# Understanding cellular and transcriptional regulatory changes in human aging.

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $71,961

## Abstract

ABSTRACT
In this project, we propose to add Ms. Marliette Rodriguez Matos as a central member in our project to study the
aging of CD4+ T lymphocytes.
The parent R01 represents an ambitious project to study a primary, purified human cell type that has been
associated with age-related diseases and has been shown to manifest the systematic changes in DNA
methylation that occur with age in multiple tissue types and species. Our goal is to understand how much of the
spectrum of changes of molecular genomic properties with age are due to cell subtype changes, how many are
cell-autonomous, how these reflect cell signalling effects on transcription factor biology, and how inter-individual
DNA sequence variation interacts with these molecular and cellular phenotypes.
Towards these goals we are performing genotyping, T cell receptor amplicon sequencing, and chromatin
accessibility studies using ATAC-seq on the samples. Our original plan was to add bulk RNA-seq and DNA
methylation studies, but we are now exploring instead a single cell RNA-seq approach with pseudobulking, and
are concerned that the DNA methylation studies will be uninformative given more recent data that indicates these
changes represent a decrease in multipotent stem cell proportions in tissues with age, which may explain why
the DNA methylation clock has not been demonstrated to work in purified cells. We have purified our cells with
the CD4+ surface marker, which depletes all precursor cells. Our ongoing work led by Dr. Katherine Crocker is
designed to shed light on this issue so that we make our experimental investments wisely.
Ms. Rodriguez Matos will take the lead in performing the chosen set of molecular genomic assays on the cohort
of 400 samples. She comes to our group with strong wet bench experience, and has proven herself to be
exceptional technically with genomic assays. Given the extensive project delays enforced by the COVID-19
pandemic, adding Ms. Rodriguez Matos is based on the practical consideration that this will allow us to deliver
the genomic data needed for the final, analytical stage of the project.
We will develop Ms. Rodriguez Matos’ participation in this project as part of a structured training experience. We
describe in this proposal how her project activities will involve activities that are designed to foster transferrable
skills. These skills will not only be related to the field of aging but also project management, communication,
leadership, and supervisory skills, and training in ethics and integrity. Her analytical skills will be fostered by
working with the group of co-PI Dr. Tuuli Lappalainen at the New York Genome Center, rounding out her skills.
Ms. Rodriguez Matos’ has defined her career goal explicitly as a future independent investigator. Our goal during
the R01 project is to give her the skills and publications that will give the foundation needed for that outcome.
We would welcome the opportunity to train a Hispanic-American woman as a future lea...

## Key facts

- **NIH application ID:** 10427922
- **Project number:** 3R01AG057422-05S1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** John Greally
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $71,961
- **Award type:** 3
- **Project period:** 2018-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427922

## Citation

> US National Institutes of Health, RePORTER application 10427922, Understanding cellular and transcriptional regulatory changes in human aging. (3R01AG057422-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10427922. Licensed CC0.

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