A computational and experimental study of HER2-signaling effects on cellular migration and proliferation

The fundamental question posed in this thesis is: how does a cell 'decide' to behave in a particular way? The human body is comprised of [approx.] 1014 cells that interpret extracellular information and respond with such behavior as migration, proliferation, apoptosis, or differentiation. Thirty years of research in the related fields of biochemistry, molecular biology, and genetics have demonstrated that, in most cases, the cellular decision-making process cannot be described or predicted by regulation of only one gene or one protein alone. Instead, it has become clear that cellular behavior is a function of information flow through multiple intracellular molecules. Furthermore, the molecules responsible for the control of cell behavior comprise a surprisingly short list, indicating that factors such as signaling dynamics and intensity coupled with combinatorial control are essential to produce the wide array of observed cell behavior. The identification of protein kinases as transducers of large amounts of intracellular information led us to pose the hypothesis that the quantitative regulation of key kinases governs cellular behavior. The goal of this thesis was to identify rules governing multi-kinase behavioral control and to then, on the basis of these rules, predict changes in cell function in response to changes in receptor expression, ligand treatment, and pharmacological intervention.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Kumar, Neil

Advisor dc:contributor.advisor

• Douglas A. Lauffenburger.

• 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/1721.1/39263
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/39263

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/39263