Pamela Kreeger

BioSketch

B.S. Chemistry, Valparaiso University 2000
Ph.D. Chemical Engineering, Northwestern University 2005
Postdoctoral Associate, Lauffenburger Lab, MIT, August 2005 – present

Primary Collaborators

Kevin Haigis, Jacks Lab, MIT

Research Interests

I am examining how two isoforms of Ras (K-Ras and N-Ras) impact apoptosis in the colon. Previous studies suggest that activated K-Ras sensitizes cells to apoptosis, while N-Ras provides an anti-apoptotic signal. This work builds upon a previous CDP research project (Janes, et al, Science 2005), and attempts to address two important issues.

First, can cue-signal-response models be developed where the ‘cue’ is an intrinsic part of the cell, such as a genetic mutation? To build such a model, we are utilizing a panel of human colon carcinoma cell lines that have distinct genetic manipulations to both K-Ras and N-Ras. These cell lines show different levels of apoptosis following treatment with TNF, and have differences in both basal and stimulated signaling of key intracellular molecules such as ERK and JNK. Secondly, can cue-signal-response models be developed for more complicated paradigms, especially in vivo models? This project will be done in collaboration with the Jacks lab, utilizing their genetic mouse models of human cancer. To correlate to our in vitro studies, we will generate a dataset of intracellular signaling and apoptosis in the intestinal epithelium of mice with defined K-Ras and N-Ras genotypes.