Characterizing the Hippo pathway in high-risk neuroblastoma
Mentor Name: Kelly Goldsmith
Neuroblastoma is the most common solid tumor that occurs outside of the brain and central nervous system in children. It accounts for 8% of childhood cancers but is responsible for 15% of all childhood cancer-related deaths. Despite multimodal treatments such as chemotherapy, surgery, and back-to-back autologous stem cells transplants after high dose chemotherapy, half of patients with high-risk neuroblastoma end up with their cancer returning. Our laboratory has previously identified the Yes-Associated Protein (YAP) as a potential therapeutic target for high-risk, relapsed neuroblastoma. Genetic inhibition of YAP in neuroblastoma led to improved chemotherapy and targeted therapy responses; however, YAP inhibitors are not as potent as expected, and we still do not currently understand how YAP becomes dysregulated in neuroblastoma. This project aims to further characterize the upstream Hippo pathway to understand the regulation of its downstream effector protein, YAP. We will utilize our molecular biology expertise to define the Hippo signaling pathway in our different high-risk neuroblastoma human-derived cell line models. The ultimate goal of the project is to identify potential vulnerabilities that will allow targeting of the Hippo/YAP pathway to improve outcomes in high-risk neuroblastoma.
