# Metabolic-Epigenetic regulation of the senescence microenvironment in ovarian cancer

> **NIH NIH F31** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $12,436

## Abstract

Project Summary
The ultimate goal of this F31 Ruth L. Kirchstein NRSA is to request support to address a fundamental gap in
knowledge on the role of metabolism in regulation the epigenetic landscape of the senescence microenvironment
(termed the senescence-associated secretory phenotype; SASP) and its contribution to the cancer stem cell
(CSC) population and chemoresistance in epithelial ovarian cancer (EOC). The F31 Ruth L. Kirschstein NRSA
support will help further contribute to my scientific training and pathway to becoming an independent researcher
in academia.
This research proposal focuses on experimentally and mechanistically determining how alteration in the
metabolite alpha-ketoglutarate (a-KG) regulates the Jumonji-C (JmjC) histone demethylase KDM2B, which in
turn modulates the SASP. Additionally, the proposal aims to determine whether alterations in KDM2B expression
will reduce detrimental paracrine effects of the SASP. The proposed studies are based on my preliminary findings
suggesting that the active histone mark, H3K79me3, along with expression of SASP-related genes, are
increased upon cisplatin-induced senescence in EOC cells. Additionally, a-KG is decreased in cisplatin-induced
senescent cells, and supplementation of these cells with exogenous a-KG suppresses the SASP. Furthermore,
preliminary data indicate that the paracrine effects of the SASP contribute to increased cancer stem cells.
I will continue addressing results obtained in my preliminary data in the following specific aims: 1) to determine
the molecular mechanism by which SASP gene expression is epigenetically regulated through H3K79 tri-
methylation in EOC and the contribution of a-KG to this process; and 2) to determine whether the paracrine
effects of the SASP contributes to increased cancer stem cell population and chemoresistance of EOC. These
studies will provide a novel mechanism for understanding how the SASP is epigenetically regulated and how it
contributes to EOC chemoresistance and tumor progression.

## Key facts

- **NIH application ID:** 10116162
- **Project number:** 5F31CA250366-02
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Kelly Esme Leon
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $12,436
- **Award type:** 5
- **Project period:** 2020-03-01 → 2021-06-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116162

## Citation

> US National Institutes of Health, RePORTER application 10116162, Metabolic-Epigenetic regulation of the senescence microenvironment in ovarian cancer (5F31CA250366-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10116162. Licensed CC0.

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