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Systemic Effects of Metabolic Enzyme Dysfunctions

Award Number: R35GM162174
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: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2031

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Systemic Effects of Metabolic Enzyme Dysfunctions - PROJECT SUMMARY Biochemical pathways are fundamental to all biological processes, and dysfunctions of the individual enzymes that comprise them are implicated in a wide array of diseases. Due to the interconnected nature of the metabolic network, dysfunction of a single enzyme can cascade through it, affecting the activity of multiple metabolic pathways and subsequently influencing animal development and physiology. The gap in knowledge regarding the molecular mechanisms that link individual enzyme dysfunctions to a multitude of molecular and physiological consequences presents a major obstacle in effective treatments for metabolic disorders. This project aims to uncover how interactions between metabolic pathways cause systemic disease. The research focuses on the systemic effects of dysfunctions in D-2-hydroxyglutarate (2HG) metabolism using the model organism Caenorhabditis elegans. 2HG, an intermediary in several major biochemical pathways, has been implicated in various disorders, including rare inborn error of metabolism D-2-hydroxyglutaric aciduria. As an oncometabolite, 2HG contributes to metabolic rewiring that promoted several types of cancer. Importantly, dysfunctions of 2HG metabolic enzymes lead to disease not only through changes in 2HG levels, but also through network-wide reshaping of metabolic flux. By examining the interactions of 2HG-processing enzymes metabolism with other biochemical pathways in the metabolic network, the project aims to uncover the molecular mechanisms behind associated pathologies. The project will systematically study 2HG metabolism using C. elegans strains with mutated 2HG enzymes and employing techniques such as metabolomics, isotope tracing, and genetic screening. The outcomes are expected to provide new insights into the connectivity of central metabolism, elucidate the role of these interactions in meeting the physiological needs of an organism, and enhance our ability to interpret changes in the metabolome. This research stands to make significant contributions to our understanding of biochemical pathway interactions and inform the development of more effective therapies.


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 = $419,375 )
2026	2026	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	1	3/24/2026	NEW	$419,375
														Subtotal = $419,375

Grand Total All Awards = $419,375

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Systemic Effects of Metabolic Enzyme Dysfunctions

Award Number: R35GM162174

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: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2031

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