Date of Award

4-11-2011

Degree Type

Thesis

First Advisor

Thesis Advisor: Amy G. Aslamkhan, Ph.D.

Second Advisor

Gerald B. Grunwald, Ph.D.

Third Advisor

James J. Monroe, Ph.D.

Abstract

Characterization of transcriptional changes after partial hepatectomy (PH) may provide an understanding of the underlying biological processes involved in compensatory growth and regeneration of liver mass after drug induced liver injury (DILI). Development of this type of model would prove useful as a model for assessment of potential drug induced liver injury that induces a compensatory proliferative response. In this project, we developed a surgical regeneration model (70% partial hepatectomy) in liver of male Sprague Dawley rats. Individual gene markers associated with a regenerative response in liver were evaluated in the partial hepatectomy model and compared to five previous studies where compounds induced histopathological changes indicative of proliferative and or regenerative responses in the liver to DILI. The liver cell population and apoptosis biomarkers exhibited no apparent robust changes, while many of the proliferation markers were up-regulated. In two studies, pathway enrichment analysis using GeneGo MetaCore revealed that regulatory pathways related to cell proliferation were differentially expressed in response to partial hepatectomy.

Thomas Jefferson University of Graduate Studies
Masters of Cell & Developmental Biology