The Yeatman/Pledger laboratory is focused on the molecular aspects of colorectal cancer (CRC) that influence tumor progression, serve as new targets for therapy and predict drug sensitivity/response. We based much of this research on a large, comprehensive human databases (n = 2000) containing both gene expression and sequencing data. We have identified a method to leverage gene expression signatures to identify impactful mutations that can influence tumor development or serve as biomarkers or targets for therapy. We have identified a receptor tyrosine phosphatase, PTPRS, that appears to regulate RAS pathway activation through ERK. We are interested in how this frequently mutated gene may alter drug sensitivity and recently described "adaptive resistance" to RAS pathway inhibitors (KRAS, BRAF, MEK, ERK). Our experiments study functional genomics of specific mutations and signal transduction that relate them to biomarkers and possible targets we have discovered. Additionally, we have now explored possible situations in CRC for repurposing FDA approved drugs such as EGFRi and SRCi. Other mutations that may be involved in CRC tumor development, progression and drug sensitivity which we may uncovered in our database will be investigated. The laboratory also seeks to explore mechanisms of growth regulation, stem cell development and metastasis that are altered in CRC.
Timothy J. Yeatman, MD
W. Jack Pledger, PhD