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Compartmentalized signaling and crosstalk in airway myocytes

Award Number: R01HL169522
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Compartmentalized signaling and crosstalk in airway myocytes - PROJECT SUMMARY/ABSTRACT This basic science grant seeks to determine fundamental mechanisms as to how a physiologically relevant cell controls the subcellular location of a signal to optimize the effect of that signal on cell function. We propose to build on recent findings by our diverse investigative team to delineate how 3 different Gs-coupled receptors in airway smooth muscle (ASM) cells - the 2AR, EP2, and EP4 receptors- have their signals compartmentalized within the cell to regulate important ASM cell functions. Aim 1 will employ novel imaging approaches to delineate spatiotemporal features of cAMP/PKA signaling by each receptor and demonstrate how this compartmentalized signaling is shaped by receptor-specific complements of AKAP and PDE isoforms, and by the competing co- activated Gq-coupled receptor. Aim 1 will also employ multiple subcellular-targeted biosensors to characterize the capacity of each receptor to signal from intracellular membrane compartments. Aim 2 will assess how these different receptors generate unique phosphoproteome signatures, and how manipulating the mechanisms shaping localized cAMP/PKA signaling regulates these signatures. Aim 3 will establish how the mechanisms dictating spatiotemporal features of ASM cAMP and the ASM proteome affect Gs-coupled GPCR regulation of ASM contraction, migration, and synthetic functions. The proposed studies will provide a foundation for understanding compartmentalized signaling in the form of both methodological advances and the knowledge gained in how Gs-coupled receptors employ distinct signaling mechanisms to render efficient and specific functional effects. From a translational perspective, our findings will constitute a critical basic science foundation for developing new drugs that target mechanisms of signaling compartments, most readily applied to better control asthma features such as airway hyperresponsiveness, airway remodeling, and possibly airway inflammation.


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 = $554,585 )
2025	2025	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BLVD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	3	7/12/2025	NON-COMPETING CONTINUATION	$554,585
														Subtotal = $554,585

Issue Date FY: 2024 ( Subtotal = $543,494 )
2024	2024	UNIVERSITY OF SOUTH ALABAMA	307 N UNIVERSITY BLVD	MOBILE	AL	36608	MOBILE	USA	Lung Diseases Research	000	2	7/20/2024	NON-COMPETING CONTINUATION	$543,494
														Subtotal = $543,494

Issue Date FY: 2023 ( Subtotal = $581,585 )
2023	2023	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	1	6/5/2023	NEW	$581,585
														Subtotal = $581,585

Grand Total All Awards = $1,679,664

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Compartmentalized signaling and crosstalk in airway myocytes

Award Number: R01HL169522

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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