Africa Fernandez, Ph.D., Memorial Sloan-Kettering Cancer Center
first year funding, 2010 – 2011
Medulloblastomas are brain tumors arising in the cerebellum, and they are the most common kind of solid tumor of childhood. Current treatments for these tumors leave patients with life-long damage, since the treatments affect the still-developing brain. Identifying therapies that attack the tumors and spare the rest of the brain is critical. Medulloblastomas are thought to arise from immature cells in the cerebellum. When the brain is developing during infancy and childhood, a growth-promoting protein, Sonic Hedgehog (Shh), is necessary for these immature cells to divide. We found that Shh induces an increase in the levels of a protein called YAP, and that high levels of YAP are present in mouse and human medulloblastomas. My work showed that YAP can make immature cerebellum cells divide even in the absence of Shh. Furthermore, in medulloblastomas, cells with high levels of YAP are resistant to radiation treatment and can start dividing, causing the tumor to grow back. Therefore, YAP is a new potential target for medulloblastoma therapies aimed at eliminating these tumor re-growing cells. My studies in mouse models for medulloblastoma focus on understanding how YAP helps tumor cells survive radiation, and how reducing YAP levels or activity can potentially make medulloblastomas more sensitive to radiation and other treatments.