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Dissecting inflammatory outcomes following eCigarette exposure

Award Number: R15HL152257
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Dissecting inflammatory outcomes following eCigarette exposure - Project Abstract Elucidating molecular pathways that coordinate inflammatory responses and histopathology is of paramount importance in the study of lung disease and possible treatments. Our current R15 led to novel discoveries related to roles for RAGE in coordinating cellular responses to tobacco smoke exposure. The use of electronic cigarettes (eCigs) is a phenomenon that has emerged in the United States during the last few decades. Flavored eCig vaping is steadily rising and troubling trends for eCig use suggest an astonishing 1 out of 10 adolescents vape regularly. eCigs involves exposure to aerosols that are generated when heating diverse flavorings, propylene glycol and glycerine. The resulting aerosols are believed to be less toxic, notwithstanding the accumulation of harmful molecules including acrolein and formaldehyde. Our preliminary studies revealed RAGE-mediated responses to eCig exposure and foreshadow the need for renewed research of this receptor. SAGEs are semi-synthetic glycosaminoglycan ethers that are potent modulators of inflammation in numerous animal models of human disease, and are in preclinical development for periodontitis, oral mucositis, and bladder inflammation. Importantly, SAGEs significantly inhibit interactions between RAGE and its many ligands necessary for signaling. The present proposal is the first to thoroughly assess the biology of RAGE signaling in the context of eCig exposure. A key innovation of this proposal is a collection of animal models that tightly control RAGE expression including RAGE knock out mice, tissue-specific transgenic mice that up-regulate RAGE, and mice harboring phosphorylation deficient RAGE alleles. The central hypothesis is that exposure to eCig aerosols adversely impacts pulmonary health, culminating in significant inflammation and parenchymal cell death. We also hypothesize that abrogation of RAGE with SAGEs diminishes the myriad inflammatory events in the exposed lung. Two specific aims are proposed, and each uses advanced molecular methodologies employed by undergraduate students to test these hypotheses. The studies outlined in this proposal will validate RAGE signaling as a target pathway for the prevention or attenuation of lung diseases in individuals unable or unwilling to remove eCig exposure but may also help to clarify RAGE-mediated pathogenesis in a number of physiological processes.


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: 2025 ( Subtotal = $428,639 )
2025	2025	BRIGHAM YOUNG UNIVERSITY	A-153 ASB	PROVO	UT	84602	UTAH	USA	Lung Diseases Research	000	2	1/13/2025	COMPETING CONTINUATION	$428,639
														Subtotal = $428,639

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2020	BRIGHAM YOUNG UNIVERSITY	A-153 ASB	PROVO	UT	84602	UTAH	USA	Lung Diseases Research	000	1	8/25/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	BRIGHAM YOUNG UNIVERSITY	A-153 ASB	PROVO	UT	84602	UTAH	USA	Lung Diseases Research	000	1	5/31/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $450,000 )
2020	2020	BRIGHAM YOUNG UNIVERSITY	A41 ASB	PROVO	UT	84602	UTAH	USA	Lung Diseases Research	000	1	7/12/2020	NEW	$450,000
														Subtotal = $450,000

Grand Total All Awards = $878,639

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Dissecting inflammatory outcomes following eCigarette exposure

Award Number: R15HL152257

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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