# Decoding hyperexcitability in malignant glioma

> **NIH NIH F99** · BAYLOR COLLEGE OF MEDICINE · 2022 · $48,252

## Abstract

PROJECT SUMMARY
 Malignant gliomas are a group of high-grade brain neoplasms that represent the most common form of
malignant brain tumors. Current treatment regimens include an amalgamation of surgical, chemotherapeutic
and radiation treatments yet 5-year survival rates following diagnosis of the most lethal glioma variant,
glioblastoma (GBM) remains stagnant at less than 6%. While new scientific inquiries continue to yield novel
disease-driving mechanisms, survival rates have remained unchanged over the past 30 years, highlighting a
need for new therapeutic approaches for these uniformly fatal diseases.
 Recent scientific investigations have revealed that malignant gliomas form direct synaptic electrochemical
connections with extratumoral neurons to sustain continued proliferation and migration. The study of this
complex interplay between glioma cells and non-tumor neural cells has launched a new line of scientific inquiry
known as cancer neuroscience. Given the existence of these neuroscientific precedents, my predoctoral
research proposes to define how programs responsible for synaptogenesis and synaptic maintenance are
utilized and sustained in malignant glioma. I have identified a novel protein, immunoglobulin superfamily
member 3 (IGSF3), with high expression levels in both in utero neurodevelopment and malignant glioma. My
preliminary data using an in utero electroporation mouse model of glioma have revealed that IGSF3
overexpression drives tumor progression by increasing proliferation and decreasing survival. Furthermore,
overexpression of IGSF3 promotes early-onset seizures in tumor mice and selectively increases excitatory
postsynaptic components at the tumor margin. Based on my initial studies, I hypothesize that increased IGSF3
drives glioma progression by increasing potassium-mediated hyperexcitability that leads secondarily to
synaptic alterations in the surrounding neuronal circuitry. This hyperexcitability then feeds back to the tumor to
promote tumor progression through increased mitogenic and promigratory signaling pathways.
 The results of my predoctoral studies have led me to hypothesize that there is aberrant electrophysiological
activity within tumor cells and that this contributes to disease progression as well. Thus, my postdoctoral
studies will focus on defining and modeling tumor-intrinsic electrophysiological activity in human GBM to
achieve a better understanding of how these networks contribute to disease progression. This research
proposal seeks to summarize previously reported research findings and my preliminary experimental results
that support my hypotheses and rationale, and aims to explain the significance and innovation of my study as
well as the scientific methodologies and techniques I will utilize in order to execute my lines of scientific inquiry.

## Key facts

- **NIH application ID:** 10529810
- **Project number:** 1F99CA274700-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Rachel Naomi Curry
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $48,252
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10529810

## Citation

> US National Institutes of Health, RePORTER application 10529810, Decoding hyperexcitability in malignant glioma (1F99CA274700-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10529810. Licensed CC0.

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