# Regulation of distal basal cells in terminal and respiratory airway regeneration

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $724,431

## Abstract

PROJECT SUMMARY
 Distal (or small) airways including the terminal and respiratory bronchioles (TRB) are the sites of damage
in several lung diseases. Pathologies of small airway lesions are poorly understood as the cellular composition
and properties of TRB regions are yet to be fully characterized. Respiratory bronchioles (RB) are extremely small
airways, about 200 µm in diameter. Importantly, the anatomy of mice – the most commonly used model
organisms – is significantly different in these regions. Murine lungs lack RBs, and their terminal bronchioles open
directly into alveoli at the bronchio-alveolar duct junction (BADJ). These challenges have resulted in RBs
remaining as a black box of human lungs. We optimized microdissection protocols to enrich RBs from human
lungs and generated single-cell transcriptomic maps. We identified seven novel cell populations in the TRB
regions. Importantly, we show that these cells have no equivalent cell types in mice. All these data point towards
the need to develop new models to effectively understand small airways in health and disease. We show here
in our preliminary data that primary human stem cell cultures well capture the small airway biology. Further, we
find that small airways of ferrets have similar cellular composition to those of humans suggesting that they can
serve as a model to study small airways. Utilizing these two models coupled with single-cell transcriptomics we
propose to address the following specific aims. 1) Delineate the terminal and respiratory bronchiolar epithelial
lineage trajectories. 2) Study the cell-intrinsic transcriptional networks that maintain distal basal cell identity. At
the conclusion of this study, we would have significantly advanced our understanding of human terminal and
respiratory bronchioles. We will develop the first TRB-specific lineage tracing model in ferrets. Our study will
determine the cell-intrinsic mechanisms that determine TRB stem cell identity and progeny. These results will
assist in developing effective therapies for diseases involving small airways.

## Key facts

- **NIH application ID:** 10941065
- **Project number:** 1R01HL174610-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Preetish Kadur Lakshminarasim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $724,431
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10941065

## Citation

> US National Institutes of Health, RePORTER application 10941065, Regulation of distal basal cells in terminal and respiratory airway regeneration (1R01HL174610-01). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10941065. Licensed CC0.

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