Stanley Fisher, MD

The Role of Lipoproteins in Developmental Susceptibility to Hepatic Injury and Fibosis:

In collaboration with Dr. Mahmood Hussain, Associate Professor in the Department of Cell Biology and Dr. Andras Divald, Instructor in the Department of Pediatrics. Dr. Fisher's research focuses on the role of lipoproteins in developmental susceptibility to hepatic injury and fibrosis.

Neonates are particularly susceptible to cholestasis and hepatic fibrosis when on total parenteral nutrition. One factor may be increased portal venous load or altered response to endotoxin that normally derives from the intestine. Synthesis and secretion of lipoproteins are thought to be affected by endotoxin, either directly or indirectly. Moreover, endotoxin is thought to be bound by lipoproteins, thereby reducing the toxic effect and/or cytokine-inflammatory response. Thus, there is an intimate relationship between lipoprotein metabolism and endotoxic effects. We propose to compare the effect of endotoxin and TNF-alpha on lipoprotein production by immature and adult hepatic cells. Likewise, the potential role of lipoprotein infusion on endotoxin/TNF effects will be studied. Hepatocytes and/or Kupffer cells are isolated from neonatal, adolescent and adult rats. In culture, molecular responses to endotoxin and TNF-alpha are determined. Kupffer cells will be used to study the effect of endotoxin on cytokine production. Furthermore, modulation of these effects by lipoproteins will be studied. Hepatocytes will be used to study the effect of endotoxin/TNF-alpha on lipoprotein production. These studies will provide significant new information about the molecular interplay between endotoxin and lipoprotein metabolism during total parental nutrition supplement to neonates.

Laboratory Members:

• Andras Divald, PhD
• Mahmood Hussain, PhD
• Stanley E. Fisher, MD

* Holds primary appointment in other department.

• Karl PI, Chusid J, Tagoe C, Fisher SE. Ca++ flux in human placental trophoblasts. Am J Physiol, 272:C1776-80, 1997
• Koniaris SG, Fisher SE, Rubin CT, Chawla A: Experimental colitis impairs linear bone growth independent of nutritional factors. J Pediatr Gastro Nutr, 25:137-141, 1997
• Akolkar PN, Gulwani-Akolkar B, Heresbach D, Lin X-Y, Fisher SE, Katz S, Silver J: Differences in risk of Crohn's disease in offspring of mothers and fathers with inflammatory bowel disease. Amer J Gastreoenterology, 92:2241-6, 1997
• Karl PI, Divald A, Diehl A-M, Fisher SE: Altered cAMP-dependent hCG production in cultured human placental trophoblasts exposed to ethanol. Biochem Pharmacol, 55:45-51, 1998
• Divald A, Karl PI, Fisher SE: Regulation of Phospholipase D in human placental trophoblasts by P2 purinergic receptors, submitted, Placenta

List of Publications (Pub Med)