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Role of IL-1alpha signaling in inflammatory diseases and host defense

Award Number: R01AR056296
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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ABSTRACT Interleukin-1 (IL-1) family cytokines IL-1a and IL-1ß, have emerged as principal mediators of multiple inflammatory diseases. Both bind to the interleukin-1 receptor (IL-1R) to induce a proinflammatory signaling cascade. Over the last decade, much progress has been made in defining the roles and regulation of IL-1ß in multiple disease models. Studies from our lab and others have highlighted the contributions of Nod-like receptors (NLRs) and multi-protein complexes known as inflammasomes, and caspase-8 in the regulation of IL-1ß production and inflammation. In stark contrast to IL-1ß, and despite being the first major human pyrogen described, the regulation of IL-1a remains poorly understood. Notwithstanding the increasing appreciation of the contribution of IL-1a in the pathogenesis of many important human diseases, the factors that control functional IL-1a maturation remain completely obscure. Novel discoveries from our lab using a mouse model of cutaneous inflammatory disease (Ptpn6spin mutant mice) suggest that the inflammatory disease progresses in an inflammasome- and IL-1ß-independent manner. Instead, inflammation in the Ptpn6spin model requires IL- 1a and is driven by receptor interacting protein kinase 1 (RIPK1). Except for these studies, our current understanding of the roles and regulation of IL-1a in inflammatory disease is severely limited. The central goal of this project is to identify the cellular and molecular mechanisms of IL-1a regulation and to provide critical information essential for understanding the function of IL-1a.


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 = -$113,058 )
2024	2022	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	15	2/27/2024	NON-COMPETING CONTINUATION	-$113,058
														Subtotal = -$113,058

Issue Date FY: 2022 ( Subtotal = $390,951 )
2022	2022	ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	15	8/10/2022	NON-COMPETING CONTINUATION	$390,951
														Subtotal = $390,951

Issue Date FY: 2021 ( Subtotal = $383,053 )
2021	2021	ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	14	8/5/2021	NON-COMPETING CONTINUATION	$383,053
														Subtotal = $383,053

Issue Date FY: 2020 ( Subtotal = $394,900 )
2020	2020	ST. JUDE CHILDREN'S RESEARCH HOSPITAL	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	13	7/28/2020	NON-COMPETING CONTINUATION	$394,900
														Subtotal = $394,900

Issue Date FY: 2019 ( Subtotal = $394,900 )
2019	2019	ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	12	7/15/2019	NON-COMPETING CONTINUATION	$394,900
														Subtotal = $394,900

Issue Date FY: 2018 ( Subtotal = $394,900 )
2018	2018	ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	11	7/24/2018	COMPETING CONTINUATION	$394,900
2018	2017	ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	10	9/25/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $394,900

Issue Date FY: 2017 ( Subtotal = $379,169 )
2017	2017	ST. JUDE CHILDREN'S RESEARCH HOSPITAL	262 DANNY THOMAS PL MAILSTOP # 509	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	10	7/18/2017	NON-COMPETING CONTINUATION	$371,875
2017	2016	ST. JUDE CHILDREN'S RESEARCH HOSPITAL	262 DANNY THOMAS PL MAILSTOP # 509	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	9	2/1/2017	EXTENSION WITH OR WITHOUT FUNDS	$7,294
2017	2015	ST. JUDE CHILDREN'S RESEARCH HOSPITAL	262 DANNY THOMAS PL MAILSTOP # 509	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	8	2/1/2017	NON-COMPETING CONTINUATION	-$7,294
2017	2013	ST. JUDE CHILDREN'S RESEARCH HOSPITAL	262 DANNY THOMAS PL MAILSTOP # 509	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	1/17/2017	COMPETING CONTINUATION	$7,294
														Subtotal = $379,169

Issue Date FY: 2016 ( Subtotal = $371,875 )
2016	2016	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	9	7/19/2016	EXTENSION WITH OR WITHOUT FUNDS	$371,875
														Subtotal = $371,875

Issue Date FY: 2015 ( Subtotal = $371,875 )
2015	2015	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	7/22/2015	NON-COMPETING CONTINUATION	$371,875
														Subtotal = $371,875

Issue Date FY: 2014 ( Subtotal = $371,875 )
2014	2014	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	9/11/2014	NON-COMPETING CONTINUATION	$371,875
														Subtotal = $371,875

Issue Date FY: 2013 ( Subtotal = $371,875 )
2013	2013	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	7/17/2013	COMPETING CONTINUATION	$371,875
														Subtotal = $371,875

Issue Date FY: 2012 ( Subtotal = $351,268 )
2012	2012	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	8/31/2012	NON-COMPETING CONTINUATION	-$59,337
2012	2012	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	7/23/2012	NON-COMPETING CONTINUATION	$410,605
														Subtotal = $351,268

Issue Date FY: 2011 ( Subtotal = $500,240 )
2011	2011	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	8/17/2011	NON-COMPETING CONTINUATION	$453,449
2011	2011	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	3/3/2011	SUPPLEMENT FOR EXPANSION	$46,791
														Subtotal = $500,240

Issue Date FY: 2010 ( Subtotal = $365,904 )
2010	2010	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	7/29/2010	NON-COMPETING CONTINUATION	$365,904
														Subtotal = $365,904

Issue Date FY: 2009 ( Subtotal = $544,600 )
2009	2009	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Trans-NIH Recovery Act Research Support	001	2	9/16/2009	SUPPLEMENT FOR EXPANSION	$175,000
2009	2009	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	7/16/2009	NON-COMPETING CONTINUATION	$369,600
														Subtotal = $544,600

Issue Date FY: 2008 ( Subtotal = $369,600 )
2008	2008	ST JUDE CHILDREN`S RESEARCH HOSPITAL	322 NORTH LAUDERDALE STREET	MEMPHIS	TN	38105	SHELBY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/15/2008	NEW	$369,600
														Subtotal = $369,600

Grand Total All Awards = $5,843,927

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Role of IL-1alpha signaling in inflammatory diseases and host defense

Award Number: R01AR056296

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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