# Regulation of memory T cell differentiation and long-term maintenance

> **NIH NIH P01** · UNIVERSITY OF FLORIDA · 2022 · $489,800

## Abstract

PROJECT SUMMARY / ABSTRACT
Project 3 (Goldrath)
In response to infection, many cellular factors cooperate to direct T cells through their expansion and
differentiation to effector cells that mediate pathogen clearance and memory cells that persist to provide long-
lived host protection from reinfection. Harnessing the functionality and longevity of memory T cells is the basis
for some vaccines and has become an attractive approach in cancer immunotherapy. However, the memory T
cell pool is heterogeneous, and it is currently unclear which subsets confer optimal protection during malignancy
or infection and how these subsets are transcriptionally programmed. We propose to define the transcriptional
and chromatin regulatory factors of memory T cell subset differentiation following infection and identify those that
promote accumulation and function of anti-tumor cytotoxic lymphocytes. Further, we will explore the relationship
between changes in chromatin configuration and memory T cell-specific transcriptional programs. We propose
highly collaborative Aims which leverage the expertise, infrastructure and technologies unique to the Crotty-
Pipkin-Goldrath laboratories and Cores. Specifically, we will: (1) Resolve the functional heterogeneity and
transcriptional programming of circulating CD8 memory T cell populations. (2) Define the transcriptional and
epigenetic programming of stem-like memory, effector, and tissue-resident CD8 T cell subsets in tumors. (3)
Resolve the roles of Blimp1 and Bcl6 in programming distinct CD4 memory T cell populations. (4) Dissect the
mechanism(s) by which the chromatin regulatory factor CTCF instructs memory T cell differentiation. By
developing an understanding of the factors that control differentiation and function of memory T cell subsets, it
may be possible to induce or regulate their activity in the context of infection, malignancy, and immunopathology.

## Key facts

- **NIH application ID:** 10488590
- **Project number:** 5P01AI145815-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Ananda W Goldrath
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $489,800
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488590

## Citation

> US National Institutes of Health, RePORTER application 10488590, Regulation of memory T cell differentiation and long-term maintenance (5P01AI145815-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10488590. Licensed CC0.

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