Yap1 as a New Therapeutic Target in Neurofibromatosis Type 2
Final rept. 1 Sep 2010-28 Feb 2014
CHILDREN'S HOSPITAL CORP BOSTON MA
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We hypothesized that Yap1 activity is critical for the growth-suppressing activity of Merlin, and that downmodulation of Yap1 function might constitute a novel therapeutic approach for the treatment of neurofibromatosis and other NF2-null tumors. In Aim 1, we tested whether ablation or reduction of Yap1 activity suppresses Nf2-null phenotypes in vivo. In aim 2, we attempted to identify novel proteins and small molecules that negatively regulate Yap1 activity. We have demonstrated in fact that Nf2-ablation induces YAP activity in multiple tissues in mice. We have also established a reporter system for YAP activity and have finished a genetic screen identifying kinases that might activate YAP1.
- Medicine and Medical Research