CNS cancers account for 26% of pediatric cancers and are the leading cause of cancer deaths and morbidity. Medulloblastoma, the most common CNS cancer in children, is typically treated with high doses of external beam radiation therapy (xRT) and surgery. However, xRT induces apoptosis (programmed cell death) in cancerous as well as normal neural cells and can cause severe neurocognitive impairments, especially in the youngest children. Thus, there is an urgent need to investigate the causes of xRT-induced neurotoxicity to aid in the development of potential neuroprotective agents that will improve quality of life for childhood CNS cancer survivors. However, it is currently unclear which cells in the developing brain are most vulnerable to loss or dysfunction in response to xRT at different stages of differentiation to potentially drive neurocognitive impairment. The candidate will pursue this gap in our knowledge and contribute to the goals of the parent grant by using well-established in vitro neural cell differentiation models originating both from humans and mice to elucidate how apoptosis is regulated during cellular differentiation. Furthermore, these models will be used to test neural cell sensitivity to ionizing radiation and elucidate the mechanisms involved. The candidate will gain hands-on experience and mastery of advanced molecular biology techniques while also building technical knowledge, scientific rigor and scientific communication skills. With the support of this supplement, we will incorporate the student’s background in neurodevelopment into our study of apoptosis regulation in the developing brain and its causative role in xRT-induced neurocognitive impairment. Her proposed work not only aligns well with the objectives of the original R37 award but also has the potential to uncover novel mechanisms linking cellular differentiation with apoptosis suppression. Furthermore, the study will enable the candidate to develop the knowledge and skills necessary for a successful transition to an independent career as a molecular biologist specializing in radiation biology, toxicology, cancer biology and neurodevelopment.