Monday, February 16, 2026 2/16/2026

Functional Dissection of Metabolic-Sensing Proline Hydroxylation Pathways

Award Number: R35GM124896
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: 09/01/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2029

Group Awards By:

View Award Description

Functional Dissection of Metabolic-Sensing Proline Hydroxylation Pathways - Project Summary Proline hydroxylation (Hyp) is a fundamental posttranslational modification and regulatory mechanism that are highly responsive to the changes in cellular metabolic conditions. During tumor progression, the rapid proliferation of cancer cells creates a hypoxic microenvironment that inhibits the hydroxyproline-mediated degradation of HIFa proteins and activates hypoxia-response cellular pathways to promote cancer cell survival in hypoxia. In addition to oxygen, the modification enzyme prolyl hydroxylases are also sensitive to the concentration of iron and key mitochondria metabolites including succinate, fumarate, and alpha-ketoglutarate, making the pathway a critical metabolic sensor in cells. Extensive studies have demonstrated that proline hydroxylation regulates protein structural stability, protein-protein interactions, or proteasomal degradation of substrate proteins. Despite its important roles in cell physiology and success in the targeted analysis of individual substrates, system-wide characterization and functional quantification of the pathway have been hindered by the lack of effective tools and strategies for site-specific identification of proline hydroxylation targets. Our overall hypothesis and long-term goal is that systematic characterization of “proline hydroxylome” through the development of functional proteomics approaches will lead to the mechanistic understanding of novel Hyp-mediated metabolic regulations in development and diseases. Moving towards this goal, in the past years, we have established HypDB for functional annotation analysis of the Hyp proteome with the development of a streamlined workflow for systematic analysis of the Hyp substrates in cells and tissues. We have gained extensive experience in biochemical characterization of Hyp targets, the interactome of specific prolyl hydroxylase as well as its crosstalk with other PTM regulatory pathways. To continue our effort, we will expand the HypDB to quantify Hyp dynamics in mouse tissues and develop functional proteomics strategies to identify key Hyp sites in protein structural stability and prolyl hydroxylase targets. We will apply recently developed chemical and biochemical strategies to investigate the crosstalk between proline hydroxylation and other metabolic-sensing modifications in regulating substrate protein degradation and activity. Furthermore, we will study the physiological significance of a new Hyp-mediated epigenetic modification pathway in regulating gene expression and chromatin activity. Overall, we anticipate that the development and application of functional proteomics technology for system-wide analysis of proline hydroxylation proteome will reveal novel metabolic-sensing pathways and potentially lead to paradigm-shifting concepts in the fields of cancer, metabolic diseases, and development.


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 = $345,937 )
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Biomedical Research and Research Training	000	8	1/19/2026	NON-COMPETING CONTINUATION	$345,937
														Subtotal = $345,937

Issue Date FY: 2025 ( Subtotal = $384,375 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Biomedical Research and Research Training	001	7	8/8/2025	NON-COMPETING CONTINUATION	$384,375
2025	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	6	11/14/2024	COMPETING CONTINUATION	$0
														Subtotal = $384,375

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	001	6	12/19/2023	COMPETING CONTINUATION	$23,579
2024	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	002	6	8/29/2024	COMPETING CONTINUATION	$0
2024	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	5	12/19/2023	NON-COMPETING CONTINUATION	-$23,579
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $384,375 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	001	6	1/16/2023	COMPETING CONTINUATION	$384,375
2023	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	5	1/16/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $384,375

Issue Date FY: 2021 ( Subtotal = $351,413 )
2021	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	5	8/24/2021	NON-COMPETING CONTINUATION	$351,413
														Subtotal = $351,413

Issue Date FY: 2020 ( Subtotal = $368,173 )
2020	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	4	8/19/2020	NON-COMPETING CONTINUATION	$368,173
														Subtotal = $368,173

Issue Date FY: 2019 ( Subtotal = $505,161 )
2019	2019	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	001	3	8/20/2019	NON-COMPETING CONTINUATION	$368,173
2019	2019	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	2	6/7/2019	SUPPLEMENT FOR EXPANSION	$136,988
														Subtotal = $505,161

Issue Date FY: 2018 ( Subtotal = $372,623 )
2018	2018	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	2	8/30/2018	NON-COMPETING CONTINUATION	$372,623
														Subtotal = $372,623

Issue Date FY: 2017 ( Subtotal = $375,261 )
2017	2017	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	1	8/16/2017	NEW	$375,261
														Subtotal = $375,261

Grand Total All Awards = $3,087,318

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Functional Dissection of Metabolic-Sensing Proline Hydroxylation Pathways

Award Number: R35GM124896

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: 09/01/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer