# Role of HDAC2 as a modulator of aging and Alzheimer's disease phenotypes in stem-cell derived neurons

> **NIH NIH K01** · UNIVERSITY OF WASHINGTON · 2022 · $120,527

## Abstract

Title: Role of HDAC2 as a modulator of aging and Alzheimer’s disease phenotypes in stem-cell derived
neurons.
Project Summary/Abstract
Brain aging is a significant contributor to many neurodegenerative disorders, including Alzheimer’s disease (AD),
and is tightly regulated by epigenetic mechanisms. Until recently, studying human neural aging has been
challenging due to the relative inaccessibility of living brain tissue. Recent advances in cellular reprogramming,
either by inducing stem cells from somatic cells and differentiating to a neural lineage or by direct
transdifferentiation of somatic cells to neurons, have been transformative. However, a global understanding of
epigenetic changes and the contribution of age in a human cellular model of AD is lacking. Recent studies
demonstrate that the epigenetic regulator histone deacetylase 2 (HDAC2) is abnormally elevated in AD and aged
brains. The applicant, Dr. Jessica E. Young, is proposing to combine her considerable experience in stem cell
biology and Alzheimer’s disease modeling with mentorship in aging biology, functional genomics, and neuronal
mitochondrial biology to test the overarching hypothesis that HDAC2 is a driver of cellular age in human neurons
and contributes to AD-relevant phenotypes. This project will ask three critical questions: 1) Does the epigenetic
regulator HDAC2 drive epigenomic and transcriptomic changes related to aging human neurons? 2) Does
modulation of HDAC2 expression alter cellular aging phenotypes in human neurons? 3) Does modulation of
HDAC2 expression affect cellular phenotypes relevant to AD pathology in human neurons? To address this
questions, Dr. Young will pursue functional genomic and cell biological experiments based on modulation of
HDAC2 expression in hiPSC-derived and transdifferentiated human neurons. This work will advance
understanding on specific pathways that link aging with AD pathogenesis and evaluate the utility of HDAC2 as
a tool to develop age-relevant AD in vitro studies. Dr. Young is a new Assistant Professor in the Department of
Pathology and a member of the Institute for Stem Cell and Regenerative Medicine at the University of
Washington. She will devote 75% of her time to research under this award and will supplement her research with
didactic training in aging biology, neuropathology, and epigenomic and transcriptomic analyses. This training will
be comprised of 1) departmental and university courses, 2) seminars and journal clubs 3) responsible conduct
of research courses and 4) national and international conferences. Dr. Young will be mentored by Dr. Peter
Rabinovitch, Dr. Jay Shendure, Dr. C.Dirk Keene, and Dr. Richard Morrison at the University of Washington.
These established scientists are renowned experts in biology of aging, functional genomics, neuropathology,
and neuronal mitochondrial biology, respectively. Dr. Young has met with each of her mentors to discuss this
project and will continue to meet with them at regular inter...

## Key facts

- **NIH application ID:** 10377380
- **Project number:** 5K01AG059841-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jessica Elaine Young
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $120,527
- **Award type:** 5
- **Project period:** 2019-05-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377380

## Citation

> US National Institutes of Health, RePORTER application 10377380, Role of HDAC2 as a modulator of aging and Alzheimer's disease phenotypes in stem-cell derived neurons (5K01AG059841-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10377380. Licensed CC0.

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