Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Investigating the role of sulfide oxidation and declining hydrogen sulfide in glioblastoma

Award Number: F31NS141426
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/02/2025
PERIOD OF PERFORMANCE END DATE: 05/31/2028

Group Awards By:

View Award Description

Investigating the role of sulfide oxidation and declining hydrogen sulfide in glioblastoma - PROJECT SUMMARY Glioblastoma (GBM) is a malignant brain tumor responsible for significant morbidity and mortality. Despite efforts to develop new and more efficacious therapeutic options for GBM, long-term survival rates trail other cancers, and a diagnosis remains universally lethal. Poor outcomes are the result of many factors, including invasion into healthy tissue beyond the reach of conventional therapies such as surgery or radiation, cellular heterogeneity which causes many chemotherapeutic agents to fail, and a highly immunosuppressive environment limiting the effectiveness of immunotherapy. The inability to improve patient survival is greatly influenced by intrinsic factors that enable cells to evade death and adapt to a new or changing environment. However, consideration of patient age as a risk factor provides the greatest predictive value for response to therapy, and disease progression. While GBM does occur in younger individuals, incidence rates increase with age, and most diagnoses occur in patients over 65 years. Aging also negatively influences length of survival. Therefore, understanding factors that contribute to this relationship will improve patient care for the majority of glioblastoma patients. One factor associated with healthy aging, increased lifespan, and reduced incidence of aging-associated morbidities is a gas known as hydrogen sulfide (H2S). This sulfur containing gas, recognizable by its rotten egg smell, provides multiple health benefits at low and supraphysiological levels, but is toxic at extremely high doses. The proposed studies in this F31 fellowship application focus on the role of H2S in suppressing tumor growth in glioblastoma and promoting anti-tumor immunity, as well as understanding what role aging has on H2S removal mediated by sulfide oxidation. Preliminary data indicates that sulfide oxidation is increased in GBM relative to non-malignant brain tissue and lower grade gliomas. A pattern reflected by decreased survival. Additionally, inhibition of sulfide oxidation results in decreased proliferation of GBM cells in vitro, likely mediated by the observed decrease in H2S. Based upon these observations, I hypothesize that sulfide oxidation increases in older individuals, thus driving the aging-related decline in H2S that enables tumor growth while also promoting an immunosuppressive tumor microenvironment. I plan to test this hypothesis using two experimental aims. Aim 1 will test the hypothesis that age-dependent upregulation of sulfide oxidation in GBM leads to reduced H2S signaling and accelerated disease progression, while simultaneously stimulating mitochondrial electron transport. Aim 2 will test the hypothesis that declining H2S signaling in aging contributes to immunosuppressive nature of GBM. These aims will be accomplished using in vitro and in vivo systems for manipulating expression of sulfide oxidizing enzymes and H2S levels, based upon pharmacological, genetic, and aging approaches. If successful, this project will elucidate the role of sulfide oxidation in GBM. A previously unexplored pathway that may identify new therapeutic targets for treating and managing glioblastoma in combination with current standard of care treatments.


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: 2026 ( Subtotal = $34,114 )
2026	2026	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/23/2026	NON-COMPETING CONTINUATION	$34,114
														Subtotal = $34,114

Issue Date FY: 2025 ( Subtotal = $43,138 )
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	9/5/2025	NEW	$564
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	6/9/2025	NEW	$0
2025	2025	CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OF CASE WESTERN RESERVE UNIVERSITY	9500 EUCLID AVE.	CLEVELAND	OH	44195	CUYAHOGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/21/2025	NEW	$42,574
														Subtotal = $43,138

Grand Total All Awards = $77,252

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating the role of sulfide oxidation and declining hydrogen sulfide in glioblastoma

Award Number: F31NS141426

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/02/2025

PERIOD OF PERFORMANCE END DATE: 05/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer