# Epigenetic regulation of neurogenesis following perinatal hypoxic-ischemic brain injury

> **NIH NIH K08** · JOHNS HOPKINS UNIVERSITY · 2021 · $199,800

## Abstract

PROJECT SUMMARY
Perinatal hypoxic-ischemic brain injury (HI) is one of the leading causes of neurologic morbidity in the pediatric
population with sequelae such as cerebral palsy, intellectual disability, and epilepsy. Despite the known
plasticity of the immature brain, we still have very little in the way of therapies to actively ameliorate the
potentially devastating consequences of this disease. Neurogenesis is one aspect of plasticity with the
potential to improve outcomes after such injury. Neural stem and progenitor cells (NSPs) reside in discrete
regions of the brain postnatally, and while we know that they can alter behavior in response to numerous
stimuli, we still do not have a strong enough understanding of the fundamental mechanisms by which these
cells respond to injury. The experiments described in this career development plan have been designed to use
advanced strategies in clonal analysis to better understand the heterogeneity of the response of subventricular
zone (SVZ) NSPs to perinatal HI. With this knowledge, I propose also to define a role for the epigenetic
mechanism of active DNA demethylation as an early trigger for perinatal HI-induced neurogenesis. Finally I
aim to investigate changes in the methylation patterns of Notch and BDNF, genes known to play important
roles in NSP regulation, to link active DNA demethylation with known players in the phenomenon of
neurogenesis. In the process we will also be using the emerging strategy of single cell RNA sequencing to
describe transcriptome shifts that occur following perinatal HI and identify novel pathways of interest in
regulating the response of NSPs to this type of injury. In conjunction with the other career development
activities described in this proposal, this plan will prepare me for an independent research career further
exploring neurogenesis after perinatal HI and translating this knowledge into strategies to better understand
and hopefully intervene during the acute recovery period following brain injury to improve our management of
such patients.

## Key facts

- **NIH application ID:** 10133159
- **Project number:** 5K08NS097704-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Ryan J Felling
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $199,800
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133159

## Citation

> US National Institutes of Health, RePORTER application 10133159, Epigenetic regulation of neurogenesis following perinatal hypoxic-ischemic brain injury (5K08NS097704-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133159. Licensed CC0.

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