Thursday, April 18, 2024 4/18/2024

Establishing a Single-Cell Proteomic Atlas for Normal and Osteoarthritic Articular Cartilage

Award Number: R01AR077530
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract Although multiple pathways and targets have been proposed for OA treatment, the rate of drug failure in clinical trials has been astoundingly high. The reasons for the limited success include the late detection of the disease and a lack of understanding of the molecular heterogeneity between patients. In this proposal, we aim to capitalize on the newly developed single-cell proteomic technique, mass cytometry (CyTOF) that allows detection of 40-80 proteins simultaneously in single cells, with the aim of identifying the diverse cellular subpopulations in OA cartilage. Although cartilage is a relatively simple tissue, with a single cell type being encapsulated in its secreted extracellular matrix (ECM), the variable degree of degeneration associated with each OA patient suggests that understanding this tissue (and other joint tissues) at a single cell level can provide novel insights into both OA pathology and patient heterogeneity. This will compliment single-cell transcriptomic data, with the additional advantage that the proteomic snapshot can also identify active signaling pathways in the identified subpopulations. The single-cell proteomic approach is especially pertinent in robustly identifying rare cell populations that are difficult to discern from RNA-sequencing data. In this proposal, we will establish single cell profiles of a large cohort of OA cartilage samples using a refined panel of rare earth metal labeled antibodies in Aim1 to identify distinct subpopulations in OA cartilage. In aim 2, we will test if the modulation of two newly identified rare subpopulations would be therapeutic in a mouse model of post-traumatic OA as well as follow their dynamics with disease progression. In Aim 3, we will analyze how drug treatments affect the cartilage subpopulations and their crosstalk in different patients especially to discern between a uniform or heterogenous response among the patient cohort. Collectively, the proposed studies will be impactful in identifying novel regenerative and pathological cell populations in OA and testing the therapeutic potential of their modulation.


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: 2024 ( Subtotal = $479,458 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	3/27/2024	NON-COMPETING CONTINUATION	$479,458
														Subtotal = $479,458

Issue Date FY: 2023 ( Subtotal = $532,730 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	3/6/2023	NON-COMPETING CONTINUATION	$532,730
														Subtotal = $532,730

Issue Date FY: 2022 ( Subtotal = $527,397 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/20/2022	NON-COMPETING CONTINUATION	$527,397
														Subtotal = $527,397

Issue Date FY: 2021 ( Subtotal = $533,282 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/14/2021	NEW	$533,282
														Subtotal = $533,282

Grand Total All Awards = $2,072,867

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Establishing a Single-Cell Proteomic Atlas for Normal and Osteoarthritic Articular Cartilage

Award Number: R01AR077530

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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