# Defining Tumor Microenvironmental Interactions that drive THY1-Mediated Treatment Resistance in Glioblastoma

> **NIH NIH K08** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $233,280

## Abstract

This K08 proposal will complete Dr. Wajd Al-Holou’s training towards his long-term career goal of directing an
independent research program that aims to define critical cellular interactions in the tumor microenvironment
that drive treatment resistance in glioblastoma (GBM) and ultimately identify therapies targeting mechanisms of
resistance. Dr. Al-Holou is an assistant professor in the department of Neurosurgery at the University of
Michigan with established success in the field of neurosurgical oncology who completed his clinical training at
the University of Michigan and MD Anderson Cancer Center. This proposal builds on Dr. Al-Holou’s previously
acquired expertise in tumor biology and the development and analysis of recurrence models in GBM and
proposes further training in defining tumor microenvironmental interactions utilizing in vitro and in vivo
modeling, cancer genomics and bioinformatics, cancer biology, research ethics, grant writing and biostatistics,
by means of investigative research and formal course work. Dr. Maria Castro, an internationally recognized
expert on glioma tumor biology and the tumor microenvironment (TME) with a strong record of training
scientists, will serve as primary mentor. Dr. Pedro Lowenstein, renowned for his work in vivo modeling and the
development of novel therapies for GBM, and Dr. Thomas Wilson, an expert in the utilization of advanced
genomics to answer critical biological questions, will serve as co-mentors and have a long track record of
mentoring success. The University of Michigan has a rich and collaborative environment, and a strong
institutional commitment to its trainees. This 5-year plan includes formal coursework, professional development
and progressively independent research, with defined milestones to ensure productivity and a successful
transition to independence.
GBM is a lethal disease with therapeutic resistance that is driven by marked heterogeneity within the tumor
microenvironment. The goal of this research is to elucidate critical TME interactions and cellular crosstalk that
drive inherently resistant GBM cells to recur following therapy. We previously identified a rare population of
inherently resistant THY1+ tumor cells in treatment naïve tumors that recurred following therapy. These cells
show evidence of important cell signaling in the TME, exhibit a mesenchymal and stem-like phenotype, and
are co-localize with macrophages in the perivascular niche. We hypothesize that THY1-mediated resistance
results from cellular interactions in the TME, especially with macrophages, driving recurrence. To test this
hypothesis, we have designed in vitro/in vivo analyses combined with spatial single cell analyses of human
GBM to unravel how cell interactions in the TME drive resistance in hopes that inhibiting these interactions will
abrogate treatment resistance. In total, this work will provide a foundation upon which Dr. Al-Holou will build a
career investigating the intersection of resistan...

## Key facts

- **NIH application ID:** 10806316
- **Project number:** 1K08NS128271-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Wajd Al-Holou
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $233,280
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806316

## Citation

> US National Institutes of Health, RePORTER application 10806316, Defining Tumor Microenvironmental Interactions that drive THY1-Mediated Treatment Resistance in Glioblastoma (1K08NS128271-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10806316. Licensed CC0.

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