# Endothelial cell signaling in regeneration of the lung

> **NIH NIH K99** · UNIVERSITY OF PENNSYLVANIA · 2022 · $161,690

## Abstract

Project Summary
 A critical function of the lung at homeostasis is delivery of oxygen to the blood through a process called
gas exchange. When the lung is functioning normally, type I alveolar epithelial cells and capillary endothelial
cells (ECs) lining blood vessels in the distal lung form a tight interface to exchange oxygen and carbon dioxide
between them. However, when the lung is damaged by chronic disease, cancer, or infections such as influenza
or COVID-19, this process can be hindered or even prevented. After lung injury, progenitor cells can regenerate
the cell types required for gas exchange, but cell-cell communication is also essential to form a functional
structure that restores delivery of oxygen to the blood. Development of improved regenerative therapies in the
lung will therefore require a detailed knowledge of not only the specific cell types that are present, but also how
they communicate to drive cell self-organization and morphogenesis. We have shown that capillary ECs in the
distal lung are heterogeneous; one population acts as an EC progenitor and proliferates after acute injury
(CAP2s), while a second population does not proliferate significantly after injury and possesses a larger, more
complex morphology and high expression of signaling molecules (CAP1s). These EC subtypes clearly contribute
differently to regeneration, but how distinct EC fates are established and maintained, the mechanisms that
promote the preferential proliferation of CAP2s, and the signaling function of CAP1s remain unknown. In addition,
the EC signaling mechanisms within the alveolar niche that are required to effect morphogenesis and rebuild the
gas exchange interface remain incompletely understood. The proposed research will further develop my skills in
transcriptomic and epigenomic analysis to address these questions and will integrate these skills with my
previous training in mouse genetics, signaling, and cell behavior to establish a strong foundation on which to
build an independent research career. My research program will focus on the role of EC signaling and behavior
in regeneration of functional alveolar structures in the lung after acute injury. My primary mentor is Dr. Edward
Morrisey, an internationally renowned scientist in the study of lung regeneration who has defined many key
regulators of cell fate and signaling mechanisms in the lung. I have also assembled an advisory committee of
experts in vascular biology, mouse and human organoid culture, epigenetics, and bioinformatics who will assist
me with additional training in these areas. The proposed work will be conducted at the University of Pennsylvania,
where I will benefit from the rich intellectual environment, extensive resources, collaborative scientific community
in pulmonary and vascular biology, and the full support of the institution. Together, my proposed research and
career development plans will facilitate a better understanding of the role of EC signaling in lung regen...

## Key facts

- **NIH application ID:** 10506642
- **Project number:** 1K99HL164960-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Terren Kathryn Niethamer
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $161,690
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10506642

## Citation

> US National Institutes of Health, RePORTER application 10506642, Endothelial cell signaling in regeneration of the lung (1K99HL164960-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10506642. Licensed CC0.

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