# The Role of Vascular Endothelial Glutaminase in Tumor Vessel Normalization and Response to Therapy

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2021 · $33,247

## Abstract

Project Summary/Abstract
Tumor blood vessels provide nutrition and oxygen and eliminate waste from tumor tissue.
However, tumor-associated vessels are dysfunctional and structurally abnormal. They are
often leaky and tortuous with chaotic blood flow, resulting in decreased drug delivery and
reduced infiltration of immune cells. Complete blockade of tumor blood vessel formation has
resulted in hypoxia, nutrient stress, and increased tumor cell motility and metastasis. A new
concept to repair abnormal tumor vasculature, known as tumor vessel normalization, has been
investigated to improve tumor vessel perfusion and oxygenation, reduce metastasis and
increase efficacy of cancer immunotherapy. Several mechanisms, including inhibition of
aerobic glycolysis in endothelium, have been shown to improve tumor vessel normalization.
In addition to glycolysis, glutamine metabolism is required for proliferation and migration of ECs.
Although glutamine metabolism is well studied in the context of cancer, its role in tumor vascular
endothelial cells (TEC) is poorly understood. Using endothelium-specific glutaminase knockout
mouse model and TNBC/basal-like cell lines, I propose to fill this gap by investigating the role of
vascular endothelial glutaminase in tumor vessel normalization, tumor growth, metastasis, and
response to therapy. To achieve this goal, I will first assess tumor vasculature for pericytes,
tortuosity, diameter, perfusion, and leakiness, as well as tumor infiltrating lymphocytes, following
GLS deletion from endothelial cells (Aim 1). Furthermore, I will use murine tumor models in the
context of GLS knockout in TEC and assess tumor growth, metastasis, and response to both
chemotherapy and immunotherapy (Aim 2). The success of this project will provide translational
impact in the treatment of aggressive breast cancer TNBC or other cancers and will give me the
knowledge and experience in the scientific method to launch my career as an independent
investigator.

## Key facts

- **NIH application ID:** 10239085
- **Project number:** 5F31CA243148-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Verra Ngwa
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,247
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239085

## Citation

> US National Institutes of Health, RePORTER application 10239085, The Role of Vascular Endothelial Glutaminase in Tumor Vessel Normalization and Response to Therapy (5F31CA243148-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10239085. Licensed CC0.

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