Using High-Precision Signaling Activity Imaging to Personalize Ras Pathway Inhibition Strategies in Neurofibromatosis
Abstract
The goal of this project is to characterize differences in Ras pathway signaling in using live cell activity measurements in cell types and genetic contexts relevant to NF1. During this award period, we have completed data collection for single-cell measurements of ERK activity in both cell lines and in patient-derived fibroblasts. While both technical and biological variability are substantial in these experiments, we have developed improved methods of statistical comparisons to enable us to detect significant differences in signaling kinetics in NF1-deficient cells. Our results indicate that deficiency for NF1 results in elevated ERK activity in unstimulated cells, but has no measureable effect on growth-factor stimulated pathway activity. Based on initial studies of gene expression in response to altered ERK activity, we have identified characteristics of genes whose expression level is regulated by the integrated level of ERK activity over time, providing a potential mechanism by which the elevated baseline level of pathway activity in NF1 cells may alter gene expression profiles.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2018
- Accession Number
- AD1063065
Entities
People
- John G Albeck
Organizations
- University of California, Davis