Keywords: Hepatotoxicity; Endothelial cell biology; Lipid metabolism and steatohepatitis
Our laboratory studies basic biological processes relevant to liver biology and disease. We use a variety of animal models, as well as primary liver cell cultures, to explore several projects as outlined below.
1. Hepatotoxicity and hepatoprotective agents . We are evaluating compounds with anti-apoptotic activity that may be useful for treating fulminant hepatic failure and for preventing early graft failure after liver transplantation. One promising compound affects endothelial cells preferentially, and thus we are exploring its effects on hepatic endothelial cell survival and repair.
2. Pathogenesis of fatty liver disease . We are investigating the metabolism of saturated fatty acids in primary hepatocyte culture in an effort to define the events that lead to lipotoxicity. In parallel, we are using animal models to determine the influence of individual dietary nutrients on the development and progression of fatty liver disease. We have determined that a polyunsaturated fat-rich diet provokes hepatic inflammation but does not cause hepatocyte cytotoxicity. In contrast, dietary sugar is hepatotoxic, probably because of its conversion in the liver to saturated fatty acid.
3. Regulation of stearoyl-CoA desaturase-1 (SCD-1). We are interested in the regulation of SCD-1 because of its pivotal role upstream of both triglyceride and phospholipid synthesis. We are interested in the potential for this enzyme to direct fatty acids toward one pathway or the other depending upon cellular needs. We are also exploring the influence of SCD-1 on fatty acid metabolism and energy expenditure.
Hanson JC, Bostick MK, Campe CB, Kodali P, Lee G, Yan J, Maher JJ. Transgenic overexpression of interleukin-8 in mouse liver protects against galactosamine/endotoxin toxicity Journal of Hepatology 2006;44:359-367.
Lee G, Yan J, Ng RK, Kakar S, Maher JJ. Polyunsaturated fat in the methionine-choline-deficient diet influences hepatic inflammation but not hepatocellular injury Journal of Lipid Research 2007, epub May 27. Rizki G, Arnaboldi L, Gabrielli B, Lee G, Yan J, Ng R, Turner S, Badger TM, Pitas RE, Maher JJ. Mice fed a lipogenic diet lacking methionine and choline develop hypermetabolism and weight loss coincident with hepatic suppression of stearoyl-CoA desaturase-1. Journal of Lipid Research 2006;47:2280-2290.