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Defining the role of lymphotoxin signaling in viral-induced lung immunopathology

Award Number: R21AI111000
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2015
PERIOD OF PERFORMANCE END DATE: 01/31/2018

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Defining the role of lymphotoxin signaling in viral-induced lung immunopathology - ¿ DESCRIPTION (provided by applicant): Lung pathology is a significant cause of the morbidity and mortality associated with acute respiratory virus infection. Respiratory viruses, such as influenza virus not only cause damage to the epithelium, but activate immune defense mechanisms. Although these immune mechanisms are employed to destroy and remove infected cells in an attempt to clear the virus, they can also promote lung pathology. However, the key cellular and molecular mechanisms that regulate the balance between protection and tissue damage during acute viral infection remain poorly understood. This lack of knowledge severely limits the development of novel therapies to treat the disease. Therefore, understanding the fundamental mechanisms whereby respiratory viral infection induces lung damage is critical for the development of improved therapies for treatment of disease. Our exciting and intriguing preliminary results suggest that the lymphotoxin beta receptor, LTßR, a member of the TNFR superfamily, promotes influenza-associated lung damage. The overall objective of this proposal is to define how LTßR controls lung damage associated with influenza infection. Our working hypothesis is that LTßR signaling in respiratory epithelial cells inhibits mucus production during influenza infection allowing for elevated viral replication and increased lung damage. To test this hypothesis, we propose two specific aims. In Aim 1, we will use biochemical and genetic approaches to determine the impact of LTßR signaling on mucus production and viral replication. In Aim 2, we will test that LTßR signaling in respiratory epitheial cells is essential to promote lung immunopathology during influenza infection. We propose that LTßR signaling in respiratory epithelial cells promotes viral replication and induction of potent inflammatory responses which cause severe lung damage. Completion of these aims will define the LTßR-dependent mechanisms that contribute to lung damage. The research proposed is significant, because it will provide a deeper understanding of the mechanisms regulating virus-induced immunopathology and will help in developing new immunotherapeutic strategies to control respiratory disease.


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: 2018 ( Subtotal = -$770 )
2018	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Allergy and Infectious Diseases Research	000	3	5/21/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$770
														Subtotal = -$770

Issue Date FY: 2017 ( Subtotal = -$47,011 )
2017	2016	TRUDEAU INSTITUTE, INC.	154 ALGONQUIN AVE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	002	2	3/31/2017	NON-COMPETING CONTINUATION	$0
2017	2016	TRUDEAU INSTITUTE, INC.	154 ALGONQUIN AVE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	2	1/2/2017	NON-COMPETING CONTINUATION	-$215,699
2017	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Allergy and Infectious Diseases Research	000	3	12/30/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$168,688
														Subtotal = -$47,011

Issue Date FY: 2016 ( Subtotal = $243,750 )
2016	2016	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	2	5/4/2016	NON-COMPETING CONTINUATION	$0
2016	2016	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	2	12/21/2015	NON-COMPETING CONTINUATION	$243,750
														Subtotal = $243,750

Issue Date FY: 2015 ( Subtotal = $292,500 )
2015	2015	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	1	1/12/2015	NEW	$292,500
														Subtotal = $292,500

Grand Total All Awards = $488,469

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Defining the role of lymphotoxin signaling in viral-induced lung immunopathology

Award Number: R21AI111000

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2015

PERIOD OF PERFORMANCE END DATE: 01/31/2018

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