A few of our ongoing projects are detailed below.

WNT Signaling in Animal Development and Human Disease

The Wnt signal transduction pathway controls cell proliferation and fate specification in all animals. Deregulation of Wnt signaling causes numerous birth defects and cancers, including nearly all colorectal cancers, the second leading cause of cancer-related death. Therefore, our understanding of Wnt regulatory mechanisms is crucial. Despite the critical role of Wnt signaling in animal development and human diseases, many of the underlying mechanisms remain poorly understood. We work at the interface between developmental biology and cancer biology to uncover these mechanisms, with the long-term goals of better understanding morphogen signaling in animal development and developing new strategies to treat Wnt-driven diseases. To identify and elucidate the roles of previously unknown Wnt pathway activators, we couple state-of-the-art CRISPR-based genetic approaches, super-resolution confocal microscopy, and biochemistry in Drosophila and in mammalian cells. In collaboration, we expand our findings to mouse and human cancer models.

Current Projects

Central mechanistic questions regarding the assembly and regulation of core Wnt signaling complexes remain unanswered. This obstacle has hindered the understanding of fundamental concepts in developmental biology and the identification of new therapeutic strategies for Wnt-driven diseases. We seek to fill these major gaps in our understanding of how Wnt ligands transmit information to the signaling machinery that ultimately activates the pathway. Enabled by genome-wide screens to uncover new Wnt signaling regulators, our current projects focus on the following: 

· Regulation of the essential receptors that engage Wnt ligands to activate signaling 

· Identification and characterization of nuclear kinases that promote Wnt target gene activation 

· Elucidation of  E3 ubiquitin ligases and deubiquitinases that regulate Wnt signaling  

· Identification of therapeutic targets for Wnt-driven cancers 

· Identification of small molecule inhibitors of Wnt signaling to facilitate drug development

 To learn more, click below for Yashi’s plenary talk at the 2018 Annual Drosophila Research Conference,  courtesy of the Genetics Society of America: