Research efforts in my laboratory center around three major areas: 1) Studies of the biochemistry and genetics of secondary bile acid formation by intestinal anaerobic bacteria: implications for colon cancer and cholesterol gallstone disease; 2) bile acids activated cell signaling pathways in hepatocytes and regulation of bile acid synthesis and glucose metabolism. Isolation and characterization of bile acid activated G-protein coupled receptors from primary rodent and human hepatocytes; 3) HIV protease inhibitors and hyperlipidemias. Increased levels of secondary bile acids (deoxycholic and lithocholic acid) in blood, bile and feces have been correlated with an increased incidence of colon cancer and cholesterol gallstone formation in some patients. We are seeking ways to inhibit secondary bile acid formation in humans. We are also investigating how bile acid activated cell signaling pathways are involved in the regulation of bile acid synthesis and glucose metabolism in the liver. Finally, we are investigating how different HIV protease inhibitors cause hyperlipidemias and accelerated heart disease in patients taking these drugs.