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Novel animal models to dissect how lung macrophages contribute to SARS-CoV2 alveolar pathology and respiratory failure

Award Number: K01OD031968
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Novel animal models to dissect how lung macrophages contribute to SARS-CoV2 alveolar pathology and respiratory failure - This application seeks support for a research-emphasis veterinarian embarking on an independent career as a translational veterinarian-scientist. The applicant proposes to study macrophages as drivers of SARS-CoV2- induced lung damage in humans and mouse models, and will develop novel indicator mice to report SARS-CoV2 cellular targets in mice. This multi-disciplinary approach brings together leading experts in lung biology, macrophage biology, virology, mouse genetics and pulmonary pathology. At Cornell University College of Veterinary Medicine, the applicant will perform research in the laboratories of Drs. David Russell and Dr. Hector Aguilar-Carreño (Department of Microbiology and Immunology), with histopathology analyses performed in the laboratory of Dr. Gerald Duhamel (Department of Biomedical Sciences). For specific hands-on training in lung epithelial repair assays, the applicant will work in the laboratory of Dr. Carla Kim (Harvard Medical School/Children’s Hospital Boston). Dr. Russell, primary mentor, is an expert in macrophage biology and their interaction with several lung pathogens, notably M.tuberculosis and HIV. He has a proven track record in training post-doctoral veterinarian-scientists that have gone on to tenure-track positions with federal research funding. Dr. Aguilar-Carreño has published extensively on the entry and egress of enveloped viruses with emphasis on paramyxoviruses, and recently has adapted his well-described mouse challenge platform for antiviral and vaccine discovery, toward SARS-CoV2. Dr. Duhamel is a veterinary anatomic pathologist with a research focus in infectious disease, including lung pathogens in mice. Finally, Dr. Carla Kim is a pioneer in lung epithelial repair and stem cell biology. Adding breadth and depth to the proposed work, the applicant has assembled a team of enthusiastic collaborators (with two practicing MD physicians), including leaders in mouse genetics and lung injury (Drs. Kahn and Morrisey), hyaluronan biology (Dr. Hascall), and human pulmonary pathology (Dr. Borczuk). The research environment at Cornell is exceptional in the disciplines of infectious disease and comparative pathology, while the combined expertise of Drs. Kim and Borczuk adds a strong translational and integrative focus on drivers of alveolar damage. The proposal will probe how resident and recruited macrophages are dysregulated during SARS-CoV2 in mice, whether dependent on direct viral infection of macrophages or on environmental cues. In Aim 1, reporter mice will be generated to identify SARS-CoV2- infected cells during infection and upon asymptomatic recovery. During Aim 2, the nature of macrophage subsets as viral targets will be studied, and their resulting functional deficits determined using assays developed by Dr. Russell. In Aim 3, viral challenge studies in human Ace2-expressing mice will interrogate macrophages as drivers of alveolar damage, and test whether macrophage interventions improve clinical outcomes in mice. The candidate will begin this research as Senior Research Associate in the Department of Microbiology and Immunology (75% research effort), with an expected junior faculty transition in the independent award phase.


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: 2026 ( Subtotal = $153,630 )
2026	2026	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Infrastructure Programs	000	5	12/10/2025	NON-COMPETING CONTINUATION	$116,759
2026	2026	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Infrastructure Programs	001	5	4/10/2026	NON-COMPETING CONTINUATION	$36,871
														Subtotal = $153,630

Issue Date FY: 2025 ( Subtotal = $153,630 )
2025	2025	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Infrastructure Programs	000	4	11/8/2024	NON-COMPETING CONTINUATION	$138,267
2025	2025	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Infrastructure Programs	001	4	7/21/2025	NON-COMPETING CONTINUATION	$15,363
														Subtotal = $153,630

Issue Date FY: 2024 ( Subtotal = $153,630 )
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Infrastructure Programs	000	3	11/3/2023	NON-COMPETING CONTINUATION	$138,267
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Infrastructure Programs	001	3	5/15/2024	NON-COMPETING CONTINUATION	$15,363
														Subtotal = $153,630

Issue Date FY: 2023 ( Subtotal = $153,630 )
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Infrastructure Programs	000	2	11/10/2022	NON-COMPETING CONTINUATION	$153,630
														Subtotal = $153,630

Issue Date FY: 2022 ( Subtotal = $154,777 )
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Infrastructure Programs	001	1	5/7/2022	NEW	$15,478
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Research Infrastructure Programs	000	1	12/1/2021	NEW	$139,299
														Subtotal = $154,777

Grand Total All Awards = $769,297

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Novel animal models to dissect how lung macrophages contribute to SARS-CoV2 alveolar pathology and respiratory failure

Award Number: K01OD031968

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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