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Aptamer Proteomic Analysis of Systemic Sclerosis Serum Exosomes

Award Number: R21AR074016
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: 07/01/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2021

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Aptamer Proteomic Analysis of Systemic Sclerosis Serum Exosomes - The discovery of objective non-invasive biomarkers that may allow to diagnose Systemic Sclerosis- associated interstitial lung disease ( SSc-ILD) at an early stage and to identify patients with Raynaud’s Phenomenon evolving into SSc would be highly valuable for prompt initiation of SSc-disease- modifying therapy. We propose to utilize novel Aptamer-Based Proteomics for the analysis of the protein cargo of Serum Exosomes isolated from patients with recent-onset diffuse SSc with and without SSc-ILD and from patients with Primary Raynaud’s Phenomenon and patients with Raynaud’s Phenomenon with positive serum antinuclear autoantibodies (ANA). The aptamer proteomic approach measures simultaneously 1,305 proteins and offers an extraordinarily high level of sensitivity (from femtomolar to micromolar). Exosomes, microvesicles secreted by all cells, contain a broad assortment of macromolecules, including proteins. The exosome cargo reflects their cell of origin and, most importantly, the pathologic status of the cells. We propose to test the following hypothesis: “The unbiased proteomic analysis of serum exosomes employing a highly sensitive aptamer-based proteomic assay will identify proteins that may serve as specific biomarkers for the early diagnosis of SSc-ILD and for the identification of patients with Raynaud’s Phenomenon at high risk of evolving into SSc.” We will pursue the following Specific Aims: Specific Aim 1: Identify employing aptamer-based proteomics differentially expressed proteins in serum exosomes from patients with recent onset SSc-ILD compared with exosomes from SSc patients without SSc-ILD. Specific Aim 2: Identify employing aptamer-based proteomics differentially expressed proteins in serum exosomes from patients with Primary Raynaud’s Phenomenon compared with exosomes from patients with Raynaud’s Phenomenon at high risk of evolving into SSc. Specific Aim 3: Examine whether the most differentially increased proteins identified in Aims 1 and 2 induce in vitro a profibrotic phenotype in normal human lung fibroblasts or endothelial to mesenchymal transition (EndMT) in normal human lung microvascular endothelial cells. To accomplish these Aims, exosomes will be isolated from serum from: 1; patients with diffuse SSc without SSc-ILD, 2; patients with diffuse SSc and recent onset SSc-ILD, 3; patients with Primary Raynaud’s Phenomenon, and 4; patients with Raynaud’s Phenomenon harboring serum ANA without other clinical evidence of SSc. The novel aptamer-based proteomic analysis should allow the identification of proteins that may serve as valuable biomarkers for the early diagnosis of SSc-ILD and of Raynaud’s Phenomenon at high risk of evolving into SSc. The proposed studies may also uncover novel proteins involved in the molecular pathogenesis of SSc tissue fibrosis and vasculopathy.


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: 2023 ( Subtotal = -$946 )
2023	2020	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	11/21/2022	NON-COMPETING CONTINUATION	-$946
														Subtotal = -$946

Issue Date FY: 2022 ( Subtotal = -$1,200 )
2022	2020	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	12/22/2021	NON-COMPETING CONTINUATION	-$1,200
														Subtotal = -$1,200

Issue Date FY: 2020 ( Subtotal = $181,661 )
2020	2020	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	5/26/2020	NON-COMPETING CONTINUATION	$181,661
														Subtotal = $181,661

Issue Date FY: 2019 ( Subtotal = $229,784 )
2019	2019	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	6/28/2019	NEW	$229,784
														Subtotal = $229,784

Grand Total All Awards = $409,299

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Aptamer Proteomic Analysis of Systemic Sclerosis Serum Exosomes

Award Number: R21AR074016

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: 07/01/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2021

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