QSB: Experimental and Computational Studies to Optimize Hepatocyte Function

Ierapetritou

0424968

The objective of this research is to develop systems-based quantitative approaches that consider the whole picture of cell metabolism, including intra and inter compartmental processes within a multi-objective framework. This is needed in order to investigate the characteristics of hepatocyte cells, the role of specific functions in bioartificial liver systems, and the optimization of their performance. Their hypothesis is that there is a finite number of hepatic functions which are most critical for patient survival, that it is possible to significantly upregulate these functions in hepatocyte cultures, and as a result, maximize cell function and reduce the cell mass required in the bioartificial liver. In particular, the specific aims for this research are: (1) to characterize and optimize substrate supplementation to enhance hepatocyte function, (2) to modulate the hepatocyte function through the use of antisense technology with the target to examine different substrates and validate the importance of different pathways as predicted by specific aim 1, and (3) to develop a quantitative analysis to study the effects of uncertainty considerations mainly due to variability of plasma concentration.