# Radiation-induced vascular reprogramming in glioblastoma

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $492,144

## Abstract

Summary
Glioblastoma (GBM), the most common primary brain tumor is virtually always fatal. The primary modes of
therapy—surgery, radiation and chemotherapy with temozolomide—have led to only marginal improvements in
survival. A hallmark of GBM is their high vascularity. Blood vessels within GBM, consisting of mostly
endothelial cells and pericytes, not only play the important role of providing nutrients and oxygen to the tumor,
but also provide direct trophic support to the tumor cells and serve as conduits for migration out of the tumor.
However, anti-angiogenic therapies directed against tumor vasculature have not been successful. A number of
studies have revealed that tumor pericytes and endothelial cells can be derived directly from tumor cells,
although tumor-derived endothelial cells are relatively rare occurrences in untreated tumors. The number of
tumor-derived endothelial cells is greatly increased in recurrent tumors, suggesting that glioma therapy, such
as radiation, could influence this process. Our preliminary studies show that radiation can induce the
production of endothelial-like and pericyte-like cells in vitro and in animal models in vivo. These reprogrammed
cells are important for the growth of the tumor following radiation in vivo and we have begun to define what
factors the reprogrammed vascular cells produce to support the growth of the remaining tumor cells following
radiation. Our preliminary data indicate that radiation induces altered chromatin states that allow for
reprogramming to occur; a process that is potentially therapeutically targetable through the inhibition of the
histone acetyltransferase (HAT), P300. The goals of the current studies are to understand the process of
vascular reprogramming (RIR) and to determine how it influences brain tumor biology. Our hypothesis is that
vascular reprogrammed cells provide critical trophic support to the remaining tumor cells under the harsh
conditions that occur following radiation. First, in Aim 1 we will determine whether therapeutically relevant
doses of radiation promote vascular RIR. We will then use cell ablation strategies to validate our preliminary
data indicating that radiation-induced reprogramming is important for the subsequent growth of the tumor
following radiation treatment using both xenotransplantation and immunocompetent syngeneic mouse models.
Next, we will explore the mechanisms by which radiation reprogrammed endothelial-like and pericyte-like cells
promote the growth of the remaining tumor, determining what specific factors they elaborate, and whether
these factors are responsible for tumor survival and growth following radiation. We will then test the hypothesis
that radiation induces the formation of vascular-like cells through modification of chromatin accessibility via
augmentation of histone acetylation through the P300 histone acetyltransferase, allowing for access of
vascular-specifying transcription factors. Finally, we will use pharmacologic ...

## Key facts

- **NIH application ID:** 10375792
- **Project number:** 1R01NS121617-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** HARLEY IAN KORNBLUM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $492,144
- **Award type:** 1
- **Project period:** 2021-12-15 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375792

## Citation

> US National Institutes of Health, RePORTER application 10375792, Radiation-induced vascular reprogramming in glioblastoma (1R01NS121617-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10375792. Licensed CC0.

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