# Transcriptional control of NK cell metabolism

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $776,159

## Abstract

Project Summary
Natural killer (NK) cells comprise an important arm of the host innate immune system that detects and
eliminates virus-infected cells. Newborns and immune-compromised patients lacking NK cells are
extremely susceptible to viral infection. In particular, human cytomegalovirus (HCMV) can cause severe
health complications or be life-threatening in these individuals. Mouse cytomegalovirus (MCMV) is an
accurate and robust model for investigating NK cell responses against HCMV. Using MCMV infection in
mice, we have discovered that NK cells possess novel adaptive immune features such as clonal
expansion and long-lived memory. In the past decade, our laboratory has uncovered many of the cellular
and molecular mechanisms underlying NK cell memory. Our long-term goals are to understand the
general biology of NK cells, and the molecular basis by which these powerful innate lymphocytes can
mediate protection against pathogen invasion. To this end, we have recently identified several
transcriptional and metabolic pathways that may influence the NK cell response against MCMV infection.
Based on this exciting preliminary data, our current R01 grant proposes to use cutting edge metabolomics
and newly engineered transgenic mouse models to study how metabolism in antiviral NK cells in
transcriptionally regulated. In Aim 1, we seek to understand how proinflammatory cytokines and the STAT
family of transcription factors control of NK cell metabolism during MCMV infection. In Aim 2, we will
determine the requirement for aerobic glycolysis and fatty acid oxidation in antiviral NK cells using
conditional ablation of genes encoding LDHA and CPT1a, respectively. In Aim 3, we will determine
whether the transcription factor Bhlhe40 regulates mitochondrial metabolism and fitness in effector NK
cells fighting MCMV infection. Altogether, the studies in this R01 proposal will greatly increase our
understanding of the underlying transcriptional and metabolic mechanisms whereby NK cells contribute
to host defense during viral infection, and establish novel translational paradigms for harnessing the NK
cell compartment for immunization and therapeutic strategies against infectious diseases.

## Key facts

- **NIH application ID:** 10348787
- **Project number:** 5R01AI155558-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Joseph Chai-Yuen Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $776,159
- **Award type:** 5
- **Project period:** 2021-02-10 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348787

## Citation

> US National Institutes of Health, RePORTER application 10348787, Transcriptional control of NK cell metabolism (5R01AI155558-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10348787. Licensed CC0.

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