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Development of resident memory T cells in the synovium

Award Number: K08AR080992
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/04/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Development of resident memory T cells in the synovium - Project Summary/Abstract Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are chronic autoimmune diseases of the joint punctuated by periodic arthritis flares. Clinicians have long recognized that each affected person develops an individual pattern of affected joints, and that this pattern remains stable over time through disease remission and flares. We recently identified the presence of synovial resident memory T cells (TRM) in arthritic joints and showed that they mediate arthritis flares. Correspondingly, depleting these cells ameliorates disease recurrence, indicating that TRM can be targeted as a novel approach in arthritis therapy. The long-term objective of the proposal is to define the mediators of TRM development and maintenance in the synovium and determine if these pathways can be therapeutically targeted to treat arthritis. The specific aims of this proposal utilize 2 complementary approaches in mice and human studies to identify the mediators of synovial TRM development. Aim 1 utilizes a mouse model of inflammatory arthritis developed by the PI to define the lineage and differentiation process of synovial TRM. Aim 2 utilizes a human synovial organoid system to interrogate the impact of the synovial microenvironment, namely synovial stromal cells, on TRM formation and survival. We expect that these studies will identify critical mediators of TRM development, which may represent novel therapeutic targets for inflammatory arthritis. The candidate is an M.D./Ph.D. pediatric rheumatologist at Boston Children’s Hospital. This proposal builds upon her foundational knowledge of immunology to extend her skillset into antibody-coupled single cell sequencing, bioinformatics, organoid models of human synovium, and CRISPR gene targeting. The proposal includes a comprehensive mentoring and didactic plan that will allow her to successfully learn new skills and gain expertise in each of these important areas. The primary mentor, Dr. Peter Nigrovic, is a rheumatologist and expert in the pathophysiology of inflammatory arthritis. The candidate has assembled a K08 advisory committee consisting of Dr. Michael Brenner, Dr. Rachael Clark, and Dr. Soumya Raychaudhuri, who each have specific expertise in various aspects of this proposal such as analysis of single-cell sequencing data, 3D models of human synovium, and expertise in TRM biology in human disease. The candidate is committed to a career in translational research with the goal of becoming an independent lab-based investigator focusing on local mechanisms to autoimmune disorders. The proposed studies, training plan, and exceptional environment at Boston Children’s Hospital, Brigham and Women’s Hospital and Harvard Medical School will enable her to successfully transition to an independent PI and leader in this field.


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 = $173,340 )
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	4/11/2025	NON-COMPETING CONTINUATION	$173,340
														Subtotal = $173,340

Issue Date FY: 2024 ( Subtotal = $173,340 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	3/19/2024	NON-COMPETING CONTINUATION	$173,340
														Subtotal = $173,340

Issue Date FY: 2023 ( Subtotal = $173,340 )
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	3/20/2023	NON-COMPETING CONTINUATION	$173,340
														Subtotal = $173,340

Issue Date FY: 2022 ( Subtotal = $173,340 )
2022	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	4/4/2022	NEW	$173,340
														Subtotal = $173,340

Grand Total All Awards = $693,360

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Development of resident memory T cells in the synovium

Award Number: K08AR080992

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/04/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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