Medulloblastoma (MB) arises in the cerebellum. Group 3, one of four MB subgroups (WNT, SHH, Group 3, and Group 4), is the most aggressive and malignant type in children. Group 3 is characterized by frequent metastasis at diagnosis and the worst prognosis. Although surgical resection, radiotherapy, and chemotherapy are effective at eliminating some forms, patients with Group 3 cannot be cured with conventional therapies and also face a paucity of molecularly targeted therapies.

Hematopoietic stem cell (HSC) transplant is an essential component of cancer therapy for pediatric patients with aggressive leukemias that have relapsed or are at high risk of relapse. Donor HSCs regenerate blood and immune cells in the patient, and if the function of these donor cells is impaired, the recovery process after HSC transplant is delayed. The number of HSCs received from the donor is traditionally used to predict the success of the HSC transplant, but cell dose is not always the best predictor of transplant success.

Cancer is the leading cause of disease-related death among American children. Despite significant progress in recent decades, which has provided the possibility of a cure for many diagnosed children, we have not succeeded in improving the prognosis for certain cancer subtypes that have seen no advancement in the last 50 years. A key player in many of these aggressive subtypes is a gene called MYC. When MYC becomes overactive, it can cause cells to grow and divide uncontrollably, as well as evade the body's natural anti-cancer mechanisms.

This study is about finding new ways to fight cancer, especially in children with a cancer called neuroblastoma. Neuroblastoma is tricky to treat because the cancer cells can become resistant to chemotherapy, meaning the drugs don't work as well over time. The cancer cells can switch between two different states: one where they are sensitive to drugs and one where usual cancer treatments do not work well. Here, I am proposing to understand how these cells switch between these states, which allows them to survive and avoid our best treatments.