Dr. Wehrli’s interest is in identifying the Wnt/?-catenin signaling mechanism, and how it differs depending on cellular context and developmental stage by using the fruit fly Drosophila as a model organism. One focus of Dr. Wehrli’s research has been how the Wnt receptor subunit Arrow/LRP, which he previously identified as a novel component in the Wnt pathway, functions.  As part of the receptor, Arrow functions in signal initiation; however, Arrow also has a second function in signal amplification, during which Arrow binds to and inhibits the cytoplasmic protein Axin. As a scaffold protein, Axin assembles the central regulatory complex in the Wnt pathway. Recent work has revealed that this complex, which also includes fly APC and GSK3ß, is assembled very robustly and largely resists inactivation by mutations. Ongoing work aims to determine the extent of this resilience and to model what combinations of mutations are sufficient to significantly disrupt its function.  This research will provide insight into understanding genetic interactions and risk factors that lead to human disease, including cancer, osteoporosis and cardiovascular disease.