Tuesday, July 1, 2025 7/1/2025

Macrophage-Mediated Lung Repair Programs Following Injury

Award Number: F31HL172650
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Macrophage-Mediated Lung Repair Programs Following Injury - Project Summary Over the past several years, we have experienced the social and physical consequences of a viral pandemic; however, the cellular and molecular mechanisms of repair following such infections are not fully understood. The lung serves as the site of gas exchange. Due to this function, it is constantly exposed to noxious environmental stimuli—including bacteria and viruses. Following viral respiratory infection, many of the epithelial cells lining the airways are lost and must be reconstituted. The epithelial-intrinsic mechanisms underlying such recovery are well understood, but the role of the immune system in this process is not well defined. In close contact with epithelial cells in the distal lung are alveolar macrophages, innate immune cells capable of sensing diverse stimuli and integrating these signals into effector responses. Our previous work has shown that macrophages engage in reciprocal growth factor exchange with fibroblasts, a communication circuit we predict to be active in other cell types and contexts. In the lung, macrophages have been observed to help mediate inflammation and repair via communication with epithelial cells following injury, however, the role of these interactions in the context of viral infection remains unknown. Using a mouse-adapted influenza A virus, we observe a marked loss of epithelial cells followed by rapid recovery, all under a constant presence of macrophages. This study aims to determine the role of macrophages in this repair process. We hypothesize that optimal epithelial repair requires macrophages at specific time points and anatomical locations following viral-induced damage. We also propose that bidirectional crosstalk between macrophages and epithelial cells promotes tissue repair. The proposed work will serve to 1) define when and where macrophages are required for optimal repair following viral injury and 2) provide mechanistic understanding of macrophage-epithelial communication networks in the injured and regenerating lung. Completion of this project will allow us to identify molecular targets whose modulation may improve patient outcomes following viral infection. The Franklin lab is the ideal research environment to perform these studies. Dr. Franklin (sponsor) is an expert in macrophage biology and has previously unraveled interactions between macrophages and non-immune cells. Our location at Harvard Medical School also grants access to world-class experts and resources to complete our aims. For example, Dr. Carla Kim (co-sponsor) is an expert on lung damage and repair and will provide guidance on lung biology and epithelial progenitor cell function following damage. Together, my mentoring team and institutional resources will help me achieve the goals outlined in this proposal and allow me to grow both as a scientist and an individual.


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 = $36,073 )
2025	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Lung Diseases Research	000	2	12/10/2024	NON-COMPETING CONTINUATION	$36,073
														Subtotal = $36,073

Issue Date FY: 2024 ( Subtotal = $39,150 )
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Lung Diseases Research	001	1	12/22/2023	NEW	$0
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Lung Diseases Research	000	1	12/22/2023	NEW	$37,870
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Lung Diseases Research	002	1	7/19/2024	NEW	$1,280
														Subtotal = $39,150

Grand Total All Awards = $75,223

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Macrophage-Mediated Lung Repair Programs Following Injury

Award Number: F31HL172650

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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