# Functional mapping of ex-regulatory T cell phenotypic diversity

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $52,694

## Abstract

PROJECT SUMMARY/ABSTRACT
Regulatory and effector T cells serve distinct immunological roles that contribute to immune homeostasis.
Whereas effector T cells have the functional capacity to protect the host from infectious threats and cancer,
regulatory T cells (Tregs) are suppressive in nature and prevent runaway effector T cell-mediated inflammation
and autoimmunity. Although these are distinct cell lineages determined primarily during thymic selection, it is
now understood that the two can interconvert – T cells can assume regulatory phenotypes in the periphery,
and Tregs may lose suppressive capacity to become pro-inflammatory “ex-regulatory” T cells (exTregs).
Because exTregs can subvert traditional regulatory T cells to exacerbate inflammation and contribute to
pathologic autoimmune progression, there is great interest in understanding how and under what conditions
exTregs develop. In preliminary work from our lab, we found that single cell RNA sequencing reveals extensive
phenotypic heterogeneity of primary Tregs and exTregs from mouse gut, lungs, and lymph nodes. I propose
using single cell genomics approaches to fully define the gene regulatory programs that govern exTreg
development and polarization from destabilized Tregs. In my first aim, I will deeply analyze the single cell
RNA sequencing data set to define the heterogeneity of exTreg phenotypes in distinct tissue
microenvironments from which they were isolated. For my second aim, I will leverage my sponsors’ expertise
in high-throughput genetic perturbation of primary mouse Tregs to perform a forward genetic screen to map the
gene regulatory programs that maintain Treg identity and destabilize Tregs to exTregs induced by
pro-inflammatory cytokines IL-4 or IL-6. My sponsor Alex Marson has extensive expertise in the genetics of
immune cell function and autoimmunity, and in genetic engineering of primary T cells using CRISPR-Cas9. My
co-sponsor Chun (Jimmie) Ye is a computational immunologist and human geneticist whose laboratory uses
innovative technologies like single cell RNA sequencing to molecularly define processes of immune cell
development and function. Additionally, I have secured scientific and career mentorship from renowned
immunologists Dr. Jeffrey Bluestone (characterized exTregs in autoimmune inflammation) and Dr. Qizhi Tang
(studies immune tolerance and autoimmunity). Concurrently, I am completing a longitudinal clinical
preceptorship in pediatric immunology with Dr. Alice Chan, director of the UCSF Benioff Children’s Hospital
Pediatric Immune Dysregulation Clinic and expert in genetic diagnosis of pediatric immune disorders. Overall,
the proposed work will further our understanding of exTregs development and their role in autoimmune
pathogenesis and progression. Moreover, this fellowship support will foster my training in immunology and
computational biology, supporting me on my path through combined MD-PhD training towards a career as an
academic pediatric immunologist...

## Key facts

- **NIH application ID:** 10526432
- **Project number:** 5F30AI157167-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Cody Mowery
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $52,694
- **Award type:** 5
- **Project period:** 2020-12-01 → 2024-05-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526432

## Citation

> US National Institutes of Health, RePORTER application 10526432, Functional mapping of ex-regulatory T cell phenotypic diversity (5F30AI157167-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10526432. Licensed CC0.

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