Dr. Robert A. Edwards

Associate Professor, Clinical X Series


We are interested in the relationship between chronic inflammation and colorectal carcinogenesis in human and animal models. There are two general areas of study in the lab. The first involves the Giα2-deficient mouse model of colitis-associated colon cancer (CAC). These mice spontaneously develop severe chronic inflammation of the colon at an early age. Left unchecked, they go on to develop mucinous, non-polypoid adenocarcinomas of the colon. We have shown that these animals are an accurate mimic of human CAC, and that hypoxic inflammation appears to suppress DNA mismatch repair activity by epigenetically silencing the expression of Mlh1. We are studying the mechanism(s) by which hypoxic and/or inflammatory signaling affects DNA mismatch repair. We are also using cre-lox technology to assess the contribution of Giα2 signaling in different cellular compartments to the loss of DNA mismatch repair activity and subsequent CAC development. The other area of interest involves translational research projects performed in collaboration with several clinical investigators at UCI and other instutitions. One ongoing project involves a proteomics approach to the serologic diagnosis of IBD and responses to biologic therapies, using patient samples collected at UCIMC. Another study involves evaluation of epigenetic alterations in DNA mismatch repair gene promoters that suppress DNA mismatch repair activity in pre-neoplastic IBD mucosa. A third aims to define a gene expression signature that predicts long-term survival in Stage II and III colorectal cancer, utilizing genome-wide mRNA expression analysis of material isolated from archival tissue specimens.