Since 2003, I studied the role of specific gene regulators involved in maintaining epithelial integrity. With the obtention of more than 9M$ in external operating funds as principal investigator (CIHR, NSERC, CCC, Weston, CRS, CFI), I addressed fundamental research questions and gradually identified a set of molecules with high relevance for intestinal diseases. Through the development of novel cellular tools, I identified HNF4A as a crucial player in driving intestinal epithelial cell fate (Babeu et al., 2009, cited 115 times). The generation of a conditional intestinal knockout mouse model for Hnf4a led to the discovery that these mice spontaneously manifest symptoms associated with human intestinal bowel diseases. Two months later, the UK IBD Genetics Consortium reported HNF4A as a susceptibility locus in ulcerative colitis. HNF4A was also suspected to act as a tumor suppressor gene in epithelial tissues because of its anti-proliferative properties. Against all odds, we found that HNF4A was essential during the initiation and progression of intestinal tumorigenesis. In addition, specific oncogenic and antitumoral functions were attributed to the two different classes of HNF4A isoforms during colorectal cancer. I was able to pair up with clinicians to discover a
provocative link between intestinal HNF4A and adipose tissue metabolism via the control of glucosedependent insulinotropic polypeptide (GIP) intestinal hormone. This work illustrates how our basic research program is now contributing to discovering novel therapeutics to be exploited in humans. Overall, I have published 82 research articles and seven reviews, including publications in both high impact and leading journals in the gastroenterology, cancer and metabolism disease fields (Nature Communications, Gastroenterology, Cancer Research, Diabetes, CMGH, IBD) and recognized journals in molecular and cell biology (FASEB Journal, Molecular & Cellular Proteomics, Journal of Biological Chemistry, Molecular and Cellular Biology). I have presented over 40 guest-speaker presentations worldwide, including Canada, USA, France, China, Spain, Greece, and Sweden. Finally, I have pioneered the launch of a local biobank for digestive disease patient-derived organoids. We recently teamed up with both UofCalgary and UBC gastrointestinal centers to create CNON. This Network aims to study how human tissues interact with resident microbes and to provide access to training, optimized protocols, and biomaterial to the Canadian research population spanning from coast to coast.