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Mucus Matters: Mucociliary Physiology in Pulmonary Fibrosis

Award Number: F31HL146083
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/01/2019
PERIOD OF PERFORMANCE END DATE: 01/30/2021

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Mucus Matters: Mucociliary Physiology in Pulmonary Fibrosis - PROJECT SUMMARY This F31 application is for support of Jacelyn Peabody’s MD/ Ph.D. training. Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive interstitial lung disease that results in loss of functional alveolar-capillary units leading to impaired gas exchange and respiratory failure. IPF has a worse prognosis than most cancers: the five-year mortality rate is 50-70%, and there are no curative medical therapies. The most significant risk factor for developing IPF is a common, gain-of-function MUC5B promoter variant rs35705950, accounting for at least 30% of the total risk. The MUC5B variant is also predictive of those with preclinical forms of pulmonary fibrosis (pre- PF), which suggests that IPF risk variants may be helpful in identifying subjects with higher risk of disease development. There could be a window of opportunity for targeted intervention, before significant loss of viable lung parenchyma has occurred in at-risk individuals with preclinical stages of fibrotic disease. Though MUC5B has been associated with IPF, the mechanistic role of MUC5B in IPF pathogenesis is unknown. Our central hypothesis is that MUC5B abnormalities contribute to pathologic mucus and decreased mucociliary clearance (MCC), which may help initiate and propagate fibrosis in IPF. Our objective is to elucidate the mechanisms by which abnormal mucociliary physiology influence pulmonary fibrosis in (1) novel bleomycin- induced pulmonary fibrosis ferret models and (2) human IPF patients stratified by rs35705950 genotype and disease severity. These aims are in line with the mission of the NHLBI because they address important basic and translational aspects for the interplay between mucociliary dysregulation and the development of pulmonary fibrosis. As a result of the proposed studies, we expect to develop novel targets within the molecular regulation of MUC5B expression or therapies to improve MCC such as mucolytics for intervention in the pre-PF to IPF transition and in IPF patients, which could alter the disease course and improve both quality and duration of life. This proposal will provide a solid training period for Jacelyn Peabody (PI) under the mentorship of Drs. Steven Rowe (Sponsor) and Victor Thannickal (Co-sponsor) which will foster her career development as an astute and creative physician-scientist. Successful completion will position her for an independent career investigating disorders of mucociliary clearance and mechanisms of fibrosis using cutting-edge techniques.


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: 2022 ( Subtotal = -$5,390 )
2022	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	001	2	6/29/2022	NON-COMPETING CONTINUATION	-$5,390
2022	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	1	6/29/2022	NEW	$0
														Subtotal = -$5,390

Issue Date FY: 2020 ( Subtotal = $38,511 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	2	2/6/2020	NON-COMPETING CONTINUATION	$38,007
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	001	2	4/13/2020	NON-COMPETING CONTINUATION	$504
														Subtotal = $38,511

Issue Date FY: 2019 ( Subtotal = $38,007 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	1	1/10/2019	NEW	$38,007
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	001	1	1/10/2019	NEW	$0
														Subtotal = $38,007

Grand Total All Awards = $71,128

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Mucus Matters: Mucociliary Physiology in Pulmonary Fibrosis

Award Number: F31HL146083

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/01/2019

PERIOD OF PERFORMANCE END DATE: 01/30/2021

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