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

> **NIH NIH K01** · CORNELL UNIVERSITY · 2022 · $154,777

## Abstract

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 outc...

## Key facts

- **NIH application ID:** 10351622
- **Project number:** 1K01OD031968-01
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** David W Gludish
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $154,777
- **Award type:** 1
- **Project period:** 2021-12-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10351622

## Citation

> US National Institutes of Health, RePORTER application 10351622, Novel animal models to dissect how lung macrophages contribute to SARS-CoV2 alveolar pathology and respiratory failure (1K01OD031968-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10351622. Licensed CC0.

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