# Progenitor cell states contributing to aging and lung cancer

> **NIH NIH U01** · HARVARD MEDICAL SCHOOL · 2024 · $54,749

## Abstract

Progenitor cell states contributing to aging and lung cancer
Abstract
Lung cancer is the single largest contributor to global cancer mortality. With the exception of smoking, age is the
single biggest risk factor for all major lung diseases, including cancer, highlighting the role of age-associated
changes in the lung for mortality. Metabolic changes and epigenetic alterations are both hallmarks of aging, but
little is known about how aging specifically impacts the lung and in particular lung progenitor cells. Furthermore,
the synergy between metabolism and epigenetic states is emerging as an exciting new field for which implications
in disease including cancer are only beginning to be explored. Preliminary data we have collected suggest that
both metabolic and epigenetic changes accompany aging in lung alveolar type II (AT2) cells, the primary cell-of-
origin of the most common form of lung cancer, lung adenocarcinoma. Our study will test the hypothesis that
alterations in metabolic pathways driven by epigenetic changes in AT2 cells contribute to increased tumor
initiation during aging. Firstly, we will map metabolic and epigenetic changes in aged AT2 cells using state of the
art technologies that will enable resolution of these differences onto highly select populations and even single
cells. Furthermore, we will create new models to study the effects of aging in cancer. New organoid models of
lung cancer initiation will be developed to support rapid modeling of the cellular and molecular aspects of cancer
in aged cells. Genetically engineered mouse models will be derived to model tumorigenesis in the aging lung.
Finally, we will probe the specific mechanism by which loss of epigenetic modifications, mediated by the
methyltransferase G9a, during aging contributes to increased tumor initiation through dysregulation of metabolic
genes and the metabolome. These studies will combine the strengths of two experienced PIs with expertise in
aging, metabolism, stem cell biology and cancer to generate new models of lung cancer and provide significant
insight into the synergy of two major hallmarks of aging in the most-deadly form of cancer.

## Key facts

- **NIH application ID:** 11065572
- **Project number:** 3U01CA267827-04S1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** MARCIA HAIGIS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $54,749
- **Award type:** 3
- **Project period:** 2021-09-24 → 2024-10-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11065572

## Citation

> US National Institutes of Health, RePORTER application 11065572, Progenitor cell states contributing to aging and lung cancer (3U01CA267827-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11065572. Licensed CC0.

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