Jacquelyn Maher, MD

Professor
Department of Medicine - Gastroenterology
Research Overview: 

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: 

Visceral Adipose Tissue Inflammation and Radiographic Visceral-to-Subcutaneous Adipose Tissue Ratio in Patients with Cirrhosis.

Digestive diseases and sciences

Ha NB, Cho SJ, Mohamad Y, Kent D, Jun G, Wong R, Swarnakar V, Lin S, Maher JJ, Lai JC

Doxycycline Significantly Enhances Induction of iPSCs to Endoderm by Enhancing Survival via AKT Phosphorylation.

The FASEB Journal

Caitlin Peaslee, Tao Su, Cristina Esteva-Font, Caroline Duwaerts, Ke Liu, Antonio Munoz-Howell, Marisa Medina, Jacquelyn Maher, Aras Mattis

Doxycycline Significantly Enhances Induction of iPSCs to Endoderm by Enhancing survival via AKT Phosphorylation.

Hepatology (Baltimore, Md.)

Peaslee C, Esteva-Font C, Su T, Munoz-Howell A, Duwaerts C, Liu Z, Rao S, Liu K, Medina M, Sneddon JB, Maher JJ, Mattis AN

iPSC-derived hepatocytes from patients with nonalcoholic fatty liver disease display a disease-specific gene expression profile.

Gastroenterology

Duwaerts CC, Le Guillou D, Her CL, Phillips NJ, Willenbring H, Mattis AN, Maher JJ

Hepatocyte-specific deletion of XBP1 sensitizes mice to liver injury through hyperactivation of IRE1α.

Cell death and differentiation

Duwaerts CC, Siao K, Soon RK, Her C, Iwawaki T, Kohno K, Mattis AN, Maher JJ