# Perivascular tissue models to overcome MGMT-mediated temozolomide resistance in glioblastoma

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2023 · $88,697

## Abstract

ABSTRACT
This application is being submitted in response to PA-21-071. Glioblastoma (GBM) is the most common and
lethal form of brain cancer. Standard of care is surgical resection followed by treatment with the alkylating agent
temozolomide (TMZ). Resection removes the tumor bulk, and TMZ provides some benefit to many patients. The
parent Cancer Tissue Engineering Collaborative project (R01 CA256481) is developing tissue engineering
approach to accelerate the evaluation of new anticancer compounds that overcome TMZ resistance. This project
is developing processes to create engineered models of the perivascular niches (PVNs) that extend from the
tumor into the surrounding parenchyma and which are believed to play a dominant role in invasion, recurrence,
TMZ resistance, and poor survival. Conventional bulk hydrogels, even miniaturized variants, do not provide an
avenue to tailor, or trace the evolution of, the local microenvironment surrounding unique cell subpopulations.
The objective of this NCI Diversity Administrative supplement is to support a female Research Assistant
Professor within a chemical engineering department to develop a fully independent research program developing
hierarchical models of neuron–glioma connectivity within the glioblastoma tumor microenvironment and after
therapeutic intervention. The unique microenvironment established in the tumor edge is responsible for neuronal
hyperexcitability, tumor invasion and recurrence after therapeutic intervention. This project will evaluate the
hypothesis that neuronal input is a key factor for tumor progression. To do this, this project will first \inspect
neuron–glioma connectivity as the main driver of tumor growth using engineered hydrogel models of the brain
microenvironment (Aim S1). We will subsequently determine the repercussions of therapeutic intervention on
the neuron-glioma unit (Aim S2). This proposed supplement will enable a junior female investigator to develop a
fully independent research program as a Research Assistant Professor at the University of Illinois at Urbana-
Champaign. Through this independent research as well as interactions within the host department, the campus
Cancer Center at Illinois, and external senior mentors, we have identified a complementary but independent
research trajectory as well as mentoring programs to support the full independence of an exemplary junior
investigator.

## Key facts

- **NIH application ID:** 10818804
- **Project number:** 3R01CA256481-03S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Brendan A. Harley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $88,697
- **Award type:** 3
- **Project period:** 2023-05-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818804

## Citation

> US National Institutes of Health, RePORTER application 10818804, Perivascular tissue models to overcome MGMT-mediated temozolomide resistance in glioblastoma (3R01CA256481-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10818804. Licensed CC0.

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