Chandrashekhar R. Gandhi, Ph.D., Associate Professor
Ph.D., Nagpur University, Nagpur, India, 1981
E-mail: gandhics@msx.upmc.edu
My laboratory investigates the mechanisms of the pathogenesis and complications of liver diseases. Our specific interests are the molecular and biochemical properties of perisinusoidal stellate cells, which form an important communicative link between hepatocytes and sinusoidal cells. Because of its ability to contract, to produce components of extracellular matrix and to synthesize an array of cytokines and growth mediators, stellate cell is a unique cell type that regulates blood flow, architecture and growth of the liver in physiology and pathology. Stellate cells produce endothelin-1 and nitric oxide, the powerful vasoactive mediators, also implicated in several critical biological reactions. We have shown that the actions of endothelin-1 on stellate cells play a major role in the pathogenesis and complications of chronic liver disease, and that antagonism of endothlin-1 receptors can reverse cirrhosis. We demonstrated that stellate cells produce as yet unknown growth mediators, which exert positive and negative actions on hepatocytes. We also found that inflammatory conditions lead to the generation of signals by stellate cells that induce apoptotic and necrotic death of hepatocytes. Molecular mechanisms of these crucial biochemical events are studied using cell culture and in vivo models. The ultimate goal of our research is to gain precise understanding of the mechanisms by which stellate cells participate in hepatic pathology for the development of therapies for diseases such as fulminant liver failure, cirrhosis and hepatocellular carcinoma..
Recent Publication
Gandhi CR, Uemura T, Kuddus RH (2000) Endotoxin causes up-regulation of endothelin receptors in cultured hepatic stellate cells via nitric oxide-dependent and -independent mechanisms. Br J Pharmacol 131:319-327.
Uemura T, Gandhi CR (2001) Inhibition of DNA synthesis in cultured hepatocytes by endotoxin-conditioned medium of activated stellate cells is transforming growth factor- - and nitric oxide-independent. Br J Pharmacol 133:1125-1133.
Anselmi K, Subbotin VM, Nemoto EM, Gandhi CR (2002) Accelerated reversal of carbon tetrachloride-induced cirrhosis in rats by endothelin receptor antagonist TAK-044. J Gastroenterol Hepatol 17:589-597.
Gandhi CR, Murase N, Subbotin VM, Uemura T, Nalesnik M, Demetris AJ, Fung JJ, Starzl TE (2002) Portacaval shunt causes apoptosis and liver atrophy despite increases in endogenous levels of major hepatic growth factors J Hepatology 37:340-348.
Yang Y, Harvey SAK, Gandhi CR. (2003) Kupffer cells are a major source of platelet-activating factor in the CCl4-induced cirrhotic rat liver. J Hepatol. 39:200-207.
Yang Y, Nemoto E, Harvey SAK, Subbotin VM, Gandhi CR. (2004) CCl4-induced cirrhosis in rats increases hepatic expression of platelet-activating factor and its receptor- Implications in chronic liver injury. In the Press: Gut.
Thirunavukkarasu C, Yang Y, Subbotin VM, Harvey SAK, Fung J, Gandhi CR. (2004) Endothelin receptor antagonist TAK-044 arrests and reverses the development of carbon tetrachloride-induced cirrhosis in rats. In the Press: Gut.
