Monday, November 17, 2025 11/17/2025

Defining and Controlling Airway Disease

Award Number: R35HL145242
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/08/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Defining and Controlling Airway Disease - Abstract Airway epithelial cells were originally regarded as an inert barrier to the environment, but are now viewed as key regulators of the response to injury and infection with a critical role in airway repair that mimics lung development. Furthermore, altered behavior of this cell population is central to the pathogenesis of common airway diseases such as asthma and COPD, making it essential to understand the mechanisms responsible to normal and abnormal programming of this cell population. My research program is thematically focused on airway epithelial cell programming with the goal of characterizing the molecular basis of airway epithelial cell function and dysfunction for airway homeostasis versus disease. Our work to date has contributed to new paradigms in airway epithelial cell biology, including the first evidence of an active role for airway epithelial cells in directing the immune response towards airway disease and now the first data for an elusive airway progenitor epithelial cell (APEC) population that can be respiratory-virus activated to orchestrate disease and thereby explain how a transient infection could lead to long-term disease. Building on this work, we will focus going forward on creating a new concept for tissue homeostasis versus disease based on a set of transformative paradigms where progenitor cell reprogramming switches a normal airway epithelial barrier to one dominated by mucus production and the consequent morbidity and mortality of airway disease. We will provide the first definition of the key population of airway progenitor epithelial cells and the first mechanisms for how these cells are switched to disease-producing cells, incorporating unprecedented roles for: (1) endogenous viral, water channel, and nucleokine control of mitotic chromatin in these cells; and (2) an exogenous danger loop from these cells to immune cells and back to drive a distinct progenitor-cell kinase now targeted with structure-based drug design to interrupt mucus production. Translational impact also derives from new mouse and pig models and validation in humans with comparable disease. This substrate is combined with new approaches to cell isolation, 3D manipulation, and transplantation based on targets identified from genomic and proteomic analyses. Each of the individual approaches within the overall Program is charged to investigators in training to integrate scientific career development into the mission for medical research and discovery. In addition, the Program relies on vital and sophisticated input from senior pulmonary scientists for additional mentoring and cutting-edge approaches and innovations. The Program also incorporates the wider University and extramural resources to deploy multidisciplinary technologies with outstanding collaborators. Together, we expect our Program to provide a transformative paradigm for true progenitor epithelial cell programming and its role in cell proliferation and differentiation, including skewing towards mucous cell formation and excess mucus production that is central to airway disease. We also fully expect that our studies will identify the first tractable cellular and molecular targets and corresponding therapeutic intervention to attenuate airway disease, consistent with the mission of NHLBI.


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: 2025 ( Subtotal = $945,000 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Lung Diseases Research	000	7	2/26/2025	NON-COMPETING CONTINUATION	$850,500
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Lung Diseases Research	001	7	8/5/2025	NON-COMPETING CONTINUATION	$94,500
														Subtotal = $945,000

Issue Date FY: 2024 ( Subtotal = $926,100 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Lung Diseases Research	000	6	4/13/2024	NON-COMPETING CONTINUATION	$850,500
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Lung Diseases Research	001	6	6/21/2024	NON-COMPETING CONTINUATION	$75,600
														Subtotal = $926,100

Issue Date FY: 2023 ( Subtotal = $945,000 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Lung Diseases Research	000	5	2/27/2023	NON-COMPETING CONTINUATION	$945,000
														Subtotal = $945,000

Issue Date FY: 2022 ( Subtotal = $945,000 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Lung Diseases Research	001	4	6/15/2022	NON-COMPETING CONTINUATION	$94,503
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Lung Diseases Research	000	4	2/24/2022	NON-COMPETING CONTINUATION	$850,497
														Subtotal = $945,000

Issue Date FY: 2021 ( Subtotal = $945,000 )
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Lung Diseases Research	000	3	2/15/2021	NON-COMPETING CONTINUATION	$945,000
														Subtotal = $945,000

Issue Date FY: 2020 ( Subtotal = $944,000 )
2020	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Lung Diseases Research	000	2	2/4/2020	NON-COMPETING CONTINUATION	$944,000
														Subtotal = $944,000

Issue Date FY: 2019 ( Subtotal = $939,000 )
2019	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Lung Diseases Research	000	1	3/8/2019	NEW	$939,000
														Subtotal = $939,000

Grand Total All Awards = $6,589,100

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Defining and Controlling Airway Disease

Award Number: R35HL145242

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/08/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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