Mark R. Frey, PhD

My laboratory’s research program is focused on the role of ErbB receptor tyrosine kinases in intestinal homeostasis and health. In particular, we are investigating how the neuregulin receptors ErbB4 and ErbB3 help maintain intestinal epithelial barrier integrity in the face of injury and inflammation. We were the first to report a functional role for ErbB4 in the intestine, showing that it is up-regulated in response to injury and necessary for survival of colon epithelial cells in the presence of TNF. We further demonstrated that the ErbB4-specific ligand NRG4 is protective in rodent models of inflammatory bowel disease and necrotizing enterocolitis.

While ErbB receptor activation is potentially therapeutic for intestinal inflammation, altered expression or activity in the context of colorectal cancer could make this pathway a double-edged sword. We have demonstrated that ErbB4 expression is elevated in a substantial subset of human colon tumors. Furthermore, ErbB4 overexpression can enhance mutant Ras- and Apc-driven colonocyte transformation. Interestingly, however, it is not able to drive transformation on its own, and a subset of human tumors have quite low expression. Thus, while ErbB4 is neither necessary nor sufficient to drive tumorigenesis, it can enhance the survival of transformed cells, and targeting ErbB4 in tumors that over-express it is a potential avenue for inhibiting tumor cell survival.

Research Interests: Signal transduction, wound healing, inflammation

Disease Models: Cell, enteroid, and in vivo models of inflammatory bowel disease, colitis-associated colon cancer, and necrotizing enterocolitis.

• The Gastrointestinal Epithelium Conference – Interface with the Outside World
  NIH · R13DK137548 · Aug 1, 2023 – Jul 31, 2024 · Role: Principal Investigator
• The role of SPRY2 in the colonic epithelial response to inflammation
  NIH · R01DK119694 · Aug 20, 2019 – May 31, 2024 · Role: Principal Investigator
• The role of the ErbB4 and ErbB3 neuregulin receptors in intestinal epithelial regeneration
  NIH · R01DK095004 · Jul 1, 2013 – May 31, 2024 · Role: Principal Investigator
• Regulation of cyclooxygenase-2 by ErbB4 in colon epithelial cells
  NIH · R03DK090295 · Apr 1, 2011 – Mar 31, 2013 · Role: Principal Investigator
• The role of ErbB-4 in inflammation-induced colon carcinogenesis
  NIH · K01DK077956 · Apr 1, 2007 – Mar 31, 2012 · Role: Principal Investigator

• Breast Milk May be Protective Against Devastating Intestinal Disorder (9/9/2014)

• Lenz, Heinz-Josef
• Chai, Yang
• Zhang, Lin
• Chuong, Cheng-Ming
• Yu, Jian
• Akbari, Omid