Tuesday, October 21, 2025 10/21/2025

Peripheral blood mononuclear cell epigenetic associations in and biomarkers for knee osteoarthritis development and progression

Award Number: R01AR076440
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/16/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Peripheral blood mononuclear cell epigenetic associations in and biomarkers for knee osteoarthritis development and progression - Project Summary / Abstract The objective of the proposed research is to better understand how peripheral blood immune cell composition and/or epigenetic patterns change during knee osteoarthritis (OA) development and progression. Our laboratory has previously examined in detail the biomarker potential of peripheral blood epigenetic changes both to predict future rapid radiographic/pain progression in patients who already have early knee OA, as well as to detect preclinical OA (e.g. patients who do not have radiographic OA but will develop it in the near future). In the current study, we will expand upon these findings both to generate higher-resolution epigenetic maps of peripheral blood as well as to determine epigenetic changes within individual immune cell subsets. Our first Aim is to perform high-resolution sequencing-based 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) analysis on OA patients from across the disease spectrum. Our second Aim is to determine epigenetic changes (and correlated gene transcription changes) within individual immune cell subsets using an innovative paired single-cell RNA- seq and ATAC-seq analysis pipeline and compare these findings with those of Aim 1. Our third Aim is to develop a novel set of high-resolution DNA methylation array-based peripheral blood composition models using scRNA- seq data from Aim 2 and additional data already generated by our institution, and then to apply these models to our previously-generated large OA peripheral blood DNA methylation datasets, thereby enabling the detection of small changes in immune cell subsets in various OA patient endotypes. The proposed work is important, as we do not have a full understanding of how the systemic immune system influence OA risk, nor do we have robust clincally-available biomarkers to distinguish future OA progressors or detect preclinical disease. Our work is quite innovative in its hypotheses as well as the use of cutting-edge deep single-cell and deep sequencing epigenetic analysis and use of machine learning methods to develop discriminatory models. Success in our proposal may open a new avenue for OA inflammation research and may offer a novel treatment strategy for OA.


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 = $1,729,917 )
2025	2025	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	8/7/2025	COMPETING CONTINUATION	$1,729,917
2025	2024	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	8/7/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,729,917

Issue Date FY: 2024 ( Subtotal = $373,023 )
2024	2024	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	5/17/2024	NON-COMPETING CONTINUATION	$373,023
														Subtotal = $373,023

Issue Date FY: 2023 ( Subtotal = $384,560 )
2023	2023	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	5/17/2023	NON-COMPETING CONTINUATION	$384,560
														Subtotal = $384,560

Issue Date FY: 2022 ( Subtotal = $380,714 )
2022	2022	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	6/2/2022	NON-COMPETING CONTINUATION	$380,714
														Subtotal = $380,714

Issue Date FY: 2021 ( Subtotal = $714,001 )
2021	2021	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	3	6/10/2021	NON-COMPETING CONTINUATION	$373,023
2021	2021	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	12/23/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$354,795
2021	2020	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	12/8/2020	NEW	-$13,817
														Subtotal = $714,001

Issue Date FY: 2020 ( Subtotal = $21,455 )
2020	2020	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	1	8/27/2020	NEW	-$255,745
2020	2020	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	6/15/2020	NEW	$319,000
2020	2020	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	6/24/2020	NEW	-$41,800
2020	2020	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	1	7/14/2020	NEW	$0
														Subtotal = $21,455

Grand Total All Awards = $3,603,670

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Peripheral blood mononuclear cell epigenetic associations in and biomarkers for knee osteoarthritis development and progression

Award Number: R01AR076440

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/16/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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