# Metabolic Control of Stemness in lung epithelial progenitors by FAM13A

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $687,150

## Abstract

Chronic obstructive pulmonary disease (COPD) ranks as the third leading cause of death in the U.S., lacking
effective pharmacological treatment. Recent progress suggested that defective lung repair/regeneration likely
contribute to emphysema development. During repair/regeneration process, tissue progenitor cells require
optimal amount of energy supplies to fulfill cell proliferation and differentiation demands, which has been well
documented in stem cells in other organs such as intestine stem cells, neuro-progenitors and hematopoietic
stem cells. However, the metabolic control of stemness in lung epithelial progenitor cells remains elusive.
FAM13A (family with sequence similarity 13, member A) has been consistently associated with susceptibility to
COPD in genome-wide association studies (GWAS). Our published work has demonstrated that FAM13A is
mainly expressed in alveolar type II epithelial cells, regarded as lung stem cells. However, whether and how
Fam13a regulates alveolar repair/regeneration, especially through modulating metabolism in lung epithelial
progenitors remain incompletely understood. In last funding cycle, we have published that Fam13a promotes
the degradation of beta-catenin and inhibits cell growth. However, depletion of beta-catenin failed to completely
revert phenotype seen in Fam13-/- mice, suggesting additional pathways regulated by FAM13A may play a role
in the lung repair/regeneration process. Our unpublished data suggested that Fam13a not only responds to
Akt-mediated growth factor signaling but also represses the energy master regulator AMPK (c-AMP activated
kinase) in cell lines and primary murine lung epithelial cells, suggesting an undiscovered metabolic control by
Fam13a in lung epithelial progenitors. We, therefore, hypothesize that FAM13A may act as a key metabolic
switch for cell growth through coupling energy homeostasis with cell growth demands in alveolar epithelial cells
during lung regeneration. In this proposal, we are going to test this hypothesis through integrative approaches
including in vitro biochemical assays, in vivo lineage tracing, smoke-induced emphysema mouse models,
CRISPR-based genome editing and ex vivo organoid co-culture models. Successful completion of this project
will shed mechanistic insights into molecular mechanism by which FAM13A transduces growth factor signals to
metabolic controls on stemness of lung epithelial progenitors through interacting its upstream regulator Akt and
downstream effector AMPK thereby possibly offering novel anti-COPD therapeutics.

## Key facts

- **NIH application ID:** 10122044
- **Project number:** 2R01HL127200-06A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Anny Xiaobo Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $687,150
- **Award type:** 2
- **Project period:** 2015-04-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122044

## Citation

> US National Institutes of Health, RePORTER application 10122044, Metabolic Control of Stemness in lung epithelial progenitors by FAM13A (2R01HL127200-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10122044. Licensed CC0.

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