# Wnt-mediated epithelial-endothelial crosstalk in the generation and regeneration of the lung alveolus

> **NIH NIH K08** · CHILDREN'S HOSP OF PHILADELPHIA · 2022 · $159,408

## Abstract

ABSTRACT:
The proposal in this application outlines a five-year training program for the development of a career as a
physician-scientist in cardiopulmonary biology. The candidate is an Instructor of Pediatrics and a pediatric
cardiologist at the Children’s Hospital of Philadelphia. The proposed research will be carried out under the
mentorship of Dr. Edward E. Morrisey, Ph.D., a leader in the field of cardiopulmonary development. Dr.
Morrisey has trained numerous young investigators including several physician-scientists who currently hold
academic appointments. An advisory committee has been assembled to provide expertise in pulmonary and
cardiovascular biology in addition to career guidance from well-established to newly appointed independent
investigators. The research environment has been carefully selected to include exposure to two institutions
allowing access to extensive resources, core facilities, and intellectual guidance. In addition, the candidate will
be participating in didactic courses and numerous professional development seminars to help ensure adequate
training for independence. Together, this provides a unique and ideal environment for the candidate to
develop the skills to transition to an independent physician-scientist in the cardiopulmonary field.
I have identified a subpopulation of Wnt signaling-responsive type 2 alveolar epithelial cells (AT2s), called
Axin2+ AT2s or AT2sAxin2, which exhibit enhanced stem cell characteristics during alveologenesis (Frank DB
et al. Cell Reports. 2016 Nov 22;17(9):2312-2325). In addition, the transcriptome of Axin2 AT2s are highly
enriched for genes that are essential for vascular development and extracellular matrix production and
interactions. The goal of this proposal is to not only further characterize this progenitor cell population in the
alveolus but also examine the mechanism by which it orchestrates alveolar epithelial and endothelial growth
during generation and regeneration of the alveolus. Therefore, the proposal will address these processes
with two overriding aims: 1) Examine the regulation of alveolar epithelial cell self-renewal by Wnt ligand
secretion; and 2) Identify and delineate the role of Wnt signaling and Wnt signaling-responsive alveolar
progenitor cell populations in the epithelial-vascular niche of the developing and regenerating alveolus.
!
The training program and research proposed in this application will provide critical tools, skills, and scientific
expertise to become a physician-scientist in the pediatric cardiopulmonary field, a relatively understudied and
underfunded area of pediatric research. There is no cure for pediatric PH and developmental lung diseases
such as BPD. Thus, the identification and characterization of alveolar epithelial progenitor or stem cells could
provide novel targets for therapy and lung growth.

## Key facts

- **NIH application ID:** 10326831
- **Project number:** 5K08HL140129-05
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** David Brian Frank
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $159,408
- **Award type:** 5
- **Project period:** 2018-01-19 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10326831

## Citation

> US National Institutes of Health, RePORTER application 10326831, Wnt-mediated epithelial-endothelial crosstalk in the generation and regeneration of the lung alveolus (5K08HL140129-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10326831. Licensed CC0.

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