# Functions of specialized pulmonary endothelial cell types in regeneration of the lung

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2020 · $64,926

## Abstract

Project Summary
 The lung possesses a low rate of cellular turnover at homeostasis but contains facultative stem cells that
can be activated to regenerate injured tissue. Efficient injury repair in the lung is critical to reestablish gas
exchange with the cardiovascular system, a process that is necessary to sustain life. Two key players in the gas
exchange process in the distal lung are the type I alveolar epithelial cells and the capillary endothelial cells (ECs),
which interface closely with each other to enable transfer of oxygen and carbon dioxide between them. During
lung regeneration, distinct subpopulations of capillary ECs may possess cellular plasticity that enables them to
act as endothelial progenitors to rebuild the gas exchange machinery. In addition, angiocrine signaling originating
from ECs in the distal lung may shape the regeneration of other alveolar cell types. Despite the importance of
ECs, however, the extent and function of their heterogeneity within the lung remains incompletely understood.
This question is critical to our understanding of the maintenance and repair of functional gas exchange.
 I have profiled pulmonary EC heterogeneity at single-cell resolution using single-cell RNA sequencing in
the adult mouse lung at homeostasis and after acute lung injury and have identified several unique EC
populations. These include a subset of ECs that express high levels of signaling molecules and preferentially
localize to regions of dense alveolar damage, as well as a population of highly proliferative ECs that arises upon
acute lung injury. Each population likely contributes to revascularization of the alveolar space during
regeneration. Determining the unique functional role of each population within the alveolus, its preferential
response to injury, and how each type of EC interacts with alveolar epithelial cells will facilitate a better
understanding of how the lung vasculature is rebuilt and gas exchange is reestablished as the lung regenerates.
This mechanistic understanding can then be used to facilitate regenerative medicine approaches that target
specific EC subtypes or signaling pathways in the lung.
 This project will expand my training to include key methods and concepts in lung regeneration and in
bioinformatics analysis of single-cell genomic datasets. It will take place under the sponsorship of Dr. Edward
Morrisey, a leader in the pulmonary biology field who has defined many key transcription factors and signaling
pathways in the lung. This work will be conducted at the University of Pennsylvania, a world-class research
institution with collaborative investigators, a rich intellectual environment, and extensive resources for the pursuit
of biomedical research focusing on pulmonary biology. Together, the research and training plans proposed
herein will facilitate a better understanding of pulmonary endothelial cell heterogeneity and its role in regeneration
while preparing me for my future career as an independent...

## Key facts

- **NIH application ID:** 9992090
- **Project number:** 1F32HL152664-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Terren Kathryn Niethamer
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992090

## Citation

> US National Institutes of Health, RePORTER application 9992090, Functions of specialized pulmonary endothelial cell types in regeneration of the lung (1F32HL152664-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9992090. Licensed CC0.

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