# Investigation of the Role of Polycomb in Epilepsy Development and Progression

> **NIH NIH K00** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $3,342

## Abstract

Project Summary
Epilepsy is the fourth most prevalent neurological disorder after stroke, Alzheimer’s disease and migraine. It is
estimated that about 3 million people in the U.S. and 65 million worldwide currently live with epilepsy. While a
number of anti-convulsants exist to treat single seizure episodes, no anti-epileptogenic drugs are currently
available to stop disease progression. Epileptogenesis (the process by which epilepsy progresses and
develops) is associated with numerous pathological changes including neuroplasticity deficits, cell death, and a
reduction in seizure threshold.
To investigate the transcriptional regulators that drive large-scale gene expression changes during
epileptogenesis, I used a bioinformatics tool developed by my advisor called the MAGIC matrix to analyze
microarray datasets of dentate granule cells laser captured after Status Epilepticus (SE) in four rat seizure
models. My analysis predicts that the Polycomb catalytic subunit Enhancer of Zeste Homolog 2 (EZH2) is the
principal driver of expression changes during epileptogenesis. This is significant because Polycomb plays an
important role during development, where it epigenetically and stably silences genes through histone
methylation.
Preliminary experiments in Aim 1 demonstrate that EZH2 protein levels dramatically increase after SE, while
expression of its target genes significantly decrease many days after. Additionally, inhibiting EZH2 function in
vivo using the pharmacological inhibitor, UNC1999, caused epileptic animals to have more seizures with
greater severity over time. In the future, I aim to determine whether promoting EZH2 activity has the potential
to alter hallmarks such as neurodegeneration, occurrence of spontaneous seizures and survival. This study
has the potential to be one of the first to use Polycomb regulators to modify the process of epileptogenesis.

## Key facts

- **NIH application ID:** 10063588
- **Project number:** 5K00NS105211-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Nadia Khan
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,342
- **Award type:** 5
- **Project period:** 2017-09-28 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063588

## Citation

> US National Institutes of Health, RePORTER application 10063588, Investigation of the Role of Polycomb in Epilepsy Development and Progression (5K00NS105211-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10063588. Licensed CC0.

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