Zheng "John" Fu, PhD
Research Interests: Protein Phosphorylation and Gastrointestinal Cancer Cell Signaling
The overall research interest of my lab is to understand the cellular and molecular mechanisms that govern cell growth, proliferation and differentiation, and their relationship to cancer. The current focus is on elucidating the role and the molecular mechanism of a novel protein kinase signaling pathway in the regulation of cell proliferation and differentiation in the intestinal epithelium. Intestinal cell kinase (ICK), originally cloned from the intestine and expressed in the intestinal crypt epithelium, is a highly conserved and ubiquitously expressed serine/threonine protein kinase. Although ICK has similarities in the catalytic domain to both CDKs and MAPKs and is regulated by dual phosphorylation within a MAPK-like TDY motif, its biological functions and signaling mechanism are still elusive. In Project 1, we are investigating the role and signaling mechanism of ICK in the regulation of cell proliferation and differentiation in the intestinal epithelium during homeostasis and regeneration using an intestine-specific knockout mouse model. In Project 2, we are elucidating the role of the ICK signaling pathway in GI cancer. Our preliminary data have indicated elevated expression of ICK in both primary and metastatic human colon cancer specimens as compared with their normal tissue controls. We will determine the oncogenic potential of ICK in vitro and using xenografts. We also plan to generate compound mouse models in which ICK gene is deleted in the background of known colon cancer mutations such as APCMin. These colon cancer mouse models will allow us to address whether ablation of the ICK gene in the intestine reduces tumor formation and/or progression. We are also interested in developing small molecule inhibitors for ICK to pursue translational research in GI cancer. This project involves collaborations with Cancer Center members Drs. Mike Weber and Chris Moskaluk.