Evidence map›Paper›PMID 42780293›Full record

ArticleResearch square2026

Microenvironment-derived acetylated amino acids promote glioblastoma treatment resistance.

Palavalasa Sravya, Leyla Nurcihan Altay, Kathy Do, Jack Freeman, Aditri Gokul, Ningning Liang, Andrew J Scott, Jie Xu, Navyateja Korimerla, Angelica Lin and 33 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

43 authors.

Palavalasa SravyaDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Leyla Nurcihan AltayDepartment of Chemical engineering, University of Michigan, Ann Arbor, MI, USA.ORCID 0009-0002-7064-0751
Kathy DoDepartment of Chemical engineering, University of Michigan, Ann Arbor, MI, USA.
Jack FreemanDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Aditri GokulDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Ningning LiangDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Andrew J ScottDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-0835-4888
Jie XuDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Navyateja KorimerlaDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Angelica LinDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Heng WangDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.ORCID 0009-0001-0197-7767
Kari Wilder-RomansDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Ava SingerDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Alexandra O'BrienDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Olamide AnimasahunDepartment of Chemical engineering, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-4032-3619
Baharan MeghdadiDepartment of Chemical engineering, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-8871-1488
Emily BakerDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Erik R PetersonDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Elizabeth C McCullaDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.ORCID 0009-0003-2583-0094
Ziqing ZhuDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Dafydd ThomasDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Anthony AndrenDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Harrison WongDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Peter SajjakulnukitDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-8556-7481
Li ZhangDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Sunita ShankarDepartment of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Visweswaran RavikumarDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-4670-3898
Zheng Hong LeeDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Joseph A Nieto CarrionDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Sagnik BhaduryDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
C Ryan MillerDepartment of Pathology, University of Alabama Birmingham, Birmingham, AL, USA.ORCID 0000-0002-0096-8762
Jann N SarkariaDepartment of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-7489-4885
Jason A HethDepartment of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Jason T HuseDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0003-4514-0640
Sandra Camelo-PiraguaDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Meredith A MorganDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Theodore S LawrenceDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-4186-8821
Arvind RaoDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Costas LyssiotisDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-9309-6141
Wajd Al-HolouDepartment of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Deepak NagrathDepartment of Chemical engineering, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-8999-2282
Weihua ZhouDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Daniel R WahlDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-9894-5085

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Veerabhadran Baladandayuthapani · 1988 to 2026
$178.2M
Translational Pathology CoreP50CA269022 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE, Meredith A Morgan · 2023 to 2026
$10.0M
Training Program in Tumor MicroenvironmentT32CA009676 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, Analisa Virginia DiFeo · 1992 to 2026
$7.3M
Synthesizing Image-derived Heterogeneity with Genomic measurements for Assessing Disease Aggressiveness in Lower Grade GliomasR37CA214955 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KURTEK, SEBASTIAN, RAO, ARVIND · 2018 to 2024
$3.9M
Targeting Nucleotide Metabolism to Overcome Therapy Resistance in GlioblastomaR37CA258346 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Daniel R Wahl · 2021 to 2026
$3.3M
Targeting Stromal Influences on BCKA Addiction in PDAC TumorsR01CA271369 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE, Deepak Nagrath · 2022 to 2026
$2.8M
New methods to measure and interrupt metabolic fluxes in brain cancerR01CA298159 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NAGRATH, DEEPAK, WAHL, DANIEL R · 2025 to 2025
$2.8M
Inhibition of wild-type IDH1 as a ferroptosis-inducing therapeutic approach for the treatment of malignant glioma.R01NS129123 · NINDS · WASHINGTON UNIVERSITY · PI Alexander H. Stegh, Daniel R Wahl · 2022 to 2026
$2.4M
Targeting the DNA damage response in combination with radiation to induce innate immunity and improve immunotherapy efficacy in pancreatic cancerR01CA240515 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORGAN, MEREDITH A · 2020 to 2024
$2.2M
De Novo Nucleotide Synthesis as a Mediator of Radiation Resistance and a Therapeutic Target in GlioblastomaK08CA234416 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WAHL, DANIEL R · 2019 to 2023
$1.1M
Defining Tumor Microenvironmental Interactions that drive THY1-Mediated Treatment Resistance in GlioblastomaK08NS128271 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Wajd Al-Holou · 2024 to 2026
$700k
Defining and interrupting metabolic crosstalk in the glioblastoma microenvironmentK99CA300923 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Andrew Joseph Scott · 2025 to 2026
$273k
NCI NIH HHS F32 CA260735NCI NIH HHS K08 CA234416NCI NIH HHS K99 CA300923NCI NIH HHS P30 CA046592NCI NIH HHS P50 CA269022NCI NIH HHS R01 CA240515NCI NIH HHS R01 CA271369NCI NIH HHS R01 CA298159NCI NIH HHS R37 CA214955NCI NIH HHS R37 CA258346NCI NIH HHS T32 CA009676NINDS NIH HHS K08 NS128271NINDS NIH HHS R01 NS129123
6 · The paper itself

Abstract

Rapid repair of genotoxic therapy induced DNA damage mediates treatment resistance in glioblastoma (GBM). The role of non-malignant cell types in the tumor microenvironment in accelerating DNA repair in neoplastic cells is poorly understood. Using spatial transcriptomics, immunofluorescence, metabolomics, patient tissues and preclinical models, we show that tumor associated macrophages (TAMs) in GBM promote DNA repair and treatment resistance in neoplastic cells through the secretion of acetylated amino acids. These acetylated amino acids are consumed by GBM cells, leading to enhanced acetyl Co-A levels, histone acetylation and nucleotide synthesis. Interrupting histone acetylation via inhibition of the acetyltransferase KAT5 breaks these metabolic links and reverses the protective capacity of microenvironment-derived acetylated amino acids and TAMs. Blocking the exchange of acetylated amino acids and their downstream effects is a potential strategy for the treatment of GBM.

Identifiers

PMID42780293
PMCPMC13596666

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