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Contribution of pulmonary ionocytes and neuroendocrine cells to ion transport-mediated airway surface liquid maintenance

Award Number: R01HL155325
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Regulation of ion transport across the epithelium is vital to the health and function of the airways. Active and passive ion and water movement is responsible for maintaining a periciliary fluid layer through which cilia can move mucus and protect the airways against particles, irritants, and pathogens. While there is clear evidence of disease caused by specific ion channel mutations (CFTR) as well acquired ion channel dysfunction during/contributing to disease severity (COPD, asthma), the contribution of individual cell types of the pulmonary epithelium to ion transport maintenance is poorly understood. Our experimental evidence demonstrates that alterations in the frequencies of pulmonary ionocytes and neuroendocrine cells in airway epithelial cultures result in dramatic differences in ion transport properties. Altogether, these cell types, along with tuft-like cells, comprise about 0.8% of the total cell numbers in the human tracheal epithelium. Pulmonary ionocytes are a newly identified cell type in the airways with extremely high expression of many ion channels with vital functions in the respiratory tract. The dramatic impact of ionocytes and pulmonary neuroendocrine cells on the ion transport properties of human airway cultures despite their rare frequencies led to our hypothesis that these cell types are highly involved in the regulation and maintenance of ion transport balance across the entire epithelium and are able to impact ion transport functions in other cell types through intercellular communication. By utilizing novel murine models and applying innovative techniques to primary murine and human airway epithelial cells, the research outlined in this proposal will define the contribution of these rare cell types to the overall ion transport functions of the airway epithelium and will also define the role of CFTR in these cells. We will thereby fully characterize the significance of pulmonary ionocytes and neuroendocrine cells to ion transport-mediated airway surface liquid regulation and identify potential cell and ion channel targets for therapeutic treatment of common airway diseases.


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 = $445,376 )
2024	2024	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	001	4	6/20/2024	NON-COMPETING CONTINUATION	$36,357
2024	2024	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	4	4/11/2024	NON-COMPETING CONTINUATION	$409,019
														Subtotal = $445,376

Issue Date FY: 2023 ( Subtotal = $457,419 )
2023	2023	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	3	3/31/2023	NON-COMPETING CONTINUATION	$457,419
														Subtotal = $457,419

Issue Date FY: 2022 ( Subtotal = $499,088 )
2022	2022	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	2	4/29/2022	NON-COMPETING CONTINUATION	$499,088
														Subtotal = $499,088

Issue Date FY: 2021 ( Subtotal = $438,748 )
2021	2021	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	1	7/25/2021	NEW	$438,748
														Subtotal = $438,748

Grand Total All Awards = $1,840,631

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Contribution of pulmonary ionocytes and neuroendocrine cells to ion transport-mediated airway surface liquid maintenance

Award Number: R01HL155325

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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