Monday, February 16, 2026 2/16/2026

Targeting abnormal immunomechanics in the glioblastoma microenvironment to improve therapeutic response

Award Number: K22CA258410
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2023

Group Awards By:

View Award Description

Targeting abnormal immunomechanics in the glioblastoma microenvironment to improve therapeutic response - ABSTRACT Newly diagnosed glioblastoma (GBM) patients have a dismal survival of less than 2 years despite aggressive currently available treatments. Immune checkpoint blockade (ICB), which has revolutionized the treatment of other solid tumors, fails to enhance survival in the majority of GBM patients. The immunosuppressive, hypoxic, and extracellular matrix (ECM)-rich tumor microenvironment (TME) may be largely responsible for this poor response. One of the largest and most immunosuppressive components of the GBM TME is the myeloid cell compartment, consisting mainly of resident microglia and infiltrating tumor-associated macrophages (TAMs). These myeloid cells exist along a spectrum of phenotypes and functions ranging from pro-tumor (pro-fibrotic, angiogenic, and immunosuppressive) to anti-tumor (immune-supporting), and can dictate response to therapy. Furthermore, the GBM TME harbors “solid stress” – a mechanical force originating from cells and ECM – that can compress blood vessels, induce hypoxia and immunosuppression, and hinder anti-tumor immunity and drug efficacy. Here it is proposed that “immunomechanics” between pro-tumor myeloid cells and solid stress are reciprocally regulated in GBM, further promoting the abnormal TME and mediating resistance to ICB. This mechanopathological feedback loop will be evaluated by i) confirming the ability of myeloid cells to exert solid stress, and ii) the reciprocal ability of solid stress to promote pro-tumor myeloid cell phenotype and function (Aim 1). Next, this reciprocal regulation will be interrupted (genetically and pharmacologically) in murine GBM models to i) establish the causal roles of myeloid cells and solid stress in mediating immunosuppression in the TME, and ii) propose translatable ways to overcome them (Aim 2). Finally, myeloid targeting approaches will be combined with ICB to enhance therapeutic outcome, and both physical (solid stress) and biological biomarkers of treatment response will be identified (Aim 3). The results of the proposed work in this K22 application will: i) facilitate my transition to independence, ii) lay the groundwork for a successful R01 application within 3 years, and iii) revealing novel and targetable biophysical mechanisms underlying tumor progression and treatment resistance.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$264,090 )
2024	2023	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Cancer Research Manpower	001	3	2/15/2024	NON-COMPETING CONTINUATION	-$191,052
2024	2022	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Cancer Research Manpower	000	2	2/15/2024	NON-COMPETING CONTINUATION	-$73,038
														Subtotal = -$264,090

Issue Date FY: 2023 ( Subtotal = $191,052 )
2023	2023	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Cancer Research Manpower	001	3	9/19/2023	NON-COMPETING CONTINUATION	$0
2023	2023	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Cancer Research Manpower	000	3	7/26/2023	NON-COMPETING CONTINUATION	$191,052
														Subtotal = $191,052

Issue Date FY: 2022 ( Subtotal = $191,052 )
2022	2022	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Cancer Research Manpower	000	2	7/14/2022	NON-COMPETING CONTINUATION	$191,052
														Subtotal = $191,052

Issue Date FY: 2021 ( Subtotal = $191,052 )
2021	2021	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Cancer Research Manpower	000	1	7/16/2021	NEW	$191,052
														Subtotal = $191,052

Grand Total All Awards = $309,066

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Targeting abnormal immunomechanics in the glioblastoma microenvironment to improve therapeutic response

Award Number: K22CA258410

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer