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The gut-lung axis influences the development of bronchopulmonary dysplasia

Award Number: K08HL151907
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/01/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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The gut-lung axis influences the development of bronchopulmonary dysplasia - This proposal presents a five-year research career development program focused on gut fungal commensal ecology, the mycobiome, in the neonatal period to advance mechanistic understanding of the gut-lung axis in bronchopulmonary dysplasia (BPD). This research development plan is designed to provide the candidate, an Assistant Professor of Pediatrics and neonatologist at the University of Alabama at Birmingham, with the mentorship, training and research experience required to accelerate his development into an independent clinician scientist in neonatal mucosal immunology. To achieve the candidate’s long-term goal of leading a productive translational research program focused on understanding mucosal immunology in BPD and facilitate his transition to independence, the candidate and his established mentors have devised a comprehensive development plan based on: 1) intensive, personal mentorship from a team with a proven history of productive mentoring; 2) in-depth experiential and focused didactic training to advance his understanding of molecular mycology, gnotobiotics and clinical research methods; and 3) an innovative research plan to produce causal evidence for gut mycobiome involvement in BPD development. The candidate’s research development plan outlines a focused path to obtain the knowledge, skills and experience required to accelerate his development into an independent clinician scientist who will have a lasting impact on neonatal mucosal immunology. BPD is the most serious pulmonary complication of preterm birth. Treatments to modify developmental risk factors for BPD are lacking. Neonatal models of the gut-lung axis in other lung diseases, epidemiological studies linking antibiotic exposure with increased risk of BPD development, and the candidate’s extensive preliminary studies in mice and preterm newborns strongly suggest the gut mycobiome represents a therapeutic target to influence BPD development. This proposal builds on the candidate’s prior experience and the expertise of his mentors to explore the mechanisms of the neonatal gut-lung axis. We will test two hypotheses. 1) Prenatal antibiotic exposure-induced mycobiome changes drive increased BPD severity by disrupting the gut-lung axis. 2) Colonization with commensal fungi favorably alters the pulmonary mucosal immune response to hyperoxia. Determining if disruption of intestinal commensal microbial communities contributes to the development of lung injury in BPD will inform the development of therapeutics for mitigating BPD. These studies are expected to lay the groundwork translational studies in human preterm newborns.


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 = $165,456 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	5	6/13/2024	NON-COMPETING CONTINUATION	$165,456
														Subtotal = $165,456

Issue Date FY: 2023 ( Subtotal = $165,456 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	4	6/19/2023	NON-COMPETING CONTINUATION	$165,456
														Subtotal = $165,456

Issue Date FY: 2022 ( Subtotal = $192,456 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	2	6/6/2022	SUPPLEMENT FOR EXPANSION	$27,000
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	001	3	7/5/2022	NON-COMPETING CONTINUATION	$165,456
														Subtotal = $192,456

Issue Date FY: 2021 ( Subtotal = $165,456 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	2	7/2/2021	NON-COMPETING CONTINUATION	$165,456
														Subtotal = $165,456

Issue Date FY: 2020 ( Subtotal = $165,456 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	1	6/29/2020	NEW	$165,456
														Subtotal = $165,456

Grand Total All Awards = $854,280

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The gut-lung axis influences the development of bronchopulmonary dysplasia

Award Number: K08HL151907

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/01/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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