# BLRD Research Career Scientist Award Application

> **NIH VA IK6** · OKLAHOMA CITY VA MEDICAL CENTER · 2022 · —

## Abstract

Project Summary/Abstract
The overarching goal of Dr. Freeman’s research has been to understand how alterations of the
genome/epigenome contribute to aging and how therapies could potentially target these changes to maintain a
‘youthful’ epigenome that retards aging, delays/prevents age-related diseases, and improves the health and
quality of life of the elderly. Epigenetic dysregulation is a hallmark of aging, but exactly how this contributes to
cellular dysfunction and disease is not known. To elucidate this contribution, Dr. Freeman’s VA research has
focused on epigenomic regulation in astrocytes, microglia, and neurons in the hippocampus with aging. Using
novel cell isolation and advanced sequencing approaches, cell-type specific base resolution maps of both
methylation (mC) and hydroxymethylation (hmC) in CG and non-CG contexts are being generated. With paired
RNA expression data, bioinformatic techniques are being used to understand the regulation of gene expression
with aging. This type of base-specific, genome-wide, and cell-type specific studies have not been performed in
aging research and will potentially offer the most in-depth view of epigenomic changes with aging to date.
Further, to demonstrate the prevention of age-related epigenomic changes, caloric restriction is being used. In
total, these studies will not only increase the understanding of the neuroepigenomics of aging but also provide
targets for future interventional studies using epigenome editing. Importantly these studies examine both males
and females to provide sex-informed insight as his prior studies have demonstrated that the majority of age-
related epigenomic changes are sexually divergent.
Dr. Freeman is also PI or co-PI on three NIH projects and one foundation funded project. These studies extend
his VA research in aging through use of novel transgenic mouse models and anti-aging interventions in the brain,
retina, and GI system. These models developed by his lab allow temporally controlled, cell-type specific tagging
of nuclei and ribosomes to isolate DNA for epigenomic analysis and RNA for expression analysis without the
need for cell sorting. In the brain and retina, heterochronic plasma transfer, in which plasma from young mice is
administered to old mice for rejuvenation, is being used to determine if age-related epigenomic changes can be
reversed after they have occurred. In parallel, using proteomic approaches, DNMT and TET interacting proteins
are being identified that target them to specific genomic regions for epigenomic alteration.
More broadly, Dr. Freeman also has an extensive collaborative portfolio with other OKC VAMC investigators. In
these VA and NIH funded studies, Dr. Freeman is examining cell-type specific mechanisms of aging in muscle,
brain, ovary, joints, and colon. In addition to bringing molecular and biochemical expertise to these studies, a
common thread of epigenetics of aging allows comparisons and contrasts to be made across the organ...

## Key facts

- **NIH application ID:** 10485705
- **Project number:** 1IK6BX006033-01
- **Recipient organization:** OKLAHOMA CITY VA MEDICAL CENTER
- **Principal Investigator:** WILLARD M FREEMAN
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10485705

## Citation

> US National Institutes of Health, RePORTER application 10485705, BLRD Research Career Scientist Award Application (1IK6BX006033-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10485705. Licensed CC0.

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