Associate Professor, Department of Medicine
Section of Gastroenterology
Committee on Molecular Metabolism and Nutrition
Cancer Research Center
University of Chicago
As a gastroenterologist and translational researcher, I have focused on interactions between diet and host responses in colon cancer development. Colon cancer is a leading cause of cancer-related deaths in the Western world. Western diets, rich in saturated animal fats and relatively deficient in vitamin D and calcium, are believed to contribute to colonic malignant transformation. Increasing evidence implicates the role of the microbiome in the effects of diet on colonic tumorigenesis. Understanding the complex interplay between diet, the microbiome and growth factor signals requires an organismal approach. Our laboratory has used carcinogen and genetic models of colonic tumorigenesis extensively to investigate growth factor signals and diet in premalignant and malignant lesions. We are also beginning to focus on diet- and tumor-induced alterations in the microbiome. We showed that the epidermal growth factor receptor (EGFR) plays an important role in AOM-induced tumor progression. More recently, we demonstrated that tumor promotion by Western diet required ADAM17, an up-stream activator of EGFR. In this regard, EGFR is rarely mutated or amplified in colon cancer, but rather activated by increases in receptor ligands that are released by ADAM17-mediated proteolysis. We showed ADAM17 was up-regulated and plays an oncogenic role in two independent models of colon cancer. Studies by others have shown that Toll like receptors that can be activated by microbes are required for EGFR ligand release in the colon, but the link between microbes and ADAM17 remains unknown and will be a future direction of our research.