Integrated characterization of cellular physiology underlying hepatic metabolism

The macroscopic metabolic phenotype of a cellular system, such as insulin resistance, is the result of the integration of many hundreds or thousands of preceding cellular events, which culminates in the cell's final response to a perturbation in the environment. The data provided by DNA microarrays and multiple types of metabolic measurements can be integrated to reconstruct the actions taken by a cellular system to arrive at a particular metabolic response to a stimulus, elucidating the underlying physiology. We employed this integrated approach for the characterization of hepatic metabolism. First, we implemented a novel method for functional genomics. The metabolic response of hepatoma cells to the depletion and repletion of glutamine was characterized in time course measurements of metabolic fluxes and metabolite pool sizes. DNA microarrays characterized the expression profiles. The metabolic data were correlated with the microarray data to identify coregulated clusters of genes. This study contributed to our understanding of glutamine metabolism in hepatomas, and advanced the field of functional genomics. Next, we identified the hexosamine biosynthetic pathway (HBP) as a mechanism for hyperglycemia-induced hepatic insulin resistance.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Wong, Matthew Sing

Advisor dc:contributor.advisor

• Gregory Stephanopoulos.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/34560
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/34560

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34560