# Mechanistic modeling of the innate immune responses of the human lung to understand the inter-individual heterogeneity of COVID-19 pneumonia

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2024 · $731,876

## Abstract

PROJECT SUMMARY/ABSTRACT
 A key feature of the COVID-19 infection is the vast inter-individual heterogeneity in the
severity of the infection. The complex biological mechanisms that underlie this variability remain
mostly obscure. We propose to provide a mechanistic understanding of this susceptibility by
leveraging 3 key innovations: First, we have developed a 3-dimensional lung culture system
that allows for detailed interrogation of the early events in SARS-CoV-2 infection. Second, we
have established an animal model of COVID-19 in mice transgenic for the human ACE2
receptor in our facility. Third, we have built a multi-scale mathematical model of lung infection in
COVID-19, that we now seek to expand and personalize to individual hosts. We have two Aims
in this project: In Aim 1, we will validate, expand, and personalize our existing multi-scale
model, using an unbiased approach to identify and test hypotheses relating to susceptibility to
severe COVID-19, and in Aim 2 we will test a specific hypothesis regarding the mechanism of
the observed inter-individual heterogeneity in COVID-19 severity, namely that it is, in part,
mediated by divergent activation of the mTOR pathway in type I alveolar epithelial cells. If
successful, this project will identify the biological basis of the immune pathways that result in
heterogeneous outcome of COVID-19, paving the way for personalized, host-specific
interventions to improve the outcome of the infection.

## Key facts

- **NIH application ID:** 10879046
- **Project number:** 5R01HL169974-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** REINHARD LAUBENBACHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $731,876
- **Award type:** 5
- **Project period:** 2023-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879046

## Citation

> US National Institutes of Health, RePORTER application 10879046, Mechanistic modeling of the innate immune responses of the human lung to understand the inter-individual heterogeneity of COVID-19 pneumonia (5R01HL169974-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10879046. Licensed CC0.

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