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A systems biology approach to identify cortical and medullary gene regulatory networks related to Hypoxia Inducible Factor-1A

Award Number: R03DK138962
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2025
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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A systems biology approach to identify cortical and medullary gene regulatory networks related to Hypoxia Inducible Factor-1A - ABSTRACT Acute Kidney Injury (AKI) is a common and costly complication in hospitalized patients, which is associated with high mortality. Many episodes of AKI are due to episodes of hypoxia, and cells in the kidney medulla are particularly susceptible to hypoxic injury. Hypoxia Inducible Factor-1A (HIF1A) is a key transcription factor regulating the response to hypoxia. While HIF1A has been well characterized, it is still poorly understood how the target genes of HIF1A are regulated in a physiologically low oxygen environment, such as the kidney medulla. Preliminary data from percutaneous kidney biopsies sampling mainly the kidney cortex of individuals show that HIF1A target genes exhibit cell type enrichment. Transcription factor cooperativity may explain cell type enrichment and in silico promoter analysis predicted transcription factors that co-modulate with HIF1A in the promoter region. To expand upon these findings, this project proposes to use multiome data from the Kidney Precision Medicine Project to validate that the predicted transcription factor motifs are located in areas of open chromatin (Aim 1A). We will additionally generate multiome data from kidney samples that are sectioned into cortical and medullary regions. This project then aims to identify the gene regulatory network for the kidney cortex and medulla with respect to HIF1A (Aim 1B). As adaptive cell states are associated with poor long-term outcomes, we will then identify aspects of the gene regulatory network that are perturbed in adaptive cell states by identifying nodes of the network with differentially accessible chromatin between healthy and adaptive cell states (Aim 2). These data will provide important insight into how HIF1A target genes are differentially regulated in kidney cortex and medulla and identify epigenetic alterations that may contribute to maladaptive repair after an episode of Acute Kidney Injury.


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 = $117,000 )
2026	2026	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/23/2025	NON-COMPETING CONTINUATION	$117,000
														Subtotal = $117,000

Issue Date FY: 2025 ( Subtotal = $117,000 )
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/26/2024	NEW	$117,000
														Subtotal = $117,000

Grand Total All Awards = $234,000

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A systems biology approach to identify cortical and medullary gene regulatory networks related to Hypoxia Inducible Factor-1A

Award Number: R03DK138962

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2025

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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