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Understanding the immunometabolic mechanism of VGLL3 mediating female-biased autoimmunity

Award Number: R01AR078781
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 Autoimmune diseases exhibit strikingly increased prevalence in females (e.g. systemic lupus erythematosus [SLE], female-to-male ratio 9:1), whereas in contrast, infectious diseases affect more men than women. Despite its clinical impact, the molecular underpinnings of sex-biased immune regulation remain elusive. To address this knowledge gap, this project focuses on the immunometabolic function of VGLL3 (Vestigial Like Family Member 3), a female-increased, keratinocyte-expressed molecule known to promote both cutaneous and systemic autoimmunity. This project tests the hypothesis that VGLL3 coordinates female-biased metabolic stress response, whose hyperactivation causes autoimmunity by: Aim 1. Define the female-biased cellular stress response mediated by VGLL3. Aim 2. Determine the molecular mechanism by which metabolic stress potentiates VGLL3 induction by IFNa. Aim 3. Establish the in vivo role of VGLL3-mediated stress response in autoimmune pathogenesis. With successful completion of the work proposed, we will have gained insights into the molecular basis underlying sexual dimorphism in immunity. By establishing the immunometabolic function of VGLL3, we will demonstrate the importance of maintaining metabolic homeostasis in combating autoimmunity, and provide a novel target and pathway for sex-specific prevention and treatment of immune-associated diseases.


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 = $300,909 )
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	3/29/2024	NON-COMPETING CONTINUATION	$300,909
														Subtotal = $300,909

Issue Date FY: 2023 ( Subtotal = $355,543 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	3	5/8/2023	NON-COMPETING CONTINUATION	$349,104
2023	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	3/20/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$123,064
2023	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/16/2023	NEW	-$116,625
														Subtotal = $355,543

Issue Date FY: 2022 ( Subtotal = $332,723 )
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/29/2022	NEW	$332,723
														Subtotal = $332,723

Grand Total All Awards = $989,175

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Understanding the immunometabolic mechanism of VGLL3 mediating female-biased autoimmunity

Award Number: R01AR078781

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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