Saturday, August 30, 2025 8/30/2025

Explore the involvement of tRNA in the pathophysiology of antisynthetase syndrome

Award Number: R21AR083063
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: 08/15/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Explore the involvement of tRNA in the pathophysiology of antisynthetase syndrome - Project Summary Antisynthetase syndrome (ASSD) is a chronic autoimmune disorder characterized by myositis and interstitial lung disease (ILD). A key feature of ASSD is the presence of autoantibodies against aminoacyl-tRNA synthe- tases (aaRSs), among which histidyl-tRNA synthetase (HARS or HisRS) causing anti-Jo-1 antibodies is the most common. aaRSs are the enzymes that attach amino acids to their appropriate tRNA and are thus essential components of the intracellular translation machinery. Interestingly, some aaRSs are also secreted and function extracellularly to regulate inflammation and immune responses. However, the mechanisms by which aaRSs are released from cells, become targets of autoimmunity, and cause symptoms are not well understood. Importantly, tRNA, a key partner of aaRS, has not been considered at all in the context of ASSD. There is growing evidence suggesting the involvement of endosomal Toll-like receptor TLR7 and type I interferon (IFN-I) signaling in sus- taining and spreading inflammation in the autoimmune disease. The ligands that activate TLR7 are single strand RNAs (ssRNAs). Therefore, we hypothesize that tRNAs or tRNA fragments bound to aaRSs play critical roles in the pathogenesis of ASSD. We propose a two-year project to explore the hypothesis using ASSD-relevant cells and to generate a novel and clinically relevant animal model for mechanistic study and future therapeutic devel- opment. The results obtained from this study would uncover a previously unrecognized involvement of tRNAs in the pathogenesis of ASSD and suggest new targets for therapeutic development of the disease.


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 = $182,160 )
2025	2025	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	7/21/2025	NON-COMPETING CONTINUATION	$182,160
														Subtotal = $182,160

Issue Date FY: 2024 ( Subtotal = $242,880 )
2024	2024	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/12/2024	NEW	$242,880
														Subtotal = $242,880

Grand Total All Awards = $425,040

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Explore the involvement of tRNA in the pathophysiology of antisynthetase syndrome

Award Number: R21AR083063

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: 08/15/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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