# Targeting lysine acetyltransferase MOF/KAT8 in lung cancer

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2024 · $352,948

## Abstract

Project Summary
 Dynamic acetylation/deacetylation of histones and nonhistone proteins is a critical switch in gene
regulation. Manipulation of the acetylation switch is emerging as a promising therapeutic strategy in the
treatment of cancer. My laboratory has a long-term interest in clarifying the functions, mechanisms of action,
and regulation of lysine acetyltransferases and deacetylases, exploring their roles in diseases, and using the
resulting knowledge to develop new and better strategies for the treatment of diseases such as cancer. The
key focus of this resubmission application is on the Males Absent on the First (MOF, also called KAT8 or
MYST1) protein, a member of the MYST lysine acetyltransferase family. MOF regulates a variety of cellular
processes including gene transcription, DNA damage responses, and embryonic development. The proposed
project is significant because although increasing evidence suggests that MOF is also closely involved in
cancer, the exact mechanism by which MOF impacts tumor development and progression is unclear. Our
preliminary studies revealed an unexpected function of MOF in the transcriptional repression of epithelial to
mesenchymal transition (EMT) and cytokine genes in lung cancer. Furthermore, MOF depletion significantly
affects lung tumorigenesis in mouse models due to release of its transcriptional repression. Based on these
exciting preliminary results, we hypothesize that MOF may be a potential target for treatments of lung cancer.
The long-term objective is to explore how MOF regulates uncharacterized gene expression and signaling
processes to impact lung cancer. The central hypothesis will be tested by pursuing three specific aims: 1)
Dissect the novel and unexpected mechanisms by which MOF represses gene transcription; 2) Examine how
MOF controls gene expression via the methyltransferase G9a and TGF-beta/SMAD; and 3) Explore the
implications of SIRT1-mediated deacetylation of MOF in lung cancer development. The expected outcome of
this work will help elucidate new functions of MOF and its mechanisms of action in lung tumorigenesis, and
provide insights into future development of new therapeutic strategies for lung cancer.

## Key facts

- **NIH application ID:** 10757447
- **Project number:** 5R01CA270149-02
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** EDWARD SETO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $352,948
- **Award type:** 5
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757447

## Citation

> US National Institutes of Health, RePORTER application 10757447, Targeting lysine acetyltransferase MOF/KAT8 in lung cancer (5R01CA270149-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10757447. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*