Dr. Gandhi was the first to report the hemodynamic and metabolic effects of a powerful endogenous peptide endothelin in the liver, and increase in its activity during liver injury. Subsequently, his group showed that endothelin receptor antagonism arrests and reverses liver fibrosis/cirrhosis. His laboratory also developed a novel mouse model of hepatic stellate cell depletion and showed that stellate cells play a critical role in acute liver injury and liver’s immunological tolerance. Recently, Dr. Gandhi edited a book entitled “Stellate Cells in Health and Disease” (Elsevier/Academic Press) that covers the entire spectrum of stellate cell biology known to date with contribution from leading experts in stellate cell and liver research.
Another major research program in Dr. Gandhi’s laboratory demonstrated that augmenter of liver regeneration (ALR) protein is a critical intracellular survival factor for hepatocytes, and that secreted ALR exerts important biological effects on nonparenchymal cells. His laboratory developed a novel liver-specific ALR-knockout and heterozygous (ALR+/-) mice. This research has shown, for the first time, that by its mitochondrial function and regulation of lipid and energy metabolism, ALR plays a major role in steatohepatitis. It is apparent that the ALR-deficient mice will be a valuable tool to investigate mechanisms of alcoholic and nonalcoholic steatohepatitis that progress to end-stage liver diseases.
Mechanisms of liver injury, immunological tolerance and steatohepatitis
Professor, UC Department of Surgery
Gastroenterology GI, Gastroenterology, Fibrosis