# Transcriptional Control of Natural Killer Cell Development

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $486,000

## Abstract

Project Summary/Abstract
Natural killer cells (NK) are the innate counterpart to CD8 T cells, endowed with the
ability to rapidly kill virus-infected cells and cancer cells and produce proinflammatory
cytokines (IFNγ, TNF). These functional attributes make NK cells an attractive target for
immunotherapy against multiple types of cancer, and they have been proven useful in
graft versus leukemia. However, appropriate regulation of NK cell function is needed to
avoid autoimmunity, immune deficiency, and NK cell transformation. Therefore,
understanding how NK cell number and function are regulated is essential for the
effective use of NK cells as therapeutic agents for eradication of disease. The mature
NK cell population is composed of multiple phenotypically distinct subsets that have
unique functional abilities. A subset of mature NK cells (mNK1), with a CD27+CD11b-
phenotype, maintains the cytotoxic effector pool (CD27-CD11b+) as well as generating
“memory” NK cells. Our work seeks to understand the transcriptional basis for
maintenance of the mNK1 population and the mechanisms controlling their
differentiation and cytokine responsiveness. In this grant we will test the hypothesis that
E protein transcription factors induce a transcriptional program that maintains the
CD27+CD11b- precursor population and that this program is ID2 during effector
maturation. We will also test the hypothesis that the transcription factor ETS1
collaborates with E proteins and E protein targets to control mNK1 differentiation and
cytokine induced activation. This work will provide a foundation for understanding the
mechanisms that control NK cell number and function and provide insight into the
transcriptional network that can be manipulated to control the function of these cells in
normal and diseased states.

## Key facts

- **NIH application ID:** 10318983
- **Project number:** 5R01AI106352-19
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** BARBARA L. KEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $486,000
- **Award type:** 5
- **Project period:** 2014-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318983

## Citation

> US National Institutes of Health, RePORTER application 10318983, Transcriptional Control of Natural Killer Cell Development (5R01AI106352-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10318983. Licensed CC0.

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