# CAREER: Deciphering T Cell Reprogramming - Toward Biomanufacturing of Regulatory T Cells

> **NSF 01002627DB NSF RESEARCH & RELATED ACTIVIT** · Regents of the University of Michigan - Ann Arbor (MI) · $605,420

## Abstract

Infections challenge the human immune system to balance two competing responses. The immediate response is acute inflammation. This targets the damaged or infected area with immune cells. The second response is to reduce inflammation as antibodies are produced and transported to the infection site. This is accomplished by producing T cells that defend against foreign entities and regulatory T cells (Tregs) that mitigate runaway inflammation. Tregs can also be effective in treating diseases associated with chronic inflammation such as diabetes, Alzheimer's, asthma, and heart disease. They are, however, difficult to produce outside the body. This CAREER project will employ an engineered three-dimensional culture system to investigate how Tregs form inside the body. An integrated education and outreach program emphasizing scientific communication skills will also be developed and delivered.

The complex balance between inflammation and self-tolerance is fundamental to immune system function. Administration of therapeutic regulatory T cells (Tregs) to restore this balance holds tremendous potential to treat inflammatory conditions. Manufacturing these cells is a challenge, because how they are naturally generated is poorly understood. Although T cells can be reprogrammed to Tregs in vivo, a mechanistic understanding of this process is lacking. Current induced Tregs generated in vitro lack the stability and epigenetic signatures of naturally occurring peripheral Tregs, limiting their therapeutic potential.  Assessing T cell reprogramming into Treg using engineered microenvironments that replicate natural cellular communication will be employed to address this knowledge gap. The primary project goal will be to understand how conventional T cells are reprogrammed into Treg through choreographed cell-cell communication. The central hypothesis is that in vitro T cell reprogramming on plastic surfaces fails due to missing microenvironmental signals, including molecular cues

## Key facts

- **NSF award ID:** 2542013
- **Awardee organization:** Regents of the University of Michigan - Ann Arbor (MI)
- **SAM.gov UEI:** GNJ7BBP73WE9
- **PI:** Aaron H Morris
- **Primary program:** 01002627DB NSF RESEARCH & RELATED ACTIVIT
- **All programs:** CAREER-Faculty Erly Career Dev, Quantitative sys bio and biotech
- **Estimated total:** $605,420
- **Funds obligated:** $605,420
- **Transaction type:** Standard Grant
- **Period:** 05/01/2026 → 04/30/2031

## Primary source

NSF Award Search: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2542013

## Citation

> US National Science Foundation, Award 2542013, CAREER: Deciphering T Cell Reprogramming - Toward Biomanufacturing of Regulatory T Cells. Retrieved via AI Analytics 2026-07-20 from https://api.ai-analytics.org/grant/nsf/2542013. Licensed CC0.

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