Sunday, October 27, 2024 10/27/2024

Mechanisms of Viral-Induced Beta Cell Damage

Award Number: R01AI044458
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Description. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by selective destruction of the insulin secreting b-cells found in pancreatic islets of Langerhans. While T-lymphocytes are the primary mediators of b-cell destruction during disease development, the pathways that initiate this autoimmune attack are unknown. There is a genetic predisposition for diabetes development, but the low concordance rate among identical twins (less than 40%) suggest that environmental factors participate in the induction of autoimmune diabetes. While virus infection is one environmental factor that has been proposed to initiate b-cell damage during the development of diabetes, the effects of infection on b-cell function and viability as well as the activation of b-cell defense responses to infection are poorly understood. The broad goals of this research program are to define the biochemical mechanisms by which environmental factors, specifically virus infection, contribute to disease development. Much of the focus of this competitive renewal application is on the mechanisms by which b-cells participate in disease tolerance to virus infection. Disease tolerance is an evolutionary conserved defense strategy that limits the impact of a pathogen on host fitness without directly modifying the pathogen. Using a mouse tropic enterovirus that is known to infect and replicate in b-cells and that induces diabetes in susceptible strains of mice (Encephalomyocarditis virus, EMCV), we have identified a novel pathway by which b-cell resist EMCV infection. This protective pathway is mediated by nitric oxide, the same free radical produced by b-cell following cytokine stimulated inducible nitric oxide synthase (NOS) expression. We show that nitric oxide, in b- cell selective manner, enhances b-cell fitness by limiting virus replication and we hypothesize that it is when this disease tolerance is broken that diabetes ensues.


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 = $468,000 )
2024	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	23	4/9/2024	NON-COMPETING CONTINUATION	$468,000
														Subtotal = $468,000

Issue Date FY: 2023 ( Subtotal = $468,000 )
2023	2023	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	22	4/20/2023	NON-COMPETING CONTINUATION	$468,000
														Subtotal = $468,000

Issue Date FY: 2022 ( Subtotal = $468,000 )
2022	2022	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	21	4/27/2022	NON-COMPETING CONTINUATION	$468,000
														Subtotal = $468,000

Issue Date FY: 2021 ( Subtotal = $468,000 )
2021	2021	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	20	4/23/2021	COMPETING CONTINUATION	$468,000
														Subtotal = $468,000

Issue Date FY: 2020 ( Subtotal = -$418 )
2020	2018	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	19	9/28/2020	NON-COMPETING CONTINUATION	-$418
														Subtotal = -$418

Issue Date FY: 2018 ( Subtotal = $382,500 )
2018	2018	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	19	3/8/2018	NON-COMPETING CONTINUATION	$382,500
														Subtotal = $382,500

Issue Date FY: 2017 ( Subtotal = $382,500 )
2017	2017	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	18	3/15/2017	NON-COMPETING CONTINUATION	$382,500
														Subtotal = $382,500

Issue Date FY: 2016 ( Subtotal = $382,500 )
2016	2016	MEDICAL COLLEGE OF WISCONSIN, INC	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	17	3/25/2016	NON-COMPETING CONTINUATION	$382,500
														Subtotal = $382,500

Issue Date FY: 2015 ( Subtotal = $382,500 )
2015	2015	MEDICAL COLLEGE OF WISCONSIN, INC	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	16	2/25/2015	NON-COMPETING CONTINUATION	$382,500
														Subtotal = $382,500

Issue Date FY: 2014 ( Subtotal = $382,500 )
2014	2014	MEDICAL COLLEGE OF WISCONSIN, INC	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	15	3/19/2014	COMPETING CONTINUATION	$382,500
														Subtotal = $382,500

Issue Date FY: 2012 ( Subtotal = $372,438 )
2012	2012	MEDICAL COLLEGE OF WISCONSIN, INC	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	14	1/30/2012	NON-COMPETING CONTINUATION	$372,438
														Subtotal = $372,438

Issue Date FY: 2011 ( Subtotal = $372,438 )
2011	2011	MEDICAL COLLEGE OF WISCONSIN, INC	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	13	1/14/2011	NON-COMPETING CONTINUATION	$338,580
2011	2011	MEDICAL COLLEGE OF WISCONSIN, INC	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	001	13	6/9/2011	NON-COMPETING CONTINUATION	$33,858
														Subtotal = $372,438

Issue Date FY: 2010 ( Subtotal = $376,200 )
2010	2010	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	000	11	1/15/2010	NON-COMPETING CONTINUATION	$358,875
2010	2010	MEDICAL COLLEGE OF WISCONSIN, INC	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	001	12	6/2/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$376,200
2010	2010	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	002	11	6/2/2010	NON-COMPETING CONTINUATION	-$358,875
														Subtotal = $376,200

Issue Date FY: 2009 ( Subtotal = $482,494 )
2009	2009	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	000	10	1/30/2009	NON-COMPETING CONTINUATION	$326,250
2009	2009	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	001	10	3/13/2009	NON-COMPETING CONTINUATION	$0
2009	2009	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	003	10	9/18/2009	NON-COMPETING CONTINUATION	$119,994
2009	2009	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	002	10	6/5/2009	NON-COMPETING CONTINUATION	$36,250
														Subtotal = $482,494

Issue Date FY: 2008 ( Subtotal = $362,500 )
2008	2008	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	000	9	1/18/2008	COMPETING CONTINUATION	$362,500
														Subtotal = $362,500

Issue Date FY: 2005 ( Subtotal = $292,960 )
2005	2005	SAINT LOUIS UNIVERSITY	3500 LINDELL BLVD/FITZG'D HALL	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	8	5/19/2005	NON-COMPETING CONTINUATION	$292,960
														Subtotal = $292,960

Issue Date FY: 2004 ( Subtotal = $293,005 )
2004	2004	SAINT LOUIS UNIVERSITY	3500 LINDELL BLVD/FITZG'D HALL	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	7	5/21/2004	NON-COMPETING CONTINUATION	$293,005
														Subtotal = $293,005

Issue Date FY: 2003 ( Subtotal = $293,039 )
2003	2003	SAINT LOUIS UNIVERSITY	3500 LINDELL BLVD/FITZG'D HALL	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	6	5/16/2003	NON-COMPETING CONTINUATION	$293,039
														Subtotal = $293,039

Issue Date FY: 2002 ( Subtotal = $279,300 )
2002	2002	SAINT LOUIS UNIVERSITY	3500 LINDELL BLVD/FITZG'D HALL	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	5	7/8/2002	NON-COMPETING CONTINUATION	$279,300
														Subtotal = $279,300

Issue Date FY: 2001 ( Subtotal = $265,493 )
2001	2001	SAINT LOUIS UNIVERSITY	3500 LINDELL BLVD/FITZG'D HALL	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	4	11/13/2001	COMPETING CONTINUATION	$265,493
														Subtotal = $265,493

Issue Date FY: 2000 ( Subtotal = $281,741 )
2000	2000	SAINT LOUIS UNIVERSITY	3500 LINDELL BLVD/FITZG'D HALL	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/8/2000	NON-COMPETING CONTINUATION	$281,741
														Subtotal = $281,741

Issue Date FY: 1999 ( Subtotal = $273,536 )
1999	1999	SAINT LOUIS UNIVERSITY	3500 LINDELL BLVD/FITZG'D HALL	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/25/1999	NON-COMPETING CONTINUATION	$273,536
														Subtotal = $273,536

Grand Total All Awards = $8,003,685

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Mechanisms of Viral-Induced Beta Cell Damage

Award Number: R01AI044458

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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