# Humanized lung implant mouse model to study Staphylococcus aureus airway interactions

> **NIH NIH R21** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2020 · $234,000

## Abstract

Summary
Staphylococcus aureus in an important Gram positive human pathogen that is capable of
infecting numerous bodily sites including the lung. It leads to significant morbidity and mortality,
has a high incidence of antibiotic resistance and is a pathogen identified as needing increased
research to discovery new therapeutics. The long term goal of our research is to better
understand the host-pathogen interaction between S. aureus and the host immune system. It is
hoped that an improved understanding of this interaction could lead to novel therapies targeting
the bacterium or modulating the host to thwart this multidrug resistant pathogen. The objective
of this proposal is to characterize the innate immune response of the human lung as well as the
initial response of S. aureus to the airway and identify the genetic factors important for causing
infection. The rationale for this approach is that new targets are needed to either develop
antibiotics/inhibitors or vaccines against S. aureus. This is due to its high level of antibiotic
resistance and previously promising vaccine candidates in murine models have failed to
translate to efficacious human vaccines. Our preliminary data shows that humanized mice
represent an improved model for the study of S. aureus infection in the lung, allowing the role of
human specific virulence factors to be studied and understand the immune response to
infection. We present a novel model of humanized mice whereby mice are implanted with
human lung tissue. We have also demonstrated the use of a Tn-seq library to identify new
factors important for infection in the airway. This contribution is significant as it will provide an
understanding of how the human immune system, including the epithelium responds to S.
aureus, as well as how S. aureus reacts to this environment and the factors that it employs to
sustain infection. The innovation of this research is the utilization of a new model of infection
that leverages our experience with humanized models of infection. This model incorporates
human lung tissue to better replicate the human lung. We will characterize this response at
multiple levels, at the transcriptional, protein and cellular level. Global approaches to understand
the pathogen response, RNA-seq and Tn-seq will be combined to identify new genetic elements
important in pathogenesis. Given present failure with vaccines and current drug pipelines,
investigating gene products in the context of human model outside of ell-characterized virulence
factors might lead to novel discoveries.

## Key facts

- **NIH application ID:** 10040592
- **Project number:** 1R21AI153646-01
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Dane Parker
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,000
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10040592

## Citation

> US National Institutes of Health, RePORTER application 10040592, Humanized lung implant mouse model to study Staphylococcus aureus airway interactions (1R21AI153646-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10040592. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*