# Targeting Purinergic Signaling to Block the Effects of Seizures on Glioma Progression

> **NIH NIH F30** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $50,937

## Abstract

PROJECT SUMMARY
There is growing evidence that neuronal activity contributes to glioma proliferation and progression, but the
molecular mechanisms by which this occurs are not well understood. Moreover, there has been limited study of
how endogenous neuronal activity, including spontaneous epileptic activity and sensory stimulus-evoked activity
affects glioma cells. A clearer mechanistic understanding of glioma responses to neuronal activity is critical to
identify novel therapeutic avenues. A consequence of neuronal hyperactivity and seizures is ATP release. The
purinergic receptor P2RX7 is expressed in human glioma and activated by high concentrations of extracellular
ATP, resulting in calcium influx. Calcium influx has been broadly implicated in glioma progression and shown to
be a functionally relevant consequence of neuron-glioma crosstalk. However, the role of P2RX7 in glioma has
not been well elucidated, and its role in tumor-promoting crosstalk between neurons and glioma cells has not
been studied. This proposal will investigate purinergic signaling as a means by which neuronal activity leads to
glioma progression at the infiltrative cortical margin. Aims 1 and 2 will utilize glioma cells genetically engineered
to express fluorescent reporters of calcium influx (GCaMP6s) and extracellular ATP (GRABATP1.0). In Aim 1, in
vitro imaging of glioma cells and ex vivo imaging and electrophysiology of acute tumor slices will be performed
to determine the function of purinergic receptors in glioma cell calcium responses to neuronal activity. Aim 1 will
also investigate the effects of purinergic signaling on glioma cell proliferation and assess P2RX7 expression in
human glioma at the infiltrative margin. Aim 2 will employ an orthotopic diffusely infiltrating GCaMP6s glioma
model that elicits neuronal pathology, including hyperexcitability and seizures. In vivo two-photon imaging and
two-color wide field optical mapping of neurons and glioma cells will be used to assess the effects of neuronal
activity, including epileptic events and stimulus-evoked activity, on glioma cell calcium activity and progression.
In both aims, purinergic signaling in glioma cells will be perturbed by P2RX7 knockout or the brain-permeable
P2RX7 inhibitor Brilliant Blue G to investigate its function in neuron-glioma crosstalk and glioma cell proliferation
and progression. As part of a comprehensive training plan, this project will be conducted at Columbia University
Irving Medical Center under the mentorship of my sponsor in collaboration with an interdisciplinary team of
physician- and basic scientists who will provide all the expertise and resources needed for me to develop a
strong foundation in brain tumor biology, ex vivo electrophysiology, and in vivo brain imaging, and an enhanced
ability to reason through research challenges. Clinical training will occur at NewYork-Presbyterian Hospital, home
to the Herbert Irving Comprehensive Cancer Center and Neurological Institut...

## Key facts

- **NIH application ID:** 10825218
- **Project number:** 1F30CA288006-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Brianna Pereira
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $50,937
- **Award type:** 1
- **Project period:** 2024-03-15 → 2028-03-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825218

## Citation

> US National Institutes of Health, RePORTER application 10825218, Targeting Purinergic Signaling to Block the Effects of Seizures on Glioma Progression (1F30CA288006-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10825218. Licensed CC0.

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