# Probing functioning lung at the cellular resolution in health and disease

> **NIH NIH DP2** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $1,485,000

## Abstract

Summary: The lung is the site of many pathophysiologies due to air-borne pathogens, pollutants, and primary
and metastatic cancer, and its diverse microenvironment is continuously exposed to chemical, mechanical,
biological, and immunological stresses. The lack of effective therapeutics for many major pulmonary diseases,
exemplified by the ongoing COVID-19 pandemic, demonstrates the urgent need to better understand the cellular
dynamics of disease pathogenesis, and to identify new therapeutic targets. The majority of our understanding of
pulmonary diseases relies on fixed/frozen specimens from patients and in vivo models, which only provide a
snapshot of the lung’s pathophysiology, and hence incapable of capturing the dynamic and early stage events
in disease progression and response to therapy. The current in vitro and ex vivo models also lack the cellular
diversity and complex biophysical and immunological environment in the lung. This lack of technologies to probe
the lung cellular dynamics with high spatial and temporal resolutions is a major obstacle underlying our limited
understanding of the following key dynamic events in health and disease: (i) real-time dynamics of respiration
(e.g., gas transport) and circulation (e.g., vascular integrity), (ii) trafficking of immune and cancer cells, and their
sequestration, extravasation, and differentiation, (iii) dynamics of cellular communication via biochemical (e.g.,
cytokine) and biophysical (e.g., shear stresses) factors and, (iv) transmission of air-borne pathogen, and the host
response dynamics. To study these dynamic events, we propose to develop a transformative platform to
mechanistically probe lung (patho)physiology in real-time and at the cellular resolution. This platform, termed
LungEx, includes the long-term ex vivo maintenance of mouse and human lungs in near-physiological conditions
that is equipped with a novel transparent ribcage, termed “crystal” ribcage, enabling real-time volumetric optical
microscopy. Utilizing this platform, we will, for the first time, visualize the dynamics of lung pathophysiology in
real-time, at the cellular resolution, and over nearly the entire surface of the lung while the respiratory/circulatory
functions are fully preserved. Additionally, LungEx allows precise control of the physical and biochemical
parameters of respiration/circulation as well as biochemical and optogenetic manipulation through the crystal
ribcage, which will enable establishing causal links between physical, biological, and immunological
determinants of lung diseases. Leveraging on our preliminary data and diverse collaborators, we will
demonstrate the capabilities of the Mouse LungEx in probing the immune response to lung metastasis from the
earliest stages of cancer cell seeding to established tumors. We will also demonstrate the unprecedented
capabilities of Human LungEx to probe the spatial heterogeneities of the host response to viral infections such
as SARS-CoV-2, and the ve...

## Key facts

- **NIH application ID:** 10473112
- **Project number:** 1DP2HL168562-01
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Hadi Tavakoli Nia
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,485,000
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10473112

## Citation

> US National Institutes of Health, RePORTER application 10473112, Probing functioning lung at the cellular resolution in health and disease (1DP2HL168562-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10473112. Licensed CC0.

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