# Mitochondrial Dynamics in Brain TumorInitiating Cells

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $322,000

## Abstract

ABSTRACT
Glioblastomas rank among the most lethal of cancers with decades of research adding only a few months
to the median survival of patients afflicted with these tumors. The limitations in current therapy have many
causes, but one contributing force is the presence of complex cellular heterogeneity that phenocopies the
normal brain hierarchy. Normal tissue specific stem cells within this hierarchy pose a danger due to their
ability to undergo sustained proliferation. In healthy tissues, stem cells reside in specific niches that provide
maintenance cues that constrain proliferation, and these same cells differentiate upon exiting the niche. The
stem cell microenvironment is associated with regional variation in oxygen, pH, and nutrient availability.
Thus, it is almost certain that the metabolic reprogramming that occurs within the context of oncogenesis
represents an element of the cancer stem cell niche. As mitochondrial morphology is linked to metabolic
capacity and lineage specification, we are investigating the role of mitochondrial dynamics in driving
bioenergetic changes that promote cancer stem cell growth and proliferation. In preliminary studies, glioma
stem cells were found to exhibit molecular regulation of mitochondrial fission that was distinct from non-
stem tumor cells and neuroprogenitors. As targeting mitochondrial dynamics has been linked to neural
protection in degenerative disease, we propose that targeting this heterogeneity in mitochondrial dynamics
may represent a selective point of vulnerability for glioma stem cells. In the proposed studies, we will
investigate the role of mitochondrial fission in sustaining cancer stem cell health and as a therapeutic
modality. Collectively, successful completion of the proposed experiments will provide an enhanced model
of glioma hierarchy and drive the development of novel clinical therapies.

## Key facts

- **NIH application ID:** 10248489
- **Project number:** 5R01CA208516-05
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Jason Mears
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $322,000
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248489

## Citation

> US National Institutes of Health, RePORTER application 10248489, Mitochondrial Dynamics in Brain TumorInitiating Cells (5R01CA208516-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10248489. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*