Molecular, Biological, and Immunological Approaches to Understanding Tissue Regeneration.

Description of projects available to graduate students:
In order to comprehend the biology of diseases such as cancer, it is necessary to first understand how the normal tissue reacts to stress. Historically, the focus of this lab has been to discern how the plasminogen activator (PA) "system" contributes to normal tissue regeneration by using normal regeneration models such as partial hepatectomy (PHx) and carbon tetrachloride poisoning of the liver. We and others have determined that in regenerating liver, both the urokinase-type plasminogen activator (u-PA) and one of its primary substrates, hepatocyte growth factor (HGF), are essential for normal liver growth. These findings were also expanded in the context of the u-PAR receptor (u-PAR) and an impact on neuronal development was found. Published and unpublished findings indicate that livers from u-PA, u-PAR and PAI-1 (a u-PA inhibitor) knockouts have significant differences at both the cellular and RNA levels from their wild type counterparts. Several projects related to expansion of these observations are available using normal and transgenic animals as a tool. Additionally, another project focuses on the ability of active HGF to suppress the acute phase response by suppressing hepatic IL-6 production. A third area of study focuses on studies related to the spatial and temporal regulation of the tissue-plasminogen activator (t-PA), as well as it's targets, competitors (alpha defensins), and receptors during the development of fibrosis, a pre-cancerous condition.

Techniques graduate student will learn:
In addition to a newly developed method of fluorescent double-labeling of mRNAs and proteins in individual cells, most molecular (northern blots, arrays, PCR, cloning, southerns, etc.) and cell biology techniques (western blots, immunoprecipitation, histochemistry, protein/protein interactions), are also standard in the lab. Animal surgeries and cell culture are also routine. In addition, we routinely use zymography to assay function of plasminogen activators and gelatinases.