). Liver (hepatocyte)-specific ALR-knockout of ALR in mouse was found to induce mitochondrial dysfunction, and progressive nonalcoholic steatohepatitis (NASH) with characteristics very similar to the human NASH. Our group has also observed that the hepatic ALR levels are lower in human NASH. The focus of this research is to discover link between ALR gene polymorphism(s) or anomaly in ALR protein and predisposition to develop aggressive form of NASH.