Sunday, August 31, 2025 8/31/2025

A novel family of conserved glyoxal toxicity response proteins.

Award Number: R01GM141230
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2026

Group Awards By:

View Award Description

A novel family of conserved glyoxal toxicity response proteins. - Advanced Glycan End Products (AGEs) are toxic and highly reactive dicarbonyl molecules produced by most life on earth from routine metabolic processes. As such, conserved and dedicated detoxifying systems have emerged for dicarbonyl removal. Owing to their importance, these removal systems are required to maintain longevity, thereby emphasizing the importance of dicarbonyl detoxification in maintaining health. One of the most prominent dicarbonyl species is glyoxal, which is predominantly produced as a byproduct of glycolysis. Glyoxal acts by mounting specific attacks on certain amino acids, namely arginines, cysteines, histidines and lysines in key proteins, thereby adversely altering protein function. In humans, these modifications can result in many diseased states, including: cancer, diabetes, nervous system disorders, heart disease, hypertension, atherosclerosis and aging. Unfortunately, although dicarbonyl stress-related toxicity is now regarded as important as oxidative stress, knowledge about how cells are able to detect and respond to glyoxal buildup is, by comparison, severely lacking. Our lab has discovered a novel class of Antibiotic Monooxygenase (ABM) domains that we hypothesize sense and respond to glyoxal and related dicarbonyls from bacteria to humans. This project proposes to elucidate the mechanism by which one of these ABM domains, we named Glyoxal-ABM Domain 1 (GAD1) responds to glyoxal in the bacterial pathogen Pseudomonas aeruginosa. We have thus far shown that GAD1 from P. aeruginosa, which is co- transcribed with the glyoxal detoxification enzyme GloA2, binds heme directly and is also covalently modified by glyoxal on a conserved arginine residue (Arg49). We hypothesize that GAD1 and its many homologs are specifically modified on conserved residues, which, in turn, signals to switch cellular metabolic flux away from glycolysis other pathways unable to produce the glyoxal toxin. Our studies here will Aim to (1) map GAD1 regulation, (2) determine its cellular distribution and its interactome and (3) solve the structures of its apo and holo forms, and in complex with interacting partners in P. aeruginosa. Studying GAD1 in P. aeruginosa is expected to reveal novel pathways that have potential as new antimicrobial targets, and at the same time advance our basic understanding of glyoxal toxicity sensing in humans and other multicellular organisms.


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: 2025 ( Subtotal = $407,733 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	004	5	4/15/2025	NON-COMPETING CONTINUATION	$413,051
2025	2024	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	3	1/17/2025	NON-COMPETING CONTINUATION	-$148,918
2025	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	003	4	3/25/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$145,995
2025	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	001	4	1/17/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$143,600
2025	2024	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	002	3	3/25/2025	NON-COMPETING CONTINUATION	-$145,995
														Subtotal = $407,733

Issue Date FY: 2024 ( Subtotal = $411,188 )
2024	2024	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	001	3	6/12/2024	NON-COMPETING CONTINUATION	$41,117
2024	2024	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	3	1/12/2024	NON-COMPETING CONTINUATION	$370,071
														Subtotal = $411,188

Issue Date FY: 2023 ( Subtotal = $411,188 )
2023	2023	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	2	2/21/2023	NON-COMPETING CONTINUATION	$411,188
														Subtotal = $411,188

Issue Date FY: 2022 ( Subtotal = $445,939 )
2022	2022	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	1	1/25/2022	NEW	$445,939
														Subtotal = $445,939

Grand Total All Awards = $1,676,048

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A novel family of conserved glyoxal toxicity response proteins.

Award Number: R01GM141230

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer