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Interoceptive functions of airway brush cells

Award Number: R21ES036349
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/03/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Interoceptive functions of airway brush cells - The primary function of the lung is gas exchange. Immune cells and airway nerves orchestrate interoceptive defensive responses and adjustments to homeostatic function that preserve airway patency, eliminate noxious irritants and pathogens from air spaces, clear airway mucus, and optimize the work of breathing. Dysfunction or dysregulation of these systems directly contribute to the emergence of the physiological and pathophysiological attributes of respiratory diseases and their associated symptoms. Sensory nerves often rely on specialized chemosensory signaling mechanisms at their nerve terminals to transduce mucosal irritation. In the airways, we have described the chemosensory functions of brush cells, their association with the peripheral terminals of vagal afferent nerves and the reflex effects resulting from their activation. The central hypothesis of this research proposal is that brush cells orchestrate both immune and reflex responses in the airways and lungs. We further hypothesize that brush cell dysfunction may contribute to the emergence of symptoms associated with both acute and chronic diseases of the airways and lungs. Studies proposed herein aim to: 1) characterize the mechanisms by which brush cells are activated, how they transmit their activation to adjacent sensory nerves, and the reflexes initiated upon their activation; and 2) determine the role of ATP and the unique expression of carbonic anhydrase by airway brush cells in transducing airway mucosal irritation, acidification of airway surface liquid and the accumulation of carbon dioxide in the airway lumen. We will utilize the innovative techniques that are unique to our laboratories, including transgenic approaches enabling optical recordings of afferent neurons and brush cells, reflex physiological recordings, single afferent neuron recording and our molecular approaches to studying both neurons and brush cells. Our focus on brush cell interactions with afferent nerves is a logical direction for our group, and our plans for hypothesis testing will be enabled by intriguing recent discoveries summarized below in our Research Strategy. We anticipate that the results of these proposed studies will reveal novel roles for brush cells and ATP in transducing reflexes resulting from mucosal irritation in the airways of patients with chronic diseases of the airways and lungs.


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: 2026 ( Subtotal = $0 )
2026	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	2	2/13/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $204,688 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	2	3/13/2025	NON-COMPETING CONTINUATION	$204,688
														Subtotal = $204,688

Issue Date FY: 2024 ( Subtotal = $245,625 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Environmental Health	000	1	4/2/2024	NEW	$245,625
														Subtotal = $245,625

Grand Total All Awards = $450,313

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Interoceptive functions of airway brush cells

Award Number: R21ES036349

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/03/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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