Assistant Professor, Eppley Institute
Ph.D. - Zhejiang University, China
Hippo signaling and Cancer
Summary of Research
My laboratory is focused on the Hippo signaling pathway, a novel tumor suppressor cascade discovered in Drosophila. Recent studies have demonstrated that the Hippo signaling plays an important role in controlling organ size by coordination of cell proliferation and cell death or apoptosis.
The Hippo signaling pathway is highly conserved in mammals and consists of five core components: tumor suppressors Hippo/Hpo (human MST1/2), Salvador/Sav (human WW45), Warts/Wts (human Lats1/2), Mob as tumor suppressor/Mats (human Mob1) and oncoprotein Yorkie/Yki (human YAP). Hpo/MST phosphorylates and activates Wts/Lats, which in turn, inactivates Yki/YAP by phosphorylating them at a critical residue (Yki-S168/YAP-S127). Tumor suppressors Fat, Merlin and Expanded functions upstream of Hippo signaling, however, the precise mechanisms by which they influence Hpo signaling have not yet been determined. Transcription factors Scalloped/TEAD mediate the growth output of the Hippo signaling.
Yki activates many genes including the microRNA bantam, however, the mammalian ortholog of bantam does not exist. It would be significant to identify the common target in Drosophila and mammalian Hippo signaling.
While extensive studies have been done in Drosophila, the mammalian Hippo signaling pathway was not established until 2007 when it was shown to inhibit the transcriptional co-activator YAP by phosphorylation. The regulation and functions of Hippo pathway in mammalian cells are largely unknown. We are currently dissecting the mammalian Hippo pathway in human cancers by combined approaches of molecular biology, biochemistry and genetics.
We are also interested in identifying additional components of the Hippo pathway. It will greatly facilitate to elucidate the physiological regulation of the pathway and to understand how dysregulation of the pathway leads to tumorigenesis.
Email: Jixin Dong