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Targeting fibroblast growth factor receptors in cystic fibrosis-associated airway inflammation and mucociliary dysfunction

Award Number: R01HL160911
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 Cystic fibrosis (CF) is one the most common life-shortening single gene defective disorders with over 70,000 cases worldwide. Mortality of CF patients has significantly decreased over the last decades and we are facing new treatment challenges for an aging CF population. While CF transmembrane conductance regulator (CFTR) modulator therapy is effective for many CF manifestations, airway inflammation as a hallmark of CF lung disease is not consistently impacted leading to impaired mucus clearance and susceptibility to chronic airway infections. Therefore, it is of great interest to identify novel therapeutic approaches that improve CF-associated chronic inflammation, mucociliary dysfunction and recurrent infections to be ultimately applicable for all CF patients. We have recently published that Fibroblast Growth Factor (FGF) signaling, a well characterized pro-inflammatory and aging signaling pathway, is activated in CF lung disease. We hypothesize that FGF receptor (FGFR) inhibition will attenuate CF-associated inflammation and impaired mucociliary clearance. We will test our hypothesis by employing a multidisciplinary approach combining cell culture with animal models including a chronic airway infection model. Aim 1 will establish the effects of FGFR inhibition in vitro on airway inflammation and mucociliary clearance in the human CF lung using primary human bronchial epithelial cells, cultured at the air liquid interface from different CF genotypes. The in vivo Aim 2 will recapitulate these findings in established CF rat models and assess FGFR inhibition and its impact on CF-associated inflammation, muco-obstructive disease and lung function. Aim 3 will further establish FGFR modulation in the chronically infected CF lung in vivo. The overall aim of this proposal is to establish the role of FGFR modulation in CF associated lung complications as an amenable therapeutic target to ultimately improve functional outcomes, quality of life, and long-term survival in the growing population of aging individuals with CF.


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 = $404,385 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	3	1/8/2024	NON-COMPETING CONTINUATION	$404,385
														Subtotal = $404,385

Issue Date FY: 2023 ( Subtotal = $453,030 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	002	2	3/3/2023	NON-COMPETING CONTINUATION	$45,303
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	001	2	12/31/2022	NON-COMPETING CONTINUATION	$407,727
2023	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	1	10/28/2022	NEW	$0
														Subtotal = $453,030

Issue Date FY: 2022 ( Subtotal = $415,905 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	1	2/1/2022	NEW	$415,905
														Subtotal = $415,905

Grand Total All Awards = $1,273,320

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Targeting fibroblast growth factor receptors in cystic fibrosis-associated airway inflammation and mucociliary dysfunction

Award Number: R01HL160911

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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