# Technology Development Project - Increasing the complexity of ex vivo human airway models for studying immune response to viral infection

> **NIH NIH U19** · JACKSON LABORATORY · 2024 · $802,385

## Abstract

PROJECT SUMMARY TECH DEV PROJECT
The goal of the Technology Development (Tech Dev) Project is to develop approaches and tools that address
the needs of The Jackson Laboratory-Icahn School of Medicine at Mt. Sinai Cooperative Center on Human
Immunology (JAX-ISMMS CCHI) and that also advance the capabilities of the broader scientific community to
tackle fundamental mechanistic questions regarding human lung immunity and human immune-epithelial cell
interactions. Major questions related to lung immune function remain unanswered—such as the cell-to-cell
interactions between immune and lung epithelial cells that shape responses to foreign agents, and how age-
dependent changes in splicing and epigenetic modifications impact tissue immunity and inflammation. A
significant technical barrier to studying human immune-lung dynamics is the sheer complexity of the human lung
and the dynamic interactions between the lung epithelium and resident immune cells such as macrophages,
dendritic cells, and T cells. This complexity cannot be easily modeled in animal systems or using deceased
human lung tissue. To surmount these challenges, the Tech Dev Project will focus on three aspects to further
increase complexity and utility of an innovative human tissue platform which we have pioneered in our current
Center: establish three-dimensional (3D) bioprinted ventilated and vascularized models of the lung and upper
respiratory environment for investigating the functional lung-immune interactome during exposure to viral agents
(Aim 1); develop improved methods for viral infection and co-culture of immune cells in lung models (Aim 2);
and develop methods for, and perform, editing of airway epithelial cells, virus, and commensal bacteria for
inclusion in lung models (Aim 3). Epithelial editing will entail development of tools to alter isoform usage (for
Project 1), epigenetic modifications (for Project 2), and generating conditional alleles in primary human airway
epithelial cells and induced-pluripotent stem cells (iPSCs). For viral editing, we will engineer various reporter
influenza viruses to enable tracking of active versus history of infection. For bacterial editing, we will alter
production of candidate immune modulating metabolites from commensal bacteria (for Project 2) by perturbing
their associated metabolic pathways either by using our CRISPRi toolkit or via overexpression. Each of these
Aims addresses a specific unmet need for the Center and will enable us to study human lung immunity within a
dynamic and physiologically relevant microenvironment and to interrogate specific cell types and molecular
pathways predicted to respond to viral infections. Through these efforts, the JAX-ISMMS CCHI will be equipped
to address previously inaccessible questions related to lung-immune dynamics, towards a more mechanistic
understanding of lung immune function.

## Key facts

- **NIH application ID:** 10824109
- **Project number:** 2U19AI142733-06
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** ADAM WILLIAMS
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $802,385
- **Award type:** 2
- **Project period:** 2019-03-05 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824109

## Citation

> US National Institutes of Health, RePORTER application 10824109, Technology Development Project - Increasing the complexity of ex vivo human airway models for studying immune response to viral infection (2U19AI142733-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10824109. Licensed CC0.

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