Gene expression-based screening of inhibitors of signal transduction

Advances in our understanding of cellular function and signal transduction have resulted in ever increasing number of therapeutical targets and, consequently, underscored a demand for simple and universally applicable markers to monitor activity of the biological system. Gene expression-based screening is based on the assumption that introduction of a compound into biological system would affect directly or indirectly the gene expression, initiating an elaborate expression response to the disturbance of the system. In my thesis work I investigated new strategies to create a limited expression signature accurately representing the activation state of a biological system and to decrease redundancy in the complex expression pattern. To test the validity of our approach, I generated an expression signature for PDGF activation of ERK pathway in human fibroblasts and used this signature to screen a chemical compound library for an inhibitor of PDGFR/ERK pathway. As a result of the screen, I identified aurintricarboxylic acid, ATA, as a new inhibitor of PDGF receptor. The success of this study suggests that endogenous mRNA expression signature is an effective tool to monitor activation state of a cell signaling pathway and can be broadly used to identify compounds modulating condition of a biological system.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Antipova, Alena A

Advisor dc:contributor.advisor

• Robert J. Silbey.

• Chemistry.

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/1721.1/34500
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/34500

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34500