# Developmental regulation of apoptosis as a modifiable driver of radiotherapy-induced neurocognitive impairment in pediatric patients

> **NIH NIH R37** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2024 · $90,053

## Abstract

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.

## Key facts

- **NIH application ID:** 10993314
- **Project number:** 3R37CA248565-05S1
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Kristopher Andrew Sarosiek
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $90,053
- **Award type:** 3
- **Project period:** 2020-03-09 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993314

## Citation

> US National Institutes of Health, RePORTER application 10993314, Developmental regulation of apoptosis as a modifiable driver of radiotherapy-induced neurocognitive impairment in pediatric patients (3R37CA248565-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10993314. Licensed CC0.

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