# Functional protein networks underlying T cell growth, proliferation and differentiation

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $377,975

## Abstract

Project Summary
 T cell is central to maintaining health. Over-exuberant T cell function leads to debilitating and fatal
inflammatory disease. Activated T cells have to grow, exit quiescence, proliferate and differentiate in order
to function. Therefore, one of the main goals for T cell research is to reveal the factors critical for the
growth, proliferation and differentiation of activated T cells. Genome-wide high-throughput approaches
have been quite powerful to reveal genes and pathways critical for T cell function. Most of the T cell high-
throughput studies performed in the past used mRNA-based analysis, with the notion that mRNA
expression will reflect the protein expression. However, accumulating evidence supports that protein and
mRNA expression does not entirely correlate and can be quite different at times. In addition, the post-
translational modifications of a protein and the factors a protein associating with can profoundly influence
the function of a protein. Thus, to appreciate how the function of activated T cells is controlled, we need to
know the protein-networks underlying T cell function in a systemic fashion, the knowledge we grossly lack
to date. The recent advance of proteomic technology afforded high-speed, high-throughput, high-sensitivity
and high-resolution protein analysis with microgram-scale protein samples. We have established robust
experimental system to evaluate functional protein-networks in T cells. This system aided us to
successfully identify new factors critical for the function of activated T cells. Encouraged by the results, we
set the overarching goal of this study to reveal the protein networks underlying the function of
activated T cells. A particular focus of this proposal is to reveal and assess the function of factors whose
protein and mRNA are discretely regulated, aiming to identify novel molecular mechanisms that could not
be revealed by classic mRNA-based analysis. By combining cutting edge MS/proteomics approach with
innovative mouse model and genomic editing/genetic methods, we strive to reach the following research
aims: Aim 1: Systemically analyze the protein expression dynamics during T cell growth, quiescence exit,
and proliferation. Aim 2: Investigate the differential protein expression and its biological significance for Th
cell differentiation.
 Systemic analysis of the protein expression and interaction in various stages of T cell function will, for
the first time, provide an atlas for the protein networks underlying T cell biology. In combination and
comparison with mRNA-based genomic analysis, it will establish a molecular map for the normal function of
activated T cells. This map will help us to identify new factors and pathways critical for specific T cell
functions and to reveal the deregulated factors in T cells in immune diseases including cancer, SCID,
inflammation and autoimmunity, aiding the efforts to discover the bio-markers for disease diagnosis and
prognosis and to find s...

## Key facts

- **NIH application ID:** 9825429
- **Project number:** 5R01AI123193-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Yisong Wan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,975
- **Award type:** 5
- **Project period:** 2016-12-12 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9825429

## Citation

> US National Institutes of Health, RePORTER application 9825429, Functional protein networks underlying T cell growth, proliferation and differentiation (5R01AI123193-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9825429. Licensed CC0.

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