# Determining the Molecular Contributions of KDM2A in NSCLC Metastasis

> **NIH NIH F31** · YALE UNIVERSITY · 2022 · $42,724

## Abstract

PROJECT SUMMARY
 Non-Small Cell Lung Cancer (NSCLC) remains the highest mortality cancer in the United States, with
approximately 70% of patients not eligible for curative surgical resection at diagnosis. Thus, the advent of
novel systemic therapeutics, especially those which are efficacious for metastatic disease, is of primary
importance. A functional genomic screen conducted in our laboratory identified the H3K36 demethylase
KDM2A as a regulator of KRAS/P53 mutant NSCLC metastasis. KDM2A is known to also have roles in DNA
damage repair, thus I hypothesize that KDM2A is important to preserving the genomic stability of NSCLC cells
by mediating genotoxic stress, and to metastasis by controlling transcriptional responses to the tumor
microenvironment. The primary aims of this project are to elucidate the molecular mechanism by which
KDM2A promotes NSCLC proliferation/survival, and to determine the steps of the metastatic cascade for which
KDM2A is important. To answer these questions I will leverage bioinformatic analysis, functional mutants, and
animal models. In Aim 1, I will use functional mutants of KDM2A to assay importance of each functional
domain to proliferation and survival, as well as assaying the impact of KDM2A loss on markers of genomic
stress. In Aim 2, I will use in vivo models of metastasis to examine the molecular functions of KDM2A that are
important to various steps of the metastatic cascade, as well as using a variety of injection and assay
techniques to pinpoint the step(s) of the cascade at which KDM2A is important. The completion of this project
will reveal the molecular mechanism of a novel potential clinical target of advanced NSCLC. My project is
easily translatable to clinical research, as a research grade chemical inhibitor of KDM2A exists and could be
optimized for clinical deployment.

## Key facts

- **NIH application ID:** 10374786
- **Project number:** 5F31CA261126-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Carolyn Kravitz
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $42,724
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374786

## Citation

> US National Institutes of Health, RePORTER application 10374786, Determining the Molecular Contributions of KDM2A in NSCLC Metastasis (5F31CA261126-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10374786. Licensed CC0.

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