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Immunological Basis of Autoimmune Addison's Disease in a Novel Canine Model System

Award Number: K01OD027058
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/01/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2024

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Immunological Basis of Autoimmune Addison's Disease in a Novel Canine Model System - Project Summary/Abstract Autoimmune Addison’s Disease (AAD) is a life-threatening endocrine disorder caused by the immune- mediated destruction of the adrenal cortex. Affected individuals lack key hormones that are critical for normal homeostasis. Because of this, patients with AAD are at high risk of developing a potentially deadly adrenal crisis characterized by hypotensive shock, vomiting, and life-threatening electrolyte abnormalities. Limited progress has been made over the past half-century in developing new therapies for AAD, in part because there is no actively studied animal model for the disease. Fortunately, dogs provide an opportunity for this very purpose. The disease is naturally occurring in both humans and dogs, and shares similar clinical, genetic, and immunologic underpinnings in both species. The goal of this study is to lay the groundwork for a canine model system to study AAD by characterizing the antigen-specific T cells that trigger the disease and determining the peptide sequences recognized by these T cells. Specifically, we will test the hypothesis that AAD is triggered by IFN-g- producing CD4+ T cells that are activated by peptides derived from steroid-producing enzymes in the adrenal cortex. Once we have identified and characterized these key players involved in triggering the immune system dysfunction in AAD, we can begin to develop approaches that manipulate or downregulate the aberrant immune response. Ultimately, we expect to use this canine model system to drive advances in our understanding of AAD and to foster the development of novel immunotherapies for humans. The work proposed in this application will be conducted at the renowned Center for Immunology at the University of Minnesota, and will provide a critical training opportunity in T cell biology, autoimmune disorders, and the benchtop methods required to study these topics comprehensively.


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 = $0 )
2024	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Research Infrastructure Programs	000	5	9/9/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $203,185 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Research Infrastructure Programs	000	5	12/12/2022	NON-COMPETING CONTINUATION	$130,302
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Research Infrastructure Programs	001	5	4/27/2023	NON-COMPETING CONTINUATION	$0
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Research Infrastructure Programs	002	5	4/28/2023	SUPPLEMENT FOR EXPANSION	$72,883
														Subtotal = $203,185

Issue Date FY: 2022 ( Subtotal = $130,302 )
2022	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Research Infrastructure Programs	001	4	6/3/2022	NON-COMPETING CONTINUATION	$13,031
2022	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Research Infrastructure Programs	000	4	12/7/2021	NON-COMPETING CONTINUATION	$117,271
														Subtotal = $130,302

Issue Date FY: 2021 ( Subtotal = $130,302 )
2021	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Research Infrastructure Programs	001	3	3/16/2021	NON-COMPETING CONTINUATION	$13,031
2021	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Research Infrastructure Programs	000	3	12/1/2020	NON-COMPETING CONTINUATION	$117,271
														Subtotal = $130,302

Issue Date FY: 2020 ( Subtotal = $130,302 )
2020	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Research Infrastructure Programs	001	2	3/24/2020	NON-COMPETING CONTINUATION	$13,031
2020	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Research Infrastructure Programs	000	2	11/30/2019	NON-COMPETING CONTINUATION	$117,271
														Subtotal = $130,302

Issue Date FY: 2019 ( Subtotal = $130,302 )
2019	2019	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Research Infrastructure Programs	000	1	2/1/2019	NEW	$130,302
														Subtotal = $130,302

Grand Total All Awards = $724,393

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Immunological Basis of Autoimmune Addison's Disease in a Novel Canine Model System

Award Number: K01OD027058

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/01/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2024

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