Jacquelyn Maher, MD

Professor
Department of Medicine - Gastroenterology
jmaher@medsfgh.ucsf.edu

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.

Primary Thematic Area: 
Tissue / Organ Biology & Endocrinology
Secondary Thematic Area: 
Vascular & Cardiac Biology
Research Summary: 
Tissue-protective cytokines; fatty liver disease

Websites

Publications: 

Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice.

Cellular and molecular gastroenterology and hepatology

Duwaerts CC, Amin AM, Siao K, Her C, Fitch M, Beysen C, Turner SM, Goodsell A, Baron JL, Grenert JP, Cho SJ, Maher JJ

Nonalcoholic fatty liver disease.

Nature reviews. Disease primers

Brunt EM, Wong VW, Nobili V, Day CP, Sookoian S, Maher JJ, Bugianesi E, Sirlin CB, Neuschwander-Tetri BA, Rinella ME

Isocaloric manipulation of macronutrients within a high-carbohydrate/moderate-fat diet induces unique effects on hepatic lipogenesis, steatosis and liver injury.

The Journal of nutritional biochemistry

Pierce AA, Duwaerts CC, Soon RK, Siao K, Grenert JP, Fitch M, Hellerstein MK, Beysen C, Turner SM, Maher JJ