Research Interests
The overall interest of the laboratory is mechanisms of liver injury. In particular, the lab focuses on the role of coagulation in liver injury induced by xenobiotics. Tissue factor (TF) is the principal initiator of the coagulation cascade. TF has been shown to play a role in several biological processes including hemostasis, thrombosis, inflammation, angiogenesis and development. Coagulation contributes to liver injury in models of hepatic ischemia-reperfusion and partial hepatectomy. In addition, the coagulation system contributes to the hepatotoxic effects of numerous xenobiotics. However, few studies have examined whether TF is involved in xenobiotic-induced coagulation and hepatotoxicity. Understanding the mechanisms by which TF is regulated by xenobiotics, and how TF contributes to liver injury may reveal novel strategies to limit toxicant-induced liver injury.
Current studies in the lab are focused on the role of TF in xenobiotic-induced coagulation and the mechanisms by which TF and coagulation contribute to the hepatotoxic effects of xenobiotics. Xenobiotics of interest include bacterial lipopolysaccharide, acetaminophen and cadmium. Studies in the lab fit one of two broad, interconnected themes:
The laboratory utilizes various cellular and molecular techniques to study the effects of xenobiotics on TF expression and activity in vitro. In addition, pharmacologic and genetic strategies are utilized to determine the role of TF in mouse models of xenobiotic-induced coagulation and hepatotoxicity.
Selected Publications
Ganey PE*, Luyendyk JP*, Newport SW, Eagle TM, Maddox JF, Mackman N and Roth RA. Role of the coagulation system in acetaminophen-induced hepatotoxicity. *Co-first author. Hepatology, In press.
Bergheim I, Guo L, Davis MA, Lambert JC, Beier JI, Duveau I, Luyendyk JP, Roth RA, and Arteel GE. (2006) Metformin prevents alcohol-induced liver injury in the mouse: critical role of plasminogen activator inhibitor-1. Gastroenterology, 130, 2099-2112.
Luyendyk JP, Lehman-McKeeman LD, Nelson DM, Bhaskaran VM, Reilly TP, Car BD, Cantor BD, Maddox JF, Ganey PE, Roth RA. (2006) Unique gene expression and hepatocellular injury in the lipopolysaccharide-ranitidine drug idiosyncrasy rat model: comparison with famotidine. Toxicol. Sci. 90, 569-585.
Luyendyk JP, Lehman-McKeeman LD, Nelson DM, Bhaskaran VM, Reilly TP, Car BD, Cantor BD, Deng X, Maddox JF, Ganey PE, Roth RA. (2006) Coagulation dependent gene expression and liver injury in rats given lipopolysaccharide with ranitidine but not with famotidine. J. Pharmacol. Exp. Ther. 317(2), 635-43.
Luyendyk JP, Shaw PJ, Green CD, Maddox JF, Ganey PE, Roth RA. (2005). Coagulation-mediated hypoxia and neutrophil-dependent hepatic injury in rats given lipopolysaccharide and ranitidine. J Pharmacol Exp Ther. 314,1023-31.
Luyendyk JP, Maddox JF, Green CD, Ganey PE, and Roth RA. (2004) Role of hepatic fibrin in idiosyncrasy-like liver injury from lipopolysaccharide-ranitidine coexposure in rats. Hepatology 40, 1342-51.
Luyendyk JP, Mattes WB, Burgoon LD, Zacharewski TR, Maddox JF, Cosma GN, Ganey PE, Roth RA. (2004) Gene Expression Analysis Points to Hemostasis in Livers of Rats Cotreated with Lipopolysaccharide and Ranitidine. Toxicol. Sci. 80, 203-13.
Luyendyk JP, Maddox JF, Cosma GN, Ganey PE, Cockerell GL and Roth RA. (2003) Ranitidine Treatment during a Modest Inflammatory Response Precipitates Idiosyncrasy-like Liver Injury in Rats. J. Pharmacol. Exp. Ther. 307, 9-16.
Luyendyk JP, Copple BL, Barton CC, Ganey PE and Roth RA (2003) Augmentation of aflatoxin B1 hepatotoxicity by endotoxin: involvement of endothelium and the coagulation system. Toxicol. Sci. 72(1), 171-81.
Search for Dr. Luyendyk’s publications using Pubmed.
Contact Information
James Luyendyk, Ph.D.
Assistant Professor
Department of Pharmacology, Toxicology and Therapeutics
The University of Kansas Medical Center
4073 KSLIC, MS1018
3901 Rainbow Boulevard
Kansas City, KS 66160
Phone: (913) 588-9974
Fax: (913) 588-7501
E-mail address: jluyendyk@kumc.edu
Updated 7/24/07
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The University of Kansas Medical Center